e424b4
Filed pursuant to Rule 424(b)(4)
Registration Statement Nos. 333-129037 and 333-131285
P R O S P E C T U S
Issued January 26, 2006
7,000,000 Shares
Common Stock
This is the initial public offering of our common stock. We are
offering 7,000,000 shares of common stock.
Prior to this offering, there has been no public market for the
common stock. Our common stock has been approved for quotation
on the Nasdaq National Market under the symbol ALTU.
Investing in our common stock involves risks that are
described in the Risk Factors section beginning on
page 7 of this prospectus.
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Per Share | |
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Total | |
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Public offering price
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$ |
15.00 |
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$ |
105,000,000 |
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Underwriting discounts and commissions
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$ |
1.05 |
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$ |
7,350,000 |
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Proceeds, before expenses, to Altus Pharmaceuticals Inc.
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$ |
13.95 |
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$ |
97,650,000 |
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The underwriters may also purchase up to an additional
1,050,000 shares of common stock from us at the public
offering price, less the underwriting discounts and commissions,
within 30 days from the date of this prospectus to cover
overallotments.
Neither the Securities and Exchange Commission nor any state
securities commission has approved or disapproved of these
securities or determined if this prospectus is truthful or
complete. Any representation to the contrary is a criminal
offense.
The shares of common stock will be ready for delivery on or
about January 31, 2006.
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Merrill Lynch & Co. |
Morgan Stanley |
SG Cowen & Co.
TABLE OF CONTENTS
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F-1 |
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You should rely only on the information contained in this
prospectus or to which we have referred you. We have not, and
the underwriters have not, authorized anyone to provide you with
different information. If anyone provides you with different or
inconsistent information, you should not rely on it. We are
offering to sell, and are seeking offers to buy, shares of
common stock only in jurisdictions where offers and sales are
permitted. The information contained in this prospectus is
accurate only as of the date of this prospectus, regardless of
the time of delivery of this prospectus or of any sale of the
common stock. Our business, financial conditions, results of
operations and prospects may have changed since that date.
For investors outside the United States: Neither we nor any of
the underwriters have done anything that would permit this
offering or possession or distribution of this prospectus in any
jurisdiction where action for that purpose is required, other
than in the United States. You are required to inform yourselves
about and to observe any restrictions relating to this offering
and the distribution of this prospectus.
PROSPECTUS SUMMARY
This summary highlights selected information contained
elsewhere in this prospectus. This summary does not contain all
of the information you should consider before buying shares of
our common stock. You should read the entire prospectus
carefully, especially the risks of investing in shares of our
common stock that we describe under Risk Factors,
and our consolidated financial statements and the related notes
included at the end of this prospectus, before deciding to
invest in shares of our common stock. Unless the context
requires otherwise, references to Altus,
we, our and us in this
prospectus refer to Altus Pharmaceuticals Inc. and our
subsidiary.
ALTUS PHARMACEUTICALS INC.
Our Company
We are a biopharmaceutical company focused on the development
and commercialization of oral and injectable protein
therapeutics for chronic gastrointestinal and metabolic
disorders, with two product candidates in clinical development.
We are using our proprietary protein crystallization technology
to develop protein therapies which we believe will have
significant advantages over existing products or will address
unmet medical needs. Our two lead product candidates are:
ALTU-135, for which we have successfully completed a
Phase II clinical trial in cystic fibrosis patients for the
treatment of malabsorption due to exocrine pancreatic
insufficiency, and ALTU-238, for which we are currently
conducting a Phase II clinical trial in adults for the
treatment of growth hormone deficiency. Our Phase II
clinical trial of ALTU-135 reached its primary efficacy
endpoint, a statistically significant improvement in fat
absorption. We also have a pipeline of other product candidates
in preclinical research and development.
Our Lead Product Candidates
ALTU-135 for Exocrine Pancreatic Insufficiency. ALTU-135
is an
orally-administered
enzyme replacement therapy for the treatment of malabsorption
due to exocrine pancreatic insufficiency. Exocrine pancreatic
insufficiency is a deficiency of digestive enzymes normally
produced by the pancreas which leads to malnutrition, impaired
growth and shortened life expectancy. Exocrine pancreatic
insufficiency can result from a number of diseases and
conditions, including cystic fibrosis, chronic pancreatitis and
pancreatic cancer. According to IMS Health, global prescription
sales of existing pancreatic enzyme replacement products were
$658 million in 2004.
We believe that ALTU-135, if approved, will have significant
competitive advantages compared to existing pancreatic enzyme
replacement therapies. The existing therapies are derived from
pig pancreases and are expected to be subject to increased
regulatory scrutiny based on the Food and Drug Administration,
or FDA, guidelines for such therapies released in
April 2004. We believe the potential advantages of
ALTU-135 include:
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benefits associated with a drug that is microbially-derived,
rather than a drug derived from pig pancreases, and manufactured
in a controlled environment; |
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a significantly lower pill burden, allowing patients to take, on
average, one capsule per meal or snack compared to, on average,
four or five larger capsules per meal or snack with existing
products; |
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more consistent and reliable dosing; |
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resistance to degradation early in the gastrointestinal tract,
permitting enzyme activity where most digestion and absorption
of fats, proteins and carbohydrates normally occurs; |
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the potential for a liquid formulation, which is currently
unavailable, for children and adults who are unable to swallow
capsules; and |
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testing in what we believe is the largest well-controlled,
scientifically-rigorous prospective clinical trial conducted to
date in the treatment of cystic fibrosis patients with
pancreatic insufficiency. |
1
We believe that many of these advantages are a result of our
proprietary protein crystalization technology, which enables
improved product consistency and stability, as well as higher
concentration and purity. We may be unable to achieve or
demonstrate the potential advantages of
ALTU-135 noted above
for many reasons, including the risks described in the section
entitled Risk Factors immediately following this
prospectus summary.
In our recently completed prospective, randomized, double-blind,
dose-ranging Phase II clinical trial of the solid form of
ALTU-135, the product
candidate was well tolerated and showed a statistically
significant improvement in fat absorption, the trials
primary efficacy endpoint, in the two high dose treatment arms.
In these two treatment arms, we also observed a statistically
significant improvement in protein absorption and a
statistically significant decrease in stool weight, each of
which was a secondary endpoint in the study. In addition, we
observed a positive trend, although not statistically
significant, in carbohydrate absorption in these treatment arms.
We recently met with the FDA to discuss the results of our
Phase II clinical trial and our planned Phase III
clinical trial for the solid form of
ALTU-135. We expect to
initiate a pivotal Phase III clinical trial of the solid
form of ALTU-135 in
cystic fibrosis patients in the second half of 2006 and to
complete clinical testing in this trial in the first half of
2007. We also expect to initiate a long-term safety study in
cystic fibrosis patients and other patients with pancreatic
insufficiency in the second half of 2006. The FDA and the
European Medicines Agency, or EMEA, have granted ALTU-135 orphan
drug designation. Additionally, the FDA has granted ALTU-135
fast track designation and admission into its Continuous
Marketing Application, or CMA, Pilot 2 Program, which is
designed to facilitate interactions between a drug developer and
the FDA during the drug development process.
ALTU-238 for Growth Hormone Deficiency and Related
Disorders. ALTU-238
is a crystallized formulation of human growth hormone, or hGH,
that is designed to be injected once weekly with a fine gauge
needle for the treatment of growth hormone deficiency and
hGH-related disorders. Human growth hormone deficiency can
result in reduced growth in children and lead to short stature
and other disorders in adults, such as lipid abnormalities,
decreased bone density, obesity, insulin resistance, decreased
cardiac performance and decreased muscle mass. Based on reported
revenues of existing products, global sales of hGH products
exceeded $2.2 billion in 2004, and the market grew at a
compound annual growth rate of approximately 15% from 2002 to
2004.
We are developing
ALTU-238 for both adult
and pediatric populations as an alternative to current
therapies. Current medical guidelines for clinical practice
generally recommend daily administration of existing therapies
by subcutaneous injection. We believe that the burden of daily
injections significantly impacts quality of life for both adults
and children being treated with hGH therapy and often leads to
reduced compliance or a reluctance to initiate therapy. Our
crystalline formulation of hGH is designed to release hGH into a
patients bloodstream over a period of time without any
alteration of the hGH molecule. In our Phase I clinical
trial of ALTU-238,
which we completed in June 2005,
ALTU-238 demonstrated
pharmacokinetic and pharmacodynamic parameters that are
consistent with once-weekly administration. We recently
initiated a Phase II clinical trial for
ALTU-238 in adults with
growth hormone deficiency and expect to have data from this
trial in the first half of 2006.
Our Protein Crystallization Technology
Our product candidates are based on our proprietary technology,
which enables the large-scale crystallization of proteins for
use as therapeutic drugs. We believe that by using our
technologies we are able to overcome many of the limitations of
existing protein therapies and deliver proteins in solid and
liquid oral forms, as well as in extended-release injectable
formulations. Our product candidates are designed to offer
improvements over existing products, such as greater
convenience, better safety and efficacy and longer shelf life.
In addition, we believe that we may be able to reduce the
development risk and time to market for our drug candidates
because we apply our technology to existing, well-understood
proteins with well-defined mechanisms of action. We believe that
our technology is broadly applicable to different classes of
proteins, including enzymes, hormones, antibodies, cytokines and
peptides. To date, we have crystallized more than 70 proteins
for evaluation in our research and development programs.
2
Our Strategy
Our goal is to become a leading biopharmaceutical company
focused on developing and commercializing protein therapies to
address unmet medical needs in chronic gastrointestinal and
metabolic disorders. The key elements of our strategy to achieve
this objective include the following:
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Focus on advancing our lead product candidates,
ALTU-135 and
ALTU-238, through
clinical trials to submission of a new drug application, or NDA; |
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Continue to build and advance our product pipeline for
gastrointestinal and metabolic disorders; |
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Establish a commercial infrastructure and targeted specialty
sales force in North America; |
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Selectively establish collaborations for our product candidates
with leading pharmaceutical and biotechnology companies in cases
where we believe their expertise can help us to accelerate the
development of or more effectively commercialize our product
candidates; and |
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Establish additional collaborations to apply our technology to
other therapeutic proteins. |
Risks Associated with Our Business
Our business is subject to numerous risks, as more fully
described in the section entitled Risk Factors
immediately following this prospectus summary. We may be unable,
for many reasons, including those that are beyond our control,
to implement our current business strategy. Those reasons could
include unfavorable clinical trial results; delays in obtaining,
or a failure to obtain, regulatory approval for our product
candidates; problems that may arise under our licensing and
collaboration agreements; and failure to maintain and protect
our proprietary intellectual property assets.
We have incurred significant losses since 1999, when we were
reorganized as a company independent from Vertex Pharmaceuticals
Incorporated, or Vertex. We incurred net losses of $17.3 million
in 2002, $15.2 million in 2003, $21.0 million in 2004 and $19.1
million in the nine months ended September 30, 2005. At
September 30, 2005, our accumulated deficit was
$112.1 million, and we expect to continue to incur losses
for at least the next several years. We have only been able to
generate limited amounts of revenue from license and milestone
payments under our collaboration agreements, payments for funded
research and development and products we no longer sell. None of
our product candidates have been approved by the FDA for
commercial sale. We expect that our annual operating losses will
increase over the next several years as we advance
ALTU-135,
ALTU-238 and our other
product candidates. We are unable to predict the extent of
future loses or when we will become profitable, if at all. Even
if we succeed in developing and commercializing one or more of
our product candidates, we may never generate sufficient revenue
to achieve and sustain profitability.
Our Corporate Information
We were incorporated in Massachusetts in October 1992 as a
wholly-owned subsidiary of Vertex, from whom we exclusively
license specified patents underlying some of our product
candidates. In February 1999, we were reorganized as an
independent company, and in August 2001 we reincorporated in
Delaware. Prior to May 2004, we were named Altus Biologics Inc.
Our principal executive offices are located at 125 Sidney
Street, Cambridge, MA 02139, and our telephone number is
(617) 299-2900. Our web site address is
www.altus.com. The information contained on, or that can
be accessed through, our web site is not incorporated by
reference into this prospectus. We have included our web site
address as a factual reference and do not intend it to be an
active link to our web site. We have one subsidiary, Altus
Pharmaceuticals Securities Corp., a Massachusetts corporation.
Altus is a trademark of Altus Pharmaceuticals Inc. Each of the
other trademarks, trade names or service marks appearing in this
prospectus belongs to its respective holder.
3
THE OFFERING
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Common stock offered by us |
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7,000,000 shares |
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Common stock to be outstanding after this offering |
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21,001,943 shares |
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Use of proceeds |
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We intend to use the net proceeds of this offering to fund
clinical trial activities, preclinical research and development
activities and for other general corporate purposes, including
capital expenditures and working capital. See Use of
Proceeds. |
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Nasdaq National Market symbol |
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ALTU |
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Risk factors |
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See Risk Factors and the other information included
in this prospectus for a discussion of factors you should
carefully consider before deciding to invest in shares of our
common stock. |
Except as otherwise indicated, the number of shares to be
outstanding after this offering throughout this prospectus is
based on the number of shares outstanding on December 31,
2005, and excludes:
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3,056,807 shares of common stock issuable upon the exercise
of outstanding stock options as of December 31, 2005, with
a weighted average exercise price of $4.26 per share; |
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4,121,189 shares of common stock issuable upon the exercise
of outstanding warrants as of December 31, 2005, with a
weighted average exercise price of $7.17 per share; and |
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1,497,030 shares available for future issuance under our
Amended and Restated 2002 Director, Employee and Consultant
Stock Plan to be effective upon the closing of this offering,
including 297,030 shares available as of December 31,
2005. |
In addition, except as otherwise indicated, the information
throughout this prospectus:
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gives effect to the conversion of all outstanding shares of our
convertible preferred stock into 10,767,306 shares of
common stock, which will occur automatically upon the closing of
this offering; |
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gives effect to the issuance of 1,391,828 shares of common
stock to the holders of our Series B and C convertible
preferred stock upon the closing of this offering in
satisfaction of accumulated dividends, as required by the terms
of the Series B and C convertible preferred stock, all
of which is described more fully under the section of this
prospectus entitled Capitalization; |
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assumes no exercise by the underwriters of their option to
purchase up to 1,050,000 additional shares of common stock from
us in the offering; |
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reflects a 1-for-2.293 reverse split of our common stock
effected in January 2006; and |
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gives effect to the filing of our restated certificate of
incorporation and the adoption of our restated bylaws upon the
completion of this offering. |
4
SUMMARY CONSOLIDATED FINANCIAL DATA
We have derived the following summary of our consolidated
statements of operations data for the years ended
December 31, 2002, 2003 and 2004 from our audited
consolidated financial statements appearing elsewhere in this
prospectus. We have derived the following summary of our
consolidated statements of operations data for the nine months
ended September 30, 2004 and 2005 and the consolidated
balance sheet data as of September 30, 2005 from our
unaudited consolidated financial statements appearing elsewhere
in this prospectus. The summary of our consolidated financial
data set forth below should be read together with our
consolidated financial statements and the related notes to those
statements, as well as Managements Discussion and
Analysis of Financial Condition and Results of Operations,
appearing elsewhere in this prospectus.
The pro forma unaudited balance sheet data as of
September 30, 2005 gives effect to the conversion of all
then outstanding shares of our convertible preferred stock into
10,767,306 shares of common stock, which will occur
automatically upon the closing of this offering. The pro forma
as adjusted consolidated balance sheet data as of
September 30, 2005 further reflects the receipt of the net
proceeds from our sale of 7,000,000 shares of common stock
at the initial public offering price of $15.00 per share in
this offering, after deducting the underwriting discounts and
commissions and estimated offering expenses payable by us.
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Nine Months Ended | |
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Year Ended December 31, | |
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September 30, | |
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2002 | |
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2003 | |
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2004 | |
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2004 | |
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2005 | |
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(in thousands, except per share amounts) | |
Consolidated Statements of Operations Data:
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Revenue
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Contract revenue
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$ |
1,885 |
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$ |
2,613 |
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$ |
4,045 |
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$ |
2,891 |
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$ |
6,727 |
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Product sales
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483 |
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1,268 |
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185 |
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185 |
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Total revenue
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2,368 |
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3,881 |
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4,230 |
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3,076 |
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6,727 |
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Operating expenses:
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Cost of product sales
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241 |
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578 |
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87 |
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87 |
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Research and development
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13,174 |
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13,282 |
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19,095 |
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11,995 |
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19,792 |
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General, sales and administrative
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6,859 |
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5,533 |
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6,320 |
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4,623 |
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6,003 |
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Total operating expenses
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20,274 |
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19,393 |
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25,502 |
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16,705 |
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25,795 |
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Loss from operations
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(17,906 |
) |
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(15,512 |
) |
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(21,272 |
) |
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(13,629 |
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(19,068 |
) |
Interest income
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853 |
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405 |
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646 |
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405 |
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701 |
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Interest expense
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(156 |
) |
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(251 |
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(469 |
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(351 |
) |
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(617 |
) |
Other (expense) income, net
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(81 |
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164 |
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138 |
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138 |
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(125 |
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Net loss
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(17,290 |
) |
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(15,194 |
) |
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(20,957 |
) |
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(13,437 |
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(19,109 |
) |
Preferred stock dividends and accretion
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(4,905 |
) |
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(4,905 |
) |
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(8,588 |
) |
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(5,845 |
) |
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(8,169 |
) |
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Net loss attributable to common stockholders
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$ |
(22,195 |
) |
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$ |
(20,099 |
) |
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$ |
(29,545 |
) |
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$ |
(19,282 |
) |
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$ |
(27,278 |
) |
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Basic and diluted net loss per common share
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$ |
(13.16 |
) |
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$ |
(11.92 |
) |
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$ |
(17.33 |
) |
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$ |
(11.34 |
) |
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$ |
(15.84 |
) |
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Shares used in computing basic and diluted net loss per common
share
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1,687 |
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1,687 |
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1,704 |
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1,700 |
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|
1,722 |
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5
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As of September 30, 2005 | |
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Pro Forma as | |
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Actual | |
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Pro Forma | |
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Adjusted | |
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(in thousands) | |
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Consolidated Balance Sheet Data:
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Cash and cash equivalents, and short-term investments
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$ |
32,009 |
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$ |
32,009 |
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$ |
127,309 |
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Working capital
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22,302 |
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22,302 |
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117,602 |
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Total assets
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44,171 |
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44,171 |
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139,471 |
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Deferred revenue
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10,426 |
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10,426 |
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10,426 |
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Long-term debt, net of current portion
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4,210 |
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4,210 |
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4,210 |
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Redeemable preferred stock
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116,634 |
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|
5,779 |
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|
5,779 |
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Total stockholders (deficit) equity
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(94,517 |
) |
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|
16,338 |
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111,638 |
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6
RISK FACTORS
Investing in our common stock involves a high degree of risk.
You should consider carefully the risks described below and the
other information in this prospectus, including our consolidated
financial statements and the related notes appearing at the end
of this prospectus, before deciding to invest in our common
stock. If any of the following risks actually occur, they may
materially harm our business, our financial condition and our
results of operations. In that event, the market price of our
common stock could decline, and you could lose part or all of
your investment.
Risks Related to Our Business and Strategy
If we fail to obtain the additional capital necessary to fund
our operations, we will be unable to successfully develop and
commercialize our product candidates.
We will require substantial future capital in order to continue
to complete clinical development and commercialize our
clinical-stage product candidates, ALTU-135 and ALTU-238, and to
conduct the research and development and clinical and regulatory
activities necessary to bring our other product candidates to
market. Our future capital requirements will depend on many
factors, including:
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the progress and results of our toxicology studies and proposed
Phase III clinical trial and long-term safety study for
ALTU-135 and any other trials we may initiate based on the
results of these trials; |
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the progress and results of our Phase II clinical trial for
ALTU-238 and any other trials we may initiate based on the
Phase II results; |
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the results of our preclinical studies and testing for our
earlier stage product candidates, and any decisions to initiate
clinical trials if supported by the preclinical results; |
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the costs, timing and outcome of regulatory review of ALTU-135
and ALTU-238, and any of our preclinical product candidates that
progress to clinical trials; |
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the costs of establishing sales and marketing functions, if any
of our product candidates are approved, and of establishing
commercial manufacturing arrangements; |
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the costs of preparing, filing and prosecuting patent
applications, maintaining and enforcing our issued patents, and
defending intellectual property-related claims; |
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our ability to establish and maintain collaborative arrangements
and obtain milestone, royalty and other payments from
collaborators; and |
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the extent to which we acquire or invest in businesses, products
or technologies. |
Additional funds may not be available when we need them on terms
that are acceptable to us, or at all. If adequate funds are not
available to us on a timely basis, we may be required to:
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terminate or delay preclinical studies, clinical trials or other
development activities for one or more of our product
candidates; or |
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delay our establishment of sales and marketing capabilities or
other activities that may be necessary to commercialize our
product candidates. |
Based on our operating plans, we estimate that our net cash used
in operating activities will be between $55 million and
$65 million in 2006. We currently expect that the proceeds
we receive from this offering, our existing cash resources and
investment securities and payments we expect to receive from our
existing collaborators will be sufficient to support the
development of our product candidates and our other operations,
as more specifically identified in the Use of
Proceeds section of this prospectus, through the first
half of 2007. We expect that in the first half of 2007 we will
have completed the clinical testing in the Phase III
clinical trial of the solid form of
ALTU-135, will be
conducting the long-term safety study for ALTU-135, and will be
conducting a Phase III clinical trial in adults and a
Phase II/III clinical trial in children for ALTU-238. We do
not expect that we will be required to make any payments to our
existing collaborators prior to approval of
ALTU-135. However, our
operating plan may change as a result of many
7
factors, including factors currently unknown to us, and we may
need additional funds sooner than planned. We do not expect the
net proceeds from this offering and our other available funds to
be sufficient to fund the completion of the development of any
of our product candidates, and we expect that we will need to
raise additional funds prior to being able to market any
products. Additional funding may not be available to us on
acceptable terms, or at all.
We are obligated under our agreement with CFFTI and under the
terms of our redeemable preferred stock to make significant
payments upon the occurrence of specified events. We may not
have sufficient resources to make these payments when they
become due.
If we receive FDA approval for ALTU-135 or related products, we
must pay one of our collaborators, Cystic Fibrosis Foundation
Therapeutics, Inc., or CFFTI, an affiliate of the Cystic
Fibrosis Foundation, an amount equal to CFFTIs aggregate
funding to us plus interest, up to a maximum of
$40.0 million, less the fair market value of the shares of
stock underlying the warrants we issued to CFFTI. This amount,
together with accrued interest, will be due in four annual
installments, commencing 30 days after the approval date.
We will also be required to pay an additional $1.5 million
to CFFTI within 30 days after the approval date. Our
initial payments to CFFTI upon approval of ALTU-135 will be due
before we receive revenue from commercial sales of the product,
which could require us to raise additional funds or make it
difficult for us to make the payments in a timely manner. In
addition, if the holder of our redeemable preferred stock elects
to redeem those shares on or after December 31, 2010, we
will be required to pay an aggregate of $7.2 million plus
dividends accruing after that date. We may require additional
funding to make any such payments. Additional funds may not be
available to us on acceptable terms, or at all.
We have a history of net losses, which we expect to continue
for at least several years and, as a result, we are unable to
predict the extent of any future losses or when, if ever, we
will achieve, or be able to maintain, profitability.
We have incurred significant losses since 1999, when we were
reorganized as a company independent from Vertex. We incurred
net losses of $17.3 million in 2002, $15.2 million in 2003,
$21.0 million in 2004 and $19.1 million in the nine months
ended September 30, 2005. At September 30, 2005, our
accumulated deficit was $112.1 million and we expect to
continue to incur losses for at least the next several years. We
have only been able to generate limited amounts of revenue from
license and milestone payments under our collaboration
agreements, and payments for funded research and development, as
well as from products we no longer sell. We expect that our
annual operating losses will increase over the next several
years as we expand our research, development and
commercialization efforts to advance ALTU-135, ALTU-238 and our
other product candidates towards commercialization.
We must generate significant revenue to achieve and maintain
profitability. All of our product candidates are still in
early-to-mid stages of
development. Even if we succeed in developing and
commercializing one or more of our product candidates, we may
not be able to generate sufficient revenue or achieve or
maintain profitability. Our failure to become and remain
profitable would depress the market price of our common stock
and could impair our ability to raise capital, expand our
business, diversify our product offerings or continue our
operations.
Our competitors may develop products that are less expensive,
safer or more effective, which may diminish or prevent the
commercial success of any product candidates that we bring to
market.
Competition in the pharmaceutical and biotechnology industries
is intense and expected to increase. We face competition from
pharmaceutical and biotechnology companies, as well as numerous
academic and research institutions and governmental agencies
engaged in drug discovery activities or funding, both in the
United States and abroad. Some of these competitors have
products or are pursuing the development of product candidates
that target the same diseases and conditions that are the focus
of
8
our drug development programs, including those set forth below.
In addition, there may be others of which we are unaware.
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ALTU-135. If approved, ALTU-135, the product candidate we
are developing for the treatment of malabsorption due to
exocrine pancreatic insufficiency, will compete with currently
marketed porcine-derived pancreatic enzyme replacement therapies
from companies such as Axcan Pharma, Johnson & Johnson,
and Solvay Pharmaceuticals, as well as from generic drug
manufacturers such as KV Pharmaceutical and IMPAX Laboratories.
In addition, we understand that Biovitrium and Meristem
Therapeutics have product candidates in clinical development
that could compete with ALTU-135. |
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ALTU-238. If approved, ALTU-238, the product candidate we
are developing as a once-weekly treatment for hGH deficiency and
related disorders, will compete with approved hGH therapies from
companies such as Genentech, Pfizer, Serono, Novo Nordisk, Teva
Pharmaceutical Industries and Eli Lilly. In addition, we
understand that
ALTU-238 may compete
with product candidates in clinical development from some of
these companies and others, including LG Life Sciences, which is
developing a long-acting hGH therapy based on an encapsulated
microparticle technology. |
Existing products to treat exocrine pancreatic insufficiency
have been marketed in the United States since before the passage
of the Federal Food, Drug, and Cosmetic Act, or FDCA, in 1938
and are currently marketed without FDA-approved NDAs. In 1995,
the FDA issued a final rule requiring that these pancreatic
enzyme products be marketed by prescription only, and in April
2004, the FDA issued a notice that manufacturers of these
products will be subject to regulatory action if they do not
obtain approved NDAs for their products by April 28, 2008.
Despite the FDAs announced position, the agency may not
pursue regulatory action against these companies if they fail to
meet the 2008 deadline because there are currently no other
products on the market for the treatment of exocrine pancreatic
insufficiency. The level of competition that
ALTU-135, if approved,
will face from these products in the United States will depend
on whether the manufacturers of these products obtain approved
NDAs by the deadline set by the FDA and, if they are unable to
do so, whether the FDA takes regulatory action against these
manufacturers and the nature of any such action. The nature of
the competition that
ALTU-135, if approved,
faces from existing pancreatic enzyme products could affect the
market acceptance of
ALTU-135 or require us
to lower the price of
ALTU-135, which would
negatively impact our margins and our ability to achieve
profitability.
Raising additional capital by issuing securities or through
collaboration and licensing arrangements may cause dilution to
existing stockholders, restrict our operations or require us to
relinquish proprietary rights.
We may seek the additional capital necessary to fund our
operations through public or private equity offerings, debt
financings, and collaboration and licensing arrangements. To the
extent that we raise additional capital through the sale of
equity or convertible debt securities, your ownership interest
will be diluted, and the terms of such securities may include
liquidation or other preferences that adversely affect your
rights as a stockholder. In addition, many of the warrants that
we have issued contain anti-dilution provisions that will result
in the issuance of additional shares of common stock upon
exercise, and thus further dilution, if we issue or are deemed
to issue equity at a per share price less than the exercise
price of the warrants. Debt financing, if available, may involve
agreements that include covenants limiting or restricting our
ability to take specific actions such as incurring additional
debt, making capital expenditures, or declaring dividends. If we
raise additional funds through collaboration and licensing
arrangements with third parties, we may have to relinquish
valuable rights to our technologies or product candidates, or
grant licenses on terms that are not favorable to us.
9
We may not be successful in maintaining our existing
collaborations or in establishing and maintaining additional
collaborations on acceptable terms, which could adversely affect
our ability to develop and commercialize our products.
An element of our business strategy is to establish
collaborative arrangements with third parties, particularly with
regard to development, regulatory approval, sales, marketing and
distribution of our products outside of North America. We may
also collaborate with other companies to accelerate the
development of some of our early-stage product candidates, or to
co-promote our product candidates
in North America in instances
where we believe that a larger sales and marketing presence will
expand the market or accelerate penetration. The process of
establishing new collaborative relationships is difficult,
time-consuming and involves significant uncertainty. We
face, and will continue to face, significant competition in
seeking appropriate collaborators. Moreover, if we do establish
collaborative relationships, our collaborators may fail to
fulfill their responsibilities or seek to renegotiate or
terminate their relationships with us due to unsatisfactory
clinical results, a change in business strategy, a change of
control or other reasons. If we are unable to establish and
maintain collaborative relationships on acceptable terms, we may
have to delay or discontinue further development of one or more
of our product candidates, undertake development and
commercialization activities at our own expense or find
alternative sources of funding.
For example, we have entered into a collaboration agreement with
CFFTI under which we have received significant funding for the
development of ALTU-135. We are also eligible to receive
additional payments if we achieve specified milestones under the
agreement. Additionally, the collaboration provides us with
access to the Cystic Fibrosis Foundations network of
medical providers, patients, researchers and others involved in
the care and treatment of cystic fibrosis patients. Our
agreement with CFFTI provides for an exclusive license from us
to CFFTI, and an exclusive sublicense back with a right to
further sublicense from CFFTI, of intellectual property rights
covering the development and commercialization of ALTU-135 in
North America. The agreement with CFFTI requires us to use
commercially reasonable efforts to develop and commercialize
ALTU-135 in North
America for the treatment of malabsorption due to exocrine
pancreatic insufficiency in patients with cystic fibrosis and
other indications. We are also required to meet specified
milestones under the agreement by agreed upon dates. If we are
unable to satisfy our obligations under the agreement, we may
lose further funding under the agreement and lose our exclusive
sublicense to ALTU-135
in North America, which will materially harm our business.
We are in discussions with our collaborator Dr. Falk
Pharma GmbH regarding its claim that we have breached a
representation in our collaboration agreement. If we are unable
to successfully resolve this matter, our business may be
materially harmed.
We have entered into a collaboration agreement with
Dr. Falk Pharma GmbH, or Dr. Falk, a specialty
pharmaceutical company headquartered in Germany. We have
received substantial funding from Dr. Falk for the
development and commercialization of
ALTU-135 in Europe, the
countries of the former Soviet Union, Egypt and Israel, and we
are eligible to receive additional payments if we achieve
specified milestones under the agreement. Dr. Falk has
asserted that there is a third-party European patent issued in
specified countries, including Germany, France and the United
Kingdom, with claims that may be relevant to
ALTU-135 and,
therefore, that we breached a representation in our agreement
with Dr. Falk and may be liable for damages under our
agreement. We do not believe that we breached our agreement, and
we are in discussions with Dr. Falk to resolve this matter.
We also believe that if this patent were asserted against us, it
is likely that we would not be found to infringe any valid claim
of the patent relevant to our development and commercialization
of ALTU-135. However,
if the patent were successfully asserted against us or
Dr. Falk and we were unable to obtain a license on
commercially acceptable terms, we and Dr. Falk would be
prevented during the patent term from commercializing
ALTU-135 in the covered
countries. Based on our current development timeline for
ALTU-135 in Europe and
excluding any patent term extensions, we expect that the patent
in question would expire approximately three years after we
would expect to receive marketing authorization for
ALTU-135 in Europe. We
may not reach a resolution of this matter with Dr. Falk, or
prevail if the patent were asserted against us, or, if
necessary, be able to
10
obtain a license under the patent on commercially acceptable
terms, if at all. If we are unable to do so, our business could
be materially harmed.
Risks Related to Development of Our Product Candidates
If we are unable to commercialize either of our lead product
candidates, or experience significant delays in doing so, our
business will be materially harmed.
We have invested a significant portion of our time and financial
resources to date in the development of oral and injectable
crystallized protein therapies, including
ALTU-135 and
ALTU-238, for the
treatment of chronic gastrointestinal and metabolic disorders.
Our ability to successfully develop and commercialize
ALTU-135 and
ALTU-238, and therefore
our ability to generate revenues, will depend on numerous
factors, including:
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obtaining supplies of ALTU-135 and ALTU-238 for completion of
our clinical trials and toxicology studies on a timely basis; |
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receiving marketing approvals from the FDA and foreign
regulatory authorities; |
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arranging for commercial-scale supplies of our products with
contract manufacturers whose manufacturing facilities are
operated in compliance with current good manufacturing practice
regulations, or cGMP; |
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establishing sales, marketing and distribution capabilities on
our own or through third parties; |
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establishing favorable pricing from foreign regulatory
authorities; and |
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obtaining commercial acceptance of ALTU-135 and ALTU-238, if
approved, in the medical community and by third-party payors. |
If we are not successful in commercializing ALTU-135 or
ALTU-238, or are significantly delayed in doing so, our business
will be materially harmed.
Because our product candidates are in early- or mid-stage
development, there is a significant risk of failure.
Of the large number of drugs in development, only a small
percentage result in the submission of an NDA to the FDA, and
even fewer are approved for commercialization. We will only
receive regulatory approval to commercialize a product candidate
if we can demonstrate to the satisfaction of the FDA or the
applicable foreign regulatory authority, in well-designed and
conducted clinical trials, that the product candidate is safe
and effective and otherwise meets the appropriate standards
required for approval for a particular indication. Clinical
trials are lengthy, complex and extremely expensive processes
with uncertain results. A failure of one or more of our clinical
trials may occur at any stage of testing. We have limited
experience in conducting and managing the clinical trials
necessary to obtain regulatory approvals, including approval by
the FDA.
We have not yet completed late-stage clinical trials for our two
lead product candidates, and we have not advanced, and may never
advance, any of our other product candidates into clinical
trials. We have completed a Phase II clinical trial for the
solid form of ALTU-135,
our most advanced product candidate, and we expect to advance
this product candidate into a Phase III clinical trial and
long-term safety study in the second half of 2006. We expect to
complete clinical testing in the Phase III clinical trial
in the first half of 2007. In order for
ALTU-135 to be approved
by the FDA, we will be required to demonstrate in the
Phase III clinical trial, to a statistically significant
degree, that ALTU-135
improves absorption of fat in patients suffering from
malabsorption as a result of exocrine pancreatic insufficiency.
We will also be required to demonstrate the safety of
ALTU-135 in a long-term
study. However, we may not be successful in meeting the primary
or secondary endpoints for this Phase III trial or the goal
of the long-term safety study. The possibility exists that even
if these trials are successful, we may still be required to
perform additional studies for approval. In addition, we will
need to complete specified
11
toxicology studies in animals before submitting an NDA, and the
results of those studies may not demonstrate sufficient safety.
For ALTU-238, we have
completed a Phase I clinical trial in healthy adults and
are currently enrolling adults with hGH deficiency in a
Phase II clinical trial. We expect to initiate a
Phase III clinical trial of
ALTU-238 in adults and
a Phase II/III clinical trial of
ALTU-238 in children in
the second half of 2006. We plan to request that the FDA
consider the single Phase II/III clinical trial in children
as a pivotal trial. The FDA may not agree with this proposal and
may require us to conduct an additional Phase III trial in
children. We have not yet tested the efficacy of
ALTU-238 in a human
clinical trial, and
ALTU-238 may prove not
to be clinically effective as an extended-release formulation of
hGH. In addition, it is possible that patients receiving
ALTU-238 will suffer
additional or more severe side effects than we observed in our
Phase I clinical trial, which could delay or preclude
regulatory approval of
ALTU-238 or limit its
commercial use.
If we observe serious or other adverse events during the time
our product candidates are in development or after our products
are approved and on the market, we may be required to perform
lengthy additional clinical trials, may be denied regulatory
approval of such products, may be forced to change the labeling
of such products or may be required to withdraw any such
products from the market, any of which would hinder or preclude
our ability to generate revenues.
To date, there has been one serious adverse event considered by
an investigator in our clinical trials as probably or possibly
related to treatment with ALTU-135 and no such serious adverse
events related to our other product candidates. The one serious
adverse event in our Phase II trial of ALTU-135 involved a
subject in the lowest dose group who developed distal intestinal
obstructive syndrome, or DIOS, which resolved itself without
further complications. DIOS is a unique condition to cystic
fibrosis and occurs due to the accumulation of viscous mucous
and fecal material in the colon. According to a 1987 study, DIOS
is relatively common in cystic fibrosis, occurring in about 16%
of patients. In our Phase II clinical trial of
ALTU-135 we also
observed elevated levels of liver transaminases, which can be
associated with harm to the liver. These elevations were
transient and asymptomatic and were not reported as drug-related
serious adverse events. Elevation of liver transaminases is
common among cystic fibrosis patients. The elevations we
observed may or may not have been caused by
ALTU-135. The increases
we observed were not associated with increases in bilirubin,
which are typically associated with harm to the liver.
If the incidence of these events increases in number or
severity, if a regulatory authority believes that these events
constitute an adverse effect caused by the drug, or if other
effects are identified either during future clinical trials or
after any of our drug candidates are approved and on the market:
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we may be required to conduct additional pre-clinical or
clinical trials, make changes in labeling of any such products,
reformulate any such products, or implement changes to or obtain
new approvals of our or our contractors manufacturing
facilities; |
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regulatory authorities may be unwilling to approve our product
candidates or may withdraw approval of our products; |
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we may experience a significant drop in the sales of the
affected products; |
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our reputation in the marketplace may suffer; and |
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we may become the target of lawsuits, including class action
suits. |
Any of these events could prevent approval or harm sales of the
affected products or could substantially increase the costs and
expenses or commercializing and marketing any such products.
If clinical trials for our product candidates are prolonged
or delayed, we may be unable to commercialize our product
candidates on a timely basis, or at all, which would require us
to incur additional costs and delay our receipt of any revenue
from potential product sales.
We may encounter problems with our ongoing or planned clinical
trials that will cause us or a regulatory authority to delay or
suspend those clinical trials or delay the analysis of data
derived from
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them. A number of events or factors, including any of the
following, could delay the completion of our ongoing and planned
clinical trials and negatively impact our ability to obtain
regulatory approval for, and to market and sell, a particular
product candidate, including our clinical-stage product
candidates, ALTU-135
and ALTU-238:
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conditions imposed on us by the FDA or any foreign regulatory
authority regarding the scope or design of our clinical trials; |
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delays in obtaining, or our inability to obtain or maintain,
required approvals from institutional review boards, or IRBs, or
other reviewing entities at clinical sites selected for
participation in our clinical trials; |
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insufficient supply or deficient quality of our product
candidates or other materials necessary to conduct our clinical
trials; |
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difficulties enrolling subjects in our clinical trials,
including finding pediatric subjects with hGH deficiency who
have not previously received hGH therapy for our pediatric
trials of ALTU-238;
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high drop-out rates of subjects in our clinical trials; |
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negative or inconclusive results from clinical trials, or
results that are inconsistent with earlier results, that
necessitate additional clinical studies; |
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serious or unexpected drug-related side effects experienced by
subjects in clinical trials; or |
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failure of our third-party contractors or our investigators to
comply with regulatory requirements or otherwise meet their
contractual obligations to us in a timely manner. |
Our clinical trials may not begin as planned, may need to be
redesigned, and may not be completed on schedule, if at all.
Delays in our clinical trials may result in increased
development costs for our product candidates, which would cause
our stock price to decline and limit our ability to obtain
additional financing. In addition, if one or more of our
clinical trials are delayed, our competitors may be able to
bring products to market before we do, and the commercial
viability of our product candidates, including our
clinical-stage product candidates, ALTU-135 and ALTU-238, could
be significantly reduced.
Risks Related to Regulatory Approval of Our Product
Candidates and
Other Government Regulations
If we do not obtain required regulatory approvals, we will be
unable to commercialize our product candidates, and our ability
to generate revenue will be materially impaired.
ALTU-135, ALTU-238 and any other product candidates we may
discover or acquire and seek to commercialize are subject to
extensive regulation by the FDA and other regulatory authorities
in the United States and other countries relating to the
testing, manufacture, safety, efficacy, recordkeeping, labeling,
packaging, storage, approval, advertising, promotion, sale and
distribution of drugs. In the United States and in many foreign
jurisdictions, rigorous preclinical testing and clinical trials
and an extensive regulatory review process must be successfully
completed before a new drug can be sold. We have not obtained
regulatory approval for any product. Satisfaction of these and
other regulatory requirements is costly, time consuming,
uncertain and subject to unanticipated delays.
The time required to obtain approval by the FDA is unpredictable
but typically takes many years following the commencement of
clinical trials, depending upon numerous factors, including the
complexity of the product candidate. Our product candidates may
fail to receive regulatory approval for many reasons, including:
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our failure to demonstrate to the satisfaction of the FDA or
comparable foreign regulatory authorities that a product
candidate is safe and effective for a particular indication; |
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the results of clinical trials may not meet the level of
statistical significance required by the FDA or other regulatory
authorities for approval; |
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our inability to demonstrate that a product candidates
benefits outweigh its risks; |
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our inability to demonstrate that the product candidate presents
an advantage over existing therapies; |
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the FDAs or comparable foreign regulatory
authorities disagreement with the manner in which we
interpret the data from preclinical studies or clinical trials; |
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the FDAs or comparable foreign regulatory
authorities failure to approve the manufacturing processes
or facilities of third-party manufacturers with which we
contract for clinical and commercial supplies; and |
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a change in the approval policies or regulations of the FDA or
comparable foreign regulatory authorities or a change in the
laws governing the approval process. |
The FDA or comparable foreign regulatory authorities might
decide that our data are insufficient for approval and require
additional clinical trials or other studies. Furthermore, even
if we do receive regulatory approval to market a commercial
product, any such approval may be subject to limitations on the
indicated uses for which we may market the product. It is
possible that none of our existing product candidates or any
product candidates we may seek to develop in the future will
ever obtain the appropriate regulatory approvals necessary for
us or our collaborators to begin selling them.
Our development of ALTU-238 could be significantly delayed
and more expensive if we are unable to follow our current
strategy for obtaining regulatory approval from the FDA.
We do not produce hGH, the active ingredient in ALTU-238. Our
current development plan assumes that we will obtain hGH from a
third-party supplier, which we will then crystallize and
formulate for use as a long-acting growth hormone replacement
therapy. We have purchased the hGH for our clinical trials to
date from Sandoz GmbH, or Sandoz, a subsidiary of Novartis AG. A
product containing Sandozs hGH has not been approved by
the FDA or the EMEA. We are currently in negotiations with
several manufacturers for a long-term supply of hGH for our
development and commercialization of ALTU-238. We believe that
our development strategy for
ALTU-238 will allow us
to pursue one of three regulatory approval paths depending on
the source of our long-term supply:
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an NDA filing under Section 505(b)(1) of the FDCA utilizing
a right of reference to the suppliers safety
and efficacy data previously approved by the FDA; |
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an NDA filing under Section 505(b)(2) relying on published
literature and the FDAs previous findings regarding the
safety and efficacy of hGH products; or |
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an NDA submission under Section 505(b)(1) in which we
include our own safety and efficacy data. |
Please see the paragraph below and the section of the prospectus
entitled Business Governmental Regulation and
Product Approval United States Government
Regulation Section 505(b)(2) Applications.
If we use a supplier with an approved NDA for its hGH product,
we will seek a right of reference to the safety and
efficacy data on the underlying growth hormone in our
suppliers NDA, and we will file an NDA under
section 505(b)(1) of the FDCA that contains additional
information relating to our crystallized dosage form. However,
we may not be able to obtain hGH from a supplier with an
approved NDA for its hGH product. If we are not able to obtain a
right of reference from a supplier with an approved
NDA for its hGH product, and if the FDA or the courts determine
that approval of a new hGH drug product is appropriate under
section 505(b)(2) of the FDCA, we plan to submit an NDA
under section 505(b)(2) of the FDCA and rely, without a
right of reference, on published literature and the
FDAs previous findings regarding the safety and efficacy
of hGH products. We expect that either of
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these routes will enable us to avoid some of the non-clinical
studies that would otherwise be required on the underlying hGH
molecule, which may reduce the cost of developing
ALTU-238 and shorten
the time to market. If neither of these two routes is available,
we would be required to submit a full NDA under
section 505(b)(1) of the FDCA, would not have the ability
to refer to third-party studies, and would need to perform
whatever studies are necessary to demonstrate the safety and
effectiveness of ALTU-238.
The availability of section 505(b)(2) for approval of
ALTU-238 is currently
uncertain. The FDA has informed us that the FDA has not approved
any hGH product under section 505(b)(2), and a manufacturer
of another hGH product candidate has initiated a lawsuit
against the FDA to compel a ruling on its NDA filed under
section 505(b)(2). If we are unable to secure a right
of reference to an FDA-approved product or submit an NDA
under section 505(b)(2), our cost and development time for
ALTU-238 may increase.
Failure to obtain regulatory approvals or to comply with
regulatory requirements in foreign jurisdictions would prevent
us or our collaborators from marketing our products
internationally.
We intend to have our product candidates marketed outside the
United States, including in Germany, Japan, the United Kingdom,
France and the countries of the former Soviet Union. In order to
market products in the European Union and many other non-United
States jurisdictions, we or our collaborators must obtain
separate regulatory approvals and comply with numerous and
varying regulatory requirements. We have no experience in
obtaining foreign regulatory approvals. The approval procedures
vary among countries and can involve additional and costly
preclinical and clinical testing and data review. The time
required to obtain approval may differ from that required to
obtain FDA approval. The foreign regulatory approval process may
include all of the risks associated with obtaining FDA approval.
Approval by the FDA does not ensure approval by regulatory
authorities in other countries, and approval by one foreign
regulatory authority does not ensure approval by regulatory
authorities in other foreign countries or by the FDA. We or our
collaborators may not receive necessary approvals to
commercialize our products in any market. The failure to obtain
these approvals could harm our business and result in decreased
revenues from milestones or royalties in our collaboration
agreements.
We may also face challenges arising from the different
regulatory requirements imposed by United States and foreign
regulators with respect to clinical trials. The EMEA may impose
different requirements than the FDA with respect to the design
of a pivotal Phase III clinical trial. For example, we
believe that the FDA may not require our Phase III clinical
trial of ALTU-135 to
include a comparison of ALTU-135 with a currently marketed
pancreatic enzyme replacement therapy. We are aware, however,
that the EMEA often requires such comparison testing of study
drugs with approved therapies, and the EMEA is likely to impose
such a requirement for our Phase III clinical trial of
ALTU-135 in Europe. Our agreement with Dr. Falk
contemplates that we will conduct a combined Phase III
clinical trial, with both United States and European clinical
sites, to be performed in a manner consistent with the
requirements of both the FDA and the EMEA. In light of the
potentially different requirements of the FDA and EMEA, we may
need to determine with Dr. Falk whether to proceed with an
alternate strategy for the Phase III clinical development
of ALTU-135.
Our product candidates will remain subject to ongoing
regulatory requirements even if they receive marketing approval,
and if we fail to comply with these requirements, we could lose
these approvals, and the sales of any approved commercial
products could be suspended.
Even if we receive regulatory approval to market a particular
product candidate, the product will remain subject to extensive
regulatory requirements, including requirements relating to
manufacturing, labeling, packaging, adverse event reporting,
storage, advertising, promotion, distribution and record
keeping. Even if regulatory approval of a product is granted,
the approval may be subject to limitations on the uses for which
the product may be marketed or to the conditions of approval, or
contain requirements for costly post-marketing testing and
surveillance to monitor the safety or efficacy of the product,
which could reduce our revenues, increase our expenses and
render the approved product candidate not commercially viable.
In addition, as clinical experience with a drug expands after
approval because it is typically used by a greater number and
more diverse group of patients after approval than during
clinical trials, side effects and other problems may be observed
after approval that were not seen or anticipated
15
during pre-approval clinical trials or other studies. Any
adverse effects observed after the approval and marketing of a
product candidate could result in limitations on the use of or
withdrawal of any approved products from the marketplace.
Absence of long-term safety data may also limit the approved
uses of our products, if any. If we fail to comply with the
regulatory requirements of the FDA and other applicable United
States and foreign regulatory authorities, or previously unknown
problems with any approved commercial products, manufacturers or
manufacturing processes are discovered, we could be subject to
administrative or judicially imposed sanctions or other
setbacks, including:
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restrictions on the products, manufacturers or manufacturing
processes; |
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warning letters; |
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civil or criminal penalties; |
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fines; |
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injunctions; |
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product seizures or detentions; |
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import or export bans or restrictions; |
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voluntary or mandatory product recalls and related publicity
requirements; |
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suspension or withdrawal of regulatory approvals; |
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total or partial suspension of production; and |
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refusal to approve pending applications for marketing approval
of new products or supplements to approved applications. |
If we or our collaborators are slow to adapt, or are unable to
adapt, to changes in existing regulatory requirements or
adoption of new regulatory requirements or policies, we or our
collaborators may lose marketing approval for our products when
and if any of them are approved, resulting in decreased revenue
from milestones, product sales or royalties.
We deal with hazardous materials and must comply with
environmental laws and regulations, which can be expensive and
restrict how we do business.
Our activities and those of our third-party manufacturers on our
behalf involve the controlled storage, use and disposal of
hazardous materials, including microbial agents, corrosive,
explosive and flammable chemicals and other hazardous compounds.
We and our manufacturers are subject to federal, state and local
laws and regulations governing the use, manufacture, storage,
handling and disposal of these hazardous materials. Although we
believe that the safety procedures for handling and disposing of
these materials comply with the standards prescribed by these
laws and regulations, we cannot eliminate the risk of accidental
contamination or injury from these materials.
In the event of an accident, state or federal authorities may
curtail our use of these materials and interrupt our business
operations. In addition, we could be liable for any civil
damages that result, which may exceed our financial resources
and may seriously harm our business. While we believe that the
amount of insurance we currently carry, providing coverage of $1
million, should be sufficient for typical risks regarding our
handling of these materials, it may not be sufficient to cover
pollution conditions or other extraordinary or unanticipated
events. Furthermore, an accident could damage, or force us to
shut down, our operations. In addition, if we develop a
manufacturing capacity, we may incur substantial costs to comply
with environmental regulations and would be subject to the risk
of accidental contamination or injury from the use of hazardous
materials in our manufacturing process.
16
Risks Related to Our Dependence on Third Parties
We have no manufacturing capacity, and we have relied and
expect to continue to rely on third-party manufacturers to
produce our product candidates.
We do not own or operate manufacturing facilities for the
production of clinical or commercial quantities of
ALTU-135,
ALTU-238 or any of the
compounds that we are testing in our preclinical programs, and
we lack the resources and the capabilities to do so. As a
result, we currently rely, and we expect to rely in the future,
on third-party manufacturers to supply the active pharmaceutical
ingredients, or APIs, for our product candidates and to produce
and package our drug products. Reliance on third-party
manufacturers entails risks to which we would not be subject if
we manufactured product candidates or products ourselves,
including:
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reliance on the third party for manufacturing process
development, regulatory compliance and quality assurance; |
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limitations on supply availability resulting from capacity and
scheduling constraints of the third party; |
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the possible breach of the manufacturing agreement by the third
party because of factors beyond our control; and |
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the possible termination or non-renewal of the agreement by the
third party, based on its own business priorities, at a time
that is costly or inconvenient for us. |
Our current and anticipated future dependence upon others for
the manufacture of our product candidates may adversely affect
our future profit margins and our ability to develop our product
candidates and commercialize any products that receive
regulatory approval on a timely basis.
We currently rely on a single manufacturer for the clinical
supply of each of our product candidates, and we have no
arrangements in place for the commercial supply of any of our
product candidates, which could delay or prevent the clinical
development and commercialization of our product candidates.
We currently depend on a single source supplier for each of our
product candidates. Any disruption in production, inability of a
supplier to produce adequate quantities to meet our needs or
other impediments could adversely affect our ability to
successfully complete the clinical trials and other studies of
our product candidates, delay submissions of our regulatory
applications or adversely affect our ability to commercialize
our product candidates in a timely manner, or at all.
We do not currently have any agreements to manufacture our
product candidates on a commercial scale. In order to
commercialize our product candidates, our existing suppliers
will need to scale up their manufacturing of our product
candidates. We may be required to fund capital improvements to
support scale-up of
manufacturing and related activities. Our existing manufacturers
may not be able to successfully increase their manufacturing
capacity for any of our product candidates for which we obtain
marketing approval in a timely or economic manner, or at all. We
may need to engage other manufacturers to provide commercial
supplies of our product candidates. It may be difficult for us
to enter into commercial supply arrangements on a timely basis
or on acceptable terms, which could delay or prevent our ability
to commercialize our product candidates. If our existing
manufacturers are unable or unwilling to increase their
manufacturing capacity or we are unable to establish alternative
arrangements, the development and commercialization of our
product candidates may be delayed or there may be a shortage in
supply.
With respect to
ALTU-135, we currently
rely on Amano Enzyme, Inc., or Amano, located in Nagoya, Japan,
for the sole supply of the enzymes that comprise the APIs for
ALTU-135. To date,
Amano has only supplied us APIs for our clinical trials and our
toxicology studies, and we do not have an arrangement for
commercial supplies of
ALTU-135. In addition,
Amanos manufacturing facility that produces the APIs for
ALTU-135 has not been
inspected or approved by the FDA, EMEA or the Japanese Ministry
of Health, Labour and Welfare. Pursuant to our agreement with
Amano, they have notified us that they will not be the primary
manufacturer of the APIs for the initial commercial supply of
ALTU-135. We expect to
negotiate a
17
new agreement with Amano that governs the commercial supply of
some of the APIs for
ALTU-135. We may not be
able to reach an agreement with Amano on the supply of APIs for
ALTU-135 for our
commercial needs on favorable terms, or at all.
We are in the process of selecting an alternative manufacturer
of the APIs for
ALTU-135. Switching
manufacturers will require cooperation with Amano, technology
transfers, training, and validation of the alternative
manufacturers processes. Changes in manufacturing
processes or procedures, including a change in the location
where the drug is manufactured or a change of a third-party
manufacturer, may require prior review and approval from the FDA
and satisfaction of comparable foreign requirements. This review
may be costly and time-consuming and could delay or prevent the
launch of a product. If we are unable to secure another contract
manufacturer to supply the APIs for
ALTU-135 at an
acceptable cost, our commercialization of
ALTU-135 could be
delayed, prevented or impaired, including an increase in our
costs of obtaining the APIs for
ALTU-135. Any dispute
over the terms of, or decisions regarding, our collaboration
with Amano or other adverse developments in our relationship
would materially harm our business and might accelerate our need
for additional capital.
With respect to ALTU-238, we have purchased the hGH for our
clinical trials to date from Sandoz. A product containing the
hGH supplied by Sandoz has not been approved by the FDA or the
EMEA. We are negotiating with various manufacturers for the
commercial supply of hGH for
ALTU-238.
Any performance failure on the part of our existing or future
manufacturers could delay clinical development or regulatory
approval of our product candidates or commercialization of any
approved products.
The failure of any of our contract manufacturers to achieve and
maintain high manufacturing standards could result in patient
injury or death, product liability claims, product recalls,
product seizures or withdrawals, delays or failures in testing
or delivery, cost overruns, failure of regulatory authorities to
grant marketing approvals, delays, suspensions or withdrawals of
approvals, injunctions, fines, civil or criminal penalties, or
other problems that could seriously harm our business. Contract
manufacturers may encounter difficulties involving production
yields, quality control and quality assurance. These
manufacturers are subject to ongoing periodic unannounced
inspection by the FDA and corresponding state and foreign
agencies which audit strict compliance with cGMP and other
applicable government regulations and corresponding foreign
standards. However, we have limited control over third-party
manufacturers compliance with these regulations and
standards. Our present or future manufacturers might not be able
to comply with cGMP and other FDA regulatory requirements or
similar regulatory requirements outside of the United States.
We rely on third parties to conduct, supervise and monitor
our clinical trials, and those third parties may not perform
satisfactorily, including failing to meet established deadlines
for the completion of such trials.
We rely on third parties such as contract research
organizations, medical institutions and clinical investigators
to enroll qualified patients and conduct, supervise and monitor
our clinical trials. Our reliance on these third parties for
clinical development activities reduces our control over these
activities. Our reliance on these third parties, however, does
not relieve us of our regulatory responsibilities, including
ensuring that our clinical trials are conducted in accordance
with good clinical practice regulations, or GCP, and the
investigational plan and protocols contained in the
investigational new drug application, or IND. Furthermore, these
third parties may also have relationships with other entities,
some of which may be our competitors. In addition, they may not
complete activities on schedule, or may not conduct our
preclinical studies or clinical trials in accordance with
regulatory requirements or our trial design. If these third
parties do not successfully carry out their contractual duties
or meet expected deadlines, our efforts to obtain regulatory
approvals for, and commercialize, our product candidates may be
delayed or prevented.
18
Risks Related to Commercialization of Our Product
Candidates
If we are unable to establish sales and marketing
capabilities or enter into agreements with third parties to
market and sell our product candidates, we may be unable to
generate product revenue.
We have no commercial products, and we do not currently have an
organization for the sales, marketing and distribution of
pharmaceutical products. In order to successfully commercialize
any products that may be approved in the future by the FDA or
comparable foreign regulatory authorities, we must build our
sales and marketing capabilities or make arrangements with third
parties to perform these services. Though we currently plan to
retain North American commercialization rights to our products
in circumstances where we believe that we can successfully
commercialize such products on our own, we may not be able to
successfully develop our own sales and marketing force for
product candidates for which we have retained marketing rights.
If we develop our own sales and marketing capability, we may be
competing with other companies that currently have experienced
and well-funded sales and marketing operations.
In addition, we may co-promote our product candidates in North
America with pharmaceutical and biotechnology companies in
instances where we believe that a larger sales and marketing
presence will expand the market or accelerate penetration. If we
do enter into arrangements with third parties to perform sales
and marketing services, our product revenues will be lower than
if we directly sold and marketed our products and any revenues
received under such arrangements will depend on the skills and
efforts of others. If we are unable to establish adequate sales,
marketing and distribution capabilities, whether independently
or with third parties, we may not be able to generate product
revenue and may not become profitable.
If physicians and patients do not accept our future products,
we may be unable to generate significant revenue, if any.
Even if we receive regulatory approval for
ALTU-135, ALTU-238 or
any other product candidates we may develop or acquire in the
future, these product candidates may not gain market acceptance
among physicians, healthcare payors, patients and the medical
community. Physicians may elect not to recommend or patients may
elect not to use these products for a variety of reasons,
including:
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lower demonstrated clinical safety and efficacy compared to
other products; |
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prevalence and severity of adverse side effects; |
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other potential advantages of alternative treatment methods; |
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ineffective marketing and distribution support; |
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lack of availability of reimbursement from managed care plans
and other third-party payors; |
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lack of cost-effectiveness; and |
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timing of market introduction of competitive products. |
If our approved drugs fail to achieve market acceptance, we will
not be able to generate significant revenue, if any.
If the government and third-party payors fail to provide
coverage and adequate payment rates for our future products, if
any, our revenue and prospects for profitability will be
harmed.
In both domestic and foreign markets, our sales of any future
products will depend in part upon the availability of
reimbursement from third-party payors. Such third-party payors
include government health programs such as Medicare, managed
care providers, private health insurers and other organizations.
These third-party payors are increasingly attempting to contain
healthcare costs by demanding price discounts or rebates and
limiting both coverage on which drugs they will pay for and the
amounts that they will pay for new drugs. As a result, they may
not cover or provide adequate payment for our drugs.
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We might need to conduct post-marketing studies in order to
demonstrate the cost-effectiveness of any future products to
such payors satisfaction. Such studies might require us to
commit a significant amount of management time and financial and
other resources. Our future products might not ultimately be
considered cost-effective. Adequate third-party reimbursement
might not be available to enable us to maintain price levels
sufficient to realize an appropriate return on investment in
product development.
Governments continue to propose and pass legislation designed to
reduce the cost of healthcare. In the United States, we expect
that there will continue to be federal and state proposals to
implement similar governmental controls. For example, in
December 2003, Congress enacted a limited prescription drug
benefit for Medicare recipients in the Medicare Prescription
Drug and Modernization Act of 2003. While this program may
increase demand for our products, if we participate in this
program, our prices will be negotiated with drug procurement
organizations for Medicare beneficiaries and are likely to be
lower than we might otherwise obtain. In some foreign markets,
the government controls the pricing of prescription
pharmaceuticals. In these countries, pricing negotiated with
governmental authorities can take six to 12 months or
longer after the receipt of regulatory marketing approval for a
product. Cost control initiatives could decrease the price that
we would receive for any products in the future, which would
limit our revenue and profitability. Accordingly, legislation
and regulations affecting the pricing of pharmaceuticals might
change before our product candidates are approved for marketing.
Adoption of such legislation could further limit reimbursement
for pharmaceuticals.
There is a substantial risk of product liability claims in
our business. If we are unable to obtain sufficient insurance, a
product liability claim against us could adversely affect our
business.
We face an inherent risk of product liability exposure related
to the testing of our product candidates in human clinical
trials and will face even greater risks upon any
commercialization by us of our product candidates. We have
product liability insurance covering our clinical trials in the
amount of $5 million, which we currently believe is
adequate to cover any product liability exposure we may have.
Clinical trial and product liability insurance is becoming
increasingly expensive. As a result, we may be unable to obtain
sufficient insurance or increase our existing coverage at a
reasonable cost to protect us against losses that could have a
material adverse effect on our business. An individual may bring
a product liability claim against us if one of our products or
product candidates causes, or is claimed to have caused, an
injury or is found to be unsuitable for consumer use. Any
product liability claim brought against us, with or without
merit, could result in:
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liabilities that substantially exceed our product liability
insurance, which we would then be required to pay from other
sources, if available; |
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an increase of our product liability insurance rates or the
inability to maintain insurance coverage in the future on
acceptable terms, or at all; |
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withdrawal of clinical trial volunteers or patients; |
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damage to our reputation and the reputation of our products,
resulting in lower sales; |
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regulatory investigations that could require costly recalls or
product modifications; |
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litigation costs; and |
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the diversion of managements attention from managing our
business. |
We have product liability insurance covering our clinical
trials, which we currently believe is adequate to cover
liabilities we may incur. However, liabilities may exceed the
extent of our coverage, resulting in material losses.
Additionally, clinical trial and product liability insurance is
becoming increasingly expensive. As a result, we may be unable
to obtain sufficient insurance or increase our existing coverage
at a reasonable cost to protect us against losses that could
have a material adverse effect on our business.
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Recent proposed legislation may permit re-importation of
drugs from foreign countries into the United States, including
foreign countries where the drugs are sold at lower prices than
in the United States, which could materially adversely affect
our operating results and our overall financial condition.
Legislation has been introduced in Congress that, if enacted,
would permit more widespread re-importation of drugs from
foreign countries into the United States, which may include
re-importation from foreign countries where the drugs are sold
at lower prices than in the United States. Such legislation, or
similar regulatory changes, could decrease the price we receive
for any approved products which, in turn, could materially
adversely affect our operating results and our overall financial
condition.
Risks Related to Our Intellectual Property
If the combination of patents, trade secrets and contractual
provisions that we rely on to protect our intellectual property
is inadequate, our ability to successfully commercialize our
product candidates will be harmed and we may not be able to
operate our business profitably.
Our success depends on our ability to obtain, maintain and
enforce our intellectual property rights domestically and
abroad. The patent position of biotechnology companies is
generally highly uncertain, involves complex legal and factual
questions and has in recent years been the subject of much
litigation. The validity, enforceability and commercial value of
these rights, therefore, are highly uncertain.
Our patents may not protect us against our competitors. The
issuance of a patent is not conclusive as to its scope, validity
or enforceability. The scope, validity or enforceability of our
patents can be challenged in litigation. Such litigation can
involve substantial costs and distraction. If the outcome of
such litigation is adverse to us, third parties may be able to
use our patented inventions and compete directly with us,
without payment to us. Third parties may also be able to
circumvent our patents by design innovations. We may not receive
any additional patents based on the applications currently
pending.
Because patent applications in the United States and many
foreign jurisdictions are typically not published until
18 months after filing or, in some cases, not at all, and
because publications of discoveries in the scientific literature
often lag behind actual discoveries, neither we nor our
licensors or collaborators can be certain that we or they were
the first to make the inventions claimed in patents or pending
patent applications, or that we or they were the first to file
for protection of the inventions set forth in these patent
applications. Assuming the other requirements for patentability
are met, in the United States, the first to make the claimed
invention is entitled to the patent, and outside the United
States, the first to file is entitled to the patent.
Many of the proteins that are the APIs in our product candidates
are off-patent. Therefore, we have obtained and are seeking to
obtain patents directed to novel compositions of matter,
formulations, methods of manufacturing and methods of treatment
to protect some of our products. Such patents may not, however,
prevent our competitors from developing products using the same
APIs but different technology that is not covered by our patents.
If third parties successfully assert that we have infringed
their patents and proprietary rights or challenge the validity
of our patents and proprietary rights, we may become involved in
intellectual property disputes and litigation that would be
costly, time consuming, and delay or prevent the development or
commercialization of our product candidates.
Our ability to commercialize our product candidates depends on
our ability to develop, manufacture, market and sell our product
candidates without infringing the proprietary rights of third
parties. Third parties may allege our product candidates
infringe their intellectual property rights. Numerous United
States and foreign patents and pending patent applications,
which are owned by third parties, exist in fields that relate to
our product candidates and our underlying technology, including
patents and patent applications claiming compositions of matter
of, methods of manufacturing, and methods of treatment using,
specific proteins, combinations of proteins, and protein
crystals.
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For example, we are aware of three issued European patents that
may be relevant to our development and commercialization of
ALTU-135. However, we
believe that, if these patents were asserted against us, it is
likely that we would not be found to infringe any valid claim of
the patents relevant to our development and commercialization of
ALTU-135. If any of
these patents were asserted against us and determined to be
valid and construed to cover
ALTU-135, our
development and commercialization of
ALTU-135 could be
materially adversely affected in Europe. With respect to one of
these patents, Dr. Falk, which holds a license from us to
commercialize ALTU-135
in Europe, has asserted that we would be liable for damages to
Dr. Falk if the patent were successfully asserted against
us. We do not believe that Dr. Falks assertion has
merit, and we are in discussions with Dr. Falk concerning
this matter. The outcome of these discussions is uncertain.
We are also aware of an issued United States patent, and its
foreign counterparts, that may be relevant to our development
and commercialization of
ALTU-238. We believe
that, if this patent and its foreign counterparts were asserted
against us, it is likely that we would not be found to infringe
any valid claim of the patents relevant to our development and
commercialization of
ALTU-238. If this
patent and its foreign counterparts were determined to be valid
and construed to cover
ALTU-238, our
development and commercialization of
ALTU-238 could be
materially adversely affected.
We may not succeed in any action in which the patents are
asserted against us. In order to successfully challenge the
validity of any United States patent, we would need to overcome
a presumption of validity. This burden is a high one requiring
clear and convincing evidence. If any of these patents were
found to be valid and we were found to infringe any of them, or
any other patent rights of third parties, we would be required
to pay damages, stop the infringing activity or obtain licenses
in order to use, manufacture or sell our product candidates. Any
required license might not be available to us on acceptable
terms, or at all. If we succeeded in obtaining these licenses,
payments under these licenses would reduce any earnings from our
products. In addition, some licenses might be non-exclusive and,
accordingly, our competitors might gain access to the same
technology as that which was licensed to us. If we failed to
obtain a required license or were unable to alter the design of
our product candidates to make the licenses unnecessary, we
might be unable to commercialize one or more of our product
candidates, which could significantly affect our ability to
establish and grow our commercial business.
In order to protect or enforce our patent rights, defend our
activities against claims of infringement of third-party
patents, or to satisfy contractual obligations to licensees of
our own intellectual property, we might be required to initiate
patent litigation against third parties, such as infringement
suits or nullity, opposition or interference proceedings. We and
our collaborators may enforce our patent rights under the terms
of our major collaboration and license agreements, but neither
is required to do so. In addition, others may sue us for
infringing their patent rights or file nullity, opposition or
interference proceedings against our patents, even if such
claims are without merit.
Intellectual property litigation is relatively common in our
industry and can be costly. Even if we prevail, the cost of such
litigation could deplete our financial resources. Litigation is
also time consuming and could divert managements attention
and resources away from our business. Furthermore, during the
course of litigation, confidential information may be disclosed
in the form of documents or testimony in connection with
discovery requests, depositions or trial testimony. Disclosure
of our confidential information and our involvement in
intellectual property litigation could materially adversely
affect our business. Some of our competitors may be able to
sustain the costs of complex patent litigation more effectively
than we can because they have substantially greater resources.
In addition, any uncertainties resulting from the initiation and
continuation of any litigation could significantly limit our
ability to continue our operations.
Many of our employees were previously employed at universities
or other biotechnology or pharmaceutical companies, including
our competitors or potential competitors. While we try to ensure
that our employees do not use the proprietary information or
know-how of others in their work for us, we may be subject to
claims that we or these employees have inadvertently or
otherwise used or disclosed intellectual property, trade secrets
or other proprietary information of any such employees
former
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employer. Litigation may be necessary to defend against these
claims and, even if we are successful in defending ourselves,
could result in substantial costs or be distracting to
management. If we fail in defending such claims, in addition to
paying monetary damages, we may lose valuable intellectual
property rights or personnel.
If we are unable to protect our trade secrets, we may be
unable to protect our interests in proprietary technology,
processes and know-how that is not patentable or for which we
have elected not to seek patent protection.
In addition to patented technology, we rely upon unpatented
proprietary technology, processes and know-how, including
particularly our manufacturing know-how relating to the
production of the crystallized proteins used in the formulation
of our product candidates. In an effort to protect our
unpatented proprietary technology, processes and know-how, we
require our employees, consultants, collaborators, contract
manufacturers and advisors to execute confidentiality
agreements. These agreements, however, may not provide us with
adequate protection against improper use or disclosure of
confidential information, in particular as we are required to
make such information available to a larger pool of people as we
seek to increase production of our product candidates and their
component proteins. These agreements may be breached, and we may
not become aware of, or have adequate remedies in the event of,
any such breach. In addition, in some situations, these
agreements may conflict with, or be subject to, the rights of
third parties with whom our employees, consultants,
collaborators, contract manufacturers or advisors have previous
employment or consulting relationships. Also, others may
independently develop substantially equivalent technology,
processes and know-how or otherwise gain access to our trade
secrets. If we are unable to protect the confidentiality of our
proprietary technology, processes and know-how, competitors may
be able to use this information to develop products that compete
with our products, which could adversely impact our business.
If we fail to comply with our obligations in the agreements
under which we license development or commercialization rights
to products or technology from third parties, we could lose
license rights that are important to our business or incur
financial obligations based on our exercise of such license
rights.
Several of our collaboration agreements provide for licenses to
us of technology that is important to our business, and we may
enter in additional agreements in the future that provide
licenses to us of valuable technology. These licenses impose,
and future licenses may impose, various commercialization,
milestone and other obligations on us. If we fail to comply with
these obligations, the licensor may have the right to terminate
the license even where we are able to achieve a milestone or
cure a default after a date specified in an agreement, in which
event we would lose valuable rights and our ability to develop
our product candidates. For example, under the terms of our
strategic alliance agreement with CFFTI, we granted CFFTI an
exclusive license under our intellectual property rights
covering ALTU-135 and
specified derivatives for use in all applications and
indications in North America, and CFFTI granted us back an
exclusive sublicense of the same scope, including the right to
grant sublicenses. CFFTI has the right to retain its exclusive
license and terminate our sublicense if we fail to meet
specified development milestones, there occurs an unresolved
deadlock under the agreement and we discontinue our development
activities, there occurs a material default in our obligations
under the agreement not cured on a timely basis, including a
failure to make required license fee payments to CFFTI on a
timely basis if
ALTU-135 is approved by
the FDA, or a bankruptcy or similar proceeding is filed by or
against us. The retention by CFFTI of its exclusive license to
ALTU-135 and
termination of our sublicense would have a material adverse
effect on our business.
In addition, we rely on Amanos intellectual property
relating to the manufacturing process used to produce the APIs
for ALTU-135, as well
as upon technology jointly developed by us and Amano related to
the production of those enzymes. If Amano elects not to be our
sole commercial supplier of APIs for
ALTU-135, Amano is
required to grant a license to us of its proprietary technology
and its rights under technology jointly developed during our
collaboration, which we may sublicense to contract manufacturers
we mutually select. Our agreement with Amano requires us to pay
Amano a royalty based
23
on the cost of the materials supplied to us by other contract
manufacturers. If we were to breach our agreement with Amano, we
would be required to pay Amano a royalty based on net sales of
ALTU-135 to retain our
rights to Amanos independently and jointly-developed
process technology.
Risks Related to Our Employees and Growth
Our future success depends on our ability to retain our chief
executive officer, our chief scientific officer and other key
executives and to attract, retain and motivate qualified
personnel.
We are a small company with 102 employees as of
December 31, 2005. Our success depends on our ability to
attract, retain and motivate highly qualified management and
scientific personnel. In particular, we are highly dependent on
Sheldon Berkle, our President and Chief Executive Officer,
Dr. Alexey L. Margolin, our Chief Scientific Officer, and
the other principal members of our executive and scientific
teams. All of the arrangements with these principal members of
our executive and scientific teams may be terminated by us or
the employee at any time without notice. Although we do not have
any reason to believe that we may lose the services of any of
these persons in the foreseeable future, the loss of the
services of any of these persons might impede the achievement of
our research, development and commercialization objectives.
Recruiting and retaining qualified scientific personnel and
possibly sales and marketing personnel will also be critical to
our success. We may not be able to attract and retain these
personnel on acceptable terms given the competition among
numerous pharmaceutical and biotechnology companies for similar
personnel. We also experience competition for the hiring of
scientific personnel from universities and research
institutions. We do not maintain key person
insurance on any of our employees other than on
Dr. Margolin. In addition, we rely on consultants and
advisors, including scientific and clinical advisors, to assist
us in formulating our research, clinical development and
commercialization strategy. Our consultants and advisors may be
employed by employers other than us and may have commitments
under consulting or advisory contracts with other entities that
may limit their availability to us.
We expect to expand, and as a result, we may encounter
difficulties in managing our growth, which could disrupt our
operations.
We expect to experience significant growth in the number of our
employees and the scope of our operations over the next several
years. To manage our anticipated future growth, we must continue
to implement and improve our managerial, operational and
financial systems, and continue to recruit and train additional
qualified personnel. Due to our limited resources, we may not be
able to effectively manage the expansion of our operations or to
recruit and train additional qualified personnel. The physical
expansion of our operations may lead to significant costs and
may divert our management and business development resources.
Any inability to manage growth could delay the execution of our
business plans or disrupt our operations.
Risks Related to Our Common Stock and This Offering
Our stock price is likely to be volatile and the market price
of our common stock after this offering may drop below the price
you pay.
You should consider an investment in our common stock as risky
and invest only if you can withstand a significant loss and wide
fluctuations in the market value of your investment. Prior to
this offering, there was not a public market for our common
stock. We will negotiate and determine the initial public
offering price with the representatives of the underwriters
based on several factors. This price may vary from the market
price of our common stock after this offering. You may be unable
to sell your shares of common stock at or above the initial
public offering price due to fluctuations in the market price of
our common stock arising from changes in our operating
performance or prospects. In addition, the stock market has
recently experienced significant volatility, particularly with
respect to pharmaceutical, biotechnology and other life sciences
company stocks. The volatility of pharmaceutical, biotechnology
and other life sciences company stocks often does not relate to
the operating performance of the companies
24
represented by the stock. Some of the factors that may cause the
market price of our common stock to fluctuate include:
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results of clinical trials or studies for our product candidates; |
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our entry into or the loss of a significant collaboration; |
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results of clinical trials conducted by others on drugs that
would compete with our product candidates; |
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failure or delays in advancing product candidates from our
preclinical programs, or other product candidates we may
discover or acquire in the future, into clinical trials; |
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failure or discontinuation of any of our research programs; |
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delays or other problems with manufacturing our product
candidates or approved products; |
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regulatory developments or enforcement in the United States and
foreign countries; |
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developments or disputes concerning patents or other proprietary
rights; |
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introduction of technological innovations or new commercial
products by us or our competitors; |
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changes in estimates or recommendations by securities analysts,
if any, who cover our common stock; |
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failure to meet estimates or recommendations by securities
analysts, if any, who cover our common stock; |
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public concern over our product candidates or any approved
products; |
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litigation; |
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future sales or anticipated sales of our common stock by us or
our stockholders; |
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general market conditions; |
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changes in the structure of health care payment systems; |
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failure of any of our product candidates, if approved, to
achieve commercial success; |
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economic and other external factors or other disasters or
crises; and |
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period-to-period
fluctuations in our financial results. |
These and other external factors may cause the market price and
demand for our common stock to fluctuate substantially, which
may limit or prevent investors from readily selling their shares
of common stock and may otherwise negatively affect the
liquidity of our common stock. In addition, in the past, when
the market price of a stock has been volatile, holders of that
stock have instituted securities class action litigation against
the company that issued the stock. If any of our stockholders
brought a lawsuit against us, we could incur substantial costs
defending the lawsuit regardless of the outcome. Such a lawsuit
could also divert the time and attention of our management.
There may not be an active, liquid trading market for our
common stock.
This is our initial public offering, and there is currently no
established trading market for our common stock. There is no
guarantee that an active trading market for our common stock
will develop and be maintained after this offering. If a trading
market does not develop or is not maintained, you may experience
difficulty in reselling, or an inability to sell, your shares
quickly or at the latest market price.
Insiders will continue to have substantial control over Altus
which could delay or prevent a change in corporate control or
result in the entrenchment of management and the board of
directors.
After this offering, our directors and executive officers,
together with their affiliates and related persons, will
beneficially own, in the aggregate, approximately 51% of our
outstanding common stock. As a result, these stockholders, if
acting together, may have the ability to determine the outcome
of matters submitted to our stockholders for approval, including
the election and removal of directors and any
25
merger, consolidation or sale of all or substantially all of our
assets. In addition, these persons, acting together, may have
the ability to control the management and affairs of our
company. Accordingly, this concentration of ownership may harm
the market price of our common stock by:
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delaying, deferring or preventing a change in control; |
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entrenching our management and the board of directors; |
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impeding a merger, consolidation, takeover or other business
combination involving Altus; or |
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discouraging a potential acquirer from making a tender offer or
otherwise attempting to obtain control of Altus. |
After the closing of this offering, entities affiliated with
Warburg Pincus Private Equity VIII, L.P., or Warburg
Pincus, one of our principal stockholders, are entitled to
designate up to two individuals as candidates to our board of
directors, for so long as Warburg Pincus owns at least
2,691,935 shares of our common stock, or one individual for
so long as Warburg Pincus owns at least 1,794,623 shares of
our common stock. We have agreed to nominate and use our
reasonable efforts to cause the election of such candidates.
Currently, Stewart Hen and Jonathan S. Leff are the members of
our board of directors designated by Warburg Pincus.
A significant portion of our total outstanding shares are
restricted from immediate resale but may be sold into the market
in the near future. This could cause the market price of our
common stock to drop significantly, even if our business is
doing well.
Sales of a substantial number of shares of our common stock in
the public market could occur at any time. These sales, or the
perception in the market that the holders of a large number of
shares intend to sell shares, could reduce the market price of
our common stock. After this offering, we will have outstanding
21,001,943 shares of common stock based on the number of
shares outstanding as of December 31, 2005. This includes
the 7,000,000 shares that we are selling in this offering,
which may be resold in the public market immediately. Of the
remaining shares, 13,536,932 shares are currently
restricted as a result of securities laws or
lock-up agreements but
will be able to be sold after the offering as described in the
Shares Eligible for Future Sale section of this
prospectus. Moreover, after this offering, holders of an
aggregate of 12,666,153 shares of our common stock will
have rights, subject to some conditions, to require us to file
registration statements covering their shares or to include
their shares in registration statements that we may file for
ourselves or other stockholders. We also intend to register all
shares of common stock that we may issue under our equity
compensation plans. Once we register these shares, they can be
freely sold in the public market upon issuance, subject to the
lock-up agreements
described in the Underwriting section of this
prospectus.
We have broad discretion in the use of the net proceeds from
this offering and may not use them effectively.
Management will retain broad discretion over the use of the net
proceeds from this offering. Stockholders may not agree with
such uses, and our use of the proceeds may not yield a
significant return or any return at all for our stockholders.
The failure by our management to apply these funds effectively
could have a material adverse effect on our business.
We intend to use the proceeds from this offering for clinical
activities, including clinical supplies, preclinical research
and development activities, general and administrative expenses,
working capital needs and other general corporate purposes,
including capital expenditures. Because of the number and
variability of factors that will determine our use of the
proceeds from this offering, their ultimate use may vary
substantially from their currently intended use. For a further
description of our intended use of the proceeds of this
offering, see the Use of Proceeds section of this
prospectus.
Provisions of our charter, bylaws, and Delaware law may make
an acquisition of us or a change in our management more
difficult.
Certain provisions of our restated certificate of incorporation
and restated bylaws that will be in effect upon the completion
of this offering could discourage, delay or prevent a merger,
acquisition or other change in control that stockholders may
consider favorable, including transactions in which you might
26
otherwise receive a premium for your shares. These provisions
also could limit the price that investors might be willing to
pay in the future for shares of our common stock, thereby
depressing the market price of our common stock. Stockholders
who wish to participate in these transactions may not have the
opportunity to do so. Furthermore, these provisions could
prevent or frustrate attempts by our stockholders to replace or
remove our management. These provisions:
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allow the authorized number of directors to be changed only by
resolution of our board of directors; |
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establish a classified board of directors, such that not all
members of the board be elected at one time; |
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|
authorize our board of directors to issue without stockholder
approval blank check preferred stock that, if issued, could
operate as a poison pill to dilute the stock
ownership of a potential hostile acquirer to prevent an
acquisition that is not approved by our board of directors; |
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require that stockholder actions must be effected at a duly
called stockholder meeting and prohibit stockholder action by
written consent; |
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establish advance notice requirements for stockholder
nominations to our board of directors or for stockholder
proposals that can be acted on at stockholder meetings; |
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limit who may call stockholder meetings; and |
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require the approval of the holders of 80% of the outstanding
shares of our capital stock entitled to vote in order to amend
certain provisions of our restated certificate of incorporation
and restated bylaws. |
In addition, because we are incorporated in Delaware, we are
governed by the provisions of Section 203 of the Delaware
General Corporation Law, which may, unless certain criteria are
met, prohibit large stockholders, in particular those owning 15%
or more of our outstanding voting stock, from merging or
combining with us for a prescribed period of time.
Investors in this offering will pay a much higher price than
the book value of our common stock and therefore you will incur
immediate and substantial dilution of your investment.
If you purchase common stock in this offering, you will pay more
for your shares than the amounts paid by existing stockholders
for their shares. You will incur immediate and substantial
dilution of $9.73 per share, representing the difference
between the initial public offering price and our pro forma net
tangible book value per share after giving effect to this
offering at the initial public offering price of $15.00 per
share. Further, investors purchasing common stock in this
offering will contribute approximately 45% of the total amount
invested by stockholders since our inception, but will only own
approximately 33% of the shares of common stock outstanding. In
the past, we also issued options and warrants to acquire common
stock at prices significantly below the initial public offering
price. To the extent these outstanding options or warrants are
ultimately exercised, you will sustain further dilution.
27
SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS
This prospectus contains forward-looking statements. The
forward-looking statements are contained principally in, but not
limited to, the sections entitled Prospectus
Summary, Risk Factors, Managements
Discussion and Analysis of Financial Condition and Results of
Operations and Business. These statements
involve known and unknown risks, uncertainties and other factors
which may cause our actual results, performance or achievements
to be materially different from any future results, performances
or achievements expressed or implied by the forward-looking
statements. Forward-looking statements include, but are not
limited to, statements about:
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the expected timing, progress or success of our preclinical
research and development and clinical programs; |
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the potential benefits of our product candidates over other
therapies; |
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the timing, costs and other limitations involved in obtaining
regulatory approval for any of our product candidates; |
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our ability to enter into any collaboration with respect to
product candidates; |
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our ability to market, commercialize and achieve market
acceptance for any of our product candidates that we are
developing or may develop in the future; |
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our ability to protect our intellectual property and operate our
business without infringing upon the intellectual property
rights of others; |
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our estimates of market sizes and anticipated uses of our
product candidates; |
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our estimates of future performance; and |
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our estimates regarding anticipated operating losses, future
revenue, expenses, capital requirements and our needs for
additional financing. |
In some cases, you can identify forward-looking statements by
terms such as anticipates, believes,
could, estimates, expects,
intends, may, plans,
potential, predicts,
projects, should, will,
would and similar expressions intended to identify
forward-looking statements. Forward-looking statements reflect
our current views with respect to future events and are based on
assumptions and subject to risks and uncertainties. Because of
these risks and uncertainties, the forward-looking events and
circumstances discussed in this prospectus may not transpire. We
discuss many of these risks in this prospectus in greater detail
under the heading Risk Factors beginning on
page 7.
Given these uncertainties, you should not place undue reliance
on these forward-looking statements. Also, forward-looking
statements represent our estimates and assumptions only as of
the date of this prospectus. You should read this prospectus and
the documents that we reference in this prospectus and have
filed as exhibits to the registration statement of which this
prospectus forms a part completely and with the understanding
that our actual future results may be materially different from
what we expect. Except as required by law, we do not undertake
any obligation to update or revise any forward-looking
statements contained in this prospectus, whether as a result of
new information, future events or otherwise.
28
USE OF PROCEEDS
We estimate that the net proceeds to us from the sale of
7,000,000 shares of our common stock in this offering will
be approximately $95.3 million, based upon the initial
public offering price of $15.00 per share, after deducting
underwriting discounts and commissions and the estimated
offering expenses payable by us. If the underwriters exercise
their overallotment option in full, we estimate the net proceeds
to us from this offering will be approximately
$109.9 million.
We currently intend to use the net proceeds of this offering as
follows:
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approximately $37 million to fund a portion of
ALTU-135 development
activities, including a Phase III clinical trial and
long-term safety study for the solid form of
ALTU-135, a
Phase II clinical trial for the liquid form of
ALTU-135, and related
toxicology studies and manufacturing and materials costs; |
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approximately $30 million to fund a portion of ALTU-238
development activities, including a Phase III clinical
trial in adults, a Phase II/III clinical trial in children,
and related toxicology studies and manufacturing and materials
costs; and |
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the remainder to fund research and development activities for
our preclinical product candidates and general corporate
purposes, including capital expenditures and working capital. |
This expected use of net proceeds of this offering represents
our current intentions based upon our present plans and business
conditions. The amounts and timing of our actual expenditures
depend on numerous factors, including the ongoing status of and
results from clinical trials and other studies for ALTU-135 and
ALTU-238, as well as the development of our preclinical product
pipeline, any collaborations we may enter into with third
parties for our product candidates and any unforeseen cash
needs. As a result, management will retain broad discretion over
the allocation of the net proceeds from this offering. We do not
expect the net proceeds from this offering and our other
available funds to be sufficient to fund the completion of the
development of any of our product candidates, and we expect that
we will need to raise additional funds prior to being able to
market any products. We have no current plans, agreements or
commitments for acquisitions of any businesses, products or
technologies.
Pending use of the net proceeds of this offering, we intend to
invest the net proceeds in accordance with our investment policy
guidelines, which currently provide for investment of funds in
cash equivalents, United States government obligations, high
grade and corporate notes and commercial paper.
DIVIDEND POLICY
We have never paid or declared any cash dividends on our common
stock and we do not anticipate paying any cash dividends on our
common stock in the foreseeable future. In addition, the terms
of our redeemable preferred stock prohibit us from declaring and
paying dividends on our common stock until we have paid all
accrued but unpaid dividends on our redeemable preferred stock.
We intend to retain all available funds and any future earnings,
if any, to fund the development and expansion of our business.
29
CAPITALIZATION
The following table describes our unaudited cash position and
our unaudited capitalization as of September 30, 2005:
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on an actual basis; |
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on a pro forma basis to reflect the conversion of all then
outstanding shares of our convertible preferred stock into an
aggregate of 10,767,306 shares of common stock, which will
occur automatically upon the closing of this offering, and the
issuance of 1,391,828 shares of common stock upon the
closing of this offering in satisfaction of accumulated
dividends on our Series B and C convertible preferred
stock; and |
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on a pro forma as adjusted basis to adjust the pro forma
balances to reflect the sale of 7,000,000 shares of common
stock by us in this offering at the initial public offering
price of $15.00 per share and our receipt of the estimated
net proceeds of that sale, after deducting the underwriting
discounts and commissions and estimated offering expenses
payable by us. |
You should read this table together with Managements
Discussion and Analysis of Financial Condition and Results of
Operations and our consolidated financial statements and
the related notes thereto appearing elsewhere in this prospectus.
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As of September 30, 2005 | |
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| |
|
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Pro Forma | |
|
|
Actual | |
|
Pro Forma | |
|
As Adjusted | |
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| |
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| |
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| |
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|
(in thousands, except share and per share amounts) | |
Cash and cash equivalents and short-term investments
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|
$ |
32,009 |
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|
$ |
32,009 |
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$ |
127,309 |
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|
Long-term debt and capital lease obligations, net of current
portion
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|
$ |
4,210 |
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|
$ |
4,210 |
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|
$ |
4,210 |
|
Redeemable preferred stock:
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Redeemable preferred stock, par value $0.01 per share;
450,000 shares authorized, issued and outstanding actual,
pro forma and pro forma as adjusted (liquidation value of $6,000
at September 30, 2005), shown at accreted redemption value
|
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5,779 |
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5,779 |
|
|
|
5,779 |
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|
Series B convertible preferred stock, par value
$0.01 per share; 12,928,155 shares authorized actual;
11,773,609 shares issued and outstanding actual
(liquidation value of $62,852 at September 30, 2005), shown
at accreted redemption value
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61,033 |
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|
Series C convertible preferred stock, par value
$0.01 per share; 14,420,359 shares authorized actual;
11,819,959 shares issued and outstanding actual
(liquidation value of $58,307 at September 30, 2005), shown
at accreted redemption value
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49,822 |
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Stockholders (deficit) equity(1):
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|
|
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|
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|
|
Series A convertible preferred stock, par value
$0.01 per share; 87,500 shares authorized, issued and
outstanding actual (liquidation value of $4 at
September 30, 2005)
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897 |
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|
Common stock, par value $0.01 per share;
47,113,986 shares authorized actual;
100,000,000 shares authorized pro forma and pro forma as
adjusted; 1,820,161 shares issued and outstanding actual;
13,979,295 shares issued and outstanding pro forma; and
20,979,295 shares issued and outstanding pro forma as
adjusted(2)
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|
|
18 |
|
|
|
140 |
|
|
|
210 |
|
30
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
As of September 30, 2005 | |
|
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| |
|
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|
|
Pro Forma | |
|
|
Actual | |
|
Pro Forma | |
|
As Adjusted | |
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| |
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| |
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| |
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|
(in thousands, except share and per share amounts) | |
|
Additional paid-in capital
|
|
|
16,687 |
|
|
|
128,317 |
|
|
|
223,547 |
|
|
Accumulated deficit
|
|
|
(112,119 |
) |
|
|
(112,119 |
) |
|
|
(112,119 |
) |
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|
|
|
|
|
|
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|
Total stockholders (deficit) equity
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|
|
(94,517 |
) |
|
|
16,338 |
|
|
|
111,638 |
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|
|
|
|
|
|
|
|
Total capitalization
|
|
$ |
26,327 |
|
|
$ |
26,327 |
|
|
$ |
121,627 |
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|
|
|
|
|
|
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|
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|
|
(1) |
On a pro forma as adjusted basis, excludes 4,550,000 additional
shares of preferred stock, par value $0.01 per share, to be
authorized upon filing of the restated certificate of
incorporation immediately following the closing of this
offering, in addition to the 450,000 shares of redeemable
preferred stock that will be authorized, issued and outstanding
as set forth above. |
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(2) |
Excludes: |
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|
3,034,111 shares of common stock issuable upon the exercise
of options outstanding as of September 30, 2005 at a
weighted average exercise price of $4.04 per share; |
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|
4,121,189 shares of common stock issuable upon exercise of
warrants outstanding as of September 30, 2005 at a weighted
average exercise price of $7.17 per share; and |
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|
an aggregate of 342,380 shares available for future
issuances under our 2002 Director, Employee and Consultant Stock
Plan as of September 30, 2005. |
Between October 1, 2005 and December 31, 2005, we
issued additional options to purchase up to 249,236 shares
of common stock at a weighted average exercise price of $6.95
per share, and options to purchase 22,653 shares of common
stock were exercised.
The terms of our existing Series B and C convertible
preferred stock require us, upon the closing of this offering,
to issue additional shares of common stock to the holders of
such preferred stock in satisfaction of accumulated dividends on
such preferred stock. The accumulated dividends will be
$20.9 million at January 31, 2006, the expected
closing date of this offering. Based on the initial public
offering price of $15.00 per share, we will issue
1,391,828 additional shares of common stock in satisfaction
of such dividends.
31
DILUTION
Our historical net tangible book value (deficit) as of
September 30, 2005 was $(96.5) million or
$(53.01) per share of common stock, based on
1,820,161 shares of common stock outstanding as of
September 30, 2005, as adjusted to reflect the 1-for-2.293
reverse split of our common stock effected in January 2006.
Historical net tangible book value (deficit) per share is
determined by dividing our total tangible assets less total
liabilities and redeemable preferred stock by the actual number
of shares of common stock outstanding. Our pro forma net
tangible book value as of September 30, 2005 was
$15.3 million, or $1.09 per share of common stock,
based on 13,979,295 shares of common stock outstanding
after giving effect to the conversion of all of our convertible
preferred stock into 10,767,306 shares of common stock upon
the closing of this offering and the issuance of
1,391,828 shares of common stock upon the closing of this
offering in satisfaction of accumulated dividends on our
Series B and C convertible preferred stock. Pro forma net
tangible book value per share is determined by dividing our
total tangible assets less total liabilities and redeemable
preferred stock by the pro forma number of shares of common
stock outstanding at September 30, 2005 before giving
effect to our sale of shares of common stock in this offering.
After giving effect to our sale of 7,000,000 shares of
common stock in this offering, at the initial public offering
price of $15.00 per share, less the underwriting discounts
and commissions and estimated offering expenses payable by us,
our pro forma as adjusted net tangible book value as of
September 30, 2005 would have been $110.6 million, or
$5.27 per share. This represents an immediate increase in
pro forma net tangible book value of $4.18 per share to
existing stockholders and an immediate dilution of
$9.73 per share to new investors. Dilution per share
represents the difference between the amount per share paid by
purchasers of shares of our common stock in this offering and
the net tangible book value per share of our common stock
immediately afterwards, after giving effect to the sale of
7,000,000 shares in this offering at the initial public
offering price of $15.00 per share and after deducting the
underwriting discounts and commissions and estimated offering
expenses payable by us.
The following table illustrates this per share dilution:
|
|
|
|
|
|
|
|
|
|
Initial public offering price per share
|
|
|
|
|
|
$ |
15.00 |
|
|
Historical net tangible book value (deficit) per share as of
September 30, 2005
|
|
$ |
(53.01 |
) |
|
|
|
|
|
Pro forma increase per share attributable to pro forma
conversion of convertible preferred stock and issuance of shares
of common stock in satisfaction of accumulated dividends on
Series B and C convertible preferred stock
|
|
$ |
54.10 |
|
|
|
|
|
|
|
|
|
|
|
|
|
Pro forma net tangible book value per share as of
September 30, 2005, before this offering
|
|
$ |
1.09 |
|
|
|
|
|
|
Increase per share attributable to this offering
|
|
$ |
4.18 |
|
|
|
|
|
|
|
|
|
|
|
|
Pro forma as adjusted net tangible book value per share as of
September 30, 2005, after this offering
|
|
|
|
|
|
$ |
5.27 |
|
|
|
|
|
|
|
|
Dilution per share to new investors in this offering
|
|
|
|
|
|
$ |
9.73 |
|
|
|
|
|
|
|
|
If the underwriters exercise their overallotment option in full
to purchase 1,050,000 additional shares of common stock in this
offering, the pro forma as adjusted net tangible book value per
share after the offering would be $5.68 per share, the
increase in the pro forma net tangible book value per share to
existing stockholders would be $4.59 per share and the
dilution to new investors purchasing common stock in this
offering would be $9.32 per share.
32
The following table summarizes as of September 30, 2005, on
the pro forma basis described above, the total number of shares
of common stock purchased from us and the total consideration
and the average price per share paid by existing shareholders
and by new investors, calculated before deduction of the
underwriting discounts and commissions and estimated offering
expenses payable by us.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Shares Purchased | |
|
Total Consideration | |
|
Average | |
|
|
| |
|
| |
|
Price | |
|
|
Number | |
|
Percent | |
|
Amount | |
|
Percent | |
|
Per Share | |
|
|
| |
|
| |
|
| |
|
| |
|
| |
Existing stockholders
|
|
|
13,979,295 |
|
|
|
67 |
% |
|
$ |
129,817,311 |
|
|
|
55 |
% |
|
$ |
9.29 |
|
New investors
|
|
|
7,000,000 |
|
|
|
33 |
|
|
|
105,000,000 |
|
|
|
45 |
|
|
|
15.00 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total
|
|
|
20,979,295 |
|
|
|
100 |
% |
|
$ |
234,817,311 |
|
|
|
100 |
% |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
The number of shares of common stock outstanding in the table
above is based on the number of shares outstanding as of
September 30, 2005 and assumes no exercise of the
underwriters overallotment option to purchase up to an
additional 1,050,000 shares of common stock. If the
underwriters overallotment option is exercised in full,
the number of shares of common stock held by existing
stockholders will be reduced to 63% of the total number of
shares of common stock outstanding after this offering and the
number of shares of common stock held by new investors will be
increased to 8,050,000, or 37% of the total number of shares of
common stock outstanding after this offering.
The information also assumes no exercise of any outstanding
stock options or warrants. As of September 30, 2005, there
were 3,034,111 shares of common stock reserved for issuance
upon the exercise of outstanding options at a weighted average
exercise price of $4.04 per share, and
4,121,189 shares of common stock reserved for issuance upon
the exercise of outstanding warrants at a weighted average
exercise price of $7.17 per share. If all of these options
and warrants had been exercised as of September 30, 2005,
pro forma as adjusted net tangible book value per share after
this offering would be $5.42 and total dilution per share to new
investors would be $9.58. In addition, options to purchase
249,236 shares of common stock were granted between
October 1, 2005 and December 31, 2005 at a weighted
average exercise price of $6.95 per share. To the extent
that any of these options or warrants are exercised, there will
be further dilution to new investors. In addition, many of the
warrants that we have issued contain anti-dilution provisions
that will result in the issuance of additional shares of common
stock upon exercise, and thus further dilution, if we issue or
are deemed to issue equity at a per share price less than the
exercise price of the warrants.
33
SELECTED CONSOLIDATED FINANCIAL DATA
The following selected consolidated financial data should be
read in conjunction with Managements Discussion and
Analysis of Financial Condition and Results of Operations
and other financial data included elsewhere in this prospectus.
The consolidated statements of operations data for the years
ended December 31, 2002, 2003 and 2004 and the consolidated
balance sheet data as of December 31, 2003 and 2004 are
derived from our audited consolidated financial statements
appearing elsewhere in this prospectus. The consolidated
statements of operations data for the years ended
December 31, 2000 and 2001 and the consolidated balance
sheet data as of December 31, 2000, 2001 and 2002 are
derived from our audited consolidated financial statements not
included in this prospectus. The consolidated statements of
operations data for the nine months ended September 30,
2004 and 2005 and the consolidated balance sheet data as of
September 30, 2005 have been derived from our unaudited
consolidated financial statements included elsewhere in this
prospectus. In the opinion of management, these unaudited
consolidated financial statements have been prepared on a basis
consistent with the audited financial statements and include all
adjustments, consisting of normal and recurring adjustments,
necessary for a fair presentation of the results for these
periods and as of such date. Historical results are not
necessarily indicative of operating results to be expected in
the future.
The pro forma basic and diluted net loss per common share data
for the year ended December 31, 2004 and the nine months
ended September 30, 2005 reflect the mandatory conversion,
upon the closing of this offering, of the Series A, B and C
convertible preferred stock at their respective conversion rates
into our common stock and the issuance of shares of common stock
in satisfaction of the accumulated dividends on the
Series B and C convertible preferred stock through the end
of the applicable period based on the initial public offering
price of $15.00 per share, as if the conversion had occurred at
the dates of original issuance.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Nine Months Ended | |
|
|
Year Ended December 31, | |
|
September 30, | |
|
|
| |
|
| |
|
|
2000 | |
|
2001 | |
|
2002 | |
|
2003 | |
|
2004 | |
|
2004 | |
|
2005 | |
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
|
(in thousands, except per share amounts) | |
Consolidated Statements of Operations Data:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Revenue:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Contract revenue
|
|
$ |
5,685 |
|
|
$ |
4,995 |
|
|
$ |
1,885 |
|
|
$ |
2,613 |
|
|
$ |
4,045 |
|
|
$ |
2,891 |
|
|
$ |
6,727 |
|
|
Product sales
|
|
|
610 |
|
|
|
1,130 |
|
|
|
483 |
|
|
|
1,268 |
|
|
|
185 |
|
|
|
185 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total revenue
|
|
|
6,295 |
|
|
|
6,125 |
|
|
|
2,368 |
|
|
|
3,881 |
|
|
|
4,230 |
|
|
|
3,076 |
|
|
|
6,727 |
|
Operating expenses:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cost of product sales
|
|
|
282 |
|
|
|
709 |
|
|
|
241 |
|
|
|
578 |
|
|
|
87 |
|
|
|
87 |
|
|
|
|
|
|
Research and development
|
|
|
3,495 |
|
|
|
7,235 |
|
|
|
13,174 |
|
|
|
13,282 |
|
|
|
19,095 |
|
|
|
11,995 |
|
|
|
19,792 |
|
|
General, sales and administrative
|
|
|
3,645 |
|
|
|
4,236 |
|
|
|
6,859 |
|
|
|
5,533 |
|
|
|
6,320 |
|
|
|
4,623 |
|
|
|
6,003 |
|
|
Non-cash contract modification expense(1)
|
|
|
|
|
|
|
759 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total operating expenses
|
|
|
7,422 |
|
|
|
12,939 |
|
|
|
20,274 |
|
|
|
19,393 |
|
|
|
25,502 |
|
|
|
16,705 |
|
|
|
25,795 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Loss from operations
|
|
|
(1,127 |
) |
|
|
(6,814 |
) |
|
|
(17,906 |
) |
|
|
(15,512 |
) |
|
|
(21,272 |
) |
|
|
(13,629 |
) |
|
|
(19,068 |
) |
Interest income
|
|
|
91 |
|
|
|
284 |
|
|
|
853 |
|
|
|
405 |
|
|
|
646 |
|
|
|
405 |
|
|
|
701 |
|
Interest expense
|
|
|
(288 |
) |
|
|
(275 |
) |
|
|
(156 |
) |
|
|
(251 |
) |
|
|
(469 |
) |
|
|
(351 |
) |
|
|
(617 |
) |
Other (expense) income, net
|
|
|
|
|
|
|
|
|
|
|
(81 |
) |
|
|
164 |
|
|
|
138 |
|
|
|
138 |
|
|
|
(125 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net loss
|
|
|
(1,324 |
) |
|
|
(6,805 |
) |
|
|
(17,290 |
) |
|
|
(15,194 |
) |
|
|
(20,957 |
) |
|
|
(13,437 |
) |
|
|
(19,109 |
) |
Preferred stock dividends and accretion
|
|
|
(401 |
) |
|
|
(1,319 |
) |
|
|
(4,905 |
) |
|
|
(4,905 |
) |
|
|
(8,588 |
) |
|
|
(5,845 |
) |
|
|
(8,169 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net loss attributable to common stockholders
|
|
$ |
(1,725 |
) |
|
$ |
(8,124 |
) |
|
$ |
(22,195 |
) |
|
$ |
(20,099 |
) |
|
$ |
(29,545 |
) |
|
$ |
(19,282 |
) |
|
$ |
(27,278 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Basic and diluted net loss per common share
|
|
$ |
(1.39 |
) |
|
$ |
(5.94 |
) |
|
$ |
(13.16 |
) |
|
$ |
(11.92 |
) |
|
$ |
(17.33 |
) |
|
$ |
(11.34 |
) |
|
$ |
(15.84 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Shares used in computing basic and diluted net loss per common
share
|
|
|
1,239 |
|
|
|
1,367 |
|
|
|
1,687 |
|
|
|
1,687 |
|
|
|
1,704 |
|
|
|
1,700 |
|
|
|
1,722 |
|
|
Pro forma basic and diluted net loss per common share
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
$ |
(1.96 |
) |
|
|
|
|
|
$ |
(1.46 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Shares used in computing pro forma basic and diluted net
loss per common share
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
10,915 |
|
|
|
|
|
|
|
13,328 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
footnote on following page
34
|
|
(1) |
Non-cash contract modification expense reflects the fair value
of warrants issued to CFFTI and warrants held by Vertex that
were repriced in conjunction with the sale of the Series B
convertible preferred stock in 2001. We granted warrants to
CFFTI to purchase 87,221 shares of our common stock at an
exercise price of $0.02 per common share as consideration
for modifying specified terms and provisions of our
collaboration agreement. In addition, we reduced the exercise
price for warrants to purchase 1,962,494 shares of our common
stock held by Vertex to $5.64 per share. |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
As of December 31, | |
|
As of | |
|
|
| |
|
September 30, | |
|
|
2000 | |
|
2001 | |
|
2002 | |
|
2003 | |
|
2004 | |
|
2005 | |
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
|
(in thousands) | |
Consolidated Balance Sheet Data:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cash and cash equivalents and short-term investments
|
|
$ |
1,354 |
|
|
$ |
43,008 |
|
|
$ |
31,808 |
|
|
$ |
22,636 |
|
|
$ |
52,638 |
|
|
$ |
32,009 |
|
Working capital
|
|
|
69 |
|
|
|
39,299 |
|
|
|
30,020 |
|
|
|
16,817 |
|
|
|
41,612 |
|
|
|
22,302 |
|
Total assets
|
|
|
3,419 |
|
|
|
47,105 |
|
|
|
41,792 |
|
|
|
29,117 |
|
|
|
62,824 |
|
|
|
44,171 |
|
Deferred revenue
|
|
|
|
|
|
|
1,337 |
|
|
|
9,888 |
|
|
|
12,865 |
|
|
|
10,617 |
|
|
|
10,426 |
|
Long-term debt, net of current portion
|
|
|
779 |
|
|
|
47 |
|
|
|
1,664 |
|
|
|
1,964 |
|
|
|
3,821 |
|
|
|
4,210 |
|
Redeemable preferred stock
|
|
|
3,870 |
|
|
|
48,420 |
|
|
|
53,325 |
|
|
|
58,230 |
|
|
|
108,465 |
|
|
|
116,634 |
|
Total stockholders deficit
|
|
|
(4,023 |
) |
|
|
(6,176 |
) |
|
|
(27,920 |
) |
|
|
(47,627 |
) |
|
|
(68,112 |
) |
|
|
(94,517 |
) |
35
MANAGEMENTS DISCUSSION AND ANALYSIS OF FINANCIAL
CONDITION
AND RESULTS OF OPERATIONS
You should read the following discussion and analysis of
financial condition and results of operations together with the
section entitled Selected Consolidated Financial
Data and our consolidated financial statements and related
notes appearing elsewhere in this prospectus. In addition to
historical financial information, the following discussion
contains forward-looking statements that reflect our plans,
estimates and beliefs. Our actual results could differ
materially from those discussed in the forward-looking
statements. Factors that could cause or contribute to these
differences include those discussed below and elsewhere in this
prospectus, particularly in the section entitled Risk
Factors.
Overview
We are a biopharmaceutical company focused on the development
and commercialization of oral and injectable protein
therapeutics for chronic gastrointestinal and metabolic
disorders, with two product candidates in clinical development.
We are using our proprietary protein crystallization technology
to develop protein therapies, which we believe will have
significant advantages over existing products or will address
unmet medical needs. Our product candidates are designed to
either increase the amount of a protein that is in short supply
in the body or degrade and remove toxic metabolites from the
blood stream. Our two lead product candidates are:
ALTU-135, for which we
have completed a Phase II clinical trial in cystic fibrosis
patients for the treatment of malabsorption due to exocrine
pancreatic insufficiency, and
ALTU-238, for which we
are currently conducting a Phase II clinical trial in
adults for the treatment of growth hormone deficiency. We also
have a pipeline of other product candidates in preclinical
research and development. We have generated significant losses
as we have progressed our lead product candidates into clinical
development and expect to continue to generate losses as
ALTU-135 and
ALTU-238 move into
later stages of clinical development. As of September 30,
2005, we had an accumulated deficit of $112.1 million.
Financial Operations Overview
Revenue. Our contract revenue consists primarily of
amounts earned under collaborative research and development
agreements relating to ALTU-135 with CFFTI and Dr. Falk.
In February 2001, we entered into a strategic alliance agreement
with CFFTI to collaborate on the development of ALTU-135 and
specified derivatives of ALTU-135 in North America for the
treatment of malabsorption due to exocrine pancreatic
insufficiency in patients with cystic fibrosis and other
indications. The agreement, in general terms, provides us with
funding from CFFTI for a portion of the development costs of
ALTU-135 upon the
achievement of specified development milestones, up to a total
of $25.0 million, in return for specified payment
obligations and our obligation to use good faith reasonable
efforts to develop and bring ALTU-135 to market in North
America. As of September 30, 2005, we had received a total
of $15.9 million of the $25.0 million available under
the CFFTI agreement and recognized cumulative revenue of
$8.9 million. We received an additional $2.5 million
in December 2005 as a result of the delivery to CFFTI of the
data from our recently completed Phase II clinical trial of
ALTU-135. In addition,
we may receive an additional milestone payment of
$6.6 million, less an amount determined by when we achieve
the milestone.
If we are successful in obtaining FDA approval of ALTU-135, we
will be required to pay CFFTI a license fee equal to the
aggregate amount of milestone payments we have received from
CFFTI, plus interest, up to a maximum of $40.0 million,
less the fair market value of the shares of stock underlying the
warrants we issued to CFFTI. This fee, plus interest on the
unpaid balance, will be due in four annual installments,
commencing 30 days after the approval date. We are also
required to pay an additional $1.5 million to CFFTI within
30 days after the approval date. In addition, we are
obligated to pay royalties to CFFTI consisting of a percentage
of worldwide net sales by us or our sublicensees of
ALTU-135 for any and
all indications until the expiration of specified United States
patents covering
ALTU-135. We have the
option to terminate our ongoing royalty obligation by making a
one-time payment to CFFTI, but
36
we currently do not expect to do so. Under the agreement, CFFTI
has also agreed to provide us with reasonable access to its
network of medical providers, patients, researchers and others
involved in the care and treatment of cystic fibrosis patients,
and to use reasonable efforts to promote the involvement of
these parties in the development of
ALTU-135.
In connection with the execution of the agreement and the first
amendment of the agreement, we have issued to CFFTI warrants to
purchase a total of 261,664 shares of our common stock at
an exercise price of $0.02 per share, including 174,443
warrants with a fair value of $1.7 million issued upon
execution of the agreement in February 2001. The fair value of
the 174,443 warrants is being recognized as a discount to
contract revenue and amortized against the gross revenue earned
under the contract. As of September 30, 2005, approximately
$1.1 million remains to be amortized against future
revenues under the agreement.
In December 2002, we entered into a development,
commercialization and marketing agreement with Dr. Falk for
the development by us of
ALTU-135 and the
commercialization by Dr. Falk of
ALTU-135, if approved,
in Europe, the countries of the former Soviet Union, Israel and
Egypt. Under the agreement, we granted Dr. Falk an
exclusive, sublicensable license under specified patents that
cover ALTU-135 to
commercialize ALTU-135
for the treatment of symptoms caused by exocrine pancreatic
insufficiency. As of September 30, 2005, we had received
upfront and milestone payments from Dr. Falk under the
agreement totaling
7.0 million,
which equated to $8.1 million based on exchange rates in
effect at the times we received the milestone payments, and
recognized cumulative revenue of $6.5 million. We received
an additional
4.0 million
in December 2005, which equated to $4.7 million based on
the exchange rate in effect at the time, as a result of the
delivery to Dr. Falk of the final report from our recently
completed Phase II clinical trial of
ALTU-135. In addition,
Dr. Falk has agreed to pay a portion of the development
expenses we incur in connection with the conduct of an
international Phase III clinical trial, including costs
relating to the process of obtaining regulatory approval,
project management costs, statistical design and studies, and
preparation of reports. Dr. Falk holds all
commercialization and marketing rights in the licensed
territory, and we are entitled to receive royalties based on the
net sales of ALTU-135
in the licensed territory and revenue for the
ALTU-135 capsules
supplied by us to Dr. Falk. Under the terms of the
agreement, the license to Dr. Falk will continue in each
country in the licensed territory until the later of the
expiration of the
last-to-expire of
specified patents that cover ALTU-135 in that country or
12 years from the date of first commercial sale of ALTU-135
in that country.
In addition to contract revenue under our collaborations with
CFFTI and Dr. Falk, we also receive research and
development funding through grants from various United States
government and non-government institutions. Research and
development funding generally compensates us for a portion of
our development and testing related to collaborative research
programs or grants.
Historically, our product sales consisted of revenue from the
sale of crystallized enzymes for use as catalysts for the
production of small molecule drugs and related development
activities for use in pharmaceutical manufacturing processes. We
stopped selling these products during the first half of 2004.
Accordingly, we do not currently generate revenue from product
sales.
Cost of Product Sales. Cost of product sales represents
the cost of manufacturing the crystallized enzyme catalysts
discussed immediately above and consists primarily of
third-party contract manufacturing expenses. For products made
internally, the costs consist primarily of payroll and
payroll-related expenses, chemicals, supplies and overhead
expenses.
Research and Development Expense. Research and
development expense consists primarily of expenses incurred in
developing and testing product candidates, including:
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salaries and related expenses for personnel, including
stock-based compensation expenses; |
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fees paid to professional service providers in conjunction with
independently monitoring our clinical trials and acquiring and
evaluating data in conjunction with our clinical trials; |
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performance of non-clinical trials, including toxicity studies
in animals; |
37
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costs of contract manufacturing services; |
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costs of materials used in clinical and non-clinical
trials; and |
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depreciation of capital resources used to develop our products
and costs of facilities. |
We expense research and development costs as incurred.
As of June 30, 2005, we had completed our Phase II
clinical trial of
ALTU-135 and were
designing and preparing for a Phase III clinical trial of
the solid form of
ALTU-135 and conducting
related development activities. In August 2005, we revised our
estimate of the total costs we will incur to complete the
development of ALTU-135
and file an NDA with the FDA to be approximately
$118 million, excluding non-cash compensation expense and
depreciation. We may further revise such estimate in the future.
As of September 30, 2005, we had incurred approximately
$45.2 million of such total costs. We also recently completed a
Phase I clinical trial and initiated enrollment in a
Phase II clinical trial of
ALTU-238. From
January 1, 2003, the date on which we began separately
tracking development costs for
ALTU-238, through
September 30, 2005, we incurred approximately
$10.8 million in total development costs for this product
candidate. We expect our research and development costs to
increase substantially in the foreseeable future.
Product candidates in clinical development have higher
associated development costs than those in the preclinical stage
since the former involve testing on humans while the latter
involve shorter-term animal studies. Moreover, as a product
candidate moves into later-stage clinical trials, such as from
Phase I to Phase II or Phase II to
Phase III, the costs are significantly higher due to the
increased size and length of the later stage trial.
The successful development of our product candidates is highly
uncertain. At this time, we cannot reasonably estimate or know
the nature, timing and estimated costs of the efforts that will
be necessary to complete the remainder of the development of, or
the period, if any, in which material net cash inflows will
commence from, ALTU-238
or any of our preclinical product candidates. This is due to the
numerous risks and uncertainties associated with developing
drugs, including the uncertainty of:
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the scope, rate of progress and expense of our clinical trials
and other research and development activities; |
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the potential benefits of our product candidates over other
therapies; |
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our ability to market, commercialize and achieve market
acceptance for any of our product candidates that we are
developing or may develop in the future; |
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future clinical trial results; |
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the terms and timing of any collaborative, licensing and other
arrangements that we may establish; |
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the expense and timing of regulatory approvals; and |
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the expense of filing, prosecuting, defending and enforcing any
patent claims and other intellectual property rights. |
A change in the outcome of any of these variables with respect
to the development of a product candidate would mean a
significant change in the costs and timing associated with the
development of that product candidate. For example, if the FDA
or other regulatory authority were to require us to conduct
clinical trials beyond those which we currently anticipate will
be required for the completion of clinical development of a
product candidate or if we experience significant delays in
enrollment in any of our clinical trials, we would be required
to expend significant additional financial resources and time on
the completion of clinical development.
General, Sales and Administrative Expense. General, sales
and administrative expense consists primarily of salaries and
other related costs for personnel, including stock-based
compensation expenses, in
38
our executive, sales, marketing, finance, accounting,
information technology and human resource functions. Other costs
primarily include facility costs not otherwise included in
research and development expense, advertising and promotion
expenses, trade shows and professional fees for legal services,
including patent-related expenses, and accounting services.
We expect that general and administrative expenses will increase
in the future due to increased payroll, expanded infrastructure,
increased consulting, legal, accounting and investor relations
expenses associated with being a public company and costs
incurred to seek collaborations with respect to any of our
product candidates.
Interest and Other Income (Expense), Net. Interest income
consists of interest earned on our cash and cash equivalents and
short-term investments. Interest expense consists of interest
incurred on capital leases and other debt financings, which are
primarily equipment loans. Other income (expense), net consists
primarily of foreign currency gains (losses) and a realized loss
on investments during the year ended December 31, 2002.
Preferred Stock Dividends and Accretion. Preferred stock
dividends and accretion consists of cumulative but undeclared
dividends payable and accretion of the issuance costs and
warrants, where applicable, on the redeemable preferred stock
and Series B and C convertible preferred stock. The
issuance costs on these shares and warrants were recorded as a
reduction to the carrying value of the preferred stock when
issued, and are accreted to preferred stock ratably through
December 31, 2010 by a charge to additional paid-in capital
and earnings attributable to common shareholders. Upon the
completion of this offering, the cumulative but unpaid dividends
on the Series B and C convertible preferred stock are
payable in shares of common stock at the price of the common
stock sold in the offering. Accordingly, upon completion of this
offering, we expect that we will no longer record preferred
dividends and accretion on the Series B and Series C
convertible preferred stock, which will convert into common
shares upon completion of this offering. As of
September 30, 2005, the cumulative dividends payable on the
Series B and C convertible preferred stock totaled
$18.3 million.
Critical Accounting Policies and Significant Judgments and
Estimates
Our discussion and analysis of our financial condition and
results of operations is based on our consolidated financial
statements and notes, which have been prepared in accordance
with accounting principles generally accepted in the United
States. The preparation of these financial statements requires
us to make estimates and judgments that affect the reported
amounts of assets, liabilities, revenues and expenses. On an
ongoing basis, we evaluate our estimates and judgments,
including those related to revenue, accrued expenses, deemed
fair valuation of stock related to stock-based compensation and
income taxes. We base our estimates on historical experience and
on various other assumptions that we believe to be reasonable
under the circumstances, the results of which form the basis for
making judgments about the carrying values of assets and
liabilities that are not readily apparent from other sources.
Actual results may differ from these estimates under different
assumptions or conditions. A summary of our significant
accounting policies is contained in Note 2 to our
consolidated financial statements included elsewhere in this
prospectus. We believe the following critical accounting
policies affect our more significant judgments and estimates
used in the preparation of our consolidated financial statements.
Revenue. Our existing collaborative agreements that
generate contract revenue relate solely to ALTU-135. We
recognize contract revenue under these collaborative agreements
using the proportional performance method based on the
percentage of costs incurred relative to the total costs
estimated to be incurred to complete the program, to the extent
such amount is not greater than the cash received. At each
reporting period, we review the status of the product candidate
in light of the most recently completed development activities
and related results and the estimated remaining development
costs and, to the extent such estimates change, the impact of
such change on revenue is recorded in operations at that time.
Significant judgments and estimates are involved in determining
the estimated costs to complete the development programs, and
different assumptions could yield materially different cost
estimates and resulting revenue.
39
For the purpose of recognizing revenue, we use an input based
measure, specifically direct costs, to determine proportional
performance under our collaboration agreements because we
believe that for our current agreements the use of an input
measure is a more accurate representation of proportional
performance than an output based measure, such as milestones. We
also believe that the direct cost method most closely reflects
the level of effort related to our research and development
collaborations. While we have considered using an output based
measure, we believe that such an approach would accelerate the
recognition of revenue and result in reported revenue that would
be disproportionate to the progress made in the earlier stages
of development of
ALTU-135, where the
product development risk is highest, as well as the level of
effort over the life of the agreements.
Since the inception of our collaboration agreements with CFFTI
and Dr. Falk, we have adjusted our estimated costs to
complete the development program for ALTU-135 on three
occasions, resulting in cumulative changes in our revenue at
each time of the change in the estimate. At the end of 2002 we
increased our estimated development costs to complete ALTU-135,
resulting in a corresponding reduction of $1.6 million in
cumulative revenue in the fourth quarter of 2002. At the end of
2003, we again increased our estimated development costs to
complete ALTU-135, resulting in a $2.5 million reduction of
our cumulative revenue in the fourth quarter of 2003. During the
third quarter of 2005, we reduced our estimated development
costs for ALTU-135, which resulted in a $3.3 million
increase in our cumulative revenue in the third quarter of 2005.
In addition, our agreement with Dr. Falk is denominated in
Euros. Accordingly, the impact of fluctuations in exchange rates
under collaborative agreements that are denominated in a foreign
currency is reflected in deferred revenue at the time the cash
is received and in revenue at each reporting period. The
possibility exists that revenue may increase or decrease in
future periods as estimated costs on the underlying program
increase or decrease or as exchange rates impact the value of
foreign currency denominated collaborations, without additional
cash inflows from the collaborative partner or non-government
institution. For example, as of September 30, 2005, if our
estimated total development costs for
ALTU-135 were to
increase by 10%, it would result in a $1.4 million
reduction of cumulative revenue. If our estimated total
development costs for
ALTU-135 were to
decrease by 10%, it would result in a $1.7 million increase
of cumulative revenue.
Contract amounts which are not due until the customer accepts or
verifies the research results are not recognized as revenue
until payment is received or the customers acceptance or
verification of the results is evidenced, whichever occurs
earlier. Contract revenue recorded under the CFFTI agreement is
recognized net of amortization of the fair value of the warrants
issued in connection with the execution of the agreement.
Deferred revenue is recorded when payments are received in
advance of revenue recognized under collaborative agreements.
Since the payments received under the collaborative agreements
are non-refundable, the termination of a collaborative agreement
prior to its completion could result in an immediate recognition
of deferred revenue relating to payments already received from
the collaborative partner but not previously recognized as
revenue.
Revenue from research and development funding under grants from
the United States government and its agencies is recognized as
revenue as development costs are incurred and billed in
accordance with the terms of the grant. Revenue from product
sales is recognized when there is persuasive evidence that an
arrangement exists, delivery and, if applicable, acceptance by
the customer has occurred, the price is fixed or determinable,
and collectibility is reasonably assured.
Accrued Expenses. As part of the process of preparing
consolidated financial statements we are required to estimate
accrued expenses. This process involves identifying services
which have been performed on our behalf and estimating the level
of service performed and the associated cost incurred for such
service as of each balance sheet date in our consolidated
financial statements. Examples of estimated expenses for which
we accrue include contract service fees, such as amounts paid to
clinical monitors, data management organizations, clinical sites
and investigators in conjunction with clinical trials, and fees
paid to contract manufacturers in conjunction with the
production of materials for clinical and non-clinical trials,
and professional service fees. In connection with these service
fees, our estimates are most affected
40
by our understanding of the status and timing of services
provided relative to the actual levels of services incurred by
such service providers. In the event that we do not identify
costs which have begun to be incurred or we under- or
over-estimate the level of services performed or the costs of
such services, our reported expenses for such period would be
too low or too high, and revenue may be overstated or
understated to the extent such expenses relate to collaborations
accounted for using the proportional performance method. The
date on which specified services commence, the level of services
performed on or before a given date and the cost of such
services is often judgmental. We attempt to mitigate the risk of
inaccurate estimates, in part, by communicating with our service
providers when other evidence of costs incurred is unavailable.
Stock-Based Compensation. On January 1, 2002, we
adopted the fair value method to record stock-based compensation
as provided under Financial Accounting Standards Board Statement
No. 123, or SFAS No. 123, Accounting for
Stock-Based Compensation. Accordingly, we account for
transactions in which goods and services are received in
exchange for equity instruments based on the fair value of such
goods and services received or the deemed fair value of the
equity instruments issued, whichever is more reliably measured.
The fair value is recorded as stock-based compensation expense
ratably over the vesting period. When equity instruments are
granted or sold in exchange for the receipt of goods or services
and the value of those goods or services can not be readily
estimated, as is true in connection with most stock options and
warrants granted to employees, directors, consultants and other
non-employees, we determine the fair value of the equity
instruments using all relevant information, including
application of the Black-Scholes option-pricing model and, in
specified situations, input from valuation specialists, all of
which require various estimates and assumptions. Different
estimates and assumptions can yield materially different
results. The factors which most affect charges or credits to
operations related to stock-based compensation include: the
deemed fair value of the common stock underlying the equity
instruments for which stock-based compensation is recorded; the
volatility of such deemed fair value; the estimated life of the
equity instrument; and the assumed risk-free rate of return.
Because shares of our common stock have not been publicly
traded, the fair value of our common stock for accounting
purposes is determined by us. Factors that we consider when
determining the fair value of our common stock include:
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pricing of private sales of our convertible preferred stock; |
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prior valuations of stock grants and convertible preferred stock
sales and the effect of events, including the progression of our
product candidates, that have occurred between the time of the
grants or sales; |
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comparative rights and preferences of the security being granted
compared to the rights and preferences of our other outstanding
equity; |
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comparative values of public companies discounted for the risk
and limited liquidity provided for in the shares we are issuing; |
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perspective provided by valuation specialists; |
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any perspective provided by any investment banks, including the
likelihood of an initial public offering and the potential value
of the company in an initial public offering; and |
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general economic trends. |
If our estimates of the deemed fair value of these equity
instruments or other judgments and assumptions are too high or
too low, it would have the effect of overstating or understating
expenses.
The fair value of our equity instruments, excluding preferred
stock, granted prior to our consideration of a public offering
of securities, has historically been determined by our board of
directors based upon information available to it on the
measurement dates. However, in 2005, we performed a
retrospective analysis to determine the deemed fair market value
of our common stock for accounting purposes in light of the
potential initial public offering. This retrospective analysis
addressed the deemed
41
fair market value of our common stock at key points in time in
2004 and 2005. We performed our analysis in accordance with
several elements of a practice aid issued by the American
Institute of Certified Public Accountants entitled
Valuation of Privately Held Company Equity Securities
Issued as Compensation. We used two primary valuation
methodologies within the market approach in the practice aid,
including a Guideline Public Company Analysis, or comparable
company IPO analysis, and a Guideline Transactions Analysis, or
comparable company M&A analysis, to determine the estimated
deemed fair market value of our equity during the period
discussed above. We then allocated value between the preferred
stock and the common stock under each analysis and arrived at
the value of the common stock based on a probability-weighted
expected return methodology.
On December 16, 2004, the Financial Accounting Standards
Board issued Statement No. 123 (revised in 2004), or
SFAS No. 123R, Share-Based Payment which
amends SFAS No. 123. The amendment is effective for us
as of January 1, 2006. We are evaluating the impact of
SFAS No. 123R on our operations.
Income Taxes. As part of the process of preparing our
consolidated financial statements, we are required to estimate
our income taxes in each of the jurisdictions in which we
operate. This process involves estimating our actual current tax
exposure together with assessing temporary differences resulting
from differing treatments of items for tax and accounting
purposes. These differences result in deferred tax assets and
liabilities. As of December 31, 2004, we had federal tax
net operating loss carryforwards of $42.7 million, which
expire starting in 2020, federal research and development credit
carryforwards of $0.6 million and total net deferred tax
assets of $24.9 million. We have recorded a valuation
allowance of $24.9 million as an offset against these
otherwise recognizable net deferred tax assets due to the
uncertainty surrounding the timing of the realization of the tax
benefit. In the event that we determine in the future that we
will be able to realize all or a portion of our net deferred tax
asset, an adjustment to the deferred tax valuation allowance
would increase net income in the period in which such a
determination is made. The Tax Reform Act of 1986 contains
provisions that may limit the utilization of net operating loss
carryforwards and credits available to be used in any given year
in the event of a change in ownership.
Results of Operations
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Nine Months Ended September 30, 2005 and 2004 |
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Nine Months Ended | |
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|
September 30, | |
|
Change | |
|
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| |
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| |
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|
2004 | |
|
2005 | |
|
$ | |
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% | |
|
|
| |
|
| |
|
| |
|
| |
|
|
(dollars in thousands) | |
Contract revenue
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|
$ |
2,891 |
|
|
$ |
6,727 |
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|
$ |
3,836 |
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|
|
133 |
% |
Product sales
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|
|
185 |
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|
(185 |
) |
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(100 |
) |
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|
|
|
|
|
|
|
|
|
Total revenue
|
|
$ |
3,076 |
|
|
$ |
6,727 |
|
|
$ |
3,651 |
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|
|
119 |
% |
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Contract revenue for the nine months ended September 30,
2005 increased 133% to $6.7 million from $2.9 million
in the corresponding period in 2004 due primarily to an increase
in development activities relating to ALTU-135 and a reduction
of our estimated development costs for ALTU-135 in the third
quarter of 2005, resulting in a $3.3 million increase in
our cumulative revenue. A significant portion of our contract
revenue is generated from revenue recognized under the
proportional performance method from collaboration agreements
for ALTU-135 with CFFTI and Dr. Falk. We incurred research
and development costs in each nine-month period to advance
ALTU-135 and recognized
additional revenue based on those costs.
Product sales decreased to $0.0 for the nine months ended
September 30, 2005 from $0.2 million in the
corresponding period in 2004 due to our decision to stop selling
crystallized enzymes for use as catalysts in the production of
small molecule drugs during the first half of 2004.
42
Cost of product sales for the nine months ended
September 30, 2005 decreased to $0.0 from $0.1 million
in 2004 as a result of no product sales.
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Research and development expense |
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|
|
|
|
|
|
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|
|
|
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|
Nine Months Ended | |
|
|
|
|
September 30, | |
|
Change | |
|
|
| |
|
| |
|
|
2004 | |
|
2005 | |
|
$ | |
|
% | |
|
|
| |
|
| |
|
| |
|
| |
|
|
(dollars in thousands) | |
ALTU-135
|
|
$ |
7,871 |
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|
$ |
9,134 |
|
|
$ |
1,263 |
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|
|
16 |
% |
ALTU-238
|
|
|
1,775 |
|
|
|
5,865 |
|
|
|
4,090 |
|
|
|
230 |
|
Other research and development
|
|
|
2,349 |
|
|
|
4,793 |
|
|
|
2,444 |
|
|
|
104 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total research and development
|
|
$ |
11,995 |
|
|
$ |
19,792 |
|
|
$ |
7,797 |
|
|
|
65 |
% |
|
|
|
|
|
|
|
|
|
|
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|
Research and development expense for the nine months ended
September 30, 2005 increased 65% to $19.8 million from
$12.0 million in the corresponding period in 2004, due
primarily to an increase in development costs relating to
ALTU-135 and ALTU-238. During 2005, we completed a Phase II
clinical trial for
ALTU-135, and filed an
IND, completed a Phase I clinical trial and started a
Phase II clinical trial for ALTU-238. Product candidates in
clinical development have greater associated development costs
than those in the research or preclinical stage, and as a
product candidate moves to later stage clinical trials, such as
a Phase II clinical trial, the costs are higher due to the
increased size and length of the clinical trial versus an
earlier stage clinical trial. In addition, we had other
preclinical product candidates advancing in our pipeline. To
support the increased activities, our headcount in the research
and development area increased to 66 full-time employees at
September 30, 2005 from 50 full-time employees at
September 30, 2004.
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General, sales and administrative expense |
General, sales and administrative expense for the nine months
ended September 30, 2005 increased 30% to $6.0 million
from $4.6 million in the corresponding period in 2004, due
primarily to $0.3 million of increased recruiting fees,
$0.3 million of increased consulting fees primarily related
to consulting fees paid to a member of our Board of Directors
and $0.4 million of increased salaries and professional
fees related to our accounting, human resource and information
technology functions. We expect that general and administrative
expenses will increase in the future due to increased payroll,
expanded infrastructure, increased consulting, legal, accounting
and investor relations expenses associated with being a public
company and costs incurred to seek collaborations with respect
to any of our product candidates.
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Interest income and interest expense |
Interest income for the nine months ended September 30,
2005 increased 73% to $0.7 million from $0.4 million
in the corresponding period in 2004, due to higher average
investment balances from funds received in our Series C
preferred stock financing in May 2004 and to higher average
interest rates in 2005.
Interest expense for the nine months ended September 30,
2005 increased 76% to $0.6 million from $0.4 million
in the corresponding period in 2004, due to an increase in our
total debt from $2.7 million outstanding at
September 30, 2004, to $6.6 million outstanding at
September 30, 2005 as a result of our capital expenditures
and higher interest rates on new borrowings in 2005.
43
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Other income (expense), net |
Other income (expense), net represents foreign currency losses
of $0.1 million in the nine months ended September 30,
2005 and foreign currency gains of $0.1 million compared to
the corresponding period in 2004.
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|
|
Preferred stock dividends and accretion |
Preferred stock dividends and accretion for the nine months
ended September 30, 2005 increased to $8.2 million
from $5.5 million in the corresponding period in 2004, due
to the issuance of the Series C preferred stock in May
2004. The Series C convertible preferred stock accrues
dividends at a rate of 9% per year.
|
|
|
Year Ended December 31, 2004 Compared to Year Ended
December 31, 2003 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Years Ended | |
|
|
|
|
December 31, | |
|
Change | |
|
|
| |
|
| |
|
|
2003 | |
|
2004 | |
|
$ | |
|
% | |
|
|
| |
|
| |
|
| |
|
| |
|
|
(dollars in thousands) | |
Contract revenue
|
|
$ |
2,613 |
|
|
$ |
4,045 |
|
|
$ |
1,432 |
|
|
|
55 |
% |
Product sales
|
|
|
1,268 |
|
|
|
185 |
|
|
|
(1,083 |
) |
|
|
(85 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
Total revenue
|
|
$ |
3,881 |
|
|
$ |
4,230 |
|
|
$ |
349 |
|
|
|
9 |
% |
|
|
|
|
|
|
|
|
|
|
|
|
|
Contract revenue for 2004 increased 55% to $4.0 million
from $2.6 million in 2003 due primarily to increased
revenue recognized under our collaborative agreements with CFFTI
and Dr. Falk for the development of ALTU-135. We initiated
a Phase II clinical trial of ALTU-135 in the second quarter
of 2004. In 2003, we completed the Phase Ib clinical trial
and conducted preparatory activities for the Phase II trial
for ALTU-135.
A significant portion of our contract revenue is generated from
revenue recognized under the proportional performance method,
limited by milestone payments received, from collaboration
agreements for ALTU-135 with CFFTI and Dr. Falk. In 2003,
we increased the estimated development costs for ALTU-135. The
increase in costs resulted in a $2.5 million reduction of
our cumulative contract revenue at the end of 2003.
Product sales for 2004 decreased 85% to $0.2 million from
$1.3 million in 2003 due to our decision to stop selling
crystallized enzymes for use as catalysts in the production of
small molecule drugs in the first quarter of 2004.
Cost of product sales for 2004 decreased 83% to
$0.1 million from $0.6 million in 2003 due to lower
product sales.
|
|
|
Research and development expense |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Years Ended | |
|
|
|
|
December 31, | |
|
Change | |
|
|
| |
|
| |
|
|
2003 | |
|
2004 | |
|
$ | |
|
% | |
|
|
| |
|
| |
|
| |
|
| |
|
|
(dollars in thousands) | |
ALTU-135
|
|
$ |
9,440 |
|
|
$ |
11,540 |
|
|
$ |
2,100 |
|
|
|
22 |
% |
ALTU-238
|
|
|
1,376 |
|
|
|
3,604 |
|
|
|
2,228 |
|
|
|
162 |
|
Other research and development
|
|
|
2,466 |
|
|
|
3,951 |
|
|
|
1,485 |
|
|
|
60 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total research and development
|
|
$ |
13,282 |
|
|
$ |
19,095 |
|
|
$ |
5,813 |
|
|
|
44 |
% |
|
|
|
|
|
|
|
|
|
|
|
|
|
44
Research and development expense for 2004 increased 44% to
$19.1 million from $13.3 million in 2003 due primarily
to costs associated with the initiation of a Phase II
clinical trial for ALTU-135 in the second quarter of 2004 and
costs incurred in 2004 to prepare an IND filing for ALTU-238 in
the first quarter of 2005. Other research and development
expenses also increased in 2004 as we continued to advance other
preclinical product candidates in our pipeline.
|
|
|
General, sales and administrative expense |
General, sales and administrative expense for 2004 increased 14%
to $6.3 million from $5.5 million in 2003 due
primarily to $0.4 million of increased legal expenses,
$0.2 million of increased accounting and board fees, and
$0.1 million of recruiting expenses. The higher legal costs
related to litigation which was settled during 2004. The
increase in accounting and board fees was due primarily to our
initiation of quarterly financial statement reviews by our
auditors and an increase in the number of and fees paid to
outside board members. Recruiting costs were higher due to a
non-refundable fee paid to a search agency upon initiation of
the search for a new President and CEO in the fourth quarter of
2004.
|
|
|
Interest income and interest expense |
Interest income for 2004 increased 60% to $0.6 million from
$0.4 million in 2003 due to higher average investment
balances due to funds received from our Series C preferred
stock financing in May 2004.
Interest expense for 2004 increased 87% to $0.5 million
from $0.3 million in 2003. We increased our total debt from
$2.9 million outstanding at December 31, 2003 to
$5.7 million outstanding at December 31, 2004 in
connection with increased capital expenditures.
|
|
|
Other income (expense), net |
Other income (expense), net primarily represents foreign
currency gains of $0.1 million in 2004 and
$0.2 million in 2003.
|
|
|
Preferred stock dividends and accretion |
Preferred stock dividends and accretion for 2004 increased 76%
to $8.6 million from $4.9 million in 2003 due to the
issuance of the Series C convertible preferred stock in May
2004.
|
|
|
Year Ended December 31, 2003 Compared to Year Ended
December 31, 2002 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Years Ended | |
|
|
|
|
December 31, | |
|
Change | |
|
|
| |
|
| |
|
|
2002 | |
|
2003 | |
|
$ | |
|
% | |
|
|
| |
|
| |
|
| |
|
| |
|
|
(dollars in thousands) | |
Contract revenue
|
|
$ |
1,885 |
|
|
$ |
2,613 |
|
|
$ |
728 |
|
|
|
39 |
% |
Product sales
|
|
|
483 |
|
|
|
1,268 |
|
|
|
785 |
|
|
|
163 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total revenue
|
|
$ |
2,368 |
|
|
$ |
3,881 |
|
|
$ |
1,513 |
|
|
|
64 |
% |
|
|
|
|
|
|
|
|
|
|
|
|
|
Contract revenue for 2003 increased 39% to $2.6 million
from $1.9 million in 2002 due primarily to our entering
into a collaboration agreement with Dr. Falk in December
2002 for the development and commercialization of
ALTU-135 in Europe, the
countries of the former Soviet Union, Israel and Egypt.
Product sales for 2003 increased 163% to $1.3 million from
$0.5 million in 2002 due primarily to higher product sales
to three customers in 2003 which represented 82% of all product
sales during 2003. Sales to our largest customer were 49% of
total product sales.
Cost of product sales for 2003 increased 140% to
$0.6 million from $0.2 million in 2002 due to the
increase in product sales in 2003.
45
|
|
|
Research and development expense |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Years Ended | |
|
|
|
|
December 31, | |
|
Change | |
|
|
| |
|
| |
|
|
2002 | |
|
2003 | |
|
$ | |
|
% | |
|
|
| |
|
| |
|
| |
|
| |
|
|
(dollars in thousands) | |
ALTU-135
|
|
$ |
10,091 |
|
|
$ |
9,440 |
|
|
$ |
(651 |
) |
|
|
(6 |
)% |
Other research and development
|
|
|
3,083 |
|
|
|
3,842 |
|
|
|
759 |
|
|
|
25 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total research and development
|
|
$ |
13,174 |
|
|
$ |
13,282 |
|
|
$ |
108 |
|
|
|
1 |
% |
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and development costs for 2003 approximated those
incurred in 2002 as lower
ALTU-135 costs were
offset by higher spending on other projects.
ALTU-135 costs during
2003 consisted of Phase Ib clinical trial costs and
preparatory activities related to a Phase II clinical
trial. Costs incurred for
ALTU-135 in 2002
related to filing an IND and conducting a Phase Ia clinical
trial. In 2003, spending on
ALTU-238 was
approximately $1.4 million and is included in other
research and development expenses in the table above. During
2002, we did not track costs of
ALTU-238 separately
from other research and development costs, as this product
candidate was in research.
|
|
|
General, sales and administrative expense |
General, sales and administrative expense for 2003 decreased 19%
to $5.5 million from $6.9 million in 2002 primarily
due to a $1.0 million reduction in legal fees and
$0.4 million in reduced consulting and business development
expenses. The legal fees decreased in 2003 due to the settlement
of a trademark lawsuit filed by us in 2002. Lower advertising,
market research, and website related costs accounted for the
decrease in consulting and business development expenses.
|
|
|
Interest income and interest expense |
Interest income for 2003 decreased 53% to $0.4 million from
$0.9 million in 2002 due to lower average investment
balances.
Interest expense for 2003 increased 61% to $0.3 million
from $0.2 million in 2002. We increased our total debt to
$2.9 million at December 31, 2003 from
$2.3 million at December 31, 2002 in connection with
increased capital expenditures.
|
|
|
Other income (expense), net |
Other income (expense), net primarily represents foreign
currency gains of $0.2 million in 2003 and a realized loss
on investments of $0.1 million in 2002.
|
|
|
Preferred stock dividends and accretion |
Preferred stock dividends and accretion were $4.9 million
for both 2003 and 2002. We recognized a full year of dividends
and accretion relating to our redeemable preferred stock and
Series B convertible preferred stock during both years.
Liquidity and Capital Resources
Historically, we have financed our business primarily through
the issuance of equity securities, revenues from collaborative
agreements and product sales, debt financings and equipment
loans and leases. At September 30, 2005, we had
$7.2 million in cash and cash equivalents and
$24.8 million in short-term investments available to
finance future operations.
Prior to September 2001, we received most of our equity and debt
financing proceeds from issuances of notes, common stock and
preferred stock to Vertex, including redeemable preferred stock
and Series A convertible preferred stock. The redeemable
preferred stock is redeemable, at the option of Vertex, on or
after December 31, 2010, or by us at our option at any time
following the completion of this
46
offering, at a price of $10.00 per share plus all accrued
but unpaid dividends and is not convertible into common stock.
Accrued but unpaid dividends on the redeemable preferred stock
amounted to $1.5 million at September 30, 2005 and
will be approximately $2.7 million on December 31,
2010.
In September and December 2001, we received net proceeds
totaling approximately $46.2 million, net of issuance costs
of approximately $4.6 million, from the private placement
of our Series B convertible preferred stock and warrants.
In May 2004, we received net proceeds of approximately
$50.4 million, net of issuance costs of approximately
$0.6 million, from the private placement of our
Series C convertible preferred stock and warrants. Under
the terms of the Series A, B and C convertible preferred
stock, these shares are subject to mandatory conversion into
common stock upon the closing of this offering. Accrued but
unpaid dividends relating to the Series B and C convertible
preferred stock are payable in the form of common stock upon the
closing of this offering at the initial public offering price in
this offering.
Our contract revenue is primarily derived from our research and
development collaborations for ALTU-135 with CFFTI and
Dr. Falk. As of September 30, 2005, we had received
$15.9 million from CFFTI under our strategic alliance
agreement. We received an additional $2.5 million in
December 2005 as a result of the delivery to CFFTI of the data
from our recently completed Phase II clinical trial of
ALTU-135. In addition, we may receive an additional milestone
payment of $6.6 million, less an amount determined by when
we achieve the milestone.
As of September 30, 2005, we had received
7.0 million,
which equated to $8.1 million based on the exchange rates
in effect at the time we received the milestone payments, under
our development, commercialization and marketing agreement with
Dr. Falk. We received an additional
4.0 million
in December 2005, which equated to $4.7 million based on
the exchange rate in effect at the time, as a result of the
delivery to Dr. Falk of the final report from our recently
completed Phase II clinical trial of
ALTU-135. In addition,
Dr. Falk has agreed to pay a portion of the development
expenses we incur in connection with the conduct of an
international Phase III clinical trial, including costs
relating to the process of obtaining regulatory approval,
project management costs, statistical design and studies, and
preparation of reports.
As of September 30, 2005, we are entitled to receive up to
$32.1 million of future milestone payments under these two
collaborations if all development milestones are met. We have no
other external sources of funding.
Since our inception, we have generated significant losses while
we have advanced our product candidates into preclinical and
clinical trials. Accordingly, we have historically used cash in
our operating activities. During the nine months ended
September 30, 2005, we used approximately
$19.9 million in cash to fund our operating activities, and
in 2004 we used approximately $18.2 million to fund these
activities. As we continue to advance our product candidates
through development and begin to incur increased sales and
marketing costs related to commercialization of our product
candidates, we expect to incur additional operating losses until
such time, if any, as our efforts result in commercially viable
drug products. We do not expect our existing capital resources,
together with the net proceeds from this offering and the
milestone payments and research and development funding we
expect to receive, to be sufficient to fund the completion of
the development of any of our product candidates, and we expect
that we will need to raise additional funds prior to being able
to market any products.
Our capital expenditures of $5.0 million in 2004, which
were partially financed through equipment loans, significantly
exceeded prior years as Amano constructed a facility to produce
ALTU-135 for the
Phase III clinical trial and toxicology studies and we
agreed to purchase production equipment which is located at the
Amano facility. Capital expenditures for the nine months ended
September 30, 2005 of $1.9 million were primarily
related to equipment in support of our research and development
activities and to leasehold improvements for our facilities. We
expect capital expenditures in 2005 and 2006 to be approximately
$3.0 million per year. However, our capital expenditures
may increase depending upon the equipment requirements of any
additional contract manufacturers with whom we work and our
needs for additional facilities.
47
We have generally financed a substantial portion of our capital
expenditures through equipment loans and leases under which the
lender retains a security interest in the equipment. Our ability
to borrow under our existing capital equipment and lease credit
facilities expired on June 30, 2005. The capital equipment
facility is governed by a security agreement that contains the
key terms of the loans. The facility provided us with the
ability to borrow at different points in time based upon our
purchase of equipment. Each borrowing carries a fixed rate of
interest which was established at the time of borrowing and is
payable in fixed monthly installments over a four year period.
Under the terms of the capital equipment lease, we lease
equipment purchased under the agreement. Each lease has a four
year term with fixed monthly payments. At the end of the lease
term, we will have the option to purchase the equipment from the
lessor. Both facilities require us to maintain insurance on the
collateral. We intend to secure additional equipment loan
facilities to continue to finance a substantial portion of our
future capital expenditures under equipment financing
arrangements. We do not engage in off-balance sheet financing
arrangements.
The following table summarizes our contractual obligations at
September 30, 2005 and the effects such obligations are
expected to have on our liquidity and cash flows in future
periods:
Payments Due by Period
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
October | |
|
|
|
|
|
|
|
|
|
|
2005 | |
|
|
|
|
|
|
|
|
|
|
Through | |
|
2006 | |
|
2008 | |
|
|
|
|
|
|
December | |
|
Through | |
|
Through | |
|
After |
|
|
Total | |
|
2005 | |
|
2007 | |
|
2009 | |
|
2009 |
|
|
| |
|
| |
|
| |
|
| |
|
|
|
|
(in thousands) |
Contractual Obligations(1):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Short and long-term debt(2)
|
|
$ |
7,307 |
|
|
$ |
717 |
|
|
$ |
4,575 |
|
|
$ |
2,015 |
|
|
$ |
|
|
|
Capital lease obligations(2)
|
|
|
320 |
|
|
|
66 |
|
|
|
254 |
|
|
|
|
|
|
|
|
|
|
Operating lease obligations
|
|
|
2,143 |
|
|
|
389 |
|
|
|
1,354 |
|
|
|
400 |
|
|
|
|
|
|
Purchase obligations(3)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total contractual cash obligations
|
|
$ |
9,770 |
|
|
$ |
1,172 |
|
|
$ |
6,183 |
|
|
$ |
2,415 |
|
|
$ |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(1) |
Excludes estimated payment of $7.2 million to Vertex in
connection with its optional redemption of shares of our
redeemable preferred stock on or after December 31, 2010,
plus dividends accruing after that date, and amounts payable to
CFFTI upon FDA approval of
ALTU-135 and royalties
to CFFTI on product sales of
ALTU-135.
|
|
(2) |
Includes interest expense. |
|
(3) |
On October 28, 2005 and on December 15, 2005, we
entered into non-cancelable purchase orders for a total of
2.5 million,
all of which is due in 2006. |
Based on our operating plans, we estimate that our net cash used
in operating activities will be between $55 million and
$65 million in 2006. We believe that the proceeds from this
offering, together with our existing cash resources, investment
securities and funding we expect to receive under our
collaborations, will be sufficient to finance our planned
operations, including increases in spending for our
ALTU-135 and
ALTU-238 clinical
programs and for our preclinical product candidates through the
first half of 2007. However, over the next several years, we may
require significant additional funds to conduct clinical and
non-clinical trials, achieve regulatory approvals and, subject
to such approvals, commercially launch
ALTU-135 and
ALTU-238. Our future
capital requirements will depend on many factors, including the
scope and progress made in our research and development
activities and our clinical trials. We may also need additional
funds for possible future strategic acquisitions of businesses,
products or technologies complementary to our business. If
additional funds are required, we may raise such funds from time
to time through public or private sales of equity or from
borrowings. Financing may not be available on acceptable terms,
or at all, and our failure to raise capital when needed could
materially adversely impact our growth plans and our financial
condition and results of operations. Additional equity financing
may be
48
dilutive to the holders of our common stock and debt financing,
if available, may involve significant cash payment obligations
and covenants that restrict our ability to operate our business.
Quantitative and Qualitative Disclosures About Market
Risks
Our cash, cash equivalents and short-term investments are
invested with highly-rated financial institutions in North
America with the primary objective of preservation of principal
and minimum risk. When purchased, the investments generally have
a maturity of less than 12 months. Some of the securities
we invest in are subject to interest rate risk and will fall in
value if market interest rates increase. To minimize the risk
associated with changing interest rates, we invest primarily in
bank certificates of deposit, United States government
securities and investment-grade commercial paper and corporate
notes that can be held to their maturity date. Substantially all
of our investments at September 30, 2005 met these
criteria. We had gross unrealized losses of $0.1 million on
our investments at September 30, 2005. If market interest
rates were to increase immediately and uniformly by 10% from
levels at September 30, 2005, we estimate that the fair
value of our investment portfolio would decline by an immaterial
amount.
Our total debt at September 30, 2005 was $6.6 million,
primarily representing drawdowns under our capital equipment and
lease credit facilities. All borrowings under these credit
facilities carried fixed rates of interest established at the
time such drawdowns were made. Accordingly, once drawdowns were
made, our future interest costs are not subject to fluctuations
in market interest rates.
Our assets are principally located in the United States and
substantially all of our historical revenues and operating
expenses are denominated in United States dollars. Contract
revenue under our collaboration with Dr. Falk and some
purchases of raw materials are denominated in Euros.
Accordingly, we are subject to market risk with respect to
foreign currency-denominated revenues and expenses. We had
foreign currency exchange losses of $0.1 million in the
nine months ended September 30, 2005 and foreign currency
exchange gains of $0.1 million in 2004. If the average
Euro/ United States dollar exchange rate were to strengthen or
weaken by 10% against the average respective exchange rates
experienced in the nine months ended September 30, 2005 or
2004, we estimate that the impact on our financial position,
results of operations and cash flows would not be material.
Since ALTU-135 has not reached commercialization in North
America or in the territory covered by the Dr. Falk
agreement, we do not believe we are subject to significant
foreign currency risk at this time. We may engage in additional
collaborations with international partners. When
ALTU-135 or any other
future drug candidates reach commercialization outside of the
United States, if at all, or we enter into additional
collaborations with international partners providing for foreign
currency-denominated revenues and expenses, we may be subject to
significant market risk.
49
BUSINESS
Overview
We are a biopharmaceutical company focused on the development
and commercialization of oral and injectable protein
therapeutics for chronic gastrointestinal and metabolic
disorders, with two product candidates in clinical development.
We are using our proprietary protein crystallization technology
to develop protein therapies which we believe will have
significant advantages over existing products or will address
unmet medical needs. Our product candidates are designed to
either increase the amount of a protein that is in short supply
in the body or degrade and remove toxic metabolites from the
blood stream. We have successfully completed a Phase II
clinical trial of
ALTU-135 for the
treatment of malabsorption due to exocrine pancreatic
insufficiency, and we are currently conducting a Phase II
clinical trial of
ALTU-238 in adults for
the treatment of growth hormone deficiency. We also have a
pipeline of other product candidates in preclinical research and
development.
Our lead product candidate,
ALTU-135, is an
orally-administered enzyme replacement therapy for the treatment
of malabsorption due to exocrine pancreatic insufficiency.
Exocrine pancreatic insufficiency is a deficiency of digestive
enzymes normally produced by the pancreas which leads to
malnutrition, impaired growth and shortened life expectancy.
Exocrine pancreatic insufficiency can result from a number of
diseases and conditions, including cystic fibrosis, chronic
pancreatitis and pancreatic cancer. According to IMS Health,
global prescription sales of existing pancreatic enzyme
replacement products were $658 million in 2004.
We believe that
ALTU-135, if approved,
will have significant competitive advantages compared to
existing pancreatic enzyme replacement therapies. We believe
these potential advantages include:
|
|
|
|
|
benefits associated with a drug that is microbially-derived,
rather than a drug derived from pig pancreases, and manufactured
in a controlled environment; |
|
|
|
a significantly lower pill burden, allowing patients to take, on
average, one capsule per meal or snack compared to, on average,
four or five larger capsules per meal or snack with existing
products; |
|
|
|
more consistent and reliable dosing; |
|
|
|
resistance to degradation early in the gastrointestinal tract,
permitting enzyme activity where most digestion and absorption
of fats, proteins and carbohydrates occurs; |
|
|
|
the potential for a liquid formulation, which is currently
unavailable, for children and adults who are unable to swallow
capsules; and |
|
|
|
testing in what we believe is the largest well-controlled,
scientifically-rigorous prospective clinical trial conducted to
date in the treatment of cystic fibrosis patients with
pancreatic insufficiency. |
We believe that many of these advantages are a result of our
proprietary protein crystalization technology, which enables
improved product consistency and stability, as well as higher
concentration and purity.
Existing pancreatic enzyme replacement products have been
marketed since before enactment of the FDCA in 1938 and are not
marketed under NDAs approved by the FDA. In April 2004, the FDA
issued a notice that manufacturers of existing pancreatic enzyme
replacement products will be subject to regulatory action if
they do not obtain approved NDAs for those products by
April 28, 2008. We believe that some of the manufacturers
of these products may not be able to satisfy the FDAs
requirements for NDAs for these products.
In our recently completed prospective, randomized, double-blind,
dose-ranging Phase II clinical trial of the solid form of
ALTU-135, the product candidate was well tolerated and showed a
statistically significant improvement in fat absorption
(p-value<0.001),
the trials primary endpoint, in the two high dose
treatment arms.
P-values are an
indication of statistical significance reflecting the
probability of an observation occurring due to chance alone. A
p-value<0.001 means
that the probability of the event measured occurring by chance
is less than 1 in 1,000. In the two high dose treatment arms, we
also observed a statistically significant improvement in protein
absorption
(p-value<0.001) and
a statistically
50
significant decrease in stool weight
(p-value<0.001),
each of which was a secondary endpoint in the study. In
addition, we observed a positive trend, although not
statistically significant, in carbohydrate absorption. However,
the results of our Phase II clinical trial may not be
predictive of the results in our Phase III clinical trial
of ALTU-135. We expect
to initiate a pivotal Phase III clinical trial of the solid
form of ALTU-135 in
patients with cystic fibrosis and a long-term safety study in
cystic fibrosis patients and other patients with pancreatic
insufficiency in the second half of 2006. The FDA and the EMEA
have granted ALTU-135
orphan drug designation, which generally provides a drug being
developed for a rare disease or condition with marketing
exclusivity for seven years in the United States and
10 years in the European Union if it is the first drug of
its type approved for such indication. Additionally, the FDA has
granted ALTU-135 fast
track designation and admission into its CMA Pilot 2
Program, both of which are designed to facilitate interactions
between a drug developer and the FDA during the drug development
process.
Our next most advanced product candidate,
ALTU-238, is a
crystallized formulation of hGH that is designed to be injected
once-weekly with a fine gauge needle for the treatment of growth
hormone deficiency and hGH-related disorders. Based on reported
revenues of existing products, global sales of hGH products
exceeded $2.2 billion in 2004, and the market grew at a
compound annual growth rate of approximately 15% from 2002 to
2004. We are developing
ALTU-238 for both adult
and pediatric populations as an alternative to current
therapies. Current medical guidelines for clinical practice
generally recommend daily administration of existing therapies
by subcutaneous injection. In our Phase I clinical trial of
ALTU-238, which we
completed in May 2005,
ALTU-238 demonstrated
pharmacokinetic and pharmacodynamic parameters that are
consistent with once-weekly administration. We believe that the
convenience of once-weekly administration of
ALTU-238, if approved,
would improve patient acceptance and compliance, and thereby
effectiveness. We recently initiated a Phase II clinical
trial for ALTU-238 in adults with growth hormone deficiency and
expect to have data from this trial in the first half of 2006.
We also have a pipeline of product candidates in preclinical
research and development that we are designing to address other
areas of unmet need in chronic gastrointestinal and metabolic
disorders. Our most advanced preclinical product candidates are
ALTU-237, designed to
treat hyperoxalurias, and
ALTU-236, designed to
treat phenylketonuria. We believe that these product candidates,
if approved, will provide treatments for these disorders, both
of which lack any approved pharmaceutical therapies. We expect
to file an IND for
ALTU-237 for the
treatment of hyperoxalurias in early 2007.
Our product candidates are based on our proprietary technology,
which enables the large-scale crystallization of proteins for
use as therapeutic drugs. We apply our technology to improve
known protein drugs, as well as to develop other proteins into
protein therapeutics. For example, our product candidate
ALTU-135 is based on known enzymes to which we apply our
proprietary crystallization technology with the goal of offering
a new and improved drug. We have developed our product candidate
ALTU-238 by applying
our proprietary crystallization technology with the goal of
offering an improved version of an approved drug. We believe
that, by using our technology, we are able to overcome many of
the limitations of existing protein therapies and deliver
proteins in solid and liquid oral form, as well as in
extended-release injectable formulations. Our product candidates
are designed to offer improvements over existing products, such
as greater convenience, better safety and efficacy and longer
shelf life. In addition, we believe that we may be able to
reduce the development risk and time to market for our drug
candidates because we apply our technology to existing,
well-understood proteins with well-defined mechanisms of action.
We believe that our technology is broadly applicable to
different classes of proteins, including enzymes, hormones,
antibodies, cytokines and peptides. To date, we have
crystallized more than 70 proteins for use in our research
and development programs.
We currently hold worldwide rights to all of our product
candidates, except for rights we have licensed to Dr. Falk
to commercialize
ALTU-135 in Europe, the
countries of the former Soviet Union, Israel and Egypt. We have
also entered into a strategic alliance agreement with CFFTI,
which is funding a portion of the development of ALTU-135. We
intend to establish a commercial infrastructure and a targeted
specialty sales force to market our products in North America.
51
Our Strategy
Our goal is to become a leading biopharmaceutical company
focused on developing and commercializing protein therapies to
address unmet medical needs in chronic gastrointestinal and
metabolic disorders. Our strategy to achieve this objective
includes the following elements:
|
|
|
|
|
Focus on advancing our lead product candidates. We have
two product candidates in clinical trials. We are preparing
ALTU-135 for a pivotal
Phase III clinical trial for the treatment of malabsorption
due to exocrine pancreatic insufficiency. In addition, we
recently initiated a Phase II clinical trial of
ALTU-238 in adult
growth hormone deficient patients. If this trial is successful,
we plan to initiate a Phase III clinical trial in adults
and plan to initiate a Phase II/III clinical trial in
pediatric patients, which we plan to request that the FDA
consider to be a pivotal trial. However, the FDA may not agree
with our proposed combined Phase II/III clinical trial in
pediatric patients and may require additional studies in
children. We believe that these product candidates, if approved,
will offer significant advantages over existing therapies. In
addition, because these product candidates are based on
well-understood proteins with known mechanisms of action, we
believe we may be able to reduce their development risk and time
to market. Our primary focus is on aggressively advancing the
clinical development of these two product candidates to NDA
submission. |
|
|
|
Continue to build and advance our product pipeline for
gastrointestinal and metabolic disorders. In addition to our
product candidates in clinical development, we have built a
pipeline of preclinical product candidates based on our
proprietary protein crystallization technology. These product
candidates are designed to address unmet needs for the treatment
of hyperoxalurias, phenylketonuria, and other chronic
gastrointestinal and metabolic diseases. We plan to apply the
manufacturing, clinical and regulatory experience gained from
our two lead product candidates to advance a number of these
preclinical product candidates into clinical trials over the
next few years. We also plan to add additional product
candidates to our pipeline through the application of our
proprietary protein crystallization technology to existing
protein therapeutics or known proteins with potential
therapeutic use. |
|
|
|
Establish a commercial infrastructure. We plan to
establish a commercial infrastructure and targeted specialty
sales force to market our two lead product candidates in North
America. In addition, we plan to leverage our sales and
marketing capabilities by targeting the same groups of physician
specialists with additional products that we bring to market
either through our own development efforts or by in-licensing
from others. |
|
|
|
Selectively establish collaborations for our product
candidates with leading pharmaceutical and biotechnology
companies. We currently have a collaboration with
Dr. Falk for the commercialization of
ALTU-135 in Europe, the
countries of the former Soviet Union, Israel and Egypt. We
intend to develop additional collaborations in markets outside
of North America where we believe that having a collaborator
will enable us to gain better access to those markets. We may
also collaborate with other companies to accelerate the
development of some of our early-stage product candidates, or to
co-promote our product candidates in North America in instances
where we believe that a larger sales and marketing presence will
expand the market or accelerate penetration. |
|
|
|
Establish additional collaborations to apply our technology
to other therapeutic proteins. We believe that our
technology has broad applicability to many classes of proteins
and can be used to enhance protein therapeutics developed by
other parties. We intend to derive value from our technology by
selectively collaborating with biotechnology and pharmaceutical
companies that will use our technology for products that they
are either currently marketing or developing. |
52
Our Product Candidates
The following table summarizes key information about our product
candidates that are in clinical trials and our most advanced
preclinical research and development programs. All of the
product candidates are based on our crystallization technology
and are the result of our internal research and development
efforts.
|
|
|
|
|
|
|
Product Candidate (Delivery) Indication
|
|
Stage of
Development |
|
Commercial Rights |
|
Status |
|
ALTU-135 (oral) Exocrine Pancreatic Insufficiency
|
|
Phase II completed |
|
Dr. Falk (Europe, the
countries of the former
Soviet Union, Israel
and Egypt) |
|
Phase III clinical trial and long-term safety study of the
solid form expected to begin in the second half of 2006;
Phase II clinical trial of the liquid form expected to
begin in early 2007 |
|
|
|
|
Altus (United States and rest of world) |
|
|
|
ALTU-238 (injectable) Growth Disorders
|
|
Phase II |
|
Altus |
|
Data from Phase II clinical trial in adults expected in the
first half of 2006; Phase III clinical trial in adults and
Phase II/III clinical trial in children expected to begin
in the second half of 2006 |
|
ALTU-237 (oral) Hyperoxalurias
|
|
Preclinical |
|
Altus |
|
IND enabling work in progress, with IND filing expected in early
2007 |
|
ALTU-236 (oral) Phenylketonuria
|
|
Preclinical |
|
Altus |
|
Preclinical testing in animal models |
We may be required to perform additional studies in order to
obtain marketing approval for ALTU-135 and ALTU-238 even if the
clinical trials we currently expect to conduct are successful.
In addition, if the FDA does not agree with our proposed
combined Phase II/III clinical trial of ALTU-238 in children, we
may be required to conduct additional studies in children.
We are developing our product candidates with the goal of
initially seeking marketing approvals in the United States and
the European Union. We have not yet sought regulatory approval
for any product candidate in the European Union or any country
outside the United States. For ALTU-135, we and Dr. Falk
have agreed with the EMEA on our pre-clinical plan and are
awaiting a response from the EMEA for our clinical plan. For
ALTU-238, we plan to submit an initial request for guidance on
regulatory matters from European regulatory authorities during
the second half of 2006. We expect that the data from the
studies we have conducted or plan to conduct pursuant to the
INDs we have filed with the FDA will form a substantial part of
the applications for marketing approval to be filed with the
EMEA and regulatory authorities in other parts of the world.
However, we may be required to perform additional clinical
trials to receive marketing approval outside the United States.
|
|
|
ALTU-135 for Exocrine Pancreatic Insufficiency |
Our lead product candidate, ALTU-135, is an orally-administered
enzyme replacement therapy for which we have successfully
completed a Phase II clinical trial of its solid form for
the treatment of malabsorption due to exocrine pancreatic
insufficiency. Pancreatic insufficiency is a deficiency of the
digestive enzymes normally produced by the pancreas and can
result from a number of disease conditions. Conditions resulting
in exocrine pancreatic insufficiency include cystic fibrosis,
chronic pancreatitis and pancreatic cancer. Patients with
exocrine pancreatic insufficiency are currently treated with
enzyme replacement products containing enzymes derived from pig
pancreases. We believe that ALTU-135 represents a significant
potential advancement as a therapeutic alternative for the
treatment of these patients.
53
ALTU-135 contains three types of digestive enzymes derived from
non-animal sources:
|
|
|
|
|
Lipase. We selected the lipase in
ALTU-135, which is used
for the digestion of fats, because it demonstrated the ability
in in vitro and animal testing to be active across a
wide range of acidity levels and more resistant to degradation
in the harsh environment of the gastrointestinal tract when
compared to other lipases. It also demonstrated the ability to
break down a broader range of fats than existing animal-derived
lipases. Because lipases are the most susceptible of the three
enzymes to degradation in the gastrointestinal tract, we use our
proprietary technology to both crystallize and cross-link the
lipase for increased activity and stability; |
|
|
|
Protease. We selected the protease in
ALTU-135, which is used
for the digestion of proteins, because it demonstrated the
ability in in vitro and animal testing to break down
as many types of proteins as the multiple proteases contained in
existing products. We crystallize the protease for greater
stability and concentration; |
|
|
|
Amylase. We selected the amylase in
ALTU-135, which is used
for the digestion of carbohydrates, because it demonstrated the
ability in in vitro testing to be active in the
highly acidic environment of the upper gastrointestinal tract.
Because the amylase is stable in soluble form, we do not
crystallize it. |
Our contract manufacturer produces these enzymes from microbial
sources using separate fermentation and purification processes.
The enzymes are then blended to achieve a specified and
consistent ratio of lipase to protease to amylase in each
capsule.
|
|
|
Disease Background and Market Opportunity |
We have designed
ALTU-135 to treat
malabsorption resulting from exocrine pancreatic insufficiency.
Malabsorption is the failure to absorb adequate amounts of
nutrients, such as fats, proteins and carbohydrates, in food and
is clinically manifested as malnutrition, weight loss or poor
weight gain, impaired growth, abdominal bloating, cramping and
chronic diarrhea. Exocrine pancreatic insufficiency is a
deficiency of digestive enzymes normally produced by the
pancreas that results in poor absorption of essential nutrients
from food. If not treated appropriately, exocrine pancreatic
insufficiency generally leads to malnutrition, impaired growth
and shortened life expectancy.
According to IMS Health, the worldwide market for pancreatic
enzyme replacement therapies grew at a compound annual growth
rate of approximately 7% from $579 million in 2002 to
$658 million in 2004. The market for these products in 2004
was approximately $190 million in North America,
$228 million in Europe and $241 million in the rest of
the world according to IMS Health. Diseases and conditions with
a prevalence of exocrine pancreatic insufficiency include:
|
|
|
|
|
Cystic fibrosis Cystic fibrosis is one of the
most prevalent genetic disorders in the Caucasian population,
according to the Medical Genetics Institute of Cedars-Sinai.
According to the Cystic Fibrosis Foundation, this disease
affects approximately 30,000 people in the United States.
Approximately 90% of cystic fibrosis patients are prescribed
pancreatic enzymes to treat exocrine pancreatic insufficiency.
Cystic fibrosis patients with exocrine pancreatic insufficiency
have a median life expectancy of 31 years, compared to
50 years for those cystic fibrosis patients who have
sufficient pancreatic enzymes. |
|
|
|
Chronic pancreatitis In many patients,
chronic pancreatitis is clinically silent and many patients with
unexplained abdominal pain may have chronic pancreatitis that
eludes diagnosis. Therefore, according to The New England
Journal of Medicine, the true prevalence of the disease is not
known, although estimates range from 0.04% to 5%. Based on
survey data reported in Medscape General Medicine, we believe
chronic pancreatitis results in more than 500,000 physician
visits per year in the United States. |
|
|
|
Pancreatic cancer The American Cancer Society
estimates that approximately 30,000 people in the United
States are diagnosed with pancreatic cancer each year. |
54
|
|
|
|
|
According to an industry estimate, approximately 65% of patients
with pancreatic cancer will have some degree of fat
malabsorption. |
|
|
|
HIV/AIDS According to the U.S. Centers for
Disease Control and Prevention, there were approximately
1.1 million people with HIV/AIDS in the United States in
2003. Approximately 50% of HIV-positive patients in an industry
study had evidence of pancreatic insufficiency. |
|
|
|
Limitations of Existing Products |
Patients with exocrine pancreatic insufficiency are typically
prescribed enzyme replacement products containing enzymes
extracted from pig pancreases. Many of these products were
available for human use prior to the passage of the FDCA in
1938, and all are currently marketed without NDAs approved by
the FDA. In 1995, the FDA issued a final rule requiring that
these pancreatic enzyme products be marketed by prescription
only, and in April 2004, the FDA issued a notice that
manufacturers of these products will be subject to regulatory
action if they do not obtain approved NDAs for these products by
April 28, 2008. At the same time, the FDA also issued draft
guidance, known as the PEP Guidance, that existing manufacturers
of pancreatic enzyme products can follow in order to obtain FDA
approval.
Existing pancreatic enzyme replacement therapies are supposed to
be taken with every meal and snack in order to permit the
digestion and absorption by the patient of sufficient amounts of
fats, proteins and carbohydrates. We believe that these products
have a number of significant limitations that affect their ease
of administration, safety and effectiveness, including:
|
|
|
|
|
High pill burden. Patients on existing pancreatic enzyme
therapies are generally required to take, on average, four or
five larger capsules per meal or snack, resulting in poor
compliance and therefore reduced long-term efficacy, due to the
following factors: |
|
|
|
|
|
Degradation of enzymes in the gastrointestinal tract. A
significant portion of the enzymes in existing products are
degraded in the gastrointestinal tract prior to exerting their
therapeutic effect. As a result, many patients are required to
take many capsules to achieve a desired level of absorption of
fats, proteins and carbohydrates. Some manufacturers have tried
to address this issue by adding a protective coating to the
enzymes, but this often results in a failure of the enzyme to
dissolve and become active early enough in the gastrointestinal
tract to break down foods and effectively assist with the
digestive process. |
|
|
|
Low concentration. Existing therapies are comprised of a
mixture of enzymes and other materials found in a pigs
pancreas. Based on comments submitted in response to the
FDAs PEP Guidance in 2004 by manufacturers of existing
products and the components of such products, we believe that
manufacturers of these products are unable to concentrate the
enzymes in the mixture to reduce the amount of material a
patient must consume. |
|
|
|
|
|
Variability of therapeutic effect. Because existing
products are extracted from pig pancreases, there is significant
variability between different manufacturing batches. As a
result, we believe that the therapeutic effect of these
therapies is also significantly variable. Each time a patient
refills a prescription the patient may need to experiment with
the number of pills taken per meal or snack to achieve effective
digestion of food intake. |
|
|
|
Short shelf life. Existing enzyme therapies tend to lose
activity quickly relative to other types of drugs. Many
manufacturers try to overcome this limitation by filling each
capsule with more drug than specified in order to achieve the
stated label claim over time, which leads to inconsistent
efficacy and raises safety concerns. We believe this also
contributes to patient uncertainty about the number of capsules
to take per meal or snack. |
55
|
|
|
|
|
Product impurities. Existing enzyme therapies are poorly
characterized and may contain impurities, including porcine
viruses, tissue components and other contaminants. Impurities
may increase the risk of antigenicity. |
|
|
|
Anticipated Advantages of ALTU-135 |
We believe that
ALTU-135, if approved,
will offer patients a more convenient and effective long-term
therapy for the treatment of malabsorption due to exocrine
pancreatic insufficiency because of the following features:
|
|
|
|
|
Reduced pill burden. ALTU-135 is a highly concentrated,
pure and stable enzyme replacement therapy designed to be as
effective as existing products with significantly fewer
capsules. Based on the clinical trials we have conducted to
date, we believe that most patients will be effectively treated
with, on average, one capsule per meal or snack. We believe that
this dosing will result in greater convenience for the patient,
which will improve compliance and, therefore, long-term
effectiveness of therapy. We believe that
ALTU-135 will reduce
the pill burden for patients due to the following factors: |
|
|
|
|
|
Stability of enzymes in the gastrointestinal tract. We
have designed ALTU-135
to withstand degradation, maintain its activity across the
different pH levels in the gastrointestinal tract, and exert its
therapeutic effect in the first part of the small intestine, or
the duodenum, where most fats, proteins and carbohydrates are
broken down and absorbed. We believe this design will provide a
more effective treatment for patients than current pancreatic
enzyme replacement products, which are often degraded earlier in
the gastrointestinal tract. |
|
|
|
High concentration. Two of the three enzymes in
ALTU-135 are
crystallized, resulting in a highly concentrated product that
requires less material to achieve a desired therapeutic effect. |
|
|
|
|
|
Consistent activity. We have designed
ALTU-135 to exhibit
consistent enzyme activity from batch to batch. The enzymes in
ALTU-135 are
microbially derived and produced through fermentation. The
amount of material and related enzyme activity in a capsule of
ALTU-135 is tightly
controlled, as each of the three enzymes in
ALTU-135 is
individually manufactured and added to the final drug product in
a specific amount. We believe this will result in consistent
product performance, eliminating the need for dose
experimentation each time a patient refills a prescription. |
|
|
|
Longer shelf life. Based on stability studies performed
as part of our development program, we believe that
ALTU-135 capsules are
significantly more stable than existing porcine-derived
products, which we expect will lead to a longer effective shelf
life. |
|
|
|
Potential liquid formulation. We have completed in
vivo studies of a liquid formulation of
ALTU-135. We believe
that a liquid formulation will significantly benefit children
and adults who are unable to swallow capsules. |
|
|
|
ALTU-135 Development Activities and Strategy |
We have successfully completed a Phase II clinical trial
for the solid form of
ALTU-135 and are
preparing to advance this product candidate into a pivotal
Phase III clinical trial in patients with cystic fibrosis
and a long-term safety study in cystic fibrosis patients and
other patients with pancreatic insufficiency in the second half
of 2006. The FDA and the EMEA have granted
ALTU-135 orphan drug
designation for malabsorption due to exocrine pancreatic
insufficiency, and the FDA has also granted
ALTU-135 fast track
designation. Fast track designation is designed to facilitate
the development of new drugs and may be granted to a product
with a specific indication where the FDA agrees that the product
is intended to treat a serious or life threatening condition and
demonstrates the potential to address unmet medical needs for
that condition. Fast track designation also permits drug
developers to submit sections of an NDA as they become
available. In February 2004,
ALTU-135 was also
admitted to the FDAs CMA Pilot 2 Program. Under the
CMA Pilot 2
56
program, one fast track designated product from each review
division of the Center for Drug Evaluation and Research, or
CDER, the center at the FDA that regulates drugs and therapeutic
biologics, and the Center for Biologics Evaluation and Research,
or CBER, the center at the FDA that regulates other biologics,
is selected for frequent scientific feedback and interactions
with the FDA, with a goal of improving the efficiency and
effectiveness of the drug development process. We plan to begin
submitting sections of our NDA for
ALTU-135 to the FDA in
the first half of 2007 and additional sections thereafter,
including data from our Phase III clinical trial and
long-term safety-study, pursuant to a timetable to be agreed
upon by the FDA and us.
We have completed four clinical trials of ALTU-135, three of
which were in cystic fibrosis patients and one of which was in
healthy volunteers. The following table summarizes the clinical
trials we have completed to date:
|
|
|
|
|
Trial |
|
Number of Subjects |
|
Primary Study Objective |
|
|
|
|
|
Phase Ia
|
|
20 healthy volunteers |
|
Safety and tolerability over 7 days of dosing |
Phase Ib
|
|
23 cystic fibrosis patients |
|
Safety, tolerability and clinical activity over 3 days of
dosing |
Phase Ic
|
|
8 cystic fibrosis patients |
|
Safety, tolerability and clinical activity over 14 days of
dosing |
Phase II
|
|
129 cystic fibrosis patients |
|
Safety, tolerability and efficacy over 28 days of dosing |
Our clinical trials with cystic fibrosis patients assessed a
number of different measures, or endpoints, of digestion and
absorption. We assessed fat absorption by measuring a
patients fat intake over a specified period of time and
comparing that to the amount of fat in their stool during the
same period. This comparison enabled us to calculate the amount
of fat a patient absorbed, using a metric known as the
coefficient of fat absorption, or CFA. The same process was
applied to determine protein absorption, using a metric called
the coefficient of nitrogen absorption, or CNA. We measured
carbohydrate absorption by analyzing a patients blood
glucose levels after a starch meal, using a test we refer to as
the starch challenge test. In our Phase Ib and
Phase II clinical trials, we also measured the number and
weight of the patients stools.
In our three Phase I clinical trials, the solid form of
ALTU-135 was generally
well tolerated at doses of up to four times the recommended
clinical dose. In addition, in our Phase Ib trial, we
observed statistically significant evidence of clinical activity
based on CFA, CNA and stool results when all cohorts in the
Phase Ib were considered together. In the Phase Ic
trial, we observed evidence of amylase activity based on a
treatment-associated increase in maximum glucose levels in a
small number of subjects.
We successfully completed our Phase II clinical trial for
ALTU-135 and presented the results of the trial at the North
American Cystic Fibrosis Conference in October 2005. In the
trial, ALTU-135 was well tolerated and showed a statistically
significant improvement in fat absorption (p-value<0.001),
the trials primary endpoint, in the two high dose
treatment arms. In these treatment arms, we also observed a
statistically significant improvement in protein absorption
(p-value<0.001) and a statistically significant decrease in
stool weight (p-value<0.001), each of which was a secondary
endpoint in the study. In addition, we observed a positive
trend, although not statistically significant, in carbohydrate
absorption in these treatment arms.
We believe that this is the first clinical trial to demonstrate
that the combination of the three enzymes in ALTU-135, lipase,
protease and amylase, may be effective in treating pancreatic
insufficiency. We also believe that this trial is the only trial
to concurrently evaluate the impact of a fixed dose of
57
enzyme replacement therapy on the absorption of fats, proteins
and carbohydrates. Based on the results from our Phase II
clinical trial and earlier trials for ALTU-135, we believe:
|
|
|
|
|
a formulation of ALTU-135 consisting of 25,000 units of lipase,
25,000 units of protease and 3,750 units of amylase,
representing a ratio of 1:1:0.15, is the minimal dose
combination that provides a clinically meaningful improvement in
fat and protein absorption; |
|
|
|
most patients will be able to be treated with one small capsule
of ALTU-135 per meal or snack; and |
|
|
|
patients with the most severe fat and protein malabsorption will
realize the greatest benefit from treatment with ALTU-135. |
|
|
|
Study Design and Demographics |
The purpose of our Phase II clinical trial of ALTU-135 was
to obtain initial efficacy data, select a dose level of
ALTU-135 for further
evaluation in our Phase III clinical trial and assess the
safety and tolerability of
ALTU-135 over a 28-day
treatment period in cystic fibrosis patients with pancreatic
insufficiency. We believe our Phase II clinical trial of
ALTU-135 represents the
largest prospective, randomized, double-blind, dose-ranging
trial conducted to date in the treatment of cystic fibrosis
patients with pancreatic insufficiency.
To establish a baseline period measurement of fat, protein and
carbohydrate absorption, at the beginning of the trial patients
were tested during a
72-hour period when
they were not taking enzyme replacement therapy. Following this
baseline period,
ALTU-135 in capsule
form was orally administered to patients with each of five meals
or snacks per day for a period of 28 days. In the middle of the
trial, we performed an additional measurement of fat, protein
and carbohydrate absorption to establish these measurements for
the treatment period. For both the baseline and treatment period
measurements, we assessed fat and protein absorption following a
72-hour, controlled,
high-fat diet by examining stools collected from patients. The
appropriate period for measuring fat and protein absorption was
determined by using a blue dye stool marker, which facilitated
accurate and complete stool collection. Changes in carbohydrate
absorption were determined by measuring blood glucose responses
using the starch challenge test. We assessed the clinical
activity of the lipase component of
ALTU-135 by measuring
the change in CFA, the clinical activity of the protease
component of ALTU-135
by measuring the change in CNA and the clinical activity of the
amylase component of
ALTU-135 by measuring
the change in carbohydrate absorption.
The Phase II clinical trial for ALTU-135 enrolled a total
of 129 subjects with cystic fibrosis and pancreatic
insufficiency in 26 cystic fibrosis centers in the United
States. The demographics and baseline characteristics of
the patients in the trial generally reflect the cystic fibrosis
patient population. Ninety-five percent of the patients in the
trial were Caucasian. The trial consisted of patients between
the ages of 11 and 55, with a median age of 21.
The study included three treatment arms of approximately equal
size, with patients in each arm receiving a fixed dose of
ALTU-135 in capsule form administered orally:
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Treatment arm 1 5,000 units lipase:
5,000 units protease: 750 units amylase per meal or
snack; |
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Treatment arm 2 25,000 units lipase:
25,000 units protease: 3,750 units amylase per meal or
snack, which is the dose we have selected to use in our planned
Phase III clinical trials; and |
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Treatment arm 3 100,000 units lipase:
100,000 units protease: 15,000 units amylase per meal or
snack. |
The trial did not include a placebo arm, as we assessed efficacy
based on the differences in fat, protein and carbohydrate
absorption between the baseline period and the treatment period.
58
Of the 129 patients who were enrolled in the trial, 117 patients
had valid stool collections during the
ALTU-135 treatment
period. We used this subset of patients for our main efficacy
analyses. The results of the Phase II clinical trial showed
a statistically significant improvement in CFA from the baseline
period to the treatment period
(p-value<0.001) for
patients in treatment arms 2 and 3. The results of the trial
also showed a statistically significant difference between
on-treatment CFAs for patients in treatment arms 2 and 3
relative to treatment arm 1; therefore, the trial achieved
its primary efficacy endpoint. We also observed a statistically
significant improvement in CNA from the baseline period to the
treatment period
(p-value<0.001) and
a statistically significant decrease in stool weight from the
baseline period to the treatment period
(p-value<0.001) for
patients in treatment arms 2 and 3. The trial results also
indicated a trend, although not statistically significant,
toward improvement in carbohydrate absorption for patients in
treatment arms 2 and 3.
We also observed statistically significant improvements in CNA
from the baseline period to the treatment period for patients in
treatment arms 2 and 3, as compared to patients in treatment arm
1. In addition, changes in CFA and CNA were highly correlated
(r=0.844, p-value<0.001),
supporting the 1:1 ratio of the units of lipase and protease in
the formulation. The correlation coefficient, r, is the measure
of correlation between two sets of data. Based on the results of
our Phase II clinical trial, we have selected a formulation
of ALTU-135 consisting
of 25,000 units of lipase, 25,000 units of protease and 3,750
units of amylase as the dose level for testing in our proposed
Phase III clinical trial.
In treatment arm 2 there was an average 11.4 percentage
point increase in CFA, from 55.6% to 67.0%, and an average 12.5
percentage point increase in CNA, from 58.8% to 71.3%, from the
baseline period to the treatment period. In treatment arm 3
there was an average 17.3 percentage point increase in CFA, from
52.2% to 69.7%, and an average 17.5 percentage point
increase in CNA, from 56.8% to 74.6%, from the baseline period
to the treatment period. There was not a statistically
significant difference between these results. Based on these
increases in CFA and CNA, we believe that cystic fibrosis
patients suffering from malabsorption who are treated with
ALTU-135 may experience
clinically meaningful improvements in fat and protein
absorption, resulting in an overall improvement in nutritional
status. We also believe that an improvement in nutritional
status may lead to weight maintenance or weight gain in
patients, both of which are important elements in the overall
health of cystic fibrosis patients and others suffering from
pancreatic insufficiency. According to the Cystic Fibrosis
Foundation 2003 Patient Registry, approximately 35% of cystic
fibrosis patients are in urgent need of improved nutrition.
We believe that an improvement in CFA of 10 percentage points or
more represents a clinically meaningful benefit to patients with
pancreatic insufficiency. Clinicians who treat cystic fibrosis
patients typically recommend a high fat diet consistent with the
diet in our Phase II clinical trial. Patients in our
Phase II clinical trial consumed, on average,
100 grams of fat per day. In these patients, an average
increase in fat absorption of 10 percentage points would equate
to 10 grams of additional fat absorbed per day. According
to the FDA, there are nine calories in a gram of fat. As a
result, an improvement in CFA of 10 percentage points would
equate to an additional 90 calories absorbed per day. Over
a period of one year, such a 90 calorie per day increase
would result in an improvement in weight of approximately nine
pounds, allowing patients to either maintain weight that they
may have otherwise lost or gain weight.
To gain a better understanding of the clinical impact of
treatment with
ALTU-135, we further
analyzed the data on CFA and CNA improvements in our Phase II
clinical trial, specifically focusing on differences experienced
by patients who began the trial with lower levels of fat and
protein absorption during the baseline period, as compared with
patients who began the trial with higher baseline levels of fat
and protein absorption. We examined two groups: patients who
absorbed not more than 40% of their fat or protein intake during
the baseline period, and patients who absorbed 41% to 80% of
their fat or protein intake during the baseline period. In this
retrospective analysis, we looked only at data from patients in
treatment arms 2 and 3, and we pooled these two groups for
purposes of the analysis, as there were no statistically
significant differences between these treatment arms in
improvements in CFA and CNA.
59
When we analyzed those patients who absorbed not more than 40%
of their fat or protein intake during the baseline period we
observed the following results:
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an average increase in CFA of 31 percentage points for combined
treatment arms 2 and 3, from the baseline period to the
treatment period (number of patients, or n,=21) |
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an average increase in CNA of 36 percentage points for combined
treatment arms 2 and 3, from the baseline period to the
treatment period (n=9) |
In patients with fat or protein absorption of 41% to 80% during
the baseline period, we observed the following results:
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an average increase in CFA of 9 percentage points for combined
treatment arms 2 and 3, from the baseline period to the
treatment period (n=50) |
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an average increase in CNA of 13 percentage points for combined
treatment arms 2 and 3, from the baseline period to the
treatment period (n=60) |
Based on these data, we believe cystic fibrosis patients
enrolled in our Phase II clinical trial had a clinically
meaningful response to
ALTU-135. In
particular, those subjects who had the most severe fat or
protein malabsorption, which we define as patients with a CFA or
CNA of not more than 40% during the baseline period, benefited
the most from their treatment with
ALTU-135. Based on our
discussions with the FDA to date, we expect that in our Phase
III clinical trial of
ALTU-135, the FDA will
look for ALTU-135 to
provide patients who have a lower baseline CFA level a
substantially greater percentage point increase in CFA than the
percentage point increase in patients who have a higher baseline
CFA level in order to demonstrate clinically meaningful
improvement.
As noted above, the trial results also indicated a trend toward
improvement in carbohydrate absorption for patients in treatment
arms 2 and 3. To obtain additional insight with respect to
carbohydrate absorption, we further analyzed the data
retrospectively by examining all three treatment arms using a
responder analysis that excluded subjects with cystic
fibrosis-related diabetes, because such subjects were receiving
diabetes medications that could have confounded the results. In
this subgroup (n=81), we observed a marked increase in the
number of subjects whom we considered responders in treatment
arms 2 and 3 compared to treatment arm 1. We defined
responders as patients who achieved a minimum predetermined
level of glucose change during the treatment period as compared
to the pre-treatment period. The number of subjects achieving
this response in treatment arm 2 was statistically
significant when compared to treatment arm 1
(p-value<0.01) and
was approaching statistical significance for treatment
arm 3
(p-value=0.0644)
compared to treatment arm 1.
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Safety and Tolerability Results |
There were no statistically significant differences among the
three treatment arms in the incidence of adverse events, or AEs,
the number of related AEs, or the number of serious adverse
events, or SAEs. The majority of AEs were mild in intensity,
similar to previous ALTU-135 studies in cystic fibrosis
subjects, and the most frequently reported AEs were
gastrointestinal disorders. There were no clear differences
across the treatment arms for any AEs considered to be related
to ALTU-135. The majority of the SAEs were gastrointestinal and
pulmonary related, which were consistent with the subjects
underlying cystic fibrosis disease. Of the SAEs, only one was
considered by an investigator in the trial as probably or
possibly related to treatment with
ALTU-135.
There were no major safety concerns identified regarding
laboratory values, vital signs or physical exams. Abnormal liver
transaminase values with frequent fluctuations were common among
the subjects during the pre-treatment, treatment and
follow-up periods, and
are common in the cystic fibrosis population in general. We
observed, however, more frequent liver transaminase elevations
in subjects during the treatment and
follow-up periods
compared to the pre-treatment period. In a 1999 published study
of 124 children with cystic fibrosis followed for four years, it
was found that 80% had abnormal elevations in liver
transaminases. Overall transaminase elevations experienced by
patients in our Phase II
60
trial were transient, asymptomatic and not associated with
increases in bilirubin. Increases in bilirubin are typically
associated with harm to the liver. In addition to normal to
abnormal transaminase shifts, abnormal to normal transaminase
shifts were also observed across treatment groups. A causal
relationship between ALTU-135 treatment and elevated liver
transaminases is unclear because of the underlying liver
disease, which is estimated to occur in up to 37% of cystic
fibrosis patients according to published studies, and other
complicating factors in these patients, including diabetes and
infections.
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Phase III Clinical Trial in Cystic Fibrosis Patients |
We recently met with the FDA to discuss the results of our
Phase II clinical trial and our planned Phase III
clinical trial for the solid form of
ALTU-135. Based on our
discussions with the FDA, we are designing our pivotal
Phase III clinical trial of ALTU-135 to be a multicenter,
randomized, double-blind, placebo-controlled clinical study to
determine, as the primary endpoint, the efficacy of ALTU-135 in
the treatment of fat malabsorption in cystic fibrosis patients
with exocrine pancreatic insufficiency through measurement of
CFA. We plan on incorporating secondary endpoints in the study,
including the evaluation of ALTU-135 in the treatment of protein
and carbohydrate absorption through measurement of CNA and use
of the starch challenge test, and in decreasing the weight of
stools in patients. In the trial, we also plan on evaluating the
safety and tolerability of ALTU-135 for approximately two
months. The draft protocol contemplates the enrollment of
approximately 150 cystic fibrosis patients over the age of seven
with exocrine pancreatic insufficiency at cystic fibrosis
centers in the United States, Canada and Europe. Patients will
take one small capsule of ALTU-135 containing 25,000 units of
lipase, 25,000 units of protease and 3,750 units of amylase with
each meal or snack. We are preparing to initiate the
Phase III clinical trial of the solid form of
ALTU-135 in the second
half of 2006 in cystic fibrosis patients and expect to complete
the clinical testing in this trial in the first half of 2007.
We are planning to initiate a clinical study evaluating the
long-term safety of
ALTU-135 in the
treatment of patients with exocrine pancreatic insufficiency in
the second half of 2006. This study will evaluate the safety of
ALTU-135 following
one year of open-label treatment in order to provide the
necessary six-month and 12-month exposure data for approval of
an NDA. We plan to enroll approximately 250 patients with
pancreatic insufficiency from a combination of sources,
including our Phase II and Phase III clinical trials
of ALTU-135. The safety
of ALTU-135 will be
evaluated based on adverse events, physical examinations, vital
signs and standard clinical laboratory testing during the
one-year study period.
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ALTU-238 for Growth Hormone Deficiency and Related
Disorders |
ALTU-238 is a crystallized formulation of hGH that is designed
to be administered once weekly through a fine gauge needle for
the treatment of hGH disorders in both pediatric and adult
populations. Based on reported revenues of existing products,
these indications generated approximately $2.2 billion in
worldwide sales of hGH in 2004, and the market grew at a
compound annual growth rate of approximately 15% from 2002 to
2004. We are developing
ALTU-238 as a
long-acting, growth hormone product that can allow patients to
avoid the inconvenience of daily injections as recommended by
current medical guidelines for existing products. We have used
our proprietary protein crystallization technology and
formulation expertise to develop ALTU-238 without altering the
underlying molecule or requiring polymer encapsulation. Since
hGH is a known protein molecule with an established record of
safety and efficacy, we believe that ALTU-238 may have less
development risk than most pharmaceutical product candidates at
a similar stage of development. We have completed a Phase I
clinical trial of ALTU-238 in healthy adults that was designed
to determine its safety, pharmacokinetics and pharmacodynamics.
Pharmacokinetics refers to the process by which a drug is
absorbed, distributed, metabolized and eliminated by the body.
Pharmacodynamics refers to the process by which a drug exerts
its biological effect. Based on the results of our Phase I
clinical trial, we recently initiated a Phase II clinical
trial for ALTU-238 in adults with growth hormone deficiency and
expect to have data from this trial in the first half of 2006.
61
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Disease Background, Market Opportunity and Limitations of
Existing Products |
Growth hormone, which is secreted by the pituitary gland, is the
major regulator of growth in the body. Growth hormone directly
stimulates the areas of bones known as epiphyseal growth plates,
which are responsible for bone elongation and growth. Growth
hormone also causes growth indirectly by triggering the release
of insulin-like growth factor 1, or IGF-1, from tissues
throughout the body. IGF-1 is a naturally occurring hormone that
stimulates the growth of bone, muscle and other body tissues in
response to hGH and, in turn, regulates hGH release from the
pituitary gland. Growth hormone also contributes to proper bone
density and plays an important role in various metabolic
functions, including lipid breakdown, protein synthesis and
insulin regulation.
Growth hormone deficiency typically results from an abnormality
within the pituitary gland that impairs its ability to produce
or secrete growth hormone. A deficiency of growth hormone can
result in reduced growth in children and lead to short stature.
Because the growth plates in the long bones fuse and additional
cartilage and bone growth can no longer occur after puberty, hGH
replacement therapy does not cause growth in adults. However, in
adults low levels of hGH are also frequently associated with
other metabolic disorders, including lipid abnormalities,
decreased bone density, obesity, insulin resistance, decreased
cardiac performance and decreased muscle mass. These disorders
typically become increasingly apparent after a prolonged period
of hGH deficiency, as occurs in adulthood.
Patients with growth hormone deficiency are typically treated
with growth hormone replacement therapy. Growth hormone is also
prescribed for many patients suffering from a range of other
diseases or disorders, including pediatric growth hormone
deficiency, adult growth hormone deficiency, small for
gestational age and idiopathic short stature in children.
According to industry estimates:
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1 in 3,500 children suffer from growth hormone deficiency; |
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1 in 10,000 adults suffer from growth hormone deficiency; |
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between 3% and 10% of births annually are small for gestational
age; and |
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between 2% and 3% of children are affected by idiopathic short
stature. |
Growth hormone is also used to treat Turner Syndrome, HIV/AIDS
wasting, Prader Willi Syndrome and short bowel syndrome. The
percentage of patients for whom hGH is prescribed varies
significantly by indication. We believe that a once-weekly
formulation of hGH, such as ALTU-238, may result in increased
use in a number of these indications.
Currently, many of the FDA approved hGH products are also in
clinical development for additional indications, including
Crohns disease, female infertility, bone regeneration and
a variety of other genetic and metabolic disorders. There are
currently eight FDA-approved hGH products on the market in the
United States from six manufacturers, all of which use
essentially the same underlying hGH molecule. Current medical
guidelines for clinical practice generally recommend daily
administration of existing products by subcutaneous injection.
We believe that the primary differences between these products
relate to their formulation and the devices employed for their
delivery.
We believe that the burden of frequent injections significantly
impacts quality of life for both adults and children being
treated with hGH therapy and often leads to reduced compliance
or a reluctance to initiate therapy. For example, we estimate
that a standard course of treatment for pediatric growth hormone
deficient patients typically lasts approximately six years
and requires more than 1,800 injections. Faced with this
protracted treatment regime, pediatric patients often take
days off and miss treatment. For adults with growth
hormone deficiency, the benefits of hGH treatment are more
subtle and relate to metabolic function and organ health instead
of increased height. As a consequence, and in contrast to hGH
deficient children, many adults with growth hormone deficiency
do not initiate hGH therapy, and many of those who do fail to
continue treatment.
62
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Anticipated Advantages of ALTU-238 |
We expect that ALTU-238, if approved, will offer patients a more
convenient and effective long-term therapy because of the
following features:
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Convenience of once-weekly dosing. Based on the results
of our Phase I clinical trial, we believe that ALTU-238
will offer growth hormone deficient patients the convenience of
a once-weekly injection. We believe this will improve compliance
and thereby increase long-term effectiveness of therapy and
potentially expand the market. |
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Administration with a fine gauge needle. ALTU-238 is
designed to provide extended release without using polymers to
encapsulate the component hGH molecules. To date, there has not
been an hGH therapy approved by the FDA for administration once
per week. The only hGH therapy approved by the FDA for
administration less frequently than once per week was withdrawn
from the market and required polymeric encapsulation for its
extended release formulation. This necessitated the use of a
substantially larger needle and prolonged injection time, which
we believe led to reduced market acceptance and eventual
withdrawal of the product from the market. We have designed
ALTU-238 using our protein crystallization technology so that,
as the crystals dissolve, the hGH is released over an extended
period. This allows
ALTU-238 to be
administered with the same size needle as used with currently
marketed products. |
In addition, we have designed ALTU-238 to be manufactured using
well-established equipment and processes consistent with other
injectable protein products. We believe this will provide
flexibility in the
scale-up and commercial
production of ALTU-238, if approved.
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ALTU-238 Development Activities and Strategy |
We have completed a Phase I clinical trial of ALTU-238 in
healthy adults and recently initiated enrollment in a
Phase II clinical trial in adults with growth hormone
deficiency. We expect to have data from this trial in the first
quarter of 2006.
In our Phase I clinical trial, we evaluated the safety,
tolerability and the pharmacokinetic and pharmacodynamic profile
of ALTU-238 in healthy adults. The following is a summary of our
Phase I clinical trial for ALTU-238:
ALTU-238 Phase I Clinical Trial Summary
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Title |
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A Single Blind, Single Dose, Randomized, Placebo-Controlled,
Parallel Group Study of ALTU-238 in Normal Healthy Adults to
Determine Pharmacokinetics, Pharmacodynamics and Drug Safety |
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Design |
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Forty-five subjects received one of the following treatment
regimens: |
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a single injection of ALTU-238 at a dose of 2.8 mg,
8.4 mg, or 16.8 mg of hGH, administered to 6 subjects
at each dose; |
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a single injection of
ALTU-238 at a dose of
24.5 mg of hGH administered to 7 subjects; |
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7 daily injections of Nutropin AQ, a daily,
FDA-approved hGH
product, at a dose of 2.4 mg of hGH, administered to 6
subjects; |
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a single injection of Nutropin AQ at a dose of
3.5 mg of hGH, administered to 6 subjects; and |
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a single injection of placebo, administered to
8 subjects. |
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Administration |
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Each regimen was administered to patients as a subcutaneous
injection. |
63
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Safety Results |
|
ALTU-238 was well tolerated and easily administered through 29
and 30 gauge needles. There were no serious adverse events
reported in the clinical trial, and the percentage of subjects
who experienced adverse events was comparable among treatment
groups. Subjects across all treatment groups experienced
injection site reactions, the most common of which were redness,
hardening of the skin and swelling. |
|
Clinical Activity Results |
|
We observed a dose-dependent rise in hGH and IGF-1
concentrations following a single dose of ALTU-238. The
pharmacokinetic profile of ALTU-238 at a dose of 16.8 mg
indicated that the maximum concentration of hGH in the blood was
achieved in approximately 51 hours and was less than the
maximum concentration of hGH in the blood from a daily dose of
2.4 mg of Nutropin AQ. The IGF-1 pharmacodynamic profile
over a seven-day period after a single injection of ALTU-238 at
a dose of 16.8 mg was comparable to that observed with the
same aggregate amount of hGH delivered through seven daily
injections of Nutropin AQ. |
Based on the results from the Phase I clinical trial, we
believe that ALTU-238, if approved, can be administered once
weekly.
In our Phase II clinical trial, we are evaluating ALTU-238
in adults with growth hormone deficiency. The primary objective
of the trial is to determine the safety and tolerability of
ALTU-238, as well as its pharmacokinetic and pharmacodynamic
profile, when administered over a
three-week period. The
clinical trial consists of two treatment groups of at least six
patients each. Patients will receive weekly injections of either
5.6 mg or 11.2 mg of ALTU-238, which we believe are
consistent with doses for adult and pediatric indications. We
will determine the pharmacokinetic and pharmacodynamic profiles
of ALTU-238 by measuring hGH, IGF-1 and other parameters. We
expect to have data from this trial by the first half of 2006.
If our Phase II clinical trial is successful, we plan to
advance ALTU-238 into a Phase III clinical trial in adults
and a Phase II/III clinical trial in children in the second
half of 2006. We plan to request that the FDA consider the
single trial in children as a pivotal trial because we are
designing the trial to meet the requirements of both a
Phase II and Phase III trial. The FDA may not agree
with this approach and may require additional studies in
children.
We believe that our development strategy for ALTU-238 will allow
us to pursue one of three approval paths. If we use a supplier
with an approved NDA for its hGH product, we will seek a
right of reference to the safety and efficacy data
on the underlying growth hormone in our suppliers NDA, and
we will file an NDA that includes additional information
relating to our crystallized dosage form. However, we may not be
able to obtain hGH and receive a right of reference from a
supplier with an approved NDA for its hGH product. If we are not
able to obtain a right of reference, and the FDA or
the courts determines that approval of a new hGH product is
appropriate under section 505(b)(2), we plan to submit an
NDA under section 505(b)(2) of the FDCA and rely, without a
right of reference, on published literature and the
FDAs previous findings regarding the safety and efficacy
of hGH products. We expect that either of these routes will
enable us to avoid some of the non-clinical studies that would
otherwise be required on the underlying hGH molecule, which may
reduce the cost of developing ALTU-238 and shorten the time to
market. If neither of these two routes are available, we would
be required to file a full NDA under section 505(b)(1) of
the FDCA, would not have the ability to refer to
third-party studies,
and would need to perform whatever studies are necessary to
demonstrate the safety and effectiveness of
ALTU-238. The
availability of section 505(b)(2) for approval of ALTU-238
is uncertain. See Government Regulation and Product
Approval Section 505(b)(2) Applications.
If we are unable to secure a right of reference to
an FDA-approved product or submit an NDA under
section 505(b)(2), our cost and development time for
ALTU-238 may increase.
64
Our Preclinical Research and Development Programs
We are currently developing a pipeline of preclinical product
candidates that are designed to either increase the amount of
protein that is in short supply in the body or degrade and
remove toxic metabolites from the blood stream. We are
developing all of these product candidates for oral delivery to
address areas of unmet need in chronic gastrointestinal and
metabolic disorders, including: an oxalate degrading enzyme for
the treatment of hyperoxalurias; and an enzyme that degrades
phenylalanine for the treatment of phenylketonuria. We believe
that our proprietary, crystallized formulations of these product
candidates will represent novel or improved therapies for the
treatment of these disorders. Our two most advanced preclinical
product candidates are described below.
Our lead preclinical product candidate, ALTU-237, is an
orally-administered crystalline formulation of an
oxalate-degrading enzyme which we have designed for the
treatment of primary hyperoxaluria and enteric hyperoxaluria, as
well as to prevent the recurrence of kidney stones in
individuals with a risk or history of recurrent kidney stones.
There are no current effective pharmacological treatments for
primary hyperoxaluria, enteric hyperoxaluria or recurrent kidney
stones. We plan to file an IND for ALTU-237 for the treatment of
hyperoxalurias in early 2007.
Primary hyperoxaluria is a rare, inherited and, if left
untreated, fatal metabolic disease that results in the
accumulation of oxalate in the body. Oxalate is the salt form of
oxalic acid, and is a natural end product of metabolism. Oxalate
does not appear to be needed for any human body process, and in
healthy individuals more than 90% of oxalate is excreted by the
kidney, with a small amount of excretion into the lower gut.
Based on prevalence data from an industry article, we estimate
that between 1-in-60,000 and
1-in-120,000 children
in North America and Europe are born with primary hyperoxaluria.
Enteric hyperoxaluria is a condition resulting from increased
intestinal absorption of oxalate, resulting in recurrent kidney
and urinary stones. Enteric hyperoxaluria can occur in people
who have intestinal diseases, such as Crohns Disease and
inflammatory bowel disease or may occur in patients following
gastric surgery.
According to the National Kidney Foundation, kidney stone
disease is a common disorder of the urinary tract affecting
approximately 20 million Americans. According to Disease
Management, between 70% and 75% of kidney stones are composed of
calcium oxalate crystals and an estimated up to 50% of patients
who do not follow recommended guidelines will suffer from a
repeated kidney stone incident within five years of their
initial incident. According to the National Kidney and Urologic
Diseases Information Clearinghouse, in 2000, kidney stones led
to approximately 600,000 emergency room visits.
In our preclinical studies using rodent models,
ALTU-237, delivered
orally, demonstrated an ability to reduce oxalate levels in
urine. We believe that these results suggest that we may be able
to use our proprietary protein crystallization technology to
orally deliver enzymes to the gastrointestinal tract, where they
can exert a therapeutic effect by drawing out toxic metabolites
from the body. This therapeutic approach is currently utilized
by some existing drugs. For example, Renagel, marketed by
Genzyme Corporation, removes excess levels of phosphate in the
body in patients with chronic kidney disease by delivering drug
to the gastrointestinal tract, where it binds to the phosphate
and removes it from the body. If we are successful in our design
of ALTU-237, we believe that this program will provide a
template for our other research and preclinical programs that
rely on the same fundamental science and mechanism of action.
We are also developing
ALTU-236, an
orally-administered enzyme replacement therapy designed to
reduce the long-term effects associated with excess levels of
phenylalanine, also known as hyperphenylalanemia. According to
the National Institutes of Health, phenylketonuria, or PKU,
which is the most severe form of hyperphenylalanemia, affects
approximately 1-in-15,000 newborns in the United States. PKU is
a rare, inherited, metabolic disorder that results from an
enzyme deficiency which causes the accumulation of the amino
acid phenylalanine in the body. If left untreated, PKU can
result in mental retardation, swelling of the brain, delayed
speech, seizures and behavior abnormalities. Virtually all
newborns in the United States
65
and in many other countries are screened prior to leaving the
hospital for PKU. PKU and hyperphenylalanemia are currently
treated by placing patients on a phenylalanine restricted diet.
This diet is expensive and difficult to maintain and does not
avoid many of the long-term effects of PKU. There are currently
no approved drugs to treat PKU. We are currently testing
ALTU-236 in animal
models.
Our Protein Crystallization Technology and Approach
Historically, scientists have crystallized proteins primarily
for use in x-ray
crystallography to examine the structure of proteins. In
contrast, we are using our technology to crystallize proteins
for use as therapeutic drugs. This requires the crystallization
process to be both reproducible and scalable, and our technology
is designed to enable large scale crystallization with
batch-to-batch
consistency.
Crystallized proteins are more stable, pure and concentrated
than proteins in solution. For example, one protein crystal may
contain several billion molecules of the underlying protein. We
believe that these characteristics will enable improved storage
and delivery, permitting delivery of the protein molecules with
fewer capsules or smaller injection volumes.
Once a protein is in the crystallized state, we formulate it for
either oral or injectable delivery. For our product candidates
that will be delivered orally, we use our crystallization
technology to deliver proteins to the gastrointestinal tract,
where they can exert their therapeutic effect locally. In
situations where we need to confer a higher level of stability
to a protein, such as in the lipase component of
ALTU-135, we cross-link
protein molecules in crystals together using multi-functional
cross-linking agents. For our product candidates that are
injected, we use our crystallization technology to develop
highly concentrated and stable proteins that can be formulated
for extended release.
Our approach to developing therapeutic product candidates using
crystallized proteins is comprised of the following general
elements:
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Establish initial crystallization conditions. Once we
choose a target protein, we rapidly screen hundreds of
crystallization conditions both manually and using robotics. We
define the conditions under which a soluble protein could
crystallize, including protein concentration, pH and temperature
of crystallization. |
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Identify key crystallization conditions and initial
crystallization scale up. After we identify the initial
conditions, we focus on the critical crystallization conditions
to define a robust and reproducible crystallization process. We
then scale the process from single drops, to microliter scale,
to milliliter scale, and finally, to liter scale. |
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Select crystallization process and crystal. If there is
more than one successful crystallization process and resulting
crystals, we use our target product profile to choose the best
protein crystal for the given application based on crystal size,
shape and other characteristics. |
We apply our proprietary protein crystallization technology to
existing, well-understood proteins in the development of our
product candidates. We believe our technology is broadly
applicable to all classes of proteins, including enzymes,
hormones, antibodies, cytokines and peptides. To date, we have
crystallized more than 70 proteins for evaluation in our
product candidates and preclinical research and development
programs.
Collaborations
Cystic
Fibrosis Foundation Therapeutics, Inc.
In February 2001, we entered into a strategic alliance agreement
with CFFTI, an affiliate of the Cystic Fibrosis Foundation.
Under this agreement, which was amended in 2001 and 2003, we and
CFTTI have agreed to collaborate for the development of
ALTU-135 and specified
derivatives of ALTU-135
in North America for the treatment of malabsorption due to
exocrine pancreatic insufficiency in patients with cystic
fibrosis and other indications. The agreement, in general terms,
provides us with funding from CFFTI for a portion of the
development costs of
ALTU-135 upon the
achievement of specified development and regulatory milestones,
up to a total of $25.0 million, in return for specified
payment
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obligations described below and our obligation to use
commercially reasonable efforts to develop and bring
ALTU-135 to market in
North America for the treatment of malabsorption due to exocrine
pancreatic insufficiency in patients with cystic fibrosis and
other indications. CFFTI has also agreed to provide us with
reasonable access to its network of medical providers, patients,
researchers and others involved in the care and treatment of
cystic fibrosis patients, and to use reasonable efforts to
promote the involvement of these parties in the development of
ALTU-135. We believe that our relationship with the Cystic
Fibrosis Foundation will help facilitate our development of
ALTU-135.
As of December 31, 2005, we had received a total of
$18.4 million of the $25.0 million available under the
agreement. In addition, we may receive an additional milestone
payment of $6.6 million, less an amount determined by when
we achieve the milestone. We have also issued to CFFTI warrants
to purchase a total of 261,664 shares of our common stock
at an exercise price of $0.02 per share. The alliance is
managed by a steering committee, comprised of an equal number of
representatives from Altus and CFFTI, which generally oversees
the progress of our clinical development of
ALTU-135 and reviews
the schedule and achievement of milestones under our agreement.
Under the terms of the agreement, we granted CFFTI an exclusive
license under our intellectual property rights covering ALTU-135
and specified derivatives for use in all applications and
indications in North America, and CFFTI granted us back an
exclusive sublicense of the same scope, including the right to
grant further sublicenses. Our exclusive license to CFFTI
continues in effect until the earliest to occur of our payment
in full of all license fees due under the agreement, as
described below; our termination of the agreement on account of
a material default or bankruptcy of CFFTI; the parties
mutual agreement not to proceed with development following a
deadlock of the alliance steering committee; or the alliance
steering committees determination that ALTU-135 is not
safe or effective for the treatment of exocrine pancreatic
insufficiency or, solely due to scientific or medical reasons,
that ALTU-135 should not be developed or marketed.
Our exclusive sublicense from CFFTI continues in effect until
our license to CFFTI terminates or CFFTI terminates the
agreement on account of our failure to meet specified
milestones, our determination not to continue development after
an unresolved deadlock of the alliance steering committee, or
our material default or bankruptcy.
If ALTU-135 is approved by the FDA, we are obligated to pay
CFFTI a license fee equal to the aggregate amount of milestone
payments we have received from CFFTI, plus interest, up to a
maximum of $40.0 million, less the fair market value at the
time of approval of the shares of stock underlying the warrants
we issued to CFFTI. This fee, together with accrued interest,
will be due in four annual installments, commencing 30 days
after the approval date. We are required to pay an additional
$1.5 million to CFFTI within 30 days after the
approval date. In addition, we are obligated to pay royalties to
CFFTI on worldwide net sales by us or our sublicensees of
ALTU-135 for any and all indications until the expiration of
specified United States patents covering ALTU-135. We have the
option to terminate our ongoing royalty obligation by making a
one-time payment to CFFTI but we currently do not expect to do
so. We are also required to pursue, prosecute, maintain and
defend all patents covered by the agreement at our own expense.
In addition to the termination rights described above, CFFTI may
terminate the agreement without cause within 30 days
following the end of the fiscal quarter in which we deliver data
to them from our Phase II clinical trial, which we
delivered in the fourth quarter of 2005. If CFFTI terminates the
agreement without cause after our delivery of Phase II
clinical trial data and we subsequently commercialize
ALTU-135, we are
obligated to pay CFFTI royalties on net sales that are subject
to a cumulative cap on our royalty obligation of
$16.9 million. Based on our discussions with CFFTI to date,
we expect CFFTI to continue our collaboration following its
receipt of the final Phase II clinical trial data. If CFFTI
terminates the agreement due to our breach, it would retain its
exclusive license to ALTU-135 and our sublicense from CFFTI
would terminate. Upon termination of the agreement by us due to
a breach by CFFTI, the license granted to CFFTI to
ALTU-135 will terminate.
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Dr. Falk
Pharma GmbH
In December 2002, we entered into a development,
commercialization and marketing agreement with Dr. Falk for
the development by us of
ALTU-135 and the
commercialization by Dr. Falk of
ALTU-135, if approved,
in Europe, the countries of the former Soviet Union, Israel and
Egypt. Under the agreement, we granted Dr. Falk an
exclusive, sublicensable license under specified patents that
cover ALTU-135 to
commercialize ALTU-135
for the treatment of symptoms caused by exocrine pancreatic
insufficiency.
As of December 31, 2005, we had received upfront and
milestone payments from Dr. Falk under the agreement
totaling
11.0 million.
In addition, we may receive from Dr. Falk an additional
15.0 million
in milestone payments based on the achievement of specified
clinical and regulatory milestones. We are also eligible to
receive royalties on net sales of ALTU-135 by Dr. Falk and
its affiliates during the term of the license, as described
below.
Under the terms of the agreement, each party is responsible for
using commercially reasonable efforts to perform specified
responsibilities relating to the development of ALTU-135, and
Dr. Falk is responsible for using commercially reasonable
efforts to obtain regulatory approvals and to commercialize
ALTU-135 in the
licensed territory. The agreement contemplates that, under the
direction of a steering committee consisting of an equal number
of representatives from Altus and Dr. Falk, we will conduct
specified clinical trials, including an international
Phase III clinical trial, required to support applications
for regulatory approvals of
ALTU-135 in the
licensed territory. Dr. Falk has agreed to pay a portion of
the development expenses, including costs relating to the
process of obtaining regulatory approval, project management
costs, statistical design and studies, and preparation of
reports, that we incur in connection with the conduct of an
international Phase III clinical trial. Expenses relating
to other clinical trials conducted for the purpose of obtaining
regulatory approvals in the licensed territory will be borne
entirely by Dr. Falk.
The collaboration is coordinated through the steering committee.
We maintain ultimate decision-making authority with respect to
clinical development matters, subject to an obligation to
exercise our decision-making authority in a manner that is
consistent with the objective of managing an effective and
efficient international Phase III clinical trial that
satisfies the development, regulatory and commercialization
requirements of the North American territory and the licensed
territory and leveraging clinical development activities in both
territories. Dr. Falk has responsibility for and control of
commercialization matters in the licensed territory.
Under the agreement, we are responsible for supplying such
quantities of ALTU-135 as may be required for the conduct of
clinical trials, subject to the development expense allocation
provisions of the agreement. We are also responsible for
establishing a commercial scale manufacturing process for
ALTU-135, for sourcing
ALTU-135 from contract
manufacturers, for ensuring that a second source supplier exists
and, if Dr. Falk elects to purchase its requirements for
commercial supply from us, for supplying Dr. Falks
requirements of
ALTU-135 for commercial
sale in the licensed territory. If Dr. Falk elects to
purchase its requirements of ALTU-135 from us, which we expect
it to do because we have not granted Dr. Falk a license to
manufacture ALTU-135,
the price at which Dr. Falk will purchase its requirements
will equal the greater of a fixed percentage of specified
Dr. Falk resale prices and our fully burdened manufacturing
costs, and the other terms and conditions of supply will be
governed by a commercial supply and distribution agreement to be
negotiated by the parties. If our fully burdened manufacturing
costs exceed the fixed percentage of the specified Dr. Falk
resale prices, Dr. Falk is entitled to offset the excess
against royalties due us up to a specified maximum offset amount.
Under the terms of the agreement, the license to Dr. Falk
will continue in each country in the licensed territory until
the later of the expiration of the
last-to-expire of
specified patents that cover
ALTU-135 in that
country or 12 years from the date of first commercial sale of
ALTU-135 in that
country. The current patents and the pending patent
applications, if issued as patents, relating to
ALTU-135 that are
relevant to our agreement with Dr. Falk will expire between
2011 and 2025, excluding any extensions that we may receive. The
agreement may be terminated by Dr. Falk for convenience by
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providing written notice to us within 30 days after
Dr. Falks receipt of the final report for the
Phase II clinical trial or Phase III clinical trial of
ALTU-135. In addition,
subject to specified conditions, Dr. Falk may terminate the
agreement if the manufacture, use or sale of
ALTU-135 in the
licensed territory is enjoined due to infringement of
third-party patent rights or if a clinical hold with respect to
ALTU-135 is imposed in
a specified country. Either party may terminate the agreement
upon the commitment of an uncured material breach by the other
party or upon the occurrence of specified bankruptcy or
insolvency events involving the other party. Upon termination of
the agreement by Dr. Falk due to a material breach by us,
Dr. Falk will retain the license to
ALTU-135 at a reduced
royalty and have no further obligation to pay additional
milestone payments. Upon termination of the agreement by us due
to a material breach by Dr. Falk, the license granted to
Dr. Falk to
ALTU-135 will terminate.
Manufacturing
We do not own or operate manufacturing facilities for the
production of clinical or commercial quantities of
ALTU-135,
ALTU-238 or any of the
compounds that we are testing in our preclinical research and
development programs. We currently have no plans to build our
own clinical- or commercial-scale manufacturing capabilities,
and we expect for the foreseeable future to rely on contract
manufacturers for both clinical and commercial supplies of our
products. Although we rely on contract manufacturers, we have
personnel with manufacturing experience to oversee the
relationships with our contract manufacturers.
Amano is currently our sole contract manufacturer of the
crystallized and cross-linked lipase, the crystallized protease,
and the amylase enzymes that comprise the APIs for
ALTU-135. We entered
into a five-year cooperative development agreement with Amano in
November 2002, which was amended in October 2005, to
collaborate on process development and
scale-up of API
production for
ALTU-135. Amano has
built a plant in Nagoya, Japan to produce the enzymes for
ALTU-135 in large-scale
batches using microbial fermentation. The plant has not been
inspected or approved by the FDA, EMEA or the Japanese Ministry
of Health, Labour and Welfare. Under our agreement, Amano
has supplied the APIs for
ALTU-135 for our
non-clinical and clinical trials to date and has agreed to
supply us with APIs for our Phase III clinical trial and
additional toxicology studies at a specified transfer price.
Under our agreement, Amano may not sell to other parties the
APIs for ALTU-135 for
use in specified competitive products. We use a third party to
perform fill, finish and packaging services for
ALTU-135.
Under the terms of the agreement, each party has contributed
technology used for the production of the APIs in
ALTU-135. Each party
owns intellectual property created solely by it, and jointly
owns any intellectual property created jointly. Pursuant to our
agreement with Amano, they have notified us that they will not
be the primary manufacturer of the APIs for the initial
commercial supply of
ALTU-135. We expect to
negotiate a new agreement with Amano that governs the commercial
supply of some of the APIs for
ALTU-135. Amano will be
required to grant licenses of its technology to other contract
manufacturers which we mutually select, and we will be required
to pay Amano a royalty based on the cost of the materials
supplied to us by such other contract manufacturers. We are in
the process of selecting a contract manufacturer that is capable
of providing us commercial quantities of APIs for
ALTU-135. We are
obligated under our agreement with Amano to use best efforts to
develop and commercialize
ALTU-135.
Our agreement with Amano expires in November 2007, unless
mutually extended by the parties. The agreement may be
terminated by either party upon an uncured material breach by
the other party or upon specified bankruptcy or insolvency
events involving the other party. In addition, either party may
terminate the agreement without cause on one years written
notice to the other party. If the agreement terminates for any
reason, our licenses under the agreement survive forever and, in
the case of a termination for our material breach or a
termination by us for reasons other than Amanos material
breach, we must pay Amano royalties on worldwide sales of
ALTU-135.
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ALTU-238
We currently purchase hGH from Sandoz and have no long-term
supply arrangements or contracts. A product containing the hGH
supplied by Sandoz has not been approved by the FDA or the EMEA.
We are negotiating with various manufacturers with respect to
commercial supply agreements for hGH.
We completed small-scale cGMP runs of
ALTU-238 at a contract
manufacturer for our Phase I and II clinical trials. We
expect that we will have to secure additional manufacturing
capacity with one or more contract manufacturers in order to
produce ALTU-238 for our subsequent trials and on a commercial
scale. We also expect to arrange for a third party to perform
fill, finish and packaging services for
ALTU-238.
Sales and Marketing
If we receive regulatory approval for any of our product
candidates, we plan to commence commercialization activities by
building a focused sales and marketing organization. Our sales
and marketing strategy is to:
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Build our own North American sales force. We plan to
establish a commercial infrastructure and targeted specialty
sales force to market our product candidates in North America.
Our sales efforts for
ALTU-135, if approved,
will initially be focused on the 500 pediatric pulmonologists
who are in approximately 100 cystic fibrosis care centers
throughout the United States, as well as the 5,000 key
gastroenterologists and pancreatologists who prescribe products
for exocrine pancreatic insufficiency. For ALTU-238, we plan to
focus initially on the approximately 400 key prescribing
pediatric endocrinologists and approximately 3,000 adult
endocrinologists who treat patients with growth hormone
deficiency. Because the target groups for
ALTU-238 are primarily
hospital-based and concentrated in major metropolitan areas, we
believe that we can effectively address the market for
ALTU-238 with a
specialized sales force that targets these key prescribers. We
also plan to leverage our sales and marketing capabilities by
targeting the same groups of physician specialists with multiple
products that we bring to market either through our own
development efforts or by in- licensing from others. |
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Assemble a marketing organization. We plan to build a
marketing, managed care and sales management organization to
create and implement marketing strategies for
ALTU-135,
ALTU-238 and other
product candidates in our product pipeline. We expect that our
marketing organization will oversee any products that we market
through our own sales force and oversee and support our sales
and reimbursement efforts. The responsibilities of the marketing
organization will include developing educational initiatives
with respect to approved products and establishing relationships
with thought leaders in relevant fields of medicine. We also
plan to conduct post-approval marketing studies for our products
to provide further data on the safety and efficacy. As we
develop our pipeline products, we will evaluate whether to
expand our marketing and sales efforts. |
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Selectively establish collaborations for our product
candidates with leading pharmaceutical and biotechnology
companies. We may enter into additional collaborations in
markets outside of North America where we believe that having a
partner will enable us to gain better access to those markets.
In addition, we may co-promote our product candidates in North
America with pharmaceutical and biotechnology companies in
instances where we believe that a larger sales and marketing
presence will expand the market or accelerate penetration. We
may also collaborate with such companies to accelerate the
development of selected early-stage product candidates. |
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Competition
Our major competitors are pharmaceutical and biotechnology
companies in the United States and abroad that are actively
engaged in the discovery, development and commercialization of
products to treat gastrointestinal and metabolic disorders. Any
product candidates that we successfully develop and
commercialize will compete with existing therapies and new
therapies that may become available in the future.
Many of the entities developing and marketing potentially
competing products may have significantly greater financial
resources and expertise in research and development,
manufacturing, preclinical testing, conducting clinical trials,
obtaining regulatory approvals and marketing than we do. These
entities also compete with us in recruiting and retaining
qualified scientific and management personnel, as well as in
acquiring technologies complementary to, or necessary for, our
programs.
Our commercial opportunity will be reduced or eliminated if our
competitors develop and commercialize products that are more
effective, have fewer side effects, are more convenient or are
less expensive than any products that we may develop. In
addition, our ability to compete may be affected because in some
cases insurers and other third-party payors seek to encourage
the use of generic products. This may have the effect of making
branded products less attractive, from a cost perspective, to
buyers.
If our two clinical-stage product candidates are approved, they
will compete with currently marketed drugs and potentially with
drug candidates currently in development for the same
indications, including the following:
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ALTU-135. If approved, ALTU-135, the product candidate we
are developing for the treatment of malabsorption due to
exocrine pancreatic insufficiency, will compete with currently
marketed porcine-derived pancreatic enzyme replacement therapies
from Axcan Pharma, Johnson & Johnson, and Solvay
Pharmaceuticals, as well as from generic drug manufacturers such
as KV Pharmaceutical and IMPAX Laboratories. In April 2004,
the FDA issued a notice that manufacturers of existing
pancreatic enzyme replacement products will be subject to
regulatory action if they do not obtain approved NDAs for these
products by April 28, 2008. We believe that some of the
manufacturers of these products may not be able to satisfy the
FDAs requirements for NDAs. In addition, we understand
that Biovitrum and Meristem Therapeutics have product candidates
in clinical development that could compete with
ALTU-135.
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ALTU-238. If approved,
ALTU-238, the product
candidate we are developing as a once-weekly treatment for hGH
deficiency and related disorders, will compete with approved hGH
therapies from companies such as Genentech, Pfizer, Serono, Novo
Nordisk, Teva Pharmaceutical Industries and Eli Lilly. In
addition, we understand that
ALTU-238 may compete
with product candidates in clinical development from some of
these companies and from others, including LG Life Sciences,
which is developing a long-acting hGH therapy based on an
encapsulated microparticle technology. |
Key differentiating elements affecting the success of all of our
product candidates are likely to be their convenience of use and
efficacy and safety profile compared to other therapies.
Intellectual Property
We actively seek patent protection for the proprietary
technology that we consider important to our business, including
compounds, compositions and formulations, their methods of use
and processes for their manufacture. In addition to seeking
patent protection in the United States, we generally file patent
applications in Canada, Europe, Japan and additional countries
on a selective basis in order to further protect the inventions
that we consider important to the development of our business
worldwide. We also rely on trade secrets, know-how, continuing
technological innovation and in-licensing opportunities to
develop and maintain our proprietary position. Our success
depends in part on our ability to obtain and
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maintain proprietary protection for our product candidates,
technology and know-how, to operate without infringing the
proprietary rights of others, and to prevent others from
infringing our proprietary rights.
Our patent portfolio includes patents and patent applications
with claims relating to protein crystals, both cross-linked and
not cross-linked, as well as compositions of specific protein
crystals, such as lipase and hGH, and methods of making and
using these compositions. In addition, we currently have patent
applications relating to compositions and formulations
containing both cross-linked and non-cross-linked protein
crystals and patent applications relating to some of our later
stage pipeline products that are not yet in clinical trials.
As of December 31, 2005, our patent estate on a worldwide basis
includes 12 patents issued in the United States,
20 issued in current member states of the European Patent
Convention and 19 issued in other counties, many of which are
foreign counterparts of our United States patents, as well as
more than 100 pending patent applications, with claims
covering all of our product candidates.
Four of our issued United States patents, expiring between 2014
and 2016, relate to
ALTU-135 and have
claims covering cross-linked protein crystals, cross-linked
enzyme crystals and methods of using those crystals in enzyme
and oral protein therapy. We also have four pending United
States patent applications relating to
ALTU-135, which if
issued as patents, would expire between 2017 and 2025. Some of
these applications include claims covering a combination of
lipase, protease and amylase in specific formulations and
methods of treatment using these formulations. We also have
29 issued foreign patents, expiring between 2011 and 2021,
relating to ALTU-135
and pending foreign patent applications, which if issued as
patents, would expire between 2011 and 2025.
We have three pending United States patent applications relating
to ALTU-238, which if
issued as patents, would expire between 2023 and 2026, and
include claims relating to hGH crystals with an extended release
profile and methods of treating hGH deficiency associated
disorders using such hGH crystals. We also have 30 pending
foreign patent applications relating to
ALTU-238, which if
issued as patents, would expire in 2023.
Our patent estate includes patent applications relating to some
of our other product candidates. Some of these applications are
pending in the United States and foreign patent offices. Others
have to date only been filed in the United States. We expect to
file these outside of the United States at the appropriate time.
These patent applications, assuming they issue as patents, would
expire between 2017 and 2026. We also have eight other issued
United States patents and various foreign counterparts that
relate to cross-linked protein crystal biosensors, methods of
using cross-linked crystals of thermolysin as a catalyst,
specific methods of making cross-linked crystals with controlled
dissolution properties, stabilized protein crystals, protein
crystal formulations as catalysts in organic solvents and
cross-linked glycoprotein crystals.
We hold an exclusive, royalty-free, fully-paid license from
Vertex to patents relating to cross-linked enzyme crystals,
including the four issued United States patents relating to
ALTU-135 and two other issued United States patents relating to
biosensors and thermolysin, as well as to a number of
corresponding foreign patents and patent applications and
know-how, including improvements developed by Vertex or its
collaborators through February 2004. Under this license, Vertex
retains non-exclusive rights to use the licensed Vertex patents
and know-how to develop and commercialize small molecule drugs
for human or animal therapeutic uses. We also granted to Vertex
a non-exclusive,
royalty-free, fully-paid license, under our patents and know-how
with respect to cross-linked protein crystals that we have
acquired, developed or licensed through February 2004, for
Vertexs use in small molecule drug development and
commercialization for human or animal therapeutic uses. The
licenses with respect to patents, unless otherwise terminated
earlier for cause, terminate on a country-by-country basis upon
the expiration of each patent covered by the license.
We also have rights to specified technology developed by Amano
under our cooperative development agreement with Amano, as
described above under the section entitled
Manufacturing.
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Individual patents extend for varying periods depending on the
effective date of filing of the patent application or the date
of patent issuance, and the legal term of the patents in the
countries in which they are obtained. Generally, patents issued
in the United States are effective for:
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the longer of 17 years from the issue date or 20 years
from the earliest effective filing date, if the patent
application was filed prior to June 8, 1995; and |
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20 years from the earliest effective filing date, if the
patent application was filed on or after June 8, 1995. |
The term of foreign patents varies in accordance with provisions
of applicable local law, but typically is 20 years from the
earliest effective filing date. In addition, in some instances,
a patent term in the United States and outside of the United
States can be extended to recapture a portion of the term
effectively lost as a result of the health authority regulatory
review period. These extensions, which may be as long as five
years, are directed to the approved product and its approved
indications. We intend to seek such extensions as appropriate.
The patent positions of companies like ours are generally
uncertain and involve complex legal and factual questions. Our
ability to maintain and solidify our proprietary position for
our technology will depend on our success in obtaining effective
claims and enforcing those claims once granted. We do not know
whether any of our patent applications or those patent
applications that are licensed to us will result in the issuance
of any patents or if issued will assist our business. Our issued
patents and those that may issue in the future, or those
licensed to us, may be challenged, invalidated or circumvented.
This could limit our ability to stop competitors from marketing
related products and reduce the length of term of patent
protection that we may have for our products. In addition, the
rights granted under any of our issued patents may not provide
us with proprietary protection or competitive advantages against
competitors with similar technology. Our competitors may develop
similar technologies, duplicate any technology developed by us,
or use their patent rights to block us from taking the full
advantage of the market. Because of the extensive time required
for development, testing and regulatory review of a potential
product, it is possible that a related patent may remain in
force for a short period following commercialization, thereby
reducing the advantage of the patent to our business and
products.
In addition to patents, we may rely, in some circumstances, on
trade secrets to protect our technology. However, trade secrets
are difficult to protect. We seek to protect the trade secrets
in our proprietary technology and processes, in part, by
entering into confidentiality agreements with commercial
partners, collaborators, employees, consultants, scientific
advisors and other contractors and into invention assignment
agreements with our employees and some of our commercial
partners and consultants. These agreements are designed to
protect our proprietary information and, in the case of the
invention assignment agreements, to grant us ownership of the
technologies that are developed. These agreements may be
breached; and we may not have adequate remedies for any breach.
In addition, our trade secrets may otherwise become known or be
independently discovered by competitors.
Many of our employees, consultants and contractors have worked
for others in the biotechnology or pharmaceutical industries. We
try to ensure that, in their work for us, they do not use the
proprietary information or know-how of others. To the extent
that our employees, consultants or contractors use proprietary
information owned by others in their work for us, disputes may
arise as to the rights in related or resulting know-how and
inventions.
Government Regulation and Product Approval
Government authorities in the United States, at the federal,
state and local level, and other countries extensively regulate,
among other things, the research, development, testing,
manufacture, labeling, packaging, promotion, storage,
advertising, distribution, marketing and export and import of
products such as those we are developing.
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United
States Government Regulation
In the United States, the information that must be submitted to
the FDA in order to obtain approval to market a new drug varies
depending on whether the drug is a new product whose safety and
effectiveness has not previously been demonstrated in humans or
a drug whose active ingredients and some other properties are
the same as those of a previously approved drug. A new drug will
follow the NDA route, and a new biologic will follow the
biologic license application, or BLA, route.
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NDA and BLA Approval Processes |
In the United States, the FDA regulates drugs and some biologics
under the FDCA, and in the case of the remaining biologics, also
under the Public Health Service Act, and implementing
regulations. Failure to comply with the applicable United States
requirements at any time during the product development process,
approval process or after approval, may subject an applicant to
administrative or judicial sanctions. These sanctions could
include:
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the FDAs refusal to approve pending applications; |
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license suspension or revocation; |
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withdrawal of an approval; |
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a clinical hold; |
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warning letters; |
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product recalls; |
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product seizures; |
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total or partial suspension of production or
distribution; or |
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injunctions, fines, civil penalties or criminal prosecution. |
Any agency or judicial enforcement action could have a material
adverse effect on us. The process of obtaining regulatory
approvals and the subsequent substantial compliance with
appropriate federal, state, local, and foreign statutes and
regulations require the expenditure of substantial time and
financial resources.
The process required by the FDA before a drug or biologic may be
marketed in the United States generally involves the following:
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completion of nonclinical laboratory tests according to good
laboratory practice regulations, or GLP; |
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submission of an IND, which must become effective before human
clinical trials may begin; |
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performance of adequate and well-controlled human clinical
trials according to GCP to establish the safety and efficacy of
the proposed drug for its intended use; |
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submission to the FDA of a NDA or BLA; |
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satisfactory completion of an FDA inspection of the
manufacturing facility or facilities at which the product is
produced to assess compliance with cGMP to assure that the
facilities, methods and controls are adequate to preserve the
drugs identity, strength, quality and purity or to meet
standards designed to ensure the biologics continued
safety, purity and potency; and |
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FDA review and approval of the NDA or BLA. |
Once a pharmaceutical candidate is identified for development it
enters the preclinical testing stage. Preclinical tests include
laboratory evaluations of product chemistry, toxicity and
formulation, as well as animal studies. An IND sponsor must
submit the results of the preclinical tests, together with
manufacturing information and analytical data, to the FDA as
part of the IND. Some preclinical or non-clinical testing may
continue even after the IND is submitted. In addition to
including the results of the
74
preclinical studies, the IND will also include a protocol
detailing, among other things, the objectives of the first phase
of the clinical trial, the parameters to be used in monitoring
safety, and the effectiveness criteria to be evaluated if the
first phase lends itself to an efficacy determination. The IND
automatically becomes effective 30 days after receipt by
the FDA, unless the FDA, within the
30-day time period,
specifically places the clinical trial on clinical hold. In such
a case, the IND sponsor and the FDA must resolve any outstanding
concerns before the clinical trial can begin.
All clinical trials must be conducted under the supervision of
one or more qualified investigators in accordance with GCP.
These regulations include the requirement that all research
subjects provide informed consent. Further, an IRB at each
institution participating in the clinical trial must review and
approve the plan for any clinical trial before it commences at
that institution. Each new clinical protocol must be submitted
to the FDA as part of the IND. Progress reports detailing the
results of the clinical trials must be submitted at least
annually to the FDA and more frequently if serious adverse
events occur.
Human clinical trials are typically conducted in three
sequential phases that may overlap or be combined:
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Phase I: The drug is initially introduced into
healthy human subjects or patients with the disease and tested
for safety, dosage tolerance, pharmacokinetics,
pharmacodynamics, absorption, metabolism, distribution and
excretion. In the case of some products for severe or
life-threatening diseases, especially when the product may be
too inherently toxic to ethically administer to healthy
volunteers, the initial human testing is often conducted in
patients. |
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Phase II: Involves studies in a limited patient
population to identify possible adverse effects and safety
risks, to preliminarily evaluate the efficacy of the product for
specific targeted diseases and to determine dosage tolerance and
optimal dosage. |
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Phase III: Clinical trials are undertaken to further
evaluate dosage, clinical efficacy and safety in an expanded
patient population at geographically dispersed clinical study
sites. These studies are intended to establish the overall
risk-benefit ratio of the product and provide, if appropriate,
an adequate basis for product labeling. |
Phase I, Phase II and Phase III testing may not
be completed successfully within any specified period, if at
all. The FDA or an IRB or the sponsor may suspend a clinical
trial at any time on various grounds, including a finding that
the research subjects or patients are being exposed to an
unacceptable health risk.
Concurrent with clinical trials, companies usually complete
additional animal studies and must also must develop additional
information about the chemistry and physical characteristics of
the drug and finalize a process for manufacturing the product in
accordance with cGMP requirements. The manufacturing process
must be capable of consistently producing quality batches of the
product candidate and the manufacturer must develop methods for
testing the quality, purity and potency of the final drugs.
Additionally, appropriate packaging must be selected and tested
and stability studies must be conducted to demonstrate that the
product candidate does not undergo unacceptable deterioration
over its shelf-life.
The results of product development, preclinical studies and
clinical studies, along with descriptions of the manufacturing
process, analytical tests conducted on the chemistry of the
drug, results of chemical studies and other relevant information
are submitted to the FDA as part of an NDA or BLA requesting
approval to market the product. The submission of an NDA or BLA
is subject to the payment of user fees, but a waiver of such
fees may be obtained under specified circumstances. The FDA
reviews all NDAs and BLAs submitted before it accepts them for
filing. It may request additional information rather than accept
an NDA or BLA for filing. In this event, the NDA or BLA must be
resubmitted with the additional information. The resubmitted
application also is subject to review before the FDA accepts it
for filing.
Once the submission is accepted for filing, the FDA begins an
in-depth review. The FDA may refuse to approve an NDA or BLA if
the applicable regulatory criteria are not satisfied or may
require
75
additional clinical or other data. Even if such data is
submitted, the FDA may ultimately decide that the NDA or BLA
does not satisfy the criteria for approval. The FDA reviews an
NDA to determine, among other things, whether a product is safe
and effective for its intended use and whether its manufacture
is cGMP-compliant to assure and preserve the products
identity, strength, quality and purity. The FDA reviews a BLA to
determine, among other things whether the product is safe, pure
and potent and the facility in which it is manufactured,
processed, packed or held meets standards designed to assure the
products continued safety, purity and potency. Before
approving an NDA or BLA, the FDA will inspect the facility or
facilities where the product is manufactured and tested.
Satisfaction of FDA requirements or similar requirements of
state, local and foreign regulatory authorities typically takes
at least several years and the actual time required may vary
substantially, based upon, among other things, the type,
complexity and novelty of the product or disease. Government
regulation may delay or prevent marketing of potential products
for a considerable period of time and impose costly procedures
upon our activities. Success in early stage clinical trials does
not assure success in later stage clinical trials. Data obtained
from clinical activities are not always conclusive and may be
susceptible to varying interpretations, which could delay, limit
or prevent regulatory approval. The FDA may not grant approval
on a timely basis, or at all. Even if a product receives
regulatory approval, the approval may be significantly limited
to specific diseases and dosages or the indications for use may
otherwise be limited which could restrict the commercial
application of the products. Further, even after regulatory
approval is obtained, later discovery of previously unknown
problems with a product may result in restrictions on the
product or even complete withdrawal of the product from the
market. Delays in obtaining, or failures to obtain regulatory
approvals for any drug candidate could substantially harm our
business and cause our stock price to drop significantly. In
addition, we cannot predict what adverse governmental
regulations may arise from future United States or foreign
governmental action.
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Section 505(b)(2) Applications |
Section 505 of the FDCA describes two types of NDAs. They
are (1) an application that contains full reports of
investigations of safety and effectiveness, or a
section 505(b)(1) application, and (2) an application
that contains full reports of investigations of safety and
effectiveness but where at least some of the information
required for approval comes from studies not conducted by or for
the applicant and the applicant has not obtained a right of
reference to such information, or a section 505(b)(2)
application.
A section 505(b)(2) application route may be appropriate
for a drug when some part of the data required for approval is
derived from studies that the applicant did not perform and to
which it has not obtained a right of reference or when the
applicant intends to modify specified characteristics of a
previously approved drug, such as the addition of a new
indication or introduction of a new dosage form, and where
studies other than bioavailability or bioequivalence are
essential to the approval of the changes. Rather than having to
redo studies that had been performed by the developer of the
previously approved, or listed drug, a section 505(b)(2)
applicant may rely on published literature and the FDAs
finding of safety and effectiveness for the listed drug. A
section 505(b)(2) application may be granted three years of
marketing exclusivity if one or more of the clinical
investigations that the applicant performed, other than
bioavailability or bioequivalence studies, was essential to
approval; it may be granted five years of exclusivity if it is
for a new chemical entity, and it may also be eligible for
orphan drug exclusivity or pediatric exclusivity. The filing or
approval of a 505(b)(2) application, however, may be delayed due
to patent or exclusivity protections covering the listed product.
We believe that ALTU-238 may be a candidate for the
section 505(b)(2) application route because the FDA has
already approved a number of NDAs for hGH, and the FDA has
publicly acknowledged the safety and effectiveness of hGH.
However, the availability of the section 505(b)(2)
application route to ALTU-238 is unclear, in part because,
unlike most other drugs regulated under the FDCA, hGH is a
biologic. The FDA has informed us that the FDA has not approved
any growth hormone under section 505(b)(2) and the
standards of evidence to support such an approval have not been
officially established. In addition, in September 2005 Sandoz
filed a lawsuit in federal district court
76
against the FDA seeking a ruling that the FDA act on
Sandozs pending NDA submitted under section 505(b)(2)
of the FDCA for its human growth hormone product, Omnitrope.
Sandoz submitted its NDA for Omnitrope in July 2003, and
received a letter from the FDA dated August 31, 2004 in
which the FDA indicated that it was unable at that time to reach
a decision on the approvability of the application because of
unspecified unresolved scientific and legal issues. No action
has been taken by the FDA since that time, although Sandoz
claims that the FDA informally confirmed that the FDA had
completed its review and that Sandoz had answered all
information requests to the FDAs satisfaction. In its
complaint, Sandoz alleges that the FDAs failure to perform
its non-discretionary statutory duty to either approve or refuse
to approve a fully FDA-reviewed NDA violates the FDCA and the
Administrative Procedure Act. Sandoz requested, among other
things, that the court enter an order setting aside or causing
the FDA to treat the August 31, 2004 letter as an approval
and to enter a declaratory judgment that section 505(b)(2)
may be used for protein-based biologic drugs regulated under
section 505 of the FDCA. We cannot predict when or how the
court will respond to this lawsuit or whether the FDA will
voluntarily change its policy with respect to the availability
of the 505(b)(2) route to Sandoz for Omnitrope or to any other
company for its hGH.
Expedited Review and Approval
The FDA has various programs, including fast track, priority
review and accelerated approval, that are intended to expedite
or simplify the process for reviewing drugs and provide for
approval on the basis of surrogate endpoints. Even if a drug
qualifies for one or more of these programs, the FDA may later
decide that the drug no longer meets the conditions for
qualification or that the time period for FDA review or approval
will be shortened. Generally, drugs that may be eligible for
these programs are those for serious or life-threatening
conditions, those with the potential to address unmet medical
needs, and those that offer meaningful benefits over existing
treatments. Fast track designation applies to the combination of
the product and the specific indication for which it is being
studied. Although fast track and priority review do not affect
the standards for approval, the FDA will attempt to facilitate
early and frequent meetings with a sponsor of a fast-track
designated drug and expedite review of the application for a
drug designated for priority review. Drugs that receive an
accelerated approval may be approved on the basis of adequate
and well-controlled clinical trials establishing that the drug
product has an effect on a surrogate endpoint that is reasonably
likely to predict clinical benefit or on the basis of an effect
on a clinical endpoint other than survival or irreversible
morbidity. As a condition of approval, the FDA may require that
a sponsor of a drug receiving accelerated approval perform
post-marketing clinical trials.
Continuous Marketing Applications Pilot 2
In conjunction with the reauthorization of the Prescription Drug
User Fee Act of 1992, or PDUFA, the FDA agreed to meet specific
performance goals, one of which was to conduct pilot programs to
explore CMAs. Under one of the CMA pilot programs called
Pilot 2, one fast-track designated product from each review
division of CDER and CBER is selected for frequent scientific
feedback and interactions with the FDA, with a goal of improving
the efficiency and effectiveness of the drug development
process. In order to be eligible for participation, the drug or
biologic must (1) have been designated fast track,
(2) have been the subject of an
end-of-Phase I
meeting or another type of meeting that FDA determines is
equivalent, and (3) not be on clinical hold. Applicants
must make a formal application as described in an FDA Guidance
on the subject and will be evaluated based on the FDAs
overall assessment of:
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the potential value of enhanced interaction, emphasizing the
potential public health benefit resulting from development of
the product; |
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the likelihood that concentrated scientific dialogue will
facilitate the availability of a promising novel
therapy; and |
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the applicants demonstration of commitment to product
development as evidenced by a thorough consideration of the
rationale for participation in Pilot 2. |
77
A maximum of one fast-track product per review division in CDER
and CBER will be chosen to participate.
Once an applicant is selected for participation in Pilot 2, the
review division and the applicant will finalize an agreement on
the nature of the timelines for feedback and interactions
between the applicant and the FDA. Pilot 2 agreements and
activities for each application will continue through
September 30, 2007, the pilot program completion date,
unless (1) an NDA or BLA is submitted, (2) the
applicant withdraws the product from the pilot program, or
(3) the agreement is terminated by the FDA because the drug
or biologic no longer meets the pre-application criteria or the
applicant deviates significantly from the negotiated
developmental plan or has other significant disagreements with
FDA.
In November 2003, ALTU-135 was granted a fast track designation
for treatment of malabsorption in patients with partial or
complete exocrine pancreatic insufficiency. In February 2004,
ALTU-135 was accepted into the Pilot 2 program pending
agreement on a schedule of interactions with the FDA.
Under the Orphan Drug Act, the FDA may grant orphan drug
designation to drugs intended to treat a rare disease or
condition, which is generally a disease or condition that
affects fewer than 200,000 individuals in the United
States, or more than 200,000 individuals in the United States
and for which there is no reasonable expectation that the cost
of developing and making available in the United States a drug
for this type of disease or condition will be recovered from
sales in the United States for that drug. Orphan drug
designation must be requested before submitting an NDA. After
the FDA grants orphan drug designation, the identity of the
therapeutic agent and its potential orphan use are disclosed
publicly by the FDA. Orphan drug designation does not convey any
advantage in or shorten the duration of the regulatory review
and approval process.
If a product that has orphan drug designation subsequently
receives the first FDA approval for the disease for which it has
such designation, the product is entitled to orphan product
exclusivity, which means that the FDA may not approve any other
applications to market the same drug for the same indication,
except in very limited circumstances, for seven years. Orphan
drug exclusivity, however, also could block the approval of one
of our products for seven years if a competitor obtains approval
of the same drug as defined by the FDA or if our product
candidate is determined to be contained within the
competitors product for the same indication or disease.
We obtained orphan drug designation for ALTU-135 and intend to
file for orphan drug designation for our other product
candidates that meet the criteria for orphan designation. We may
not be awarded orphan exclusivity for any of our product
candidates or indications. In addition, obtaining FDA approval
to market a product with orphan drug exclusivity may not provide
us with a material commercial advantage.
The FDA Modernization Act of 1997 included a pediatric
exclusivity provision that was extended by the Best
Pharmaceuticals for Children Act of 2002. Pediatric exclusivity
is designed to provide an incentive to manufacturers for
conducting research about the safety of their products in
children. Pediatric exclusivity, if granted, provides an
additional six months of market exclusivity in the United States
for new or currently marketed drugs. Under Section 505A of
the FDCA, six months of market exclusivity may be granted in
exchange for the voluntary completion of pediatric studies in
accordance with an FDA-issued Written Request. The
FDA may not issue a Written Request for studies on unapproved or
approved indications where it determines that information
relating to the use of a drug in a pediatric population, or part
of the pediatric population, may not produce health benefits in
that population.
We have not requested or received a Written Request for such
pediatric studies, although we may ask the FDA to issue a
Written Request for such studies in the future. To receive the
six-month pediatric market exclusivity, we would have to receive
a Written Request from the FDA, conduct the requested
78
studies, and submit reports of the studies in accordance with a
written agreement with the FDA or, if there is no written
agreement, in accordance with commonly accepted scientific
principles. The FDA may not issue a Written Request for such
studies if we ask for one, and it may not accept the reports of
the studies. The current pediatric exclusivity provision is
scheduled to end on October 1, 2007, and it may not be
reauthorized.
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FDA Policy on Drugs to Treat Exocrine Pancreatic
Insufficiency |
Drugs to treat exocrine pancreatic insufficiency have been
marketed in the United States since before the passage of the
FDCA in 1938. Most of these drugs were available as over the
counter, or OTC, drug products. As part of an OTC drug review,
and over the period that stretched from 1979 to 1991, the FDA
evaluated the safety and effectiveness of drug products used to
treat exocrine pancreatic insufficiency. In July 1991, the FDA
announced that it had concluded that all exocrine pancreatic
insufficiency drug products, whether marketed on an OTC or a
prescription basis, were new drugs for which an approved
application would be required for marketing. On April 28,
2004, the FDA published a notice in the Federal Register
reiterating its determination that all pancreatic extract drug
products are new drugs requiring an approved NDA for marketing,
indicating that they should be marketed as prescription drugs
only, and stating that after April 28, 2008, any
prescription exocrine pancreatic insufficiency drug product
being marketed without an approved NDA will be subject to
regulatory action.
In April 2004, the FDA also issued for comment a draft guidance
titled Guidance for Industry Exocrine Pancreatic Drug
Products Submitting NDAs, also termed the PEP
Guidance. A number of manufacturers of these products or the
components of these products submitted comments, but final
guidance has not yet been issued by the FDA. The PEP Guidance,
if and when finalized, will represent the FDAs then
current thinking on the topic, but will not bind the FDA or any
other person. An alternative approach may be used to submit an
NDA if the approach satisfies the requirements of the applicable
law and regulations. The FDA has approved an NDA for only one
pancreatic enzyme product, although the product is not currently
on the market.
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Post-Approval Requirements |
Once an approval is granted, the FDA may withdraw the approval
if compliance with regulatory standards is not maintained or if
problems occur after the product reaches the market. After
approval, some types of changes to the approved product, such as
adding new indications, manufacturing changes and additional
labeling claims, are subject to further FDA review and approval.
In addition, the FDA may require testing and surveillance
programs to monitor the effect of approved products that have
been commercialized, and the FDA has the power to prevent or
limit further marketing of a product based on the results of
these post-marketing programs.
Any drug products manufactured or distributed by us pursuant to
FDA approvals are subject to continuing regulation by the FDA,
including, among other things:
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record-keeping requirements; |
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reporting of adverse experiences with the drug; |
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providing the FDA with updated safety and efficacy information; |
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drug sampling and distribution requirements; |
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notifying the FDA and gaining its approval of specified
manufacturing or labeling changes; |
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complying with certain electronic records and signature
requirements; and |
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complying with FDA promotion and advertising requirements. |
Drug manufacturers and their subcontractors are required to
register their manufacturing facilities with the FDA and some
state agencies, and are subject to periodic unannounced
inspections by the FDA and some state agencies for compliance
with cGMP and other laws.
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We rely, and expect to continue to rely, on third parties for
the production of clinical and commercial quantities of our
products. Future FDA and state inspections may identify
compliance issues at the facilities of our contract
manufacturers that may disrupt production or distribution, or
require substantial resources to correct.
From time to time, legislation is drafted, introduced and passed
in Congress that could significantly change the statutory
provisions governing the approval, manufacturing and marketing
of products regulated by the FDA. In addition, FDA regulations
and guidance are often revised or reinterpreted by the agency in
ways that may significantly affect our business and our
products. It is impossible to predict whether legislative
changes will be enacted, or FDA regulations, guidance or
interpretations changed or what the impact of such changes, if
any, may be.
Foreign
Regulation
In addition to regulations in the Untied States, we will be
subject to a variety of foreign regulations governing clinical
trials and commercial sale and distribution of our products.
Whether or not we obtain FDA approval for a product, we must
obtain approval by the comparable regulatory authorities of
foreign countries before we can commence clinical trials or
marketing of the product in those countries. The approval
process varies from country to country and the time may be
longer or shorter than that required for FDA approval. The
requirements governing the conduct of clinical trials, product
licensing, pricing and reimbursement vary greatly from country
to country.
Under European Union regulatory systems, we may submit marketing
authorization applications either under a centralized or
decentralized procedure. The centralized procedure, which is
compulsory for medicines produced by biotechnology and optional
for those which are highly innovative, provides for the grant of
a single marketing authorization that is valid for all European
Union member states. The decentralized procedure provides for
mutual recognition of national approval decisions. Under this
procedure, the holder of a national marketing authorization may
submit an application to the remaining member states. Within
90 days of receiving the applications and assessments
report each member state must decide whether to recognize
approval. If a member state does not recognize the marketing
authorization, the disputed points are eventually referred to
the European Commission, whose decision is binding on all member
states.
As in the United States, we may apply for designation of our
products as orphan drugs for the treatment of specific
indications in the European Union before the application for
marketing authorization is made. Orphan drugs in the European
Union enjoy economic and marketing benefits, including a
10-year market
exclusivity period for the approved indication, but not for the
same drug, unless another applicant can show that its product is
safer, more effective or otherwise clinically superior to the
orphan-designated product.
Reimbursement
Sales of biopharmaceutical products depend in significant part
on the availability of third-party reimbursement. We anticipate
third-party payors will provide reimbursement for our products.
It will be time consuming and expensive for us to seek
reimbursement from third-party payors. Reimbursement may not be
available or sufficient to allow us to sell our products on a
competitive and profitable basis.
The passage of the Medicare Prescription Drug and Modernization
Act of 2003, or the MMA, imposes new requirements for the
distribution and pricing of prescription drugs for Medicare
beneficiaries, which may affect the marketing of our products.
The MMA also introduced a new reimbursement methodology, part of
which went into effect in 2004. It is not clear what effect the
MMA will have on the prices paid for currently approved drugs
and the pricing options for new drugs approved after
January 1, 2006. Moreover, while the MMA applies only to
drug benefits for Medicare beneficiaries, private payors often
follow Medicare coverage policy and payment limitations in
setting their own payment rates. Any reduction in payment that
results from the MMA may result in a similar reduction in
payments from non-governmental payors.
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In addition, in some foreign countries, the proposed pricing for
a drug must be approved before it may be lawfully marketed. The
requirements governing drug pricing vary widely from country to
country. For example, the European Union provides options for
its member states to restrict the range of medicinal products
for which their national health insurance systems provide
reimbursement and to control the prices of medicinal products
for human use. A member state may approve a specific price for
the medicinal product or it may instead adopt a system of direct
or indirect controls on the profitability of the company placing
the medicinal product on the market.
We expect that there will continue to be a number of federal and
state proposals to implement governmental pricing controls.
While we cannot predict whether such legislative or regulatory
proposals will be adopted, the adoption of such proposals could
have a material adverse effect on our business, financial
condition and profitability.
Facilities
As of December 31, 2005 we leased or subleased a total of
approximately 55,250 square feet of office and laboratory
space. The leased and subleased properties are described below:
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625 Putnam Avenue, Cambridge, MA
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15,750 |
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Laboratory and Office |
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618 Putnam Avenue, Cambridge, MA
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3,000 |
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Laboratory |
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125 Sidney Street, Cambridge, MA
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20,500 |
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Laboratory and Office |
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195 Albany Street, Cambridge, MA
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16,000 |
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Laboratory and Office |
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12/31/08 |
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We believe that these facilities are adequate to meet our
current needs, although we are presently considering options to
consolidate our facilities. We believe that if additional space
is needed in the future, such space will be available on
commercially reasonable terms as needed.
Employees
We believe that our success will depend greatly on our ability
to identify, attract and retain capable employees. As of
December 31, 2005, we had 102 employees, of whom 26
hold Ph.D. or M.D. degrees. 72 of our employees are primarily
engaged in research and development activities, and 30 are
primarily engaged in general and administrative activities. We
believe that relations with our employees are good. None of our
employees is represented under a collective bargaining agreement.
Legal Proceedings
We are not currently a party to any material legal proceedings.
81
MANAGEMENT
Executive Officers and Directors
Our executive officers and directors and their respective ages
and positions are as follows:
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Position |
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Sheldon Berkle
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60 |
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President and Chief Executive Officer; Director |
Don G. Burstyn, Ph.D.
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51 |
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Vice President, Regulatory Affairs and Quality Assurance |
Richard D. Forrest, Esq.
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38 |
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Corporate Counsel and Secretary |
Robert Gallotto
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40 |
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Vice President, Strategic Planning and Alliance Management |
Alan Kimura, M.D., Ph.D.
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51 |
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Vice President, Clinical Development and Medical Affairs |
Gerhard F. Klement
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53 |
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Vice President, Manufacturing and Technical Operations |
Jonathan I. Lieber
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36 |
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Vice President, Chief Financial Officer and Treasurer |
Alexey L. Margolin, Ph.D.
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53 |
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Chief Scientific Officer |
John P. Richard(1)
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48 |
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Chairman of the Board |
Richard H. Aldrich(2)
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51 |
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Director |
Lynne H. Brum(3)
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41 |
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Director |
Stewart Hen(2)(3)
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38 |
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Director |
Peter L. Lanciano
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49 |
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Director |
Jonathan S. Leff(1)
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37 |
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Director |
Manuel A. Navia, Ph.D.(2)(3)
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59 |
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Director |
Jonathan D. Root, M.D.(1)(2)
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45 |
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Director |
Michael S. Wyzga(1)
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50 |
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Director |
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Member of the Audit Committee. |
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Member of the Compensation Committee. |
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Member of the Nominating and Governance Committee. |
The following is a brief summary of the background of each of
our executive officers and directors.
Sheldon Berkle joined Altus as our President and Chief
Executive Officer in May 2005 and was elected as a member
of our board of directors. Prior to joining us, Mr. Berkle
served as Executive Vice President of Boehringer Ingelheim
Pharmaceuticals Inc. from November 1994 to December 2003. In
this position, Mr. Berkle was responsible for United States
pharmaceutical operations, including portfolio management, new
product launches, commercialization, marketing, sales, business
development, mergers and acquisitions, strategic planning and
alliance management. Mr. Berkle was also a co-founder of
Boehringer Ingelheim Canada, a pharmaceutical company, and
served as its Chief Executive Officer from 1989 to 1994. From
January 2004 to April 2005, Mr. Berkle was not actively
employed. Mr. Berkle holds a B.Sc. in pharmacy from the
University of Manitoba and an M.B.A. from the University of
Toronto.
Don G. Burstyn, Ph.D. has served as our Vice
President, Regulatory Affairs and Quality Assurance since July
2004. Dr. Burstyn currently represents the Biotechnology
Industry Organization on the Product Quality Research Institute
Steering Committee. Before joining us, Dr. Burstyn served
as Vice President of Regulatory Affairs for Alkermes, Inc., a
biotechnology company, from December 1993 to March 2004, where
he was responsible for leading that companys activities
related to the approvals of Nutropin Depot and Risperdal Consta.
From 1987 to 1993, Dr. Burstyn held various management
positions at Biogen, Inc., including Director of Quality and
Director of Development Operations. Dr. Burstyn worked from
1979 to 1987 as a microbiologist at the FDA. He was awarded an
FDA Award of Merit in 1985 and an FDA Group Recognition Award in
1991. Dr. Burstyn holds a B.S., an M.S. and a Ph.D. in
82
microbiology from the University of Maryland, where he received
the Isabel R. McDonald Memorial Award in 1979.
Richard D. Forrest, Esq. has served as our Corporate
Counsel and Secretary since May 2002. From September 1995 to
April 2002, Mr. Forrest was a corporate lawyer with Testa,
Hurwitz & Thibeault, a law firm, where he represented
private and public technology companies, investment banks and
venture capital funds in a variety of transactions. Prior to
attending law school, Mr. Forrest was an electrical
engineer with Hewlett-Packards medical products group.
Mr. Forrest received his J.D. from Harvard Law School and
received a B.S. in electrical engineering and a B.A. in
philosophy from Cornell University.
Robert Gallotto currently serves as our Vice President,
Strategic Planning and Alliance Management. From January 2003
through December 2005, Mr. Gallotto served as our Vice
President, Commercial Development and Alliance Management.
Mr. Gallotto joined us in July 2001 as Director of
Commercial Development where he was responsible for marketing,
product planning and business development. Before joining us,
Mr. Gallotto served as Vice President of Marketing and
Business Development at Sage BioPharma, Inc., a pharmaceutical
company, from August 1999 to June 2001. From January 1996 to
July 1999, Mr. Gallotto served in various positions at
Serono, Inc. and Biogen, Inc., where he was responsible for
overall brand positioning, product launch planning, strategic
planning and key alliance management for a portfolio of drugs
including Gonal-F and Avonex. From 1987 to 1995,
Mr. Gallotto served in various positions in sales,
marketing and managed healthcare with The Upjohn Company.
Mr. Gallotto received a B.S. in biology from Stonehill
College.
Alan Kimura, M.D., Ph.D. has served as our Vice
President, Clinical Development and Medical Affairs since May
2005. Prior to joining us, Dr. Kimura was Executive
Director, Clinical Affairs at Transkaryotic Therapies, Inc., a
pharmaceutical company, from June 2001 to May 2005, where he was
involved in the clinical development of protein-based therapies
for rare genetic diseases. Before joining Transkaryotic
Therapies, Dr. Kimura was the Director of Clinical
Development at Biochem Pharma, Inc., a pharmaceutical company,
from July 1999 to June 2001. Prior to that, Dr. Kimura held
various positions in clinical research and medical affairs at
SmithKline Beecham Biologicals S.A. and the Wyeth-Lederle
Vaccines division of American Home Products Corporation.
Dr. Kimura also held bacteriology research positions in the
research departments of the Praxis Biologicals and Lederle
Biologicals divisions of American Cyanamid Company.
Dr. Kimura received his M.D. from the University of Miami
School of Medicine. He received a Ph.D. and M.S. in microbiology
from the University of California, Davis and a B.A. in
bacteriology from the University of California, Berkeley.
Gerhard F. Klement has served as our Vice President,
Manufacturing and Technical Operations since November 2005.
Prior to joining us, from June 2005 to October 2005,
Mr. Klement served as Chief Technology Officer for the
worldwide Biologics and Chemicals Group at Lonza Biologics, a
contract manufacturer, where he was responsible for new
technologies and business development. From 2003 to June 2005,
Mr. Klement was the Head of Operations, USA and Chief
Operating Officer Biopharmaceuticals, Worldwide at Lonza
Biologics. In 2002, Mr. Klement was a self-employed
consultant. From 1994 to 2002, Mr. Klement held various
positions in manufacturing and engineering at Serono, Inc., a
biotechnology company. Mr. Klement holds a B.Sc. from the
University of Agriculture in Vienna, Austria. He received
executive training in general management and leadership from
IMD International Institute for Management
Development in Lausanne, Switzerland and Babson College.
Jonathan I. Lieber currently serves as our Vice
President, Chief Financial Officer and Treasurer.
Mr. Lieber joined us in July 2002 as our Vice President,
Finance. From 1998 to June 2002, Mr. Lieber was a member of
SG Cowens Health Care Investment Banking Group, most
recently as a vice president focused on the biotechnology and
specialty pharmaceuticals sectors. Prior to joining SG Cowen,
Mr. Lieber was a member of the Health Care and High Yield
Groups at Salomon Brothers Inc. Mr. Lieber received an
M.B.A. in finance from the Stern School of Business of New York
University and a B.Sc. in business administration from Boston
University.
Alexey L. Margolin, Ph.D. has served as our Chief
Scientific Officer since August 2004. He served as our Vice
President of Science from 1996 to 2004 and as our Director of
Research from 1993 to 1996.
83
Prior to joining us, Dr. Margolin was responsible for
biocatalysis activities on a global basis at Merrell Dow
Research Institute. From 1986 to 1988, he worked at the
Massachusetts Institute of Technology on enzyme-catalyzed
processes. In 2003, Dr. Margolin was elected a fellow of
the American Institute of Medicine and Biological Engineering.
Dr. Margolin received his M.S. in chemistry and Ph.D. in
bio-organic chemistry from Moscow University.
John P. Richard has served as chairman of our board of
directors since October 2004. Mr. Richard has served as an
independent strategic and commercial development advisor in the
biotechnology industry since April 1999. He currently serves as
Senior Business Advisor to GPC Biotech AG, a biotechnology
company, as a partner of Georgia Venture Partners, a
biotechnology investing firm, and as a consultant to Nomura
Phase4 Ventures. He also serves as a director of Targacept,
Inc., Zygogen, LLC, and Metastatix, Inc. Mr. Richard was
previously Executive Vice President, Business Development at
SEQUUS Pharmaceuticals, Inc., where he was responsible for
negotiating the acquisition of SEQUUS by ALZA Corporation. Prior
to joining SEQUUS, Mr. Richard held the positions of Vice
President, Corporate Development for VIVUS, Inc. and Senior Vice
President, Business Development of Genome Therapeutics
Corporation, where he was responsible for establishing numerous
pharmaceutical alliances. He was also co-founder and original
Chief Executive Officer of IMPATH Laboratories, Inc., a leading
cancer pathology reference laboratory in the United States.
Mr. Richard received his M.B.A. from Harvard Business
School and his B.S. from Stanford University.
Richard H. Aldrich has served as a member of our board of
directors since October 2001. Since May 2001, Mr. Aldrich
has headed RA Capital LLC, a biotechnology investment firm.
From June 1989 to January 2001, he served as the Senior Vice
President and Chief Business Officer at Vertex, a biotechnology
company. Prior to joining Vertex, he headed business development
at Integrated Genetics from January 1988 to June 1989. From June
1982 to January 1988, he held several managerial positions at
Biogen, Inc. Mr. Aldrich currently serves on the board of
directors of Combinatorx, Inc. and Sirtris Pharmaceuticals, Inc.
Mr. Aldrich received a B.S. in management from Boston
College and an M.B.A. from Dartmouth Colleges Amos Tuck
School of Business Administration.
Lynne H. Brum has served as a member of our board of
directors since January 2004. Ms. Brum has served as
Vertexs Vice President of Corporate Communications and
Financial Planning since September 1994. In this capacity, she
leads Vertexs financial planning group as well as its
corporate communications, investor relations and media relations
programs. Ms. Brum has also been an executive officer of
Vertex and a member of the senior management team since August
2001. Prior to joining Vertex in 1994, Ms. Brum served as a
vice president at Feinstein Kean Healthcare, a communications
and business consulting firm. Prior to that, Ms. Brum held
corporate communications and research positions at Biogen, Inc.
Ms. Brum holds an M.B.A. from the Simmons Graduate School
of Management and a B.A. in biological sciences from Wellesley
College.
Stewart Hen has served as a member of our board of
directors since May 2004. Mr. Hen has been with Warburg
Pincus LLC, a venture capital and private equity firm, since May
2000 and is currently a managing director, where he focuses on
investments in the life sciences sector, including
biotechnology, pharmaceuticals, specialty pharmaceuticals, drug
delivery and diagnostics. Prior to joining Warburg Pincus, he
was a management consultant at McKinsey & Company,
where he advised pharmaceutical and biotechnology companies on a
range of strategic management issues. Prior to joining McKinsey,
he worked at Merck in research and development and
manufacturing. Mr. Hen is also a director of Allos
Therapeutics, Inc. and Neurogen Corporation. Mr. Hen holds
an M.B.A. from The Wharton School at the University of
Pennsylvania, an M.S. in chemical engineering from the
Massachusetts Institute of Technology and a B.S. in chemical
engineering from the University of Delaware.
Peter L. Lanciano is one of our founders and has served
as a member of our board of directors since 1995.
Mr. Lanciano worked with us from our founding in 1992 until
October 2004, most recently as President and Chief Executive
Officer from 1999 until October 2004. Mr. Lanciano also
served as Vice Chairman of our board of directors from October
2004 to October 2005. Prior to joining us, Mr. Lanciano was
President and Director of IG Laboratories Inc., which he founded
in 1988 in conjunction with a group
84
of scientists from Integrated Genetics Inc. Prior to his role at
IG Laboratories, Mr. Lanciano served as Corporate
Controller for Integrated Genetics and Gene-Trak Systems.
Mr. Lanciano holds B.S. degrees in both finance and
information systems design from Bentley College and is a
Certified Public Accountant.
Jonathan S. Leff has served as a member of our board of
directors since May 2004. Mr. Leff has been a managing
director at Warburg Pincus LLC since January 2000. Mr. Leff
is responsible for Warburg Pincus North American
investment activities in biotechnology, pharmaceuticals and
related industries. Prior to joining Warburg Pincus,
Mr. Leff was a consultant at Oliver, Wyman & Co.
Mr. Leff is a director of Allos Therapeutics, Inc.,
Neurogen Corporation, InterMune, Inc., Sunesis Pharmaceuticals,
Inc. and ZymoGenetics, Inc. Mr. Leff received an A.B. in
government from Harvard College and an M.B.A. from Stanford
University.
Manuel A. Navia, Ph.D. is one of our founders and
has served as a member of our board of directors since 1992. He
is also a member of our scientific advisory board.
Dr. Navia is a drug discovery and development advisor in
the Boston area. Since March 2004, Dr. Navia has been an
Executive-in-Residence
at Oxford Bioscience Partners, a venture capital firm. In
addition, since March 2003, Dr. Navia has served as an
advisor and consultant to various companies in the biotechnology
industry. Prior to that time, from January 2001 to March 2003,
Dr. Navia was Executive Vice President for Research at
Essential Therapeutics, Inc., a biotechnology company. He was a
founder of The Althexis Company, Inc. in 1997, and served as its
President and Chief Executive Officer until January 2001, when
it merged with Microcide Pharmaceuticals Inc. to
form Essential Therapeutics. From 1989 to 1997,
Dr. Navia served as Vice President and Senior Scientist at
Vertex. Dr. Navia holds a Ph.D. and an M.S. in biophysics
from the University of Chicago and a B.A. in physics from New
York University.
Jonathan D. Root, M.D. has served as a member of our
board of directors since September 2001. Having joined
U.S. Venture Partners, a venture capital firm, in July
1995, Dr. Root is presently a general partner and focuses
on investments in therapeutic medical devices, diagnostics, drug
discovery tools and services, and biopharmaceutical development.
Prior to joining U.S. Venture Partners, Dr. Root spent
nine years in clinical practice, most recently on the faculty
and clinical staff at The New York Hospital-Cornell Medical
Center in New York City, where he was an Assistant Professor of
Neurology and Director of the Neurology-Neurosurgery Special
Care Unit. Dr. Root holds an A.B. in economics/government
from Dartmouth College, an M.D. from the University of Florida
College of Medicine, and an M.B.A. from Columbia University.
Michael S. Wyzga has served as a member of our board of
directors since May 2004. Mr. Wyzga is Executive Vice
President and Chief Financial Officer of Genzyme Corporation, a
biotechnology company. Mr. Wyzga joined Genzyme Corp. as
Vice President and Corporate Controller in March 1998, was
promoted to Senior Vice President and Corporate Controller in
December 1998, and to Chief Financial Officer in June 1999.
Mr. Wyzga became an Executive Vice President of Genzyme
Corp. in June 2003 and is responsible for its global financial
reporting. Prior to joining Genzyme, Mr. Wyzga was Chief
Financial Officer for Sovereign Hill Software, Inc. Prior to his
role at Sovereign Hill Software, Mr. Wyzga was the Chief
Financial Officer for CacheLink Corporation, and prior to that,
Mr. Wyzga held various management positions at Lotus
Development Corporation, including Vice President of Finance and
Director of Plans and Controls. Prior to joining Lotus,
Mr. Wyzga held management positions at Digital Equipment
Corporation. Mr. Wyzga received an M.B.A. in business
administration from Providence College and a B.S. in business
administration from Suffolk University.
Board Composition
Our restated certificate of incorporation and restated bylaws
provide that the authorized number of directors may be changed
only by resolution of the board of directors. Ten directors are
currently authorized. In accordance with our restated
certificate of incorporation, immediately upon the closing of
this offering, our board of directors will be divided into three
classes with staggered three-year terms. At each annual meeting
of stockholders following the offering, the successors to the
directors whose terms
85
then expire will be elected to serve until the third annual
meeting following the election. At the closing of this offering,
our directors will be divided among the three classes as follows:
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The Class I directors will be Messrs. Aldrich,
Lanciano and Richard, and their terms will expire at the annual
meeting of stockholders to be held in 2006; |
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The Class II directors will be Ms. Brum, Mr. Leff
and Dr. Root, and their terms will expire at the annual
meeting of stockholders to be held in 2007; and |
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The Class III directors will be Dr. Navia and
Messrs. Berkle, Hen and Wyzga, and their terms will expire
at the annual meeting of stockholders to be held in 2008. |
Any additional directorships resulting from an increase in the
number of directors will be distributed among the three classes
so that, as nearly as possible, each class will consist of
one-third of the directors.
After the closing of this offering, entities affiliated with
Warburg Pincus, one of our principal stockholders, are entitled
to designate up to two individuals as candidates to our board of
directors, for so long as Warburg Pincus owns
2,691,935 shares of our common stock, and one individual
for so long as Warburg Pincus owns 1,794,623 shares of our
common stock. We have agreed to nominate and use our reasonable
efforts to cause the election of such candidates. Currently,
Messrs. Hen and Leff are the members of our board of
directors designated by Warburg Pincus.
Committees of the Board of Directors
Our board of directors has an audit committee, a compensation
committee and a nominating and governance committee, each of
which is described below.
Our audit committee is composed of Messrs. Leff, Richard
and Wyzga and Dr. Root, and is authorized to:
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approve and retain the independent registered public accounting
firm to conduct the annual audit of our books and records; |
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review the proposed scope and results of the audit; |
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review and pre-approve the independent registered public
accounting firms audit and non-audit services rendered; |
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approve the audit fees to be paid; |
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review accounting and financial controls with the independent
registered public accounting firm and our financial and
accounting staff; |
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review and approve transactions between us and our directors,
officers and affiliates; |
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recognize and prevent prohibited non-audit services; |
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establish procedures for complaints received by us regarding
accounting matters; |
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oversee internal audit functions; and |
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prepare the report of the audit committee that SEC rules
require to be included in our annual meeting proxy statement. |
The rules of the Nasdaq National Market, or Nasdaq, require that
all members of the audit committee be independent directors, as
defined by the rules of the Nasdaq and the SEC. The Nasdaq rules
also permit a company, such as us, listing on the Nasdaq
National Market in connection with its initial public offering
to have only one member of the audit committee comply with the
independence requirements on the date of listing, provided that
a majority of the members satisfy the requirements within
90 days after listing and all of the members satisfy the
requirements within one year after listing. Currently, our Board
of Directors has determined that Mr. Wyzga satisfies the
independence requirements for service on the audit committee,
and we are seeking other independent directors to join the audit
86
committee prior to the end of the phase-in period referenced
above. Our Board of Directors has also determined that
Mr. Wyzga is an audit committee financial expert as defined
by the SECs rules.
Our compensation committee is composed of Messrs. Aldrich
and Hen, Dr. Navia and Dr. Root, and is authorized to:
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review and recommend the compensation arrangements for
management, including the compensation for our president and
chief executive officer; |
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establish and review general compensation policies, with the
objectives of attracting and retaining superior talent,
rewarding individual performance and achieving our financial
goals; |
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administer our stock incentive plans; and |
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prepare the report of the compensation committee that SEC rules
require to be included in our annual meeting proxy statement. |
Currently, our board of directors has determined that Messrs.
Aldrich and Hen and Dr. Root satisfy the Nasdaq
independence requirements for service on the compensation
committee, and we expect all members to satisfy these
requirements prior to the end of the phase-in period permitted
by Nasdaq.
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Nominating and Governance Committee |
Our nominating and governance committee is composed of
Ms. Brum, Mr. Hen and Dr. Navia, and is
authorized to:
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identify and nominate members of the board of directors; |
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develop and recommend to the board of directors a set of
corporate governance principles applicable to our
company; and |
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oversee the evaluation of the board of directors. |
Currently, our board of directors has determined that
Ms. Brum and Mr. Hen satisfy the Nasdaq independence
requirements for service on the Nominating and Governance
Committee, and we expect that membership of this committee will
be changed to comply with these requirements prior to the end of
the phase-in period permitted by Nasdaq.
Compensation of Directors
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Compensation for Board Service |
Between January 1, 2004 and the date of this prospectus,
our non-employee directors received the following compensation
for service on our board of directors and committees thereof:
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Directors |
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Cash | |
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Stock Options(1) | |
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John P. Richard
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$ |
30,000 |
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102,707 |
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Richard H. Aldrich
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35,000 |
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43,611 |
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Lynne H. Brum
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17,500 |
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Stewart Hen
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15,000 |
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Peter L. Lanciano
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Jonathan S. Leff
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15,000 |
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Manuel A. Navia, Ph.D.
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35,000 |
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43,611 |
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Jonathan D. Root, M.D.
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17,500 |
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Michael S. Wyzga
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45,000 |
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54,514 |
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(1) |
All options have a ten-year term and an exercise price of $3.92
per share, and vest quarterly over four years, except for 42,742
options granted to Mr. Richard, which were fully vested upon
grant, and 5,451 options granted to Mr. Richard, which have
an exercise price of $4.36 per share. In addition, all of these
options may be exercised immediately for shares of restricted
stock, which are subject to a repurchase right by us that lapses
on the same vesting schedule as the options. |
87
The board of directors has adopted the following policy with
respect to compensation of directors to take effect following
this offering. Non-employee directors will receive options to
purchase 17,444 shares of common stock, vesting quarterly
over a four-year period upon initial election to the board, and
options to purchase 8,722 shares, vesting quarterly over a
four-year period, each year thereafter. They will also receive
an annual cash retainer of $20,000. Non-employee directors
serving as chairs of the nominating and governance committee and
the compensation committee will also receive an option to
purchase 4,361 shares of common stock initially and an
option to purchase 2,181 shares each year thereafter, each
vesting quarterly over a four-year period, as well as an annual
cash retainer of $10,000. The non-employee director serving as
the chair of the audit committee will also receive an option to
purchase 4,361 shares of common stock initially and an
option to purchase 2,181 shares each year thereafter, each
vesting quarterly over a four year period, as well as an annual
cash retainer of $12,500. Non-employee directors serving as
members of committees of the board, other than the chairs of
those committees, shall receive an option to purchase
2,181 shares of common stock initially and an option to
purchase 1,090 shares each year thereafter, each vesting
quarterly over a four-year period, as well as an annual cash
retainer of $5,000, for each committee on which such person
serves. Continued vesting of the options granted under the
policy is subject to continued service on the board.
Peter L. Lanciano. We have an agreement with Peter L.
Lanciano, our director and former Chairman of the Board,
President and Chief Executive Officer. Pursuant to the
agreement, effective October 29, 2004, Mr. Lanciano
resigned from his positions as our Chairman of the Board,
President and Chief Executive Officer, as well as from all
committees of our board of directors, and was appointed
Vice-Chairman of our board of directors. Pursuant to the
agreement, Mr. Lanciano provided management transition and
support services through October 31, 2005. In consideration
for his services, Mr. Lanciano received payments at a rate
equal to his most recent monthly base salary in effect prior to
October 29, 2004; received a bonus in 2004 in the amount of
$95,000; benefited from a continuation of vesting of his stock
options during the service term; and during the service term,
participated in our medical insurance plans at our cost. In
2004, Mr. Lanciano earned $56,566 under this agreement. In
November 2005, we amended Mr. Lancianos agreement to
permit him to exercise any of his stock options that had vested
as of October 31, 2005 until the earlier of three months
after he ceases to be a member of our board of directors or
December 31, 2006. In addition, Mr. Lanciano resigned
as Vice Chairman of the Board effective October 31, 2005
but remains a member of our board of directors.
Manuel A. Navia, Ph.D. In 2003, we entered into a
consulting agreement with Dr. Navia, pursuant to which
Dr. Navia, as a scientific founder of ours, agreed to
consult with our scientists, provide direction with respect to
grant funding and develop relationships with potential industry
partners. In 2004, we paid Dr. Navia $20,938 pursuant to
this agreement. Dr. Navia no longer provides such services
to us.
John P. Richard. From October 2004 to June 2005, we had
an arrangement with Mr. Richard, the chairman of our board
of directors, to provide management oversight services during
our search for a chief executive officer. For such services, we
granted him options to purchase 12,212 shares of our
common stock and paid him $24,000 in fees in 2004, and granted
him options to purchase 30,530 shares of our common
stock and paid him $66,000 in fees and $53,250 as a bonus in
2005. All options granted to Mr. Richard under this
arrangement have an exercise price of $3.92 per share, a
ten-year term and were fully vested as of the date of grant.
Pursuant to our 2002 Stock Plan, in the event a merger or other
reorganization event also constitutes a change of control, as
defined in the plan, all options issued to directors, whether or
not employees, shall become exercisable in full immediately
prior to such event.
Compensation Committee Interlocks and Insider
Participation
No member of our compensation committee has at any time been an
employee of ours. None of our executive officers serves as a
member of the board of directors or compensation committee of
any entity that has one or more executive officers serving as a
member of our board of directors or compensation committee.
88
Drs. Root and Navia and Mr. Hen and their affiliates
have participated in transactions with us. For a detailed
description of these transactions, see the
Management Compensation of Directors and
Related Party Transactions sections of this
prospectus.
Executive Compensation
The following summary compensation table sets forth summary
information as to compensation received by our chief executive
officer, our four other most highly compensated executive
officers who were employed by us as of December 31, 2005
and earned more than $100,000 in salary and bonus for the year
ended December 31, 2005, and one additional executive
officer who was not employed by us as of December 31, 2005
but who earned more than $100,000 in salary and bonus for the
year ended December 31, 2005.
Summary Compensation Table
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Long-Term | |
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Compensation | |
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Securities | |
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Name and Principal |
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All Other | |
Position |
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Year | |
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Salary | |
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Bonus | |
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Options(#) | |
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Compensation | |
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Sheldon Berkle,
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2005 |
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$ |
244,615 |
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$ |
153,500 |
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566,943 |
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$ |
10,245 |
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President and Chief Executive Officer(1)
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2004 |
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Don G. Burstyn, Ph.D.,
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2005 |
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256,875 |
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25,000 |
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17,444 |
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10,860 |
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Vice President, Regulatory Affairs and
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2004 |
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120,192 |
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141,736 |
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966 |
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Quality Assurance(2)
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|
|
|
Robert Gallotto,
|
|
|
2005 |
|
|
|
210,000 |
|
|
|
38,000 |
|
|
|
37,069 |
|
|
|
10,729 |
(5) |
|
Vice President, Strategic Planning and
|
|
|
2004 |
|
|
|
200,325 |
|
|
|
40,976 |
|
|
|
28,347 |
|
|
|
10,904 |
(5) |
|
Alliance Management
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Jonathan I. Lieber,
|
|
|
2005 |
|
|
|
206,000 |
|
|
|
38,000 |
|
|
|
21,805 |
|
|
|
10,734 |
(6) |
|
Vice President, Chief Financial Officer and
|
|
|
2004 |
|
|
|
198,430 |
|
|
|
31,000 |
|
|
|
28,347 |
|
|
|
11,089 |
(6) |
|
Treasurer
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Alexey L. Margolin, Ph.D.,
|
|
|
2005 |
|
|
|
271,282 |
|
|
|
67,000 |
|
|
|
34,889 |
|
|
|
10,859 |
(7) |
|
Chief Scientific Officer
|
|
|
2004 |
|
|
|
269,585 |
|
|
|
52.000 |
|
|
|
39,250 |
|
|
|
11,140 |
(7) |
Martin D. Williams,
|
|
|
2005 |
|
|
|
263,039 |
|
|
|
30,000 |
|
|
|
141,735 |
|
|
|
10,755 |
(9) |
|
Former Vice President and Head of
|
|
|
2004 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Corporate Development(8)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(1) |
Sheldon Berkle was appointed our President and Chief Executive
Officer in May 2005. |
|
(2) |
Mr. Burstyn joined the company in July 2004. |
|
(3) |
Represents $9,450 in matching contributions under our 401(k)
plan and $795 in life insurance premiums in 2005. |
|
(4) |
Represents $966 in life insurance premiums in 2004 and $9,450 in
matching contributions under our 401(k) plan and $1,410 in life
insurance premiums in 2005. |
|
(5) |
Represents $9,225 in matching contributions under our 401(k)
plan and $1,679 in life insurance premiums in 2004 and $9,450 in
matching contributions under our 401(k) plan and $1,279 in
life insurance premiums in 2005. |
|
(6) |
Represents $9,225 in matching contributions under our 401(k)
plan and $1,864 in life insurance premiums in 2004 and $9,450 in
matching contributions under our 401(k) plan and $1,284 in
life insurance premiums in 2005. |
|
(7) |
Represents $9,225 in matching contributions under our 401(k)
plan and $1,915 in life insurance premiums in 2004 and $9,450 in
matching contributions under our 401(k) plan and $1,409 in
life insurance premiums in 2005. |
|
(8) |
Mr. Williams was employed by the company from January 2005
through December 2005. |
|
(9) |
Represents $9,450 in matching contributions under our
401(k) plan and $1,305 in life insurance premiums. |
89
Option Grants in Last Fiscal Year
The following table shows information regarding stock options
granted to the executive officers named in the summary
compensation table above during our fiscal year ended
December 31, 2005. Options were granted with an exercise
price per share equal to the fair market value of our common
stock on the date of grant, as determined by our board of
directors. The potential realizable value is based on the
assumption that our common stock appreciates at the annual rate
shown, compounded annually, from the date of grant until the
expiration of the ten-year term of the option. These numbers are
calculated based on SEC requirements and do not reflect
projections or estimates of future stock price growth. Potential
realizable values are computed by:
|
|
|
|
|
multiplying the number of shares of common stock underlying each
option by $15.00 per share, the initial public offering
price per share; |
|
|
|
assuming that the total stock value derived from that
calculation compounds at the annual 5% or 10% rate shown in the
table for the entire ten-year term of the option; and |
|
|
|
subtracting from that result the total option exercise price. |
Actual gains, if any, on stock option exercises will be
dependent on the future performance of the common stock. The
percentage of total options granted is based on an aggregate of
1,512,428 options granted by us to our employees in 2005,
including the executive officers listed in the table below.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Individual Grants | |
|
|
|
|
|
|
|
|
| |
|
|
|
Potential Realizable Value at | |
|
|
Number of | |
|
% of Total | |
|
|
|
|
|
Assumed Annual Rates of | |
|
|
Securities | |
|
Options | |
|
|
|
|
|
Stock Price Appreciation for | |
|
|
Underlying | |
|
Granted to | |
|
Exercise | |
|
|
|
Option Term | |
|
|
Options | |
|
Employees in | |
|
Price | |
|
|
|
| |
Name |
|
Granted | |
|
Fiscal Year | |
|
($/Share) | |
|
Expiration Date | |
|
5% | |
|
10% | |
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
Sheldon Berkle
|
|
|
566,943 |
|
|
|
37.5 |
% |
|
$ |
3.92 |
|
|
|
May 8, 2015 |
|
|
$ |
11,629,940 |
|
|
$ |
19,835,145 |
|
Don G. Burstyn
|
|
|
17,444 |
|
|
|
1.2 |
|
|
|
3.92 |
|
|
|
January 26, 2015 |
|
|
|
357,836 |
|
|
|
610,298 |
|
Robert Gallotto
|
|
|
37,069 |
|
|
|
2.5 |
|
|
|
3.92 |
|
|
|
January 26, 2015 |
|
|
|
760,412 |
|
|
|
1,296,901 |
|
Jonathan I. Lieber
|
|
|
21,805 |
|
|
|
1.4 |
|
|
|
3.92 |
|
|
|
January 26, 2015 |
|
|
|
447,295 |
|
|
|
762,873 |
|
Alexey L. Margolin, Ph.D.
|
|
|
34,889 |
|
|
|
2.3 |
|
|
|
3.92 |
|
|
|
January 26, 2015 |
|
|
|
715,693 |
|
|
|
1,220,631 |
|
Martin D. Williams(1)
|
|
|
141,735 |
|
|
|
9.4 |
|
|
|
3.92 |
|
|
|
January 4, 2015 |
|
|
|
2,907,470 |
|
|
|
4,958,760 |
|
|
|
(1) |
At December 31, 2005, Mr. Williams was no longer
employed by the company. As a result, 115,161 of his unvested
options were cancelled in December 2005 and 26,574 vested
options remained outstanding. |
90
Aggregated Option Exercises in 2005 and Year-End Option
Values
The following table sets forth certain information with respect
to the total value of options held by each executive officer
named in the summary compensation table above as of
December 31, 2005. Because there was no public trading
market for the common stock as of December 31, 2005, the
value realized upon the exercise of options and the value of the
unexercised
in-the-money options at
year-end have been calculated using the initial public offering
price of $15.00 per share minus the applicable per share
exercise price.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Number of Securities | |
|
Value of Unexercised | |
|
|
Underlying Unexercised | |
|
In-the-Money Options at | |
|
|
Options at Fiscal Year-End | |
|
Fiscal Year-End | |
|
|
| |
|
| |
Name |
|
Exercisable(1) | |
|
Unexercisable | |
|
Exercisable | |
|
Unexercisable | |
|
|
| |
|
| |
|
| |
|
| |
Sheldon Berkle
|
|
|
490,434 |
|
|
|
76,509 |
|
|
$ |
5,434,009 |
|
|
$ |
847,720 |
|
Don G. Burstyn
|
|
|
159,180 |
|
|
|
|
|
|
|
1,763,714 |
|
|
|
|
|
Robert Gallotto
|
|
|
141,735 |
|
|
|
|
|
|
|
1,519,398 |
|
|
|
|
|
Jonathan I. Lieber
|
|
|
185,346 |
|
|
|
|
|
|
|
2,053,634 |
|
|
|
|
|
Alexey L. Margolin, Ph.D.
|
|
|
195,158 |
|
|
|
|
|
|
|
2,107,892 |
|
|
|
|
|
Martin D. Williams
|
|
|
26,574 |
|
|
|
|
|
|
|
294,440 |
|
|
|
|
|
|
|
(1) |
All of these options may be exercised immediately for shares of
restricted stock, which are subject to a repurchase right by us
that lapses on the same vesting schedule as the options. |
Employee Benefit Plans
We have terminated our 1993 Stock Option Plan, under which
options to purchase 354,186 shares of common stock remained
outstanding as of December 31, 2005. Although no more
options may be granted under the plan, the terms of the plan
continue to apply to all outstanding options. Our board of
directors or any committee to which the board of directors
delegates authority may, with the consent of the affected plan
participants, amend outstanding awards consistent with the terms
of the plan.
|
|
|
Amended and Restated 2002 Employee, Director and
Consultant Stock Plan |
Our 2002 Employee, Director and Consultant Stock Plan, or 2002
Stock Plan, initially was adopted by our board of directors in
February 2002 and approved by our stockholders in January 2003.
In January 2006, our board of directors adopted and our
stockholders approved an amended and restated form of our 2002
Stock Plan. Our 2002 Stock Plan, as amended and restated, will
become effective upon completion of the offering and expire on
January 5, 2016. Under this plan, we may grant incentive
stock options, nonqualified stock options, restricted and
unrestricted stock awards and other stock-based awards. Upon
effectiveness, the number of shares of common stock authorized
for issuance under our plan will equal the sum of
(1) 4,199,651 shares of our common stock plus
(2) any shares of our common stock that are represented by
awards granted under our 1993 Stock Option Plan that are
forfeited, expire or are cancelled without delivery of shares or
which result in the forfeiture of shares of our common stock
back to us on or after December 31, 2005; provided,
however, that no more than 354,186 shares shall be added to
the plan pursuant to clause (2) above.
In addition, our plan contains an evergreen
provision, which allows for an annual increase in the number of
shares available for issuance under the plan on the first day of
each fiscal year during the period beginning on the first day of
fiscal year 2007, and ending on the second day of fiscal year
2015. The annual increase in the number of shares shall be equal
to the lowest of:
|
|
|
|
|
1,500,000 shares; |
|
|
|
3% of the number of shares of our common stock outstanding on a
fully diluted basis as of the close of business on the
immediately preceding day, which is calculated by adding to the |
91
|
|
|
|
|
number of shares of common stock outstanding, the number of
shares of common stock issuable upon conversion or exercise of
any convertible securities; and |
|
|
|
an amount determined by our board of directors. |
The board of directors has authorized our compensation committee
to administer our plan. In accordance with the provisions of the
plan, the compensation committee will determine the terms of
options and other awards, including:
|
|
|
|
|
the determination of which employees, directors and consultants
shall be granted options and other awards; |
|
|
|
the number of shares subject to options and other awards; |
|
|
|
the exercise price of each option which generally shall not be
less than fair market value on the date of grant; |
|
|
|
the schedule upon which options become exercisable; |
|
|
|
the termination or cancellation provisions applicable to options; |
|
|
|
the terms and conditions of other awards, including conditions
for repurchase, termination or cancellation, issue price and
repurchase price; and |
|
|
|
all other terms and conditions upon which each award may be
granted in accordance with our plan. |
No participant may receive awards for more than
560,000 shares of common stock in any fiscal year.
In addition, our board of directors or any committee to which
the board of directors delegates authority may, with the consent
of the affected plan participants, reprice or otherwise amend
outstanding awards consistent with the terms of our plan.
Upon a merger or other reorganization event, our board of
directors, or the board of directors of any corporation assuming
our obligations, may, in its sole discretion, take any one or
more of the following actions pursuant to our plan, as to some
or all outstanding awards:
|
|
|
|
|
provide that outstanding options shall be assumed or substituted
by the successor corporation; |
|
|
|
terminate unexercised outstanding options immediately prior to
the consummation of such transaction unless exercised by the
optionee; |
|
|
|
make or provide for a cash payment to the participants equal to
the difference between the merger price times the number of
shares of our common stock subject to such outstanding options,
to the extent then exercisable at prices not in excess of the
merger price, and the aggregate exercise price of all such
outstanding options, in exchange for the termination of such
options; |
|
|
|
provide that all or any outstanding options shall become
exercisable in full immediately prior to such event; and |
|
|
|
provide that outstanding awards shall be assumed or substituted
by the successor corporation, become realizable or deliverable,
or restrictions applicable to an award will lapse, in whole or
in part, prior to or upon the merger or reorganization event. |
Pursuant to the stock plan, in the event a merger or other
reorganization event also constitutes a change of control, all
options issued to directors, whether or not employees, shall
become exercisable in full immediately prior to such event.
92
As of December 31, 2005, 27,963 shares had been issued
pursuant to options granted under our 2002 Stock Plan,
2,702,621 shares were subject to outstanding options and
1,497,030 shares were available for future grant, assuming
effectiveness of our amended and restated 2002 Stock Plan.
We have a 401(k) defined contribution retirement plan in which
all full-time employees are eligible to participate. Our 401(k)
plan is intended to qualify under Section 401 of the
Internal Revenue Code so that contributions by employees and by
us to our 401(k) plan and income earned on plan contributions
are not taxable to employees until withdrawn or distributed from
the plan, and so that contributions, including employee salary
deferral contributions, will be deductible by us when made. We
provide matching contributions under our 401(k) plan for all
participants.
Employment Agreements and Change of Control Arrangements
Sheldon Berkle. We entered into an employment agreement
with Sheldon Berkle, our President, Chief Executive Officer and
a director in May 2005. Pursuant to the agreement,
Mr. Berkle receives an annualized base salary of $400,000
and has an opportunity to earn an annual performance bonus of up
to 50% of his salary, based on achievement of a series of
personal and corporate objectives that our board of directors
and Mr. Berkle define annually. Mr. Berkle also
received a signing bonus of $153,500. Such bonus replaced a loan
from us to Mr. Berkle in the amount of $150,000 at the
commencement of his employment, which loan was repaid prior to
the filing of the registration statement of which this
prospectus is a part. He will be required to repay $150,000 of
the bonus amount in the event that he voluntarily terminates his
employment or is terminated for cause prior to May 9, 2006,
or $75,000 of the bonus amount in the event that he voluntarily
terminates his employment or is terminated for cause after
May 9, 2006 and before May 9, 2007, in each case less
the amount of taxes he incurred in connection with his receipt
of such portion of the bonus. Pursuant to the employment
agreement, Mr. Berkle will be entitled to
12 months severance at a rate equal to his
then-current base salary in the event that we terminate his
employment without cause or he resigns for good reason, or if he
resigns for good reason within six months after a change in
control, as defined in our 2002 Stock Plan. We have agreed, in
these circumstances, to assume payments under
Mr. Berkles house and automobile leases in the Boston
area for the 12-month
severance period, or, if shorter, until the expiration of the
respective terms of the leases, up to an aggregate of $25,000.
Upon appointment as our President and Chief Executive Officer,
Mr. Berkle received options to purchase 566,943 shares
of our common stock at an exercise price of $3.92 per
share. One quarter of the options will vest on the first
anniversary of his employment, with the balance vesting monthly
for three additional years. Of the 566,943 options, options to
purchase 490,434 shares are immediately exercisable
for shares of restricted stock, which are subject to a
repurchase right by us that lapses based on the same vesting
schedule as the options.
Executive Retention Arrangements. Commencing on
May 9, 2005 and for a period of one year thereafter, if we
terminate the employment of any of our executive officers, other
than Mr. Klement, without cause, we will either provide him
with six months notice, or with his base salary and
medical benefits for a period of six months following notice of
termination.
Acceleration of Vesting of Stock Options Upon a Change of
Control. Pursuant to our 2002 Stock Plan, in the event a
merger or other reorganization event also constitutes a change
of control, all options issued to directors, whether or not
employees, shall become exercisable in full immediately prior to
such event.
Pursuant to the stock option agreements of our executive
officers, in the event that within one year after the date of a
change in control, as defined in our 2002 Stock Plan,
|
|
|
|
|
the executive officer is terminated for any reason other than
cause, as defined in our 2002 Stock Plan, or |
|
|
|
the executive officer, as a condition to his remaining an
employee, is required to relocate at least 50 miles from
his or her current location of employment, or |
93
|
|
|
|
|
there occurs a material adverse change in the executive
officers duties, authority or responsibilities which
causes his position with us to become of significantly less
responsibility or authority than his position was immediately
prior to the change in control, or |
|
|
|
there occurs a material reduction in the executive
officers base salary from the base salary received
immediately prior to the change in control, |
the executive officers options will be fully vested and
immediately exercisable as of the date of his last day of
employment, unless the options have otherwise expired or been
terminated pursuant to their terms or the terms of our 2002
Stock Plan.
Limitation of Directors and Officers Liability
and Indemnification
The Delaware General Corporation Law authorizes corporations to
limit or eliminate, subject to specified conditions, the
personal liability of directors to corporations and their
stockholders for monetary damages for breach of their fiduciary
duties. Our restated certificate of incorporation limits the
liability of our directors to the fullest extent permitted by
Delaware law.
We have obtained director and officer liability insurance to
cover liabilities our directors and officers may incur in
connection with their services to us, including matters arising
under the Securities Act of 1933. Our restated certificate of
incorporation and restated bylaws also provide that we will
indemnify and advance expenses to any of our directors and
officers who, by reason of the fact that he or she is one of our
officers or directors, is involved in a legal proceeding of any
nature. We will repay certain expenses incurred by a director or
officer in connection with any civil, criminal, administrative
or investigative action or proceeding, specifically including
actions by us or in our name. Such indemnifiable expenses
include, to the maximum extent permitted by law, attorneys
fees, judgments, fines, settlement amounts and other expenses
reasonably incurred in connection with legal proceedings. A
director or officer will not receive indemnification if he or
she is found not to have acted in good faith and in a manner he
or she reasonably believed to be in, or not opposed to, our best
interest.
Prior to completion of this offering, we plan to enter into
agreements to indemnify our directors and officers. These
agreements, among other things, will indemnify and advance
expenses to our directors and officers for certain expenses,
including attorneys fees, judgments, fines and settlement
amounts incurred by any such person in any action or proceeding,
including any action by us arising out of such persons
services as our director or officer, or any other company or
enterprise to which the person provides services at our request.
We believe that these provisions and agreements are necessary to
attract and retain qualified persons as directors and officers.
Such limitation of liability and indemnification does not affect
the availability of equitable remedies. In addition, we have
been advised that in the opinion of the SEC, indemnification for
liabilities arising under the Securities Act is against public
policy as expressed in the Securities Act and is therefore
unenforceable.
There is no pending litigation or proceeding involving any of
our directors, officers, employees or agents in which
indemnification will be required or permitted. We are not aware
of any threatened litigation or proceeding that may result in a
claim for such indemnification.
94
RELATED PARTY TRANSACTIONS
The following is a description of transactions that we entered
into with our executive officers, directors or 5% stockholders
since January 1, 2003. We believe that all of the
transactions described below were made on terms no less
favorable to us than could have been obtained from unaffiliated
third parties. All future related party transactions will be
approved by our audit committee.
Sales of Securities
On May 21, 2004, Warburg Pincus, one of our principal
stockholders, and affiliated entities, purchased
7,413,222 shares of our Series C convertible preferred
stock at a price of $4.3147358 per share and warrants to
purchase 1,630,914 shares of our Series C
convertible preferred stock at an exercise price of
$4.3147358 per share, for an aggregate purchase price of
$31,986,094. After the closing of this offering, Warburg Pincus
and its affiliated entities are entitled to designate up to two
individuals to our board of directors and we have agreed to
nominate and use our reasonable efforts to cause Warburg
Pincus designees to be elected. Messrs. Hen and Leff
are managing directors of Warburg Pincus and are the current
members of our board of directors designated by Warburg Pincus.
On May 21, 2004, U.S. Venture Partners VIII, L.P., one
of our principal stockholders, and affiliated entities,
purchased 1,907,741 shares of our Series C convertible
preferred stock at a price of $4.3147358 per share and
warrants to purchase 419,704 shares of our
Series C convertible preferred stock at an exercise price
of $4.3147358 per share, for an aggregate purchase price of
$8,231,398. Dr. Root is a general partner of
U.S. Venture Partners and is the current member of our
board of directors designated by U.S. Venture Partners.
On May 21, 2004, Nomura International plc, one of our
principal stockholders, and affiliated entities, purchased
1,140,570 shares of our Series C convertible preferred
stock at a price of $4.3147358 per share and warrants to
purchase 250,926 shares of our Series C
convertible preferred stock at an exercise price of
$4.3147358 per share, for an aggregate purchase price of
$4,921,258. Nomura and its affiliated entities are entitled to
appoint one member to our board of directors. This right will
expire upon the closing of this offering. Mr. Richard is a
consultant to Nomura and is the current member of our board of
directors designated by Nomura.
On May 21, 2004, CMEA Venture Life Sciences 2000, L.P., one
of our principal stockholders, and affiliated entities,
purchased 570,285 shares of Series C convertible
preferred stock at a price of $4.3147358 per share and warrants
to purchase 125,463 shares of Series C convertible
preferred stock at an exercise price of $4.3147358 per share,
for an aggregate purchase price of $2,460,629.
On May 21, 2004, P/S BI Biomedicinsk Venture III, one of
our principal stockholders, purchased 570,285 shares of
Series C convertible preferred stock at a price of
$4.3147358 per share and warrants to purchase
125,463 shares of Series C convertible preferred stock
at an exercise price of $4.3147358 per share, for an aggregate
purchase price of $2,460,629.
The holders of the above described shares of our convertible
preferred stock and warrants to purchase shares of our
convertible preferred stock are entitled to registration rights.
See Description of Capital Stock Registration
Rights.
Laboratory Space and Equipment Lease
Vertex, one of our principal stockholders, leased us laboratory
space and equipment during the three years ended
December 31, 2004 pursuant to a Sublease Agreement dated
February 1, 1999, as amended. The total amounts paid to
Vertex under the lease were approximately $91,000 in 2004,
$121,000 in 2003, and $137,000 in 2002. Ms. Brum is an
executive officer of Vertex and is the current member of our
board of directors designated by Vertex.
95
Director and Executive Officer Compensation
Please see Management Compensation of
Directors for a discussion of options granted and payments
made to our non-employee directors. Please see
Management Executive Compensation and
Management Option Grants in Last Fiscal
Year for additional information regarding compensation of
our executive officers.
In addition, on January 9, 2006, our compensation committee
granted options to the named executive officers to purchase
shares of our common stock, each at an exercise price of
$11.47 per share, as follows: Sheldon Berkle received an
option to purchase 26,166 shares; Don G. Burstyn, Ph.D.,
received an option to purchase 15,263 shares; Robert
Gallotto received an option to purchase 27,890 shares;
Jonathan I. Lieber received an option to purchase
26,488 shares; and Alexey L. Margolin received an option to
purchase 26,954 shares. Each of such options has a term of
ten years vesting over four years, with 1/16th of the options
vesting every three months.
Employment and Consulting Agreements
We have entered into an employment agreement with
Mr. Berkle, our President and Chief Executive Officer, and
into other agreements with our executive officers. For
information regarding these agreements, please refer to the
section entitled Management Employment
Agreements and Change of Control Arrangements and
Management Director Compensation.
96
PRINCIPAL STOCKHOLDERS
The following table sets forth information regarding the
beneficial ownership of our common stock as of December 31,
2005, and as adjusted to reflect the sale of our common stock
offered by this prospectus, by:
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each stockholder known by us to own beneficially more than 5% of
our common stock; |
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each of the executive officers named in the summary compensation
table; |
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each of our directors; and |
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all of our current directors and executive officers as a group. |
Beneficial ownership is determined in accordance with the rules
of the SEC and includes voting or investment power with respect
to the securities. Shares of common stock that may be acquired
by an individual or group within 60 days after
December 31, 2005 pursuant to the exercise of options or
warrants are deemed to be outstanding for the purpose of
computing the percentage ownership of such individual or group,
but are not deemed to be outstanding for the purpose of
computing the percentage ownership of any other person shown in
the table. Percentage of common stock beneficially owned before
the offering is based on 14,001,943 shares of common stock
outstanding on December 31, 2005, which assumes the
conversion of all outstanding shares of our convertible
preferred stock into 10,767,306 shares of common stock and
1,391,828 shares of common stock in satisfaction of
dividends on our Series B and C convertible preferred stock
accrued through the closing date of January 31, 2006.
Except as indicated in the footnotes to this table, we believe
that the stockholders named in this table have sole voting and
investment power with respect to all shares of common stock
shown to be beneficially owned by them, based on information
provided to us by such stockholders. Unless otherwise indicated,
the address for each director and executive officer listed is
c/o Altus Pharmaceuticals Inc., 125 Sidney Street,
Cambridge, MA 02139.
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Percentage of Common Stock | |
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Beneficially Owned | |
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Number of Shares | |
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Beneficial Owner |
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Beneficially Owned | |
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Before Offering | |
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After Offering | |
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5% or more stockholders
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Warburg Pincus Private Equity VIII, L.P.(1)
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4,307,163 |
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29.3 |
% |
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19.8 |
% |
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466 Lexington Avenue
New York, NY 10017 |
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Entities affiliated with U.S. Venture Partners(2)
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3,371,421 |
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23.5 |
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15.8 |
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2735 Sand Hill Road |
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Menlo Park, CA 94025 |
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Vertex Pharmaceuticals Incorporated(3)
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2,780,243 |
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17.4 |
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12.1 |
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130 Waverly Street
Cambridge, Massachusetts 02139 |
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Entities affiliated with Nomura International plc(4)
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1,956,962 |
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13.8 |
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9.2 |
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Nomura House |
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1 St. Martins-le-Grand |
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London EC1A 4NP |
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United Kingdom |
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P/ S BI Biomedicinsk Venture III(5)
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978,478 |
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6.9 |
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4.6 |
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Sundkrogsgade 7, P.O. Box 2672 |
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DK 2100 Copenhagen |
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Denmark |
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97
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Percentage of Common Stock | |
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Beneficially Owned | |
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Number of Shares | |
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Beneficial Owner |
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Beneficially Owned | |
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Before Offering | |
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After Offering | |
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Entities affiliated with CMEA Ventures(6)
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974,530 |
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6.9 |
% |
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4.6 |
% |
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One Embarcadero Center, Suite 3250 |
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San Francisco, CA 94111 |
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China Development Industrial Bank(7)
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707,511 |
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5.0 |
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3.4 |
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125 Nanking East Road |
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Section 5 Taipei 105 |
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Taiwan ROC 105 |
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Named Executive Officers
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Sheldon Berkle(8)
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515,936 |
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3.6 |
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2.4 |
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Don G. Burstyn(9)
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159,180 |
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1.1 |
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* |
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Robert Gallotto(10)
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141,735 |
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1.0 |
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* |
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Jonathan I. Lieber(11)
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185,346 |
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1.3 |
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* |
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Alexey L. Margolin, Ph.D.(12)
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405,362 |
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2.9 |
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1.9 |
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Martin D. Williams(13)
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26,574 |
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* |
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* |
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Directors
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John P. Richard(14)
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111,429 |
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* |
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* |
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Richard H. Aldrich(15)
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85,041 |
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* |
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* |
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Lynne H. Brum(16)
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2,780,243 |
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17.4 |
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12.1 |
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Stewart Hen(17)
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4,307,163 |
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29.3 |
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19.8 |
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Peter L. Lanciano(18)
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699,394 |
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4.9 |
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3.3 |
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Jonathan S. Leff(19)
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4,307,163 |
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29.3 |
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19.8 |
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Manuel A. Navia, Ph.D.(20)
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119,930 |
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* |
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* |
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Jonathan D. Root, M.D.(21)
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3,380,143 |
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23.5 |
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15.8 |
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Michael S. Wyzga(22)
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54,514 |
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* |
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* |
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All current executive officers and directors as a group
(17 persons)(23)
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13,371,712 |
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69.8 |
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51.1 |
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(1) |
Consists of 3,589,246 shares of common stock owned of
record by and warrants to purchase 717,917 shares of common
stock held by Warburg Pincus Private Equity VIII, L.P. and
two affiliated partnerships, or collectively, WP VIII.
Warburg Pincus Partners LLC, or WP Partners LLC, a subsidiary of
Warburg Pincus & Co., or WP, is the sole general
partner of WP VIII. WP VIII is managed by Warburg
Pincus LLC, or WP LLC. Charles R. Kaye and Joseph P. Landy are
each Managing General Partners of WP and Co-Presidents and
Managing Members of WP LLC. Messrs. Hen and Leff are
general partners of WP and Managing Directors and Members of
WP LLC. Each of these individuals disclaims beneficial
ownership of the shares held by WP VIII except to the
extent of any pecuniary interest therein. |
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(2) |
Consists of 2,947,459 shares of common stock owned of
record by and warrants to purchase 359,823 shares of common
stock held by U.S. Venture Partners VIII, L.P.;
21,696 shares of common stock owned of record by and
warrants to purchase 2,592 shares of common stock held by
USVP VIII Affiliates Fund, L.P.; 27,665 shares of
common stock owned of record by and warrants to purchase
3,303 shares of common stock held by USVP Entrepreneur
Partners VIII-A,
L.P.; and 14,778 shares of common stock owned of record by
and warrants to purchase 1,765 shares of common stock held
by USVP Entrepreneur
Partners VIII-B,
L.P. Voting and/or dispositive decisions with respect to the
shares held by U.S. Venture Partners VIII, L.P,
USVP VIII Affiliates Fund, L.P., USVP Entrepreneur
Partners VIII-A,
L.P. and USVP Entrepreneur
Partners VIII-B,
L.P. are made by their managing members: Dr. Root, Timothy
Connors, Irwin Federman, Winston Fu, Steven Krausz, David
Liddle, Christopher Rust, and Philip Young. Each |
98
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disclaims beneficial ownership of the shares held by the
entities except to the extent of any pecuniary interest therein. |
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(3) |
Consists of 817,749 shares of common stock and warrants to
purchase 1,962,494 shares of common stock held by
Vertex. Vertex also holds 450,000 shares of redeemable
preferred stock, which are not convertible into common stock and
which are redeemable at the option of Vertex on or after
December 31, 2010, or by us at any time following the
completion of this offering. Voting and/or dispositive decisions
with respect to the shares held by Vertex are made by
Ms. Brum and other individuals. Each disclaims beneficial
ownership of the shares held by Vertex except to the extent of
any pecuniary interest therein. |
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(4) |
Consists of 1,194,236 shares of common stock owned of
record by and warrants to purchase 100,044 shares of common
stock held by Nomura International plc; and 552,227 shares
of common stock owned of record by and warrants to purchase
110,455 shares of common stock held by Nomura Phase4
Ventures L.P. Nomura Phase4 Ventures Limited, as appointee of
Nomura International plc and as manager of Nomura Phase4
Ventures L.P. has voting and investment power over the shares
held by Nomura International plc and Nomura Phase4 Ventures L.P.
Nomura Phase4 Ventures Limited is a subsidiary of Nomura
International plc which is a subsidiary of Nomura Holdings Inc.,
a publicly traded company. The address for Nomura Phase4
Ventures L.P., Nomura Phase4 Ventures Limited and Nomura
International plc is Nomura House, 1 St Martins-le-Grand,
London, EC1A 4NP. Mr. Yoshiki Hashimoto, the Head of
Merchant Banking, Nomura International plc, and Dr. Denise
Pollard-Knight, the Head of Nomura Phase4 Ventures, are the only
two members of the board of directors of Nomura Phase4 Ventures
Limited and both of them, acting together, exercise the voting
and investment power of Nomura Phase4 Ventures Limited.
Mr. Hashimoto and Dr. Pollard-Knight disclaim
beneficial ownership over any of the above shares. |
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(5) |
Consists of 873,230 shares of common stock owned of record
and warrants to purchase 105,248 shares of common stock
held by P/S BI Biomedicinsk Venture III. P/ S BI Biomedicinsk
Venture IIIs investment decisions are made by and
voting powers allocated to the Board of Directors, consisting of
Uffe Ellemann- Jensen, Bórge Obel, Lars Kolind, Asger Ib
Mardahl-Hansen and Bent Pedersen, and to the Management Board,
consisting of Jesper Zeuthen. Each of these individuals
disclaims beneficial ownership of the shares held by the entity
except to the extent of any pecuniary interest therein. |
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(6) |
Consists of 816,314 shares of common stock owned of record
by and warrants to purchase 98,906 shares of common stock
held by CMEA Ventures Life Sciences 2000 L.P.; and
52,966 shares of common stock owned of record by and
warrants to purchase 6,342 shares of common stock owned by
CMEA Venture Life Sciences 2000 Civil Law Partnership. CMEA
Ventures Life Sciences 2000, L.P. and CMEA Ventures Life
Sciences 2000, Civil Law Partnership both have, as their general
partner, CMEA Ventures LS Management 2000 L.P. The general
partners of that entity are Thomas Baruch, David Collier, Karl
Handelsman and Gordon Hull. Each of these individuals disclaims
beneficial ownership of the shares held by the entity except to
the extent of any pecuniary interest therein. |
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(7) |
Consists of 593,172 shares of common stock owned of record
and warrants to purchase 50,021 shares of common stock held
by China Development Industrial Bank Inc.; and
59,316 shares of common stock owned of record and warrants
to purchase 5,002 shares of common stock held by CDIB
Biotech USA Investments. Voting and dispositive power for these
shares is shared by the board of directors and managing
directors of China Development Industrial Bank. |
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(8) |
Consists of options to purchase 515,936 shares of common
stock. One quarter of the options will vest on May 9, 2006,
and thereafter an additional 1/48th of the total underlying
option grant vests on a monthly basis, such that all options
will be vested after four years. In addition, all of these
options are immediately exercisable for shares of restricted
stock, which are subject to a repurchase right by us that lapses
based on the vesting schedule set forth in the previous sentence. |
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(9) |
Consists of options to purchase 159,180 shares of common
stock. 148,277 of such options have a term of ten years vesting
over four years, with 1/16th of the options vesting every three
months. 10,903 of these options have a term of ten years,
vesting over two years, with 1/8th of the options vesting every
three months. In addition, all of these options are immediately
exercisable for shares of restricted stock, which are subject to
a repurchase right by us that lapses based on the vesting
schedule set forth in the previous sentences. |
99
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(10) |
Consists of options to purchase 141,735 shares of common
stock. All of such options have a term of ten years vesting over
four years, with 1/16th of the options vesting every three
months. In addition, all of these options are immediately
exercisable for shares of restricted stock, which are subject to
a repurchase right by us that lapses based on the vesting
schedule set forth in the previous sentence. |
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(11) |
Consists of options to purchase 185,346 shares of common
stock. 174,443 of such options have a term of ten years vesting
over four years, with 1/16th of the options vesting every three
months. 10,903 of such options have a term of ten years, vesting
over two years, with 1/8th of the options vesting every three
months. In addition, all of these options are immediately
exercisable for shares of restricted stock, which are subject to
a repurchase right by us that lapses based on the vesting
schedule set forth in the previous sentences. |
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(12) |
Consists of 210,204 shares of common stock and options to
purchase 195,158 shares of common stock. 184,255 of such
options have a term of ten years vesting over four years, with
1/16th of the options vesting every three months. 10,903 of
these options have a term of ten years, vesting over two years
with 1/8th of the options vesting every three months. In
addition, all of these options are immediately exercisable for
shares of restricted stock, which are subject to a repurchase
right by us that lapses based on the vesting schedule set forth
in the previous sentences. |
|
(13) |
Consists of options to purchase 26,574 shares of common
stock. The options are fully vested but will expire if not
exercised by March 30, 2006. |
|
(14) |
Consists of options to purchase 111,429 shares of
common stock. 68,687 of such options have a term of ten years
vesting over four years, with 1/16th of the options vesting
every three months. 42,742 of such options have a term of ten
years and vested immediately upon grant. In addition, all of the
options are immediately exercisable for shares of restricted
stock, which are subject to a repurchase right by us that lapses
based on the vesting schedule set forth above. |
|
(15) |
Consists of 30,527 shares of common stock and options to
purchase 54,514 shares of common stock. All options
have a term of ten years vesting over four years, with 1/16th of
the options vesting every three months. In addition, all of
these options are immediately exercisable for shares of
restricted stock, which are subject to a repurchase right by us
that lapses based on the vesting schedule set forth above. |
|
(16) |
Consists of the shares owned by Vertex as described in
footnote 3 above. Ms. Brum disclaims beneficial
ownership of the shares owned by Vertex except to the extent of
her pecuniary interest therein. |
|
(17) |
Consists of the shares owned by WP VIII as described in
footnote 1 above. Mr. Hen is a partner of WP and a
managing director and member of WP LLC. Mr. Hen disclaims
beneficial ownership of the shares owned by WP VIII except
to the extent of his pecuniary interest therein. |
|
(18) |
Consists of 224,398 shares of common stock and options to
purchase 222,074 shares of common stock held by
Mr. Lanciano and 252,922 shares held in various trusts
for the benefit of Mr. Lancianos minor children. Does
not include 198,000 shares of common stock gifted by
Mr. Lanciano to other members of his family. All of the
options have a term of ten years and are exercisable until the
earlier of three months after Mr. Lanciano ceases to be a
member of our board of directors or December 31, 2006. The
options were vested as of October 31, 2005. |
|
(19) |
Consists of the shares owned by WP VIII as described in
footnote 1 above. Mr. Leff is a partner of WP and a
managing director and member of WP LLC. Mr. Leff disclaims
beneficial ownership of the shares owned by WP VIII except
to the extent of his pecuniary interest therein. |
|
(20) |
Consists of 71,958 shares of common stock and options to
purchase 47,972 shares of common stock. All options
have a term of ten years vesting over four years, with
1/16th of the options vesting every three months. In
addition, all of these options are immediately exercisable for
shares of restricted stock, which are subject to a repurchase
right by us that lapses based on the vesting schedule set forth
above. |
100
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|
(21) |
Consists of the shares owned by U.S. Venture Partners and
affiliated entities as described in footnote 2 above, in
addition to options to purchase 8,722 shares of common
stock. All options have a term of ten years vesting over four
years, with 1/16th of the options vesting every three
months. In addition, all of these options are immediately
exercisable for shares of restricted stock, which are subject to
a repurchase right by us that lapses based on the vesting
schedule set forth above. Dr. Root disclaims beneficial
ownership of the shares owned by the funds except to the extent
of his pecuniary interest therein. |
|
(22) |
Consists of options to purchase 54,514 shares of
common stock. All options have a term of ten years vesting over
four years, with 1/16th of the options vesting every three
months. In addition, all of these options are immediately
exercisable for shares of restricted stock, which are subject to
a repurchase right by us that lapses based on the vesting
schedule set forth above. |
|
(23) |
See footnotes 7 through 12 and 14 through 22. |
101
DESCRIPTION OF CAPITAL STOCK
Our authorized capital stock as of December 31, 2005
consists of 47,113,986 shares of common stock and
27,886,014 shares of preferred stock, of which 450,000
shares have been designated redeemable preferred stock, 87,500
shares have been designated Series A convertible preferred
stock, 12,928,155 shares have been designated Series B
convertible preferred stock and 14,420,359 shares have been
designated Series C convertible preferred stock. Upon
completion of this offering, we will be authorized to issue
100,000,000 shares of common stock, $0.01 par value
per share, and 5,000,000 shares of preferred stock,
$0.01 par value per share, of which 450,000 shares will be
designated redeemable preferred stock, and there will be
21,001,943 shares of common stock and 450,000 shares
of redeemable preferred stock outstanding. On December 31,
2005, the following numbers of shares of common stock,
redeemable preferred stock and convertible preferred stock were
outstanding:
|
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Common Stock
|
|
|
1,842,809 |
|
Redeemable Preferred Stock
|
|
|
450,000 |
|
Series A Convertible Preferred Stock
|
|
|
87,500 |
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Series B Convertible Preferred Stock
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|
|
11,773,609 |
|
Series C Convertible Preferred Stock
|
|
|
11,819,959 |
|
Upon completion of this offering, all of our shares of
convertible preferred stock will convert into
10,767,306 shares of common stock. Assuming such
conversion, as of December 31, 2005, we had
12,610,115 shares of common stock outstanding held of
record by 144 stockholders and 450,000 shares of
redeemable preferred stock outstanding held by one stockholder.
We will also issue 1,391,828 shares of common stock upon
the closing of this offering in satisfaction of accumulated
dividends on our convertible preferred stock. As of
December 31, 2005, there were outstanding options to
purchase 3,056,807 shares of common stock and
outstanding warrants to purchase 4,121,189 shares of
common stock. All outstanding shares of common stock are fully
paid and nonassessable, and the shares of common stock to be
issued upon completion of this offering will be fully paid and
nonassessable.
Common Stock
Holders of common stock are entitled to one vote for each share
held of record on all matters submitted to a vote of the
stockholders, and do not have cumulative voting rights. Subject
to preferences that may be applicable to any outstanding shares
of preferred stock, holders of common stock are entitled to
receive ratably such dividends, if any, as may be declared from
time to time by our board of directors out of funds legally
available for dividend payments. The holders of common stock
have no preferences or rights of conversion, exchange,
pre-emption or other subscription rights. There are no
redemption or sinking fund provisions applicable to the common
stock. In the event of any liquidation, dissolution or
winding-up of our
affairs, holders of common stock will be entitled to share
ratably in our assets that are remaining after payment or
provision for payment of all of our debts and obligations and
after liquidation payments to holders of outstanding shares of
preferred stock, if any.
Redeemable Preferred Stock
Upon completion of this offering, we will have outstanding
450,000 shares of our redeemable preferred stock, which are
redeemable on or after December 31, 2010 at the option of
Vertex, which is the sole holder of such shares, or by us at our
option at any time following the completion of the offering, at
a price of $10.00 per share plus all accrued but unpaid
dividends, prior to payment of any amounts on common stock. All
of the shares of redeemable preferred stock were issued on
February 1, 1999 with an allocated value of $3,100,000.
Vertex is entitled to receive dividends at an annual rate of 5%
of the purchase price per year and has no voting rights other
than with respect to specified changes to our certificate of
incorporation. As of September 30, 2005, dividends in the
amount of $1.5 million were accrued and unpaid on our
redeemable preferred stock. Upon liquidation, including deemed
liquidations
102
pursuant to a merger, consolidation or a sale of all or
substantially all of our assets, Vertex will be entitled to
payment of $10.00 per share plus accrued but unpaid
dividends prior to payment of any amounts on the common stock.
We have agreed not to declare any dividends on our common stock,
other than to implement a stock split or shareholder rights
plan, or to purchase or acquire any shares of our own capital
stock until after we have paid all accrued but unpaid dividends
on our redeemable preferred stock.
Preferred Stock
Our board of directors has the authority, without further
stockholder authorization, to issue from time to time shares of
preferred stock in one or more series and to fix the terms,
limitations, relative rights and preferences and variations of
each series. Although we have no present plans to issue any
other shares of preferred stock, the issuance of shares of
preferred stock, or the issuance of rights to purchase such
shares, could decrease the amount of earnings and assets
available for distribution to the holders of common stock, could
adversely affect the rights and powers, including voting rights,
of the common stock, and could have the effect of delaying,
deterring or preventing a change in control of us or an
unsolicited acquisition proposal.
Warrants
As of December 31, 2005, assuming the completion of the
offering as of such date, we had warrants outstanding for the
number of shares of common stock, at the exercise prices and
expiration dates set forth below:
|
|
|
|
|
|
|
|
|
Number of Shares |
|
Exercise Price | |
|
Expiration Date | |
|
|
| |
|
| |
1,962,494(1)
|
|
$ |
5.64 |
|
|
|
February 1, 2009 |
|
1,144,670(1)(2)
|
|
$ |
9.80 |
|
|
|
May 21, 2011 |
|
508,214(1)(2)
|
|
$ |
9.80 |
|
|
|
September 26, 2008 |
|
261,664(1)(2)
|
|
$ |
0.02 |
|
|
|
September 26, 2011 February 22, 2013 |
|
187,708(2)
|
|
$ |
9.79 |
|
|
|
December 7, 2006 October 28, 2009 |
|
43,610(2)
|
|
$ |
6.88 |
|
|
|
June 21, 2006 |
|
6,535(2)
|
|
$ |
9.88 |
|
|
|
August 31, 2009 June 24, 2010 |
|
6,294(2)
|
|
$ |
9.79 |
|
|
|
April 4, 2007 October 27, 2008 |
|
|
|
(1) |
These warrants contain price-based anti-dilution provisions
providing for adjustments to the exercise price upon the
occurrence of specified events, excluding shares issuable upon
exercise of options, warrants, conversion of convertible
securities, stock splits or other distributions on our
securities. |
|
(2) |
These warrants have net exercise provisions under which the
holder may, in lieu of payment of the exercise price in cash,
surrender the warrant and receive a net amount of shares based
on the fair market value of our convertible preferred stock, or
the fair market value of the underlying common stock, at the
time of exercise of the warrant after deduction of the aggregate
exercise price. |
Registration Rights
The holders of 12,666,153 shares of common stock, assuming
the conversion of our convertible preferred stock and payments
of dividends thereon and holders of 3,931,555 shares of
common stock issuable pursuant to the exercise of warrants or
options, or their transferees, are entitled to certain
registration rights with respect to these securities as set
forth in an agreement between us and the holders of these
securities. These registration rights are subject to certain
conditions and limitations, including the right of the
underwriters of an offering to limit the number of shares
included in any such registration under certain circumstances.
We are generally required to pay all expenses incurred in
connection with registrations effected in connection with the
following rights, excluding underwriting discounts and
commissions. All registration rights described below shall
terminate five years after the closing of this offering.
103
Demand Rights. At any time after 180 days following
the completion of this offering, a stockholder or stockholders
having demand registration rights may request, in writing, that
we effect the registration on
Form S-1 or
Form S-2 (or any
successor form) of securities owned by such stockholder or
stockholders having an aggregate value of at least
$20.0 million (based on the then current market price or
fair value of our common stock as determined in good faith by
our board of directors) for sale under the Securities Act. We
may be required to effect up to three such registrations in
total. In addition, we will not be required to effect any such
registrations within six months after the effective date of the
registration statement of which this prospectus is a part or
within three months after the effective date of any other
registration statement relating to an underwritten public
offering. Stockholders with these registration rights who are
not part of an initial registration demand are entitled to
notice and are entitled to include their shares of common stock
in the registration.
Form S-3
Rights. At any time after we become eligible to file a
registration statement on
Form S-3, or any
successor form relating to secondary offerings, a stockholder or
stockholders having demand registration rights may request, in
writing, that we effect the registration on
Form S-3 or its
successor form, of securities having an aggregate value of at
least $10.0 million, based on the then current public
market price of our common stock. We may be required to effect
up to two such registrations in any
12-month period.
Stockholders with these registration rights who are not part of
an initial registration demand are entitled to notice and are
entitled to include their shares of common stock in the
registration.
Incidental Rights. During the period from 180 days
following the completion of this offering to five years
following this offering, whenever we propose to file a
registration statement, other than a registration statement
filed pursuant to an exercise of demand rights described above,
we will, prior to such filing, give written notice to all
stockholders having registration rights of our intention to do
so. Upon the written request of a stockholder or stockholders
given within 20 days after we provide such notice, we shall
use our reasonable best efforts to cause all securities which we
have been requested by such stockholder or stockholders to
register to be registered under the Securities Act to the extent
necessary to permit their sale or other disposition in
accordance with the intended methods of distribution specified
in the request of the stockholder or stockholders. We shall have
the right to postpone or withdraw any such registration without
obligation to any stockholder. In addition, under certain
circumstances, the underwriters, if any, may limit the number of
shares included in any such registration.
Anti-Takeover Provisions
The provisions of Delaware law, our restated certificate of
incorporation to be filed upon completion of this offering and
our restated bylaws to be effective upon completion of this
offering discussed below could discourage or make it more
difficult to accomplish a proxy contest or other change in our
management or the acquisition of control by a holder of a
substantial amount of our voting stock. It is possible that
these provisions could make it more difficult to accomplish, or
could deter, transactions that stockholders may otherwise
consider to be in their best interests or in our best interests.
These provisions are intended to enhance the likelihood of
continuity and stability in the composition of our board of
directors and in the policies formulated by the board of
directors and to discourage certain types of transactions that
may involve an actual or threatened change of our control. These
provisions are designed to reduce our vulnerability to an
unsolicited acquisition proposal and to discourage certain
tactics that may be used in proxy fights. Such provisions also
may have the effect of preventing changes in our management.
Delaware Statutory Business Combinations Provision. We
are subject to the anti-takeover provisions of Section 203
of the Delaware General Corporations Law. In general,
Section 203 prohibits a publicly-held Delaware corporation
from engaging in a business combination with an
interested stockholder for a period of three years
after the date of the transaction in which the person became an
interested stockholder, unless the business combination is, or
the transaction in which the person became an interested
stockholder was, approved in a prescribed manner or another
prescribed exception applies. For purposes of Section 203,
a business combination is defined broadly to include
a merger, asset sale or other transaction resulting in a
financial benefit to the interested stockholder, and, subject to
certain
104
exceptions, an interested stockholder is a person
who, together with his or her affiliates and associates, owns,
or within three years prior, did own, 15% or more of the
corporations voting stock.
Classified Board of Directors; Removal of Directors for
Cause. Our restated certificate of incorporation and
restated bylaws provide that upon completion of this offering,
our board of directors will be divided into three classes, with
the term of office of the first class to expire at the first
annual meeting of stockholders following the initial
classification of directors, the term of office of the second
class to expire at the second annual meeting of stockholders
following the initial classification of directors, and the term
of office of the third class to expire at the third annual
meeting of stockholders following the initial classification of
directors. At each annual meeting of stockholders, directors
elected to succeed those directors whose terms expire will be
elected for a three-year term of office. All directors elected
to our classified board of directors will serve until the
election and qualification of their respective successors or
their earlier resignation or removal. The board of directors is
authorized to create new directorships and to fill such
positions so created and is permitted to specify the class to
which any such new position is assigned. The person filling such
position would serve for the term applicable to that class. The
board of directors, or its remaining members, even if less than
a quorum, is also empowered to fill vacancies on the board of
directors occurring for any reason for the remainder of the term
of the class of directors in which the vacancy occurred. Members
of the board of directors may only be removed for cause and only
by the affirmative vote of 80% of our outstanding voting stock.
These provisions are likely to increase the time required for
stockholders to change the composition of the board of
directors. For example, in general, at least two annual meetings
will be necessary for stockholders to effect a change in a
majority of the members of the board of directors.
Advance Notice Provisions for Stockholder Proposals and
Stockholder Nominations of Directors. Our restated bylaws
provide that, for nominations to the board of directors or for
other business to be properly brought by a stockholder before a
meeting of stockholders, the stockholder must first have given
timely notice of the proposal in writing to our Secretary. For
an annual meeting, a stockholders notice generally must be
delivered not less than 45 days nor more than 75 days
prior to the anniversary of the mailing date of the proxy
statement for the previous years annual meeting. For a
special meeting, the notice must generally be delivered not
earlier than the 90th day prior to the meeting and not later
than the later of (1) the 60th day prior to the meeting or
(2) the 10th day following the day on which public
announcement of the meeting is first made. Detailed requirements
as to the form of the notice and information required in the
notice are specified in the restated bylaws. If it is determined
that business was not properly brought before a meeting in
accordance with our bylaw provisions, such business will not be
conducted at the meeting.
Special Meetings of Stockholders. Special meetings of the
stockholders may be called only by our board of directors
pursuant to a resolution adopted by a majority of the total
number of directors.
No Stockholder Action by Written Consent. Our restated
certificate of incorporation and restated bylaws do not permit
our stockholders to act by written consent. As a result, any
action to be effected by our stockholders must be effected at a
duly called annual or special meeting of the stockholders.
Super-Majority Stockholder Vote Required for Certain
Actions. The Delaware General Corporation Law provides
generally that the affirmative vote of a majority of the shares
entitled to vote on any matter is required to amend a
corporations certificate of incorporation or bylaws,
unless the corporations certificate of incorporation or
bylaws, as the case may be, requires a greater percentage. Our
restated certificate of incorporation requires the affirmative
vote of the holders of at least 80% of our outstanding voting
stock to amend or repeal any of the provisions discussed in this
section of this prospectus entitled Anti-Takeover
Provisions or to reduce the number of authorized shares of
common stock or preferred stock. This 80% stockholder vote would
be in addition to any separate class vote that might in the
future be required pursuant to the terms of any preferred stock
that might then be outstanding. In addition, an 80% vote is also
required for any amendment to, or repeal of, our restated bylaws
by the stockholders. Our restated bylaws may be amended or
repealed by a simple majority vote of the board of directors.
105
Transfer Agent and Registrar
The transfer agent and registrar for the common stock is
Computershare Trust Company, N.A.
Listing
Our common stock has been approved for quotation on the Nasdaq
National Market under the symbol ALTU.
106
SHARES ELIGIBLE FOR FUTURE SALE
Prior to this offering, there has been no market for our common
stock and a significant public market for our common stock may
not develop or be sustained after this offering. Future sales of
substantial amounts of our common stock in the public market
could adversely affect market prices prevailing from time to
time. Furthermore, because only a limited number of shares will
be available for sale shortly after this offering due to
existing contractual and legal restrictions on resale as
described below, there may be sales of substantial amounts of
our common stock in the public market after the restrictions
lapse. This may adversely affect the prevailing market price of
our common stock and our ability to raise equity capital in the
future.
Upon completion of this offering, we will have
21,001,943 shares of common stock outstanding, assuming the
conversion of all outstanding shares of convertible preferred
stock and payment of dividends thereon. Of these shares, the
shares sold in this offering will be freely transferable without
restriction or registration under the Securities Act, except for
any shares purchased by one of our existing
affiliates, as that term is defined in Rule 144
under the Securities Act. The remaining shares of common stock
are restricted securities as defined in
Rule 144. Restricted securities may be sold in the public
market only if registered or if they qualify for an exemption
from registration under Rules 144, 144(k) or 701 of the
Securities Act, as described below. Taking into account the
lock-up agreements
described below and the provisions of Rules 144, 144(k) and
701, the number of shares of common stock that will be available
for sale in the public market is as follows:
|
|
|
Number of Shares |
|
Date |
|
|
|
465,011 |
|
On the date of this prospectus. |
46,719
|
|
After 90 days from the date of this prospectus. |
13,490,213
|
|
After 180 days from the date of this prospectus, subject,
in some cases, to volume limitations. |
The lock-up agreements
may be extended or shortened in certain circumstances. Please
see the section below entitled
Lock-up
Agreements for further information.
Rule 144
In general, under Rule 144 as currently in effect,
beginning 90 days after the effective date of the
registration statement of which this prospectus is a part, a
person, or persons whose shares are aggregated, who owns shares
that were purchased from us at least one year previously, is
entitled to sell within any three-month period a number of
shares that does not exceed the greater of
|
|
|
|
|
1% of our then-outstanding shares of common stock, which will
equal approximately 210,000 shares immediately after this
offering, or |
|
|
|
the average weekly trading volume of our common stock on the
Nasdaq National Market during the four calendar weeks preceding
the filing of a notice of the sale on Form 144. |
Sales under Rule 144 are also subject to manner of sale
provisions, notice requirements and the availability of current
public information about us. Rule 144 also provides that
affiliates that sell our common stock that are not restricted
securities must still comply with certain other restrictions of
that rule on their manner of sale of our shares, other than the
holding period requirement. We are unable to estimate the number
of shares that will be sold under Rule 144 since this will
depend on the market price for our common stock, the personal
circumstances of the stockholder and other factors.
Rule 144(k)
Under Rule 144(k), a person who is not deemed to have been
one of our affiliates at any time during the 90 days
preceding a sale, and who owns shares within the definition of
restricted securities
107
under Rule 144 that were purchased from us at least two
years previously would be entitled to sell shares under
Rule 144(k) without regard to the volume limitations,
manner of sale provisions, public information requirements or
notice requirements described above.
Rule 701
In general, under Rule 701, any of our employees,
directors, officers, consultants or advisors who acquires common
stock from us in connection with a compensatory stock or option
plan or other written agreement before the effective date of
this offering to the extent not subject to a
lock-up agreement is
entitled to resell such shares 90 days after the effective
date of this offering in reliance on Rule 144.
The SEC has indicated that Rule 701 will apply to typical
stock options granted by an issuer before it becomes subject to
the reporting requirements of the Securities Exchange Act, along
with the shares acquired upon exercise of such options,
including exercises after the date of this prospectus.
Securities issued in reliance on Rule 701 are restricted
securities and, subject to the
lock-up agreements
described below, beginning 90 days after the date of this
prospectus, may be sold by persons other than affiliates, as
defined in Rule 144, subject only to the manner of sale
provisions of Rule 144 and by affiliates under
Rule 144 without compliance with its one-year minimum
holding period requirement.
Warrants
As of December 31, 2005, after giving effect to this
offering, we had outstanding warrants to purchase a total of
4,121,189 shares of our common stock at a weighted average
exercise price of $7.17 per share. See Description of
Capital Stock Warrants.
Registration Rights
Upon completion of this offering, the holders of
12,666,153 shares of common stock and holders of
3,931,555 shares of common stock issuable upon exercise of
warrants or options, or their transferees, will be entitled to
various rights with respect to the registration of these shares
under the Securities Act. Registration of these shares under the
Securities Act would result in these shares becoming freely
tradable without restriction under the Securities Act
immediately upon the effectiveness of the registration, except
for shares held by affiliates. See Description of Capital
Stock Registration Rights.
Stock Options
As of December 31, 2005, options to purchase a total of
3,056,807 shares of common stock were outstanding, of which
2,980,298 were exercisable. 3,021,909 of the shares subject
to options are subject to
lock-up agreements. An
additional 297,030 shares of common stock were available
for future option grants under our stock plans.
Upon completion of this offering, we intend to file one or more
registration statements on
Form S-8 under the
Securities Act covering all shares of common stock subject to
outstanding options or issuable pursuant to our stock plans.
These registration statements are expected to become effective
upon filing. Subject to Rule 144 volume limitations
applicable to affiliates, shares registered under any
registration statements will be available for sale in the open
market, except to the extent that the shares are subject to
vesting restrictions with us or the
lock-up agreements
described below.
Lock-up
Agreements
We and our officers, directors, stockholders, warrant holders
and option holders who hold an aggregate of approximately
20,563,602 shares of our common stock, on a fully diluted
basis, have agreed, subject to limited exceptions, not to offer,
pledge, sell, contract to sell, sell any option or contract to
purchase, purchase any option or contract to sell, grant any
option, right or warrant to purchase, or otherwise transfer or
dispose of, directly or indirectly, or enter into any swap or
other arrangement that transfers to another, in whole or in
part, any of the economic consequences of ownership of any
shares of
108
common stock or any securities convertible into or exercisable
or exchangeable for shares of common stock held prior to the
offering for a period of 180 days after the date of this
prospectus, without the prior written consent of Merrill Lynch.
Merrill Lynch, in its sole discretion, at any time or from time
to time and without notice, may release for sale in the public
market all or any portion of the shares restricted by the terms
of the lock-up
agreements. The lock-up
restrictions will not apply to transactions relating to common
stock acquired in open market transactions after the closing of
this offering provided that no filing by the transferor under
Rule 144 of the Securities Act or Section 16 of the
Securities Exchange Act is required or will be voluntarily made
in connection with such transactions. The
lock-up restrictions
also will not apply to certain transfers not involving a
disposition for value, provided that the recipient agrees to be
bound by these lock-up
restrictions and provided that no filing by the transferor under
Rule 144 of the Securities Act or Section 16 of the
Securities Exchange Act is required or will be voluntarily made
in connection with such transfers.
109
UNDERWRITING
Merrill Lynch, Pierce, Fenner & Smith Incorporated,
Morgan Stanley & Co. Incorporated and SG
Cowen & Co., LLC are acting as representatives of the
underwriters named below. Subject to the terms and conditions
described in a purchase agreement among us and the underwriters,
we have agreed to sell to the underwriters, and the underwriters
severally have agreed to purchase from us, the number of shares
listed opposite their names below.
|
|
|
|
|
|
|
Number | |
Underwriter |
|
of Shares | |
|
|
| |
Merrill Lynch, Pierce, Fenner & Smith
Incorporated
|
|
|
2,660,000 |
|
Morgan Stanley & Co. Incorporated
|
|
|
2,660,000 |
|
SG Cowen & Co., LLC
|
|
|
1,330,000 |
|
Leerink Swann & Company
|
|
|
87,500 |
|
Oppenheimer & Co. Inc.
|
|
|
87,500 |
|
Susquehanna Financial Group, LLLP
|
|
|
87,500 |
|
Toussaint Capital Partners, LLC
|
|
|
87,500 |
|
|
|
|
|
Total
|
|
|
7,000,000 |
|
|
|
|
|
The underwriters have agreed to purchase all of the shares sold
under the purchase agreement if any of these shares are
purchased. If an underwriter defaults, the purchase agreement
provides that the purchase commitments of the nondefaulting
underwriters may be increased or the purchase agreement may be
terminated.
We have agreed to indemnify the underwriters against certain
liabilities, including liabilities under the Securities Act, or
to contribute to payments the underwriters may be required to
make in respect of those liabilities.
The underwriters are offering the shares, subject to prior sale,
when, as and if issued to and accepted by them, subject to
approval of legal matters by their counsel, including the
validity of the shares, and other conditions contained in the
purchase agreement, such as the receipt by the underwriters of
officers certificates and legal opinions. The underwriters
reserve the right to withdraw, cancel or modify offers to the
public and to reject orders in whole or in part.
Commissions and Discounts
The representatives have advised us that the underwriters
propose initially to offer the shares to the public at the
initial public offering price on the cover page of this
prospectus and to dealers at that price less a concession not in
excess of $0.63 per share. The underwriters may allow, and
the dealers may reallow, a discount not in excess of
$0.10 per share to other dealers. After the initial public
offering, the public offering price, concession and discount may
be changed.
The following table shows the public offering price,
underwriting discount and proceeds before expenses to us. The
information assumes either no exercise or full exercise by the
underwriters of their overallotment option.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Per Share | |
|
Without Option | |
|
With Option | |
|
|
| |
|
| |
|
| |
Public offering price
|
|
$ |
15.00 |
|
|
$ |
105,000,000 |
|
|
$ |
120,750,000 |
|
Underwriting discount
|
|
$ |
1.05 |
|
|
$ |
7,350,000 |
|
|
$ |
8,452,500 |
|
Proceeds, before expenses, to us
|
|
$ |
13.95 |
|
|
$ |
97,650,000 |
|
|
$ |
112,297,500 |
|
The expenses of the offering, not including the underwriting
discount, are estimated at $2,350,000 and are payable by us.
110
Overallotment Option
We have granted an option to the underwriters to purchase up to
1,050,000 additional shares at the public offering price less
the underwriting discount. The underwriters may exercise this
option for 30 days from the date of this prospectus solely
to cover any overallotments. If the underwriters exercise this
option, each will be obligated, subject to conditions contained
in the purchase agreement, to purchase a number of additional
shares proportionate to that underwriters initial amount
reflected in the above table.
No Sales of Similar Securities
We and our officers, directors, stockholders, warrant holders
and option holders, who hold an aggregate of approximately
20,563,602 shares of our common stock, on a fully diluted
basis, have agreed, with exceptions, not to sell or transfer any
common stock for 180 days after the date of this prospectus
without first obtaining the written consent of Merrill Lynch.
Specifically, we and these other individuals have agreed not to
directly or indirectly
|
|
|
|
|
offer, pledge, sell or contract to sell any common stock, |
|
|
|
sell any option or contract to purchase any common stock, |
|
|
|
purchase any option or contract to sell any common stock, |
|
|
|
grant any option, right or warrant for the sale of any common
stock, |
|
|
|
lend or otherwise dispose of or transfer any common stock, |
|
|
|
request or demand that we file a registration statement related
to the common stock, or |
|
|
|
enter into any swap or other agreement that transfers, in whole
or in part, the economic consequence of ownership of any common
stock, whether any such swap or transaction is to be settled by
delivery of shares or other securities, in cash or otherwise. |
This lockup provision applies to common stock and to securities
convertible into or exchangeable or exercisable for or repayable
with common stock. It also applies to common stock owned now or
acquired later by the person executing the agreement or for
which the person executing the agreement later acquires the
power of disposition.
Quotation on the Nasdaq National Market
The shares have been approved for quotation on the Nasdaq
National Market, subject to notice of issuance, under the symbol
ALTU.
Before this offering, there has been no public market for our
common stock. The initial public offering price will be
determined through negotiations among us and the representatives
and the lead managers. In addition to prevailing market
conditions, the factors to be considered in determining the
initial public offering price are:
|
|
|
|
|
the valuation multiples of publicly traded companies that the
representatives and the lead managers believe to be comparable
to us; |
|
|
|
our financial information; |
|
|
|
the history of, and the prospects for, our company and the
industry in which we compete; |
|
|
|
an assessment of our management, its past and present
operations, and the prospects for, and timing of, our future
revenues; |
|
|
|
the present state of our development; and |
|
|
|
the above factors in relation to market values and various
valuation measures of other companies engaged in activities
similar to ours. |
111
An active trading market for the shares may not develop. It is
also possible that after the offering the shares will not trade
in the public market at or above the initial public offering
price.
The underwriters do not expect to sell more than 5% of the
shares in the aggregate to accounts over which they exercise
discretionary authority.
Price Stabilization, Short Positions and Penalty Bids
Until the distribution of the shares is completed, SEC rules may
limit underwriters and selling group members from bidding for
and purchasing our common stock. However, the representatives
may engage in transactions that stabilize the price of the
common stock, such as bids or purchases to peg, fix or maintain
that price.
If the underwriters create a short position in the common stock
in connection with the offering, i.e., if they sell more shares
than are listed on the cover of this prospectus, the
representatives may reduce that short position by purchasing
shares in the open market. The representatives may also elect to
reduce any short position by exercising all or part of the
overallotment option described above. Purchases of the common
stock to stabilize its price or to reduce a short position may
cause the price of the common stock to be higher than it might
be in the absence of such purchases.
The representatives may also impose a penalty bid on
underwriters and selling group members. This means that if the
representatives purchase shares in the open market to reduce the
underwriters short position or to stabilize the price of
such shares, they may reclaim the amount of the selling
concession from the underwriters and selling group members who
sold those shares. The imposition of a penalty bid may also
affect the price of the shares in that it discourages resales of
those shares.
Neither we nor any of the underwriters makes any representation
or prediction as to the direction or magnitude of any effect
that the transactions described above may have on the price of
the common stock. In addition, neither we nor any of the
underwriters makes any representation that the representatives
or the lead managers will engage in these transactions or that
these transactions, once commenced, will not be discontinued
without notice.
Electronic Distribution
A prospectus in electronic format will be made available on the
websites maintained by one or more of the underwriters of this
offering. Other than the electronic prospectus, the information
on the websites of the underwriters is not part of this
prospectus. The underwriters may agree to allocate a number of
shares to underwriters for sale to their online brokerage
account holders. Internet distributions will be allocated to
underwriters that may make Internet distributions on the same
basis as other allocations.
Other Relationships
Some of the underwriters and their affiliates have engaged in,
and may in the future engage in, investment banking and other
commercial dealings in the ordinary course of business with us.
An affiliate of Merrill Lynch Pierce Fenner & Smith
Incorporated holds a non-voting equity interest in Warburg
Pincus Partners, LLC, the general partner of Warburg Pincus, one
of our principal stockholders. See the section entitled
Principal Stockholders for further information
regarding Warburg Pincuss beneficial ownership. In
addition, affiliates, including some officers and employees, of
SG Cowen & Co., LLC hold shares of our capital stock and
warrants to purchase shares of our capital stock.
Disclosure Directed to Offers in the U.K.
Each underwriter has represented, warranted and agreed that:
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|
it has not made and will not make an offer of the shares to the
public in the United Kingdom prior to the publication of a
prospectus in relation to the shares of our common |
112
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|
stock and the offer that has been approved by the Financial
Services Authority (FSA) or, where appropriate,
approved in another Member State and notified to the FSA, all in
accordance with the Prospectus Directive, except that it may
make an offer of the shares to persons who fall within the
definition of qualified investor as that term is
defined in Section 86(1) of the Financial Services and
Markets Act 2000 (FSMA) or otherwise in
circumstances which do not result in an offer of transferable
securities to the public in the United Kingdom within the
meaning of the FSMA; |
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|
it has only communicated or caused to be communicated and will
only communicate or cause to be communicated any invitation or
inducement to engage in investment activity (within the meaning
of Section 21 of FSMA) received by it in connection with
the issue or sale of any shares in circumstances in which
Section 21(1) of FSMA does not apply to us; and |
|
|
|
it has complied and will comply with all applicable provisions
of FSMA with respect to anything done by it in relation to the
shares in, from or otherwise involving the United Kingdom. |
LEGAL MATTERS
The validity of the issuance of the common stock offered by us
in this offering will be passed upon for us by Mintz, Levin,
Cohn, Ferris, Glovsky and Popeo, P.C., Boston,
Massachusetts. Certain legal matters will be passed upon for the
underwriters by Wilmer Cutler Pickering Hale and Dorr LLP,
Boston, Massachusetts. Wilmer Cutler Pickering Hale and Dorr LLP
has from time to time represented us on other matters. As of the
date of this prospectus, persons and entities affiliated with
Mintz Levin own an aggregate of 11,054 shares of our common
stock and warrants to purchase 1,000 shares of common stock.
EXPERTS
The consolidated financial statements of Altus Pharmaceuticals
Inc. as of December 31, 2003 and 2004 and for each of the
three years in the period ended December 31, 2004 included
in this prospectus have been audited by Deloitte &
Touche LLP, an independent registered public accounting firm, as
stated in their report appearing herein, and are included in
reliance on the report of such firm given upon their authority
as experts in accounting and auditing.
113
WHERE YOU CAN FIND ADDITIONAL INFORMATION
We have filed with the SEC a registration statement on
Form S-1 under the
Securities Act, with respect to the common stock offered by this
prospectus. This prospectus, which is part of the registration
statement, omits certain information, exhibits, schedules and
undertakings set forth in the registration statement. For
further information pertaining to us and our common stock,
reference is made to the registration statement and the exhibits
and schedules to the registration statement. Statements
contained in this prospectus as to the contents or provisions of
any documents referred to in this prospectus are not necessarily
complete, and in each instance where a copy of the document has
been filed as an exhibit to the registration statement,
reference is made to the exhibit for a more complete description
of the matters involved.
You may read and copy all or any portion of the registration
statement without charge at the public reference room of the SEC
at 100 F Street, N.E., Washington, D.C. 20549.
Copies of the registration statement may be obtained from the
SEC at prescribed rates from the public reference room of the
SEC at such address. You may obtain information regarding the
operation of the public reference room by calling
1-800-SEC-0330. In
addition, registration statements and certain other filings made
with the SEC electronically are publicly available through the
SECs web site at http://www.sec.gov. The
registration statement, including all exhibits and amendments to
the registration statement, has been filed electronically with
the SEC.
Upon completion of this offering, we will become subject to the
information and periodic reporting requirements of the
Securities Exchange Act and, accordingly, will file annual
reports containing financial statements audited by an
independent registered public accounting firm, quarterly reports
containing unaudited financial data, current reports, proxy
statements and other information with the SEC. You will be able
to inspect and copy such periodic reports, proxy statements and
other information at the SECs public reference room, and
the web site of the SEC referred to above.
114
Altus Pharmaceuticals Inc.
Index to Financial Statements
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Page(s) | |
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F-2 |
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F-3 |
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F-4 |
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F-5 |
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F-7 |
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F-8 |
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F-1
REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
To the Stockholders and Board of Directors of
Altus Pharmaceuticals Inc. and Subsidiary:
We have audited the accompanying consolidated balance sheets of
Altus Pharmaceuticals Inc. and subsidiary (the
Company) as of December 31, 2003 and 2004, and
the related consolidated statements of operations, redeemable
preferred stock and stockholders deficit, and cash flows
for each of the three years in the period ended
December 31, 2004. These financial statements are the
responsibility of the Companys management. Our
responsibility is to express an opinion on these financial
statements based on our audits.
We conducted our audits in accordance with the standards of the
Public Company Accounting Oversight Board (United States). Those
standards require that we plan and perform the audit to obtain
reasonable assurance about whether the financial statements are
free of material misstatement. The Company is not required to
have, nor were we engaged to perform, an audit of its internal
control over financial reporting. Our audit included
consideration of internal control over financial reporting as a
basis for designing audit procedures that are appropriate in the
circumstances, but not for the purpose of expressing an opinion
on the effectiveness of the Companys internal control over
financial reporting. Accordingly, we express no such opinion. An
audit also includes examining, on a test basis, evidence
supporting the amounts and disclosures in the financial
statements, assessing the accounting principles used and
significant estimates made by management, as well as evaluating
the overall financial statement presentation. We believe that
our audits provide a reasonable basis for our opinion.
In our opinion, such consolidated financial statements present
fairly, in all material respects, the financial position of the
Company as of December 31, 2003 and 2004, and the results
of its operations and its cash flows for each of the three years
in the period ended December 31, 2004 in conformity with
accounting principles generally accepted in the United States of
America.
Deloitte & Touche LLP
Boston, Massachusetts
May 6, 2005 (January 10, 2006 as to the effects
of the reverse stock split described in Note 17)
F-2
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
CONSOLIDATED BALANCE SHEETS
(In thousands, except share and per share amounts)
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December 31, | |
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| |
|
September 30, | |
|
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2003 | |
|
2004 | |
|
2005 | |
|
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| |
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| |
|
| |
|
|
|
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(Unaudited) | |
ASSETS
|
|
|
|
|
|
|
|
|
|
|
|
|
CURRENT ASSETS:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cash and cash equivalents
|
|
$ |
6,656 |
|
|
$ |
9,489 |
|
|
$ |
7,220 |
|
|
Investments
|
|
|
15,980 |
|
|
|
43,149 |
|
|
|
24,789 |
|
|
Accounts receivable
|
|
|
109 |
|
|
|
|
|
|
|
2,500 |
|
|
Prepaid expenses and other current assets
|
|
|
1,370 |
|
|
|
954 |
|
|
|
1,233 |
|
|
|
|
|
|
|
|
|
|
|
|
|
Total current assets
|
|
|
24,115 |
|
|
|
53,592 |
|
|
|
35,742 |
|
PROPERTY AND EQUIPMENT, Net
|
|
|
3,383 |
|
|
|
7,586 |
|
|
|
7,029 |
|
OTHER ASSETS, Net
|
|
|
1,619 |
|
|
|
1,646 |
|
|
|
1,400 |
|
|
|
|
|
|
|
|
|
|
|
TOTAL ASSETS
|
|
$ |
29,117 |
|
|
$ |
62,824 |
|
|
$ |
44,171 |
|
|
|
|
|
|
|
|
|
|
|
LIABILITIES, REDEEMABLE PREFERRED STOCK AND
STOCKHOLDERS DEFICIT |
CURRENT LIABILITIES:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Accounts payable and accrued expenses
|
|
$ |
2,713 |
|
|
$ |
6,125 |
|
|
$ |
5,017 |
|
|
Current portion of long-term debt
|
|
|
972 |
|
|
|
1,908 |
|
|
|
2,401 |
|
|
Current portion of deferred revenue
|
|
|
3,613 |
|
|
|
3,947 |
|
|
|
6,022 |
|
|
|
|
|
|
|
|
|
|
|
|
|
Total current liabilities
|
|
|
7,298 |
|
|
|
11,980 |
|
|
|
13,440 |
|
|
|
|
|
|
|
|
|
|
|
|
Long-term debt
|
|
|
1,964 |
|
|
|
3,821 |
|
|
|
4,210 |
|
|
Long-term portion of deferred revenue
|
|
|
9,252 |
|
|
|
6,670 |
|
|
|
4,404 |
|
|
|
|
|
|
|
|
|
|
|
TOTAL LIABILITIES
|
|
|
18,514 |
|
|
|
22,471 |
|
|
|
22,054 |
|
|
|
|
|
|
|
|
|
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|
COMMITMENTS AND CONTINGENCIES (Note 9)
|
|
|
|
|
|
|
|
|
|
|
|
|
REDEEMABLE PREFERRED STOCK:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Redeemable Preferred stock, par value $.01 per share;
450,000 shares authorized, issued and outstanding in 2003,
2004 and 2005 (liquidation value of $5,831 at December 31,
2004 and $6,000 at September 30, 2005) at accreted
redemption value
|
|
|
5,076 |
|
|
|
5,478 |
|
|
|
5,779 |
|
|
Series B Convertible Preferred Stock, par value
$.01 per share; 12,928,155 shares authorized;
11,773,609 shares issued and outstanding in 2003, 2004 and
2005 (liquidation value of $60,566 at December 31, 2004 and
$62,852 at September 30, 2005) at accreted redemption value
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|
|
53,154 |
|
|
|
57,656 |
|
|
|
61,033 |
|
|
Series C Convertible Preferred Stock, par value
$.01 per share; 14,420,359 shares authorized;
11,819,959 shares issued and outstanding in 2004 and 2005
(liquidation value of $53,817 at December 31, 2004 and
$58,307 at September 30, 2005) at accreted redemption value
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|
|
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|
45,331 |
|
|
|
49,822 |
|
STOCKHOLDERS DEFICIT:
|
|
|
|
|
|
|
|
|
|
|
|
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|
Series A Convertible Preferred Stock, par value
$.01 per share; 87,500 shares authorized, issued and
outstanding in 2003, 2004 and 2005 (liquidation value of $4)
|
|
|
897 |
|
|
|
897 |
|
|
|
897 |
|
|
Common stock, par value $.01 per share;
27,490,000 shares authorized in 2003 and 47,113,986 in 2004
and 2005; 1,688,831, 1,718,576, 1,820,161 shares issued and
outstanding in 2003, 2004 and 2005, respectively
|
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|
17 |
|
|
|
17 |
|
|
|
18 |
|
|
Additional paid-in capital
|
|
|
23,512 |
|
|
|
23,984 |
|
|
|
16,687 |
|
|
Accumulated deficit
|
|
|
(72,053 |
) |
|
|
(93,010 |
) |
|
|
(112,119 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
Total stockholders deficit
|
|
|
(47,627 |
) |
|
|
(68,112 |
) |
|
|
(94,517 |
) |
|
|
|
|
|
|
|
|
|
|
TOTAL LIABILITIES, REDEEMABLE PREFERRED STOCK AND
STOCKHOLDERS DEFICIT
|
|
$ |
29,117 |
|
|
$ |
62,824 |
|
|
$ |
44,171 |
|
|
|
|
|
|
|
|
|
|
|
See notes to consolidated financial statements.
F-3
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
CONSOLIDATED STATEMENTS OF OPERATIONS
(In thousands, except per share amounts)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Nine Months Ended | |
|
|
Year Ended December 31, | |
|
September 30, | |
|
|
| |
|
| |
|
|
2002 | |
|
2003 | |
|
2004 | |
|
2004 | |
|
2005 | |
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
|
|
|
|
|
|
|
(Unaudited) | |
REVENUE:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Contract revenue
|
|
$ |
1,885 |
|
|
$ |
2,613 |
|
|
$ |
4,045 |
|
|
$ |
2,891 |
|
|
$ |
6,727 |
|
|
Product sales
|
|
|
483 |
|
|
|
1,268 |
|
|
|
185 |
|
|
|
185 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total revenue
|
|
|
2,368 |
|
|
|
3,881 |
|
|
|
4,230 |
|
|
|
3,076 |
|
|
|
6,727 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
COSTS AND EXPENSES:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cost of product sales
|
|
|
241 |
|
|
|
578 |
|
|
|
87 |
|
|
|
87 |
|
|
|
|
|
|
Research and development
|
|
|
13,174 |
|
|
|
13,282 |
|
|
|
19,095 |
|
|
|
11,995 |
|
|
|
19,792 |
|
|
General, sales, and administrative
|
|
|
6,859 |
|
|
|
5,533 |
|
|
|
6,320 |
|
|
|
4,623 |
|
|
|
6,003 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total costs and expenses
|
|
|
20,274 |
|
|
|
19,393 |
|
|
|
25,502 |
|
|
|
16,705 |
|
|
|
25,795 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
LOSS FROM OPERATIONS
|
|
|
(17,906 |
) |
|
|
(15,512 |
) |
|
|
(21,272 |
) |
|
|
(13,629 |
) |
|
|
(19,068 |
) |
OTHER INCOME (EXPENSE):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Interest income
|
|
|
853 |
|
|
|
405 |
|
|
|
646 |
|
|
|
405 |
|
|
|
701 |
|
|
Interest expense
|
|
|
(156 |
) |
|
|
(251 |
) |
|
|
(469 |
) |
|
|
(351 |
) |
|
|
(617 |
) |
|
Foreign currency gain (loss)
|
|
|
|
|
|
|
157 |
|
|
|
138 |
|
|
|
138 |
|
|
|
(125 |
) |
|
Gain on sale of equipment
|
|
|
|
|
|
|
7 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Realized loss on investments
|
|
|
(81 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Other income (expense), net
|
|
|
616 |
|
|
|
318 |
|
|
|
315 |
|
|
|
192 |
|
|
|
(41 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
NET LOSS
|
|
|
(17,290 |
) |
|
|
(15,194 |
) |
|
|
(20,957 |
) |
|
|
(13,437 |
) |
|
|
(19,109 |
) |
PREFERRED STOCK DIVIDENDS AND ACCRETION
|
|
|
(4,905 |
) |
|
|
(4,905 |
) |
|
|
(8,588 |
) |
|
|
(5,845 |
) |
|
|
(8,169 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
NET LOSS ATTRIBUTABLE TO COMMON STOCKHOLDERS
|
|
$ |
(22,195 |
) |
|
$ |
(20,099 |
) |
|
$ |
(29,545 |
) |
|
$ |
(19,282 |
) |
|
$ |
(27,278 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
NET LOSS ATTRIBUTABLE TO COMMON STOCKHOLDERS PER
SHARE BASIC AND DILUTED
|
|
$ |
(13.16 |
) |
|
$ |
(11.92 |
) |
|
$ |
(17.33 |
) |
|
$ |
(11.34 |
) |
|
$ |
(15.84 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
WEIGHTED AVERAGE SHARES OUTSTANDING BASIC AND DILUTED
|
|
|
1,687 |
|
|
|
1,687 |
|
|
|
1,704 |
|
|
|
1,700 |
|
|
|
1,722 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PRO FORMA NET LOSS ATTRIBUTABLE TO COMMON STOCKHOLDERS PER
SHARE BASIC AND DILUTED (UNAUDITED)
|
|
|
|
|
|
|
|
|
|
$ |
(1.96 |
) |
|
|
|
|
|
$ |
(1.46 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PRO FORMA WEIGHTED AVERAGE SHARES OUTSTANDING BASIC
AND DILUTED (UNAUDITED)
|
|
|
|
|
|
|
|
|
|
|
10,915 |
|
|
|
|
|
|
|
13,328 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
See notes to consolidated financial statements.
F-4
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
CONSOLIDATED STATEMENTS OF REDEEMABLE PREFERRED STOCK AND
STOCKHOLDERS DEFICIT
(In thousands, except share amounts)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Redeemable Preferred Stock |
|
Stockholders Deficit | |
|
|
|
|
| |
|
|
|
|
Series B | |
|
Series C |
|
Series A | |
|
|
|
|
Redeemable | |
|
Convertible | |
|
Convertible |
|
Convertible | |
|
|
|
|
|
Accumulated | |
|
|
|
|
Preferred Stock | |
|
Preferred Stock | |
|
Preferred Stock |
|
Preferred Stock | |
|
Common Stock | |
|
Additional | |
|
Other | |
|
|
|
|
| |
|
| |
|
|
|
| |
|
| |
|
Paid-In | |
|
Comprehensive | |
|
Deferred | |
|
Accumulated | |
|
|
|
|
Shares | |
|
Amount | |
|
Shares | |
|
Amount | |
|
Shares | |
|
Amount |
|
Shares | |
|
Amount | |
|
Shares | |
|
Amount | |
|
Capital | |
|
Loss | |
|
Compensation | |
|
Deficit | |
|
Total | |
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
BALANCE January 1, 2002
|
|
|
450,000 |
|
|
$ |
4,272 |
|
|
|
11,773,609 |
|
|
$ |
44,148 |
|
|
|
|
|
|
$ |
|
|
|
|
87,500 |
|
|
$ |
897 |
|
|
|
1,686,492 |
|
|
$ |
17 |
|
|
$ |
33,027 |
|
|
$ |
(75 |
) |
|
$ |
(473 |
) |
|
$ |
(39,569 |
) |
|
$ |
(6,176 |
) |
|
Adoption of SFAS No. 123 (see Note 2)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(473 |
) |
|
|
|
|
|
|
473 |
|
|
|
|
|
|
|
|
|
|
Preferred stock dividends and accretion
|
|
|
|
|
|
|
402 |
|
|
|
|
|
|
|
4,503 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(4,905 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(4,905 |
) |
|
Exercise of stock options
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
13 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Stock-based compensation expense related to options granted to
employees
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
352 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
352 |
|
|
Stock-based compensation expense related to options granted to
nonemployees
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
11 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
11 |
|
|
Warrants issued in connection with debt financing
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
13 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
13 |
|
|
Realized gain on marketable securities
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
75 |
|
|
|
|
|
|
|
|
|
|
|
75 |
|
|
Net loss
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(17,290 |
) |
|
|
(17,290 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
BALANCE December 31, 2002
|
|
|
450,000 |
|
|
|
4,674 |
|
|
|
11,773,609 |
|
|
|
48,651 |
|
|
|
|
|
|
|
|
|
|
|
87,500 |
|
|
|
897 |
|
|
|
1,686,505 |
|
|
|
17 |
|
|
|
28,025 |
|
|
|
|
|
|
|
|
|
|
|
(56,859 |
) |
|
|
(27,920 |
) |
|
Preferred stock dividends and accretion
|
|
|
|
|
|
|
402 |
|
|
|
|
|
|
|
4,503 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(4,905 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(4,905 |
) |
|
Exercise of stock options
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
2,649 |
|
|
|
|
|
|
|
3 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
3 |
|
|
Restricted common stock repurchased
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(323 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Stock-based compensation expense related to options granted to
employees
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
378 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
378 |
|
|
Stock-based compensation expense related to options granted to
nonemployees
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
3 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
3 |
|
|
Warrants issued in connection with debt financing
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
8 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
8 |
|
|
Net loss
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(15,194 |
) |
|
|
(15,194 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
BALANCE December 31, 2003
|
|
|
450,000 |
|
|
|
5,076 |
|
|
|
11,773,609 |
|
|
|
53,154 |
|
|
|
|
|
|
|
|
|
|
|
87,500 |
|
|
|
897 |
|
|
|
1,688,831 |
|
|
|
17 |
|
|
|
23,512 |
|
|
|
|
|
|
|
|
|
|
|
(72,053 |
) |
|
|
(47,627 |
) |
(Continued)
F-5
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
CONSOLIDATED STATEMENTS OF REDEEMABLE PREFERRED STOCK AND
STOCKHOLDERS DEFICIT
(In thousands, except share amounts)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Redeemable Preferred Stock | |
|
Stockholders Deficit | |
|
|
| |
|
| |
|
|
|
|
Series B | |
|
Series C | |
|
Series A | |
|
|
|
|
Redeemable | |
|
Convertible | |
|
Convertible | |
|
Convertible | |
|
|
|
|
|
Accumulated |
|
|
|
|
Preferred Stock | |
|
Preferred Stock | |
|
Preferred Stock | |
|
Preferred Stock | |
|
Common Stock | |
|
Additional | |
|
Other |
|
|
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
Paid-In | |
|
Comprehensive |
|
Deferred |
|
Accumulated | |
|
|
|
|
Shares | |
|
Amount | |
|
Shares | |
|
Amount | |
|
Shares | |
|
Amount | |
|
Shares | |
|
Amount | |
|
Shares | |
|
Amount | |
|
Capital | |
|
Loss |
|
Compensation |
|
Deficit | |
|
Total | |
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
|
|
|
|
| |
|
| |
BALANCE December 31, 2003 (Carried forward)
|
|
|
450,000 |
|
|
|
5,076 |
|
|
|
11,773,609 |
|
|
|
53,154 |
|
|
|
|
|
|
|
|
|
|
|
87,500 |
|
|
|
897 |
|
|
|
1,688,831 |
|
|
|
17 |
|
|
|
23,512 |
|
|
|
|
|
|
|
|
|
|
|
(72,053 |
) |
|
|
(47,627 |
) |
|
Preferred stock dividends and accretion
|
|
|
|
|
|
|
402 |
|
|
|
|
|
|
|
4,502 |
|
|
|
|
|
|
|
3,684 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(8,588 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(8,588 |
) |
|
Exercise of stock options
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
29,745 |
|
|
|
|
|
|
|
82 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
82 |
|
|
Issuance of Series C Convertible Preferred Stock
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
11,819,959 |
|
|
|
51,000 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Warrants issued in connection with Series C Preferred Stock
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(8,717 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
8,717 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
8,717 |
|
|
Costs associated with issuance of Series C Preferred Stock
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(636 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Stock-based compensation expense related to options granted to
employees
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
253 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
253 |
|
|
Stock-based compensation expense related to options granted to
nonemployees
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 |
|
|
Warrants issued in connection with debt financing
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
7 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
7 |
|
|
Net loss
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(20,957 |
) |
|
|
(20,957 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
BALANCE December 31, 2004
|
|
|
450,000 |
|
|
|
5,478 |
|
|
|
11,773,609 |
|
|
|
57,656 |
|
|
|
11,819,959 |
|
|
|
45,331 |
|
|
|
87,500 |
|
|
|
897 |
|
|
|
1,718,576 |
|
|
|
17 |
|
|
|
23,984 |
|
|
|
|
|
|
|
|
|
|
|
(93,010 |
) |
|
|
(68,112 |
) |
|
Preferred stock dividends and accretion (unaudited)
|
|
|
|
|
|
|
301 |
|
|
|
|
|
|
|
3,377 |
|
|
|
|
|
|
|
4,491 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(8,169 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(8,169 |
) |
|
Exercise of stock options (unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
102,335 |
|
|
|
1 |
|
|
|
295 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
296 |
|
|
Restricted common stock repurchased (unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(750 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Stock-based compensation expense related to options granted to
employees (unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
571 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
571 |
|
|
Warrants issued in connection with debt financing (unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
6 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
6 |
|
|
Net loss (unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(19,109 |
) |
|
|
(19,109 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
BALANCE September 30, 2005 (unaudited)
|
|
|
450,000 |
|
|
$ |
5,779 |
|
|
|
11,773,609 |
|
|
$ |
61,033 |
|
|
|
11,819,959 |
|
|
$ |
49,822 |
|
|
|
87,500 |
|
|
$ |
897 |
|
|
|
1,820,161 |
|
|
$ |
18 |
|
|
$ |
16,687 |
|
|
$ |
|
|
|
$ |
|
|
|
$ |
(112,119 |
) |
|
$ |
(94,517 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(Concluded)
See notes to consolidated financial statements.
F-6
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
CONSOLIDATED STATEMENTS OF CASH FLOWS
(In thousands)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Nine Months Ended | |
|
|
Year Ended December 31, | |
|
September 30, | |
|
|
| |
|
| |
|
|
2002 | |
|
2003 | |
|
2004 | |
|
2004 | |
|
2005 | |
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
|
|
|
|
|
|
|
(Unaudited) | |
CASH FLOWS FROM OPERATING ACTIVITIES:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net loss
|
|
$ |
(17,290 |
) |
|
$ |
(15,194 |
) |
|
$ |
(20,957 |
) |
|
$ |
(13,347 |
) |
|
$ |
(19,109 |
) |
|
Adjustments to reconcile net loss to net cash used in operating
activities:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Depreciation and amortization
|
|
|
896 |
|
|
|
1,231 |
|
|
|
1,736 |
|
|
|
1,084 |
|
|
|
2,116 |
|
|
|
Gain on sale of equipment
|
|
|
|
|
|
|
(7 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Stock-based compensation expense related to the issuance of
stock options and restricted stock
|
|
|
363 |
|
|
|
381 |
|
|
|
254 |
|
|
|
145 |
|
|
|
571 |
|
|
|
Realized loss on investments
|
|
|
81 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Noncash interest expense related to advance of milestone
|
|
|
|
|
|
|
|
|
|
|
225 |
|
|
|
169 |
|
|
|
169 |
|
|
|
Noncash interest expense related to common stock warrants
|
|
|
13 |
|
|
|
7 |
|
|
|
|
|
|
|
|
|
|
|
6 |
|
|
|
Provision for doubtful accounts
|
|
|
|
|
|
|
(42 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Changes in assets and liabilities:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Accounts receivable
|
|
|
(3,925 |
) |
|
|
4,583 |
|
|
|
109 |
|
|
|
(7 |
) |
|
|
|
|
|
|
|
Prepaid expenses and other current assets
|
|
|
(327 |
) |
|
|
(982 |
) |
|
|
416 |
|
|
|
(103 |
) |
|
|
(279 |
) |
|
|
|
Other noncurrent assets
|
|
|
(166 |
) |
|
|
6 |
|
|
|
(162 |
) |
|
|
|
|
|
|
|
|
|
|
|
Accounts payable and accrued expenses
|
|
|
1,391 |
|
|
|
(1,503 |
) |
|
|
2,393 |
|
|
|
1,596 |
|
|
|
(661 |
) |
|
|
|
Milestones received as deferred revenue
|
|
|
9,580 |
|
|
|
5,000 |
|
|
|
1,500 |
|
|
|
1,500 |
|
|
|
3,974 |
|
|
|
|
Deferred revenue recognized
|
|
|
(1,029 |
) |
|
|
(2,023 |
) |
|
|
(3,748 |
) |
|
|
(2,552 |
) |
|
|
(6,664 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net cash used in operating activities
|
|
|
(10,413 |
) |
|
|
(8,543 |
) |
|
|
(18,234 |
) |
|
|
(11,515 |
) |
|
|
(19,877 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
CASH FLOWS FROM INVESTING ACTIVITIES:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Purchases of investments
|
|
|
(79,627 |
) |
|
|
(40,042 |
) |
|
|
(51,206 |
) |
|
|
(37,648 |
) |
|
|
(31,844 |
) |
|
Maturities/sales of investments
|
|
|
65,299 |
|
|
|
45,309 |
|
|
|
24,036 |
|
|
|
8,689 |
|
|
|
50,204 |
|
|
Purchases of property and equipment
|
|
|
(1,767 |
) |
|
|
(1,295 |
) |
|
|
(5,011 |
) |
|
|
(2,466 |
) |
|
|
(1,930 |
) |
|
Sale of equipment
|
|
|
|
|
|
|
10 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net cash (used in) provided by investing activities
|
|
|
(16,095 |
) |
|
|
3,982 |
|
|
|
(32,181 |
) |
|
|
(31,425 |
) |
|
|
16,430 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
CASH FLOWS FROM FINANCING ACTIVITIES:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net proceeds from issuance of preferred stock and related
warrants
|
|
|
|
|
|
|
|
|
|
|
50,372 |
|
|
|
50,635 |
|
|
|
|
|
|
Proceeds from exercise of stock options
|
|
|
|
|
|
|
3 |
|
|
|
82 |
|
|
|
81 |
|
|
|
296 |
|
|
Proceeds from long-term debt
|
|
|
1,993 |
|
|
|
1,449 |
|
|
|
3,792 |
|
|
|
443 |
|
|
|
2,569 |
|
|
Repayment of debt
|
|
|
(1,007 |
) |
|
|
(796 |
) |
|
|
(998 |
) |
|
|
(716 |
) |
|
|
(1,687 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net cash provided by financing activities
|
|
|
986 |
|
|
|
656 |
|
|
|
53,248 |
|
|
|
50,443 |
|
|
|
1,178 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
NET INCREASE (DECREASE) IN CASH AND CASH EQUIVALENTS
|
|
|
(25,522 |
) |
|
|
(3,905 |
) |
|
|
2,833 |
|
|
|
7,503 |
|
|
|
(2,269 |
) |
CASH AND CASH EQUIVALENTS Beginning of period
|
|
|
36,083 |
|
|
|
10,561 |
|
|
|
6,656 |
|
|
|
6,656 |
|
|
|
9,489 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
CASH AND CASH EQUIVALENTS End of period
|
|
$ |
10,561 |
|
|
$ |
6,656 |
|
|
$ |
9,489 |
|
|
$ |
14,159 |
|
|
$ |
7,220 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
SUPPLEMENTAL DISCLOSURE OF CASH FLOW INFORMATION:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cash paid for interest
|
|
$ |
155 |
|
|
$ |
249 |
|
|
$ |
243 |
|
|
$ |
190 |
|
|
$ |
491 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Equipment acquired under capital lease
|
|
$ |
598 |
|
|
$ |
394 |
|
|
$ |
|
|
|
$ |
|
|
|
$ |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
SUPPLEMENTAL DISCLOSURE OF NONCASH FINANCING ACTIVITIES:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
First and last months payments withheld from long-term
debt proceeds
|
|
$ |
113 |
|
|
$ |
66 |
|
|
$ |
107 |
|
|
$ |
9 |
|
|
$ |
70 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
See notes to consolidated financial statements.
F-7
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
Altus Pharmaceuticals Inc., or the Company, was incorporated in
Massachusetts in October 1992 as a wholly owned subsidiary of
Vertex Pharmaceuticals Incorporated, or Vertex, a Massachusetts
corporation. In February 1999, the Company was reorganized as an
independent company, and in August 2001 it was reincorporated as
a Delaware corporation. Prior to May 2004, the Company was named
Altus Biologics Inc.
The Company is subject to risks common to companies in the
biotechnology industry including, but not limited to, product
development risks, new technological innovations, protection of
proprietary technology, compliance with government regulations,
dependence on key personnel, the need to obtain additional
financing, uncertainty of market acceptance of products, and
product liability.
|
|
2. |
Summary of Significant Accounting Policies |
Unaudited Pro Forma Presentation On
October 17, 2005, the Company filed a registration
statement with the Securities and Exchange Commission, or the
SEC, for the Company to sell shares of its common stock to the
public. The Series A, B and C convertible preferred
stock are subject to mandatory conversion to common stock upon
the closing of an initial public offering at a price of at least
$6.48 per share and with net proceeds to the Company of at least
$50.0 million, or a Qualified Public Offering. The
unaudited pro forma net loss attributable to common stockholders
per share for the year ended December 31, 2004 and the nine
months ended September 30, 2005 reflect the assumed
conversion of the Series A, B and C convertible
preferred stock and payment of accrued dividends in common stock
as of the beginning of each period presented (at an assumed
common stock price of $15.00 per share).
Unaudited Interim Financial Statements The
accompanying unaudited consolidated financial statements as of
September 30, 2005 and for the nine months ended
September 30, 2004 and 2005 have been prepared in
accordance with generally accepted accounting principles and
with the instructions to
Form 10-Q and
Article 10 of
Regulation S-X.
Accordingly, they do not include all of the information and
footnotes required by generally accepted accounting principles
for complete financial statements. The unaudited consolidated
financial statements have been prepared on the same basis as the
annual financial statements and, in the opinion of management,
reflect all adjustments, consisting only of normal recurring
accruals, considered necessary to present fairly the
Companys financial position as of September 30, 2005
and results of operations and cash flows for the nine months
ended September 30, 2004 and 2005. The results of
operations for the nine months ended September 30, 2005 are
not necessarily indicative of the results that may be expected
for the year ending December 31, 2005.
Principles of Consolidation The consolidated
financial statements include the accounts of Altus
Pharmaceuticals Inc. and its wholly owned subsidiary, Altus
Pharmaceuticals Securities Corporation. All intercompany
transactions and balances have been eliminated.
Use of Estimates The preparation of the
Companys consolidated financial statements in conformity
with accounting principles generally accepted in the United
States of America necessarily requires management to make
estimates and assumptions that affect the reported amounts of
assets and liabilities, the disclosure of contingent assets and
liabilities at the date of the consolidated financial
statements, and the reported amounts of revenue and expenses
during the reporting period. Actual results could differ from
those estimates.
F-8
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
Cash and Cash Equivalents Cash and cash
equivalents represent cash and highly liquid investments
purchased within three months of the maturity date and consist
of money market funds and government securities.
Investments The Company invests available
cash primarily in bank certificates of deposit and
investment-grade commercial paper, corporate notes, government
securities and auction rate preferred securities. Securities
that the Company has the positive intent and ability to hold to
maturity are reported at amortized cost and are classified as
held-to-maturity. Auction rate preferred securities are
classified as available-for-sale and carried at fair market
value. All of the Companys other investments at
December 31, 2003 and 2004 are classified as
held-to-maturity and have maturity dates of less than one year.
Property and Equipment Property and equipment
are recorded at cost. Depreciation is provided using the
straight-line method over the following estimated useful lives
of the assets: computer equipment three years;
software five years; laboratory
equipment four years; office equipment
seven years; and leasehold improvements over the
lesser of the estimated life of the asset or the lease term.
Included in property and equipment at December 31, 2004 is
general equipment costing $1,451,000 not yet placed in service
and leasehold improvements of newly leased laboratory space of
$1,381,000 not completed as of December 31, 2004.
Other Assets Other assets is primarily
composed of the deferral of costs related to the fair value of a
warrant issuance in 2001. The warrant was issued in order to
induce Cystic Fibrosis Foundation Therapeutics, Inc., or CFFTI,
to provide the Company with future research and development
funding (revenue). This cost deferral is being amortized against
research and development revenue over the period of funding.
Impairment of Long-Lived Assets The Company
continually evaluates whether events or circumstances have
occurred that indicate that the estimated remaining useful lives
of long-lived assets may require revision or that the carrying
value of these assets may be impaired. To determine whether
assets have been impaired, the estimated undiscounted future
cash flows for the estimated remaining useful life of the
respective assets are compared to the carrying value. To the
extent that the undiscounted future cash flows are less than the
carrying value, a new fair value of the asset is required to be
determined. If such fair value is less than the current carrying
value, the asset is written down to its estimated fair value.
There were no impairments of the Companys assets during
the periods presented.
Fair Value of Financial Instruments The
carrying amounts of cash and cash equivalents, investments,
accounts receivable, accounts payable, and accrued expenses
approximate fair value because of their short-term nature.
Investments at December 31, 2003 and December 31,
2004, carried at an amortized cost of approximately $15,980,000
and $43,149,000, respectively, had a fair value of approximately
$15,979,000 and $43,012,000, respectively, based on quoted
market prices. The carrying amounts of the Companys
long-term debt instruments approximate fair value.
Concentrations of Credit Risk and Financial
Instruments The Companys financial
instruments that potentially subject it to concentrations of
credit risk are cash and cash equivalents, and investments. The
Company invests cash that is not currently being used for
operational purposes in accordance with its investment policy.
The policy allows for the purchase of low-risk debt securities
issued by the United States government and very highly-rated
banks and corporations, subject to certain concentration limits.
The policy allows for maturities that are no longer than
13 months. The Company believes its established guidelines
for investment of excess cash maintain safety and liquidity
through its policy on diversification
F-9
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
and investment maturity. During 2003 and 2004, the Company
derived a majority of its revenue from two customers (see
Note 10).
Revenue Recognition The Company recognizes
revenue using two different methodologies that are dependent
upon the process used to generate such revenue. Revenue consists
of (i) contract revenue earned under collaborative
agreements and (ii) product sales.
Contract revenue consists of non-refundable research and
development funding under collaborative agreements with
corporate partners and grants from various United States
government and non-government institutions. Research and
development funding compensates the Company for a portion or all
of the development and testing related to the collaborative
research programs or grants.
Revenue under collaborative agreements with collaborative
partners and non-government institutions is primarily recognized
using the proportional performance method and is based on the
percentage of costs incurred relative to the total costs
estimated to be incurred to complete the research program, to
the extent such amount is not greater than the cash received.
The Company uses an input based measure, specifically direct
costs, to determine proportional performance, because, for its
current agreements, the use of an input measure is a more
accurate representation of proportional performance than an
output based measure, such as milestones. The direct cost method
most closely reflects the level of effort related to the
Companys research and development collaborations. The
impact of fluctuations in exchange rates under collaborative
agreements that are denominated in a foreign currency is
reflected in deferred revenue at the time cash is received and
in revenue at each reporting period. The Company periodically
reviews the estimated development costs and, to the extent such
estimates change, the cumulative impact of such change is
recorded in operations at that time. As a result, the
possibility exists that revenue may increase or decrease in
future periods as estimated costs increase or decrease, without
additional cash inflows from the collaborative partner or
non-government institution.
Contract amounts which are not due until the customer accepts or
verifies the research results are not recognized as revenue
until payment is received or the customers acceptance or
verification of the results is evidenced, whichever occurs
earlier. In the event warrants are issued in connection with a
collaborative agreement, contract revenue is recorded net of
amortization of the related warrants (see Note 6).
Deferred revenue at December 31, 2003 and 2004 consisted
primarily of payments received in advance of revenue recognized
under collaborative agreements. Since the payments received
under the collaborative agreements are non-refundable, the
termination of a collaborative agreement prior to its completion
could result in an immediate recognition of deferred revenue
relating to payments already received from the collaborative
partner but not previously recognized as revenue.
Research and development funding under grants from the United
States government and its agencies is recognized as revenue as
development costs are incurred and billed in accordance with the
terms of the grant.
Revenue from product sales is recognized when there is
persuasive evidence that an arrangement exists, delivery and, if
applicable, acceptance by the customer has occurred, the price
is fixed or determinable, delivery has occurred, and
collectibility is reasonably assured.
Research and Development Expenses Research
and development expenses are charged to operations as incurred.
F-10
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
Stock-Based Compensation and Change in Accounting
Principle At December 31, 2004 and
September 30, 2005, the Company administered the 2002
Employee, Director, and Consultant Stock Option Plan (the
2002 Plan), which replaced the 1993 Stock Option
Plan (the 1993 Plan) on February 7, 2002 (see
Note 14).
The Company follows the fair value recognition provisions of
Financial Accounting Standards Board (FASB)
Statement of Financial Accounting Standards (SFAS)
No. 123, Accounting for Stock-Based Compensation.
Accordingly, the Company accounts for transactions in which
goods and services are received in exchange for equity
instruments based on the fair value of such goods and services
received or of the equity instruments issued, whichever is more
reliably measured. When equity instruments are granted or sold
in exchange for the receipt of goods or services and the value
of those goods or services can not be readily estimated, as is
true in connection with most stock options and warrants granted
to employees, directors, consultants and other non-employees,
the Company determines the fair value of the equity instruments
using all relevant information, including application of the
Black-Scholes option-pricing model, and, in specified
situations, input from valuation specialists.
Deferred compensation included in stockholders deficit as
of January 1, 2002 related to compensatory awards under the
Companys stock option plan and restricted stock purchase
agreements and was being amortized over the vesting period in
accordance with APB Opinion No. 25. As a result of the
adoption of SFAS No. 123 on January 1, 2002, the
deferred compensation balance of $473,000 was reclassified to
additional paid-in capital.
In December 2004, the FASB issued SFAS No. 123R,
Share-Based Payment (SFAS No. 123R).
This Statement is a revision of SFAS No. 123 and supersedes
APB Opinion No. 25 and its related implementation guidance.
SFAS No. 123R focuses primarily on accounting for
transactions in which a company obtains employee services in
share-based payment transactions. The Statement requires
companies to recognize stock compensation expense for awards of
equity instruments to employees based on grant-date fair value
of those awards (with limited exceptions). SFAS No. 123R
will be effective for the Companys 2006 fiscal year.
Management is currently evaluating the impact of SFAS
No. 123R on the Companys financial statements.
Income Taxes The Company provides deferred
tax assets and liabilities for the expected future tax
consequences of temporary differences between the Companys
financial statement carrying amounts and the tax bases of assets
and liabilities using enacted tax rates expected to be in effect
in the years in which the differences are expected to reverse. A
valuation allowance is provided to reduce the deferred tax
assets to the amount that will more likely than not be realized.
Net Loss per Share Basic and diluted net loss
per common share is calculated by dividing net loss attributable
to common stockholders by the weighted average number of common
shares outstanding during the period. Diluted net loss per
common share is the same as basic net loss per common share,
since the effects of potentially dilutive securities are
antidilutive for all periods presented.
The unaudited pro forma basic and diluted net loss per share
calculations assume the conversion of the Series A, B and C
convertible preferred stock into shares of common stock using
the if-converted method as of January 1, 2004 or the date
of issuance, if later.
F-11
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Nine Months Ended | |
|
|
Year Ended December 31, | |
|
September 30, | |
|
|
| |
|
| |
|
|
2002 | |
|
2003 | |
|
2004 | |
|
2004 | |
|
2005 | |
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
|
(In thousands, except per share amounts) | |
Historical
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Numerator:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net loss attributable to common stockholders
|
|
$ |
(22,195 |
) |
|
$ |
(20,099 |
) |
|
$ |
(29,545 |
) |
|
$ |
(19,282 |
) |
|
$ |
(27,278 |
) |
Denominator:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Weighted average common shares outstanding
|
|
|
1,687 |
|
|
|
1,687 |
|
|
|
1,704 |
|
|
|
1,700 |
|
|
|
1,722 |
|
Net loss attributable to common stockholders per
share basic and diluted
|
|
$ |
(13.16 |
) |
|
$ |
(11.92 |
) |
|
$ |
(17.33 |
) |
|
$ |
(11.34 |
) |
|
$ |
(15.84 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Historical outstanding dilutive securities not included in
diluted net loss per share attributable to common
stockholders
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Series A, B and C convertible preferred stock:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Preferred shares
|
|
|
5,564 |
|
|
|
5,564 |
|
|
|
10,767 |
|
|
|
10,767 |
|
|
|
10,767 |
|
|
Preferred stock warrants
|
|
|
508 |
|
|
|
508 |
|
|
|
1,653 |
|
|
|
1,653 |
|
|
|
1,653 |
|
Options to purchase common stock
|
|
|
1,183 |
|
|
|
1,598 |
|
|
|
2,118 |
|
|
|
1,721 |
|
|
|
3,034 |
|
Warrants to purchase common stock
|
|
|
2,460 |
|
|
|
2,464 |
|
|
|
2,468 |
|
|
|
2,464 |
|
|
|
2,468 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total
|
|
|
9,715 |
|
|
|
10,134 |
|
|
|
17,006 |
|
|
|
16,605 |
|
|
|
17,922 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Unaudited Pro Forma
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Numerator:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net loss attributable to common stockholders used above
|
|
|
|
|
|
|
|
|
|
$ |
(29,545 |
) |
|
|
|
|
|
$ |
(27,278 |
) |
Pro forma adjustment to eliminate dividends and accretion on
Series B and C convertible preferred stock
|
|
|
|
|
|
|
|
|
|
|
8,186 |
|
|
|
|
|
|
|
7,868 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Pro forma net loss attributable to common stockholders
|
|
|
|
|
|
|
|
|
|
$ |
(21,359 |
) |
|
|
|
|
|
$ |
(19,410 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Denominator:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Shares used above
|
|
|
|
|
|
|
|
|
|
|
1,704 |
|
|
|
|
|
|
|
1,722 |
|
Pro forma adjustment to reflect weighted average effect of
assumed conversion of Series A, B and C convertible
preferred stock and accrued dividends payable in common stock
|
|
|
|
|
|
|
|
|
|
|
9,211 |
|
|
|
|
|
|
|
11,606 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Shares used to compute pro forma basic and diluted net loss
attributable to common stockholders
|
|
|
|
|
|
|
|
|
|
|
10,915 |
|
|
|
|
|
|
|
13,328 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Pro forma net loss attributable to common stockholders per
share basic and diluted
|
|
|
|
|
|
|
|
|
|
$ |
(1.96 |
) |
|
|
|
|
|
$ |
(1.46 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
F-12
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
Comprehensive Loss Comprehensive loss equals
net loss for all periods presented.
Segment Reporting Operating segments are
identified as components of an enterprise about which separate
discrete financial information is available for evaluation by
the chief decision-maker, or decision-making group, in making
decisions regarding resource allocation and assessing
performance. The Company, which uses consolidated financial
information in determining how to allocate resources and assess
performance, has determined that it operates in one segment,
which focuses on developing and commercializing novel protein
therapeutics for patients with chronic gastrointestinal and
metabolic diseases.
|
|
3. |
Related-Party Transactions |
Vertex During the three years ended
December 31, 2004, the Company leased a laboratory and
certain equipment from Vertex which is also a stockholder.
Vertexs ownership interest in the Company on a fully
converted basis at December 31, 2004 was approximately 14%,
consisting of Series A convertible preferred stock,
redeemable preferred stock, common stock and warrants to
purchase common stock. The total amounts paid to Vertex for the
laboratory and equipment during the years ended
December 31, 2002, 2003 and 2004 were approximately
$137,000, $121,000 and $91,000, respectively. Amounts payable to
Vertex at December 31, 2003 and 2004 were approximately
$8,000 and $0, respectively. Vertex granted the Company an
exclusive royalty-free, fully-paid license to patents relating
to cross-linked enzyme crystals, and retained non-exclusive
right to use the licensed patents and know-how for specified
uses. These licenses expire on a patent-by-patent basis.
Consulting Agreements In March 2003, the
Company entered into a consulting agreement with a member of the
Board of Directors, who also is a stockholder. During the years
ended December 31, 2003 and 2004, the Company paid
approximately $50,000 and $21,000, respectively, to this
individual. In October 2004, the Company entered into a
consulting agreement with another member of the Board of
Directors, who is also a stockholder. Under the latter
agreement, the Company recognized expense of approximately
$57,000 in the year ended December 31, 2004, which was
included in accounts payable at December 31, 2004.
Investments consisted of the following at December 31, 2003:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Gross | |
|
|
|
|
Amortized | |
|
Unrealized | |
|
Aggregate | |
|
|
Cost | |
|
Losses | |
|
Fair Value | |
|
|
| |
|
| |
|
| |
Corporate fixed income
|
|
$ |
7,639,000 |
|
|
$ |
(1,000 |
) |
|
$ |
7,638,000 |
|
Government securities
|
|
|
991,000 |
|
|
|
|
|
|
|
991,000 |
|
Auction rate preferred securities
|
|
|
7,150,000 |
|
|
|
|
|
|
|
7,150,000 |
|
Certificates of deposit
|
|
|
200,000 |
|
|
|
|
|
|
|
200,000 |
|
|
|
|
|
|
|
|
|
|
|
Total
|
|
$ |
15,980,000 |
|
|
$ |
(1,000 |
) |
|
$ |
15,979,000 |
|
|
|
|
|
|
|
|
|
|
|
F-13
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
Investments consisted of the following at December 31, 2004:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Gross | |
|
|
|
|
Amortized | |
|
Unrealized | |
|
Aggregate | |
|
|
Cost | |
|
Losses | |
|
Fair Value | |
|
|
| |
|
| |
|
| |
Corporate fixed income
|
|
$ |
20,892,000 |
|
|
$ |
(81,000 |
) |
|
$ |
20,811,000 |
|
Government securities
|
|
|
18,707,000 |
|
|
|
(54,000 |
) |
|
|
18,653,000 |
|
Auction rate preferred securities
|
|
|
3,050,000 |
|
|
|
|
|
|
|
3,050,000 |
|
Certificates of deposit
|
|
|
500,000 |
|
|
|
(2,000 |
) |
|
|
498,000 |
|
|
|
|
|
|
|
|
|
|
|
Total
|
|
$ |
43,149,000 |
|
|
$ |
(137,000 |
) |
|
$ |
43,012,000 |
|
|
|
|
|
|
|
|
|
|
|
In January 2005, the auction rate preferred securities were sold
and the proceeds were subsequently reinvested into
held-to-maturity
securities.
|
|
5. |
Property and Equipment |
Property and equipment are summarized as follows:
|
|
|
|
|
|
|
|
|
|
|
December 31, | |
|
|
| |
|
|
2003 | |
|
2004 | |
|
|
| |
|
| |
Laboratory equipment
|
|
$ |
4,060,000 |
|
|
$ |
8,179,000 |
|
Computer equipment
|
|
|
755,000 |
|
|
|
840,000 |
|
Office equipment
|
|
|
306,000 |
|
|
|
372,000 |
|
Leasehold improvements
|
|
|
792,000 |
|
|
|
2,266,000 |
|
Software
|
|
|
261,000 |
|
|
|
321,000 |
|
|
|
|
|
|
|
|
Total property and equipment, at cost
|
|
|
6,174,000 |
|
|
|
11,978,000 |
|
Less accumulated depreciation
|
|
|
(2,791,000 |
) |
|
|
(4,392,000 |
) |
|
|
|
|
|
|
|
Property and equipment, net
|
|
$ |
3,383,000 |
|
|
$ |
7,586,000 |
|
|
|
|
|
|
|
|
Depreciation expense related to property and equipment totaled
$824,000, $1,198,000 and $1,601,000 for the years ended
December 31, 2002, 2003 and 2004, respectively. Included in
property and equipment is equipment held under capital leases
with a cost of $1,116,000 and $1,092,000, and accumulated
depreciation of $326,000 and $575,000 at December 31, 2003
and 2004, respectively.
In connection with the execution of the Companys strategic
alliance agreement with CFFTI in 2001, the Company issued CFFTI
warrants to purchase 174,443 shares of common stock at
an exercise price of $.02 per share. The fair value of the
warrants on the date of grant was $1,747,600. The Company
determined the value of the warrants with the assistance of
valuation specialists. The warrants are being accounted for as a
discount to contract revenue and amortized against the gross
revenue earned under the contract. The net carrying amount of
the warrants was approximately $1,459,000 and $1,324,000 as of
December 31, 2003 and 2004, respectively. Warrant
amortization totaled approximately $72,000, $33,000 and $135,000
during the years ended December 31, 2002, 2003 and 2004,
respectively (see Note 12).
F-14
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
|
|
7. |
Accounts Payable and Accrued Expenses |
Accounts payable and accrued expenses consisted of the following:
|
|
|
|
|
|
|
|
|
|
|
December 31, | |
|
|
| |
|
|
2003 | |
|
2004 | |
|
|
| |
|
| |
Accounts payable trade
|
|
$ |
1,475,000 |
|
|
$ |
2,768,000 |
|
Accounts payable related party
|
|
|
8,000 |
|
|
|
57,000 |
|
Accrued compensation
|
|
|
436,000 |
|
|
|
445,000 |
|
Accrued clinical costs
|
|
|
362,000 |
|
|
|
1,120,000 |
|
Other accrued expenses
|
|
|
432,000 |
|
|
|
1,735,000 |
|
|
|
|
|
|
|
|
Total
|
|
$ |
2,713,000 |
|
|
$ |
6,125,000 |
|
|
|
|
|
|
|
|
Indebtedness consisted of the following at December 31:
|
|
|
|
|
|
|
|
|
|
|
|
2003 | |
|
2004 | |
|
|
| |
|
| |
Borrowings under loan agreements:
|
|
|
|
|
|
|
|
|
|
Equipment loans, due March 2006, June 2006, September 2006,
February 2007, April 2007, June 2007, and October 2007, each
bearing interest at 10.465%, payable in monthly installments of
$18,715, $23,784, $7,174, $8,140, $6,060, $9,260, and $5,156,
respectively, including interest
|
|
$ |
2,194,000 |
|
|
$ |
1,468,000 |
|
Equipment loans, due August 2008, November 2008, December 2008,
January 2009, March 2009, April 2009, and June 2009 each bearing
interest at 9.137%, 9.106%, 9.136%, 9.509%, 10.016%, 9.976%, and
9.786%, respectively, payable in monthly installments of
$11,260, $11,264 $74,016, $37,395, $15,895, $5,717, and $5,346,
respectively, including interest
|
|
|
|
|
|
|
3,761,000 |
|
Capital lease obligations
|
|
|
742,000 |
|
|
|
500,000 |
|
|
|
|
|
|
|
|
Total indebtedness
|
|
|
2,936,000 |
|
|
|
5,729,000 |
|
Less current portion
|
|
|
(972,000 |
) |
|
|
(1,908,000 |
) |
|
|
|
|
|
|
|
Long-term portion
|
|
$ |
1,964,000 |
|
|
$ |
3,821,000 |
|
|
|
|
|
|
|
|
In April 2002, the Company entered into an equipment loan
expansion agreement under an existing 1999 master loan and
security agreement providing up to $1,900,000 in equipment
borrowings, subject to certain restrictions. Borrowings are
collateralized by the underlying equipment. Total borrowings in
2002 were approximately $1,958,000 under this loan, including
approximately $58,000 of excess borrowings mutually agreed upon
between the Company and the lender at the time of funding. In
February 2003, the Company entered into a new equipment loan
agreement with this lender providing up to $2,000,000 of
additional funding. The Company borrowed an additional amount of
approximately $1,128,000 in 2003 under this agreement. The
unused portion of the equipment loan agreement expired in
January 2004. In May 2004, the Company entered into a new master
loan and security agreement with this lender and entered into a
new equipment loan under this master loan and security agreement
providing
F-15
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
up to $6,900,600 of additional funding. During 2004, the Company
borrowed $3,889,000 under this agreement. At December 31,
2004, $3,071,600 of additional funding was available under this
equipment loan. This agreement expired in June 2005. At
December 31, 2004, outstanding borrowings under these
security agreements were $5,229,000.
In April 2002, the Company entered into a capital lease
agreement to lease up to $3,837,000 of general equipment for a
period of four years. The total amount of borrowings under this
agreement in 2002 was approximately $394,000, which represented
the fair market value of the equipment (and the book value) at
the time of borrowing. The total amount of borrowings under this
agreement in 2003 was $598,000, which represented the fair
market value of the equipment (and the book value) at the time
of borrowings. The unused portion of the capital lease agreement
expired in March 2003. At December 31, 2004, outstanding
borrowings under this capital lease agreement were $500,000.
Future maturities with respect to indebtedness at
December 31, 2004 are as follows:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Capital | |
|
Loan | |
|
Total Long- | |
Year Ending December 31 |
|
Leases | |
|
Agreements | |
|
Term Debt | |
|
|
| |
|
| |
|
| |
2005
|
|
$ |
266,000 |
|
|
$ |
1,657,000 |
|
|
$ |
1,923,000 |
|
2006
|
|
|
229,000 |
|
|
|
1,461,000 |
|
|
|
1,690,000 |
|
2007
|
|
|
25,000 |
|
|
|
1,129,000 |
|
|
|
1,154,000 |
|
2008
|
|
|
|
|
|
|
982,000 |
|
|
|
982,000 |
|
|
|
|
|
|
|
|
|
|
|
Total minimum payments
|
|
|
520,000 |
|
|
|
5,229,000 |
|
|
|
5,749,000 |
|
Less amount representing interest
|
|
|
20,000 |
|
|
|
|
|
|
|
20,000 |
|
|
|
|
|
|
|
|
|
|
|
Total principal
|
|
|
500,000 |
|
|
|
5,229,000 |
|
|
|
5,729,000 |
|
Less current portion
|
|
|
251,000 |
|
|
|
1,657,000 |
|
|
|
1,908,000 |
|
|
|
|
|
|
|
|
|
|
|
Total long-term debt
|
|
$ |
249,000 |
|
|
$ |
3,572,000 |
|
|
$ |
3,821,000 |
|
|
|
|
|
|
|
|
|
|
|
|
|
9. |
Commitments and Contingencies |
Leases The Company leases its office and
laboratory space and certain equipment under noncancelable
operating leases, with an option to renew one of its facilities
through 2008. Future minimum payments under the Companys
operating leases are as follows at December 31, 2004:
|
|
|
|
|
|
|
Operating | |
Year Ending December 31 |
|
Leases | |
|
|
| |
2005
|
|
$ |
1,557,000 |
|
2006
|
|
|
615,000 |
|
2007
|
|
|
400,000 |
|
2008
|
|
|
400,000 |
|
|
|
|
|
Total
|
|
$ |
2,972,000 |
|
|
|
|
|
Total rent expense under the Companys operating lease
agreements during the years ended December 31, 2002, 2003
and 2004, was approximately $657,000, $725,000 and $1,120,000,
respectively.
Commitment to CFFTI On the date the Company
obtains approval for
ALTU-135, if at all,
from the FDA under the strategic alliance agreement with CFFTI
(see Note 6 and Note 10, CFFTI), the Company shall be
obligated to pay the CFFTI a license fee equal to the lesser of
(a) the excess of the
F-16
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
amounts funded by such partner, plus accrued interest at an
annual rate of 12%, over the fair market value on the approval
date of the common stock issued or issuable upon the exercise of
the warrants, or (b) $40,000,000. The license fee is
payable in four annual installments, commencing 30 days
after the approval date, with interest accruing at an annual
rate of 12% on the unpaid balance. After the approval date, the
Company will be obligated to pay a royalty on combined net
sales, as defined in the agreement, on a quarterly basis until
such time as certain patents expire. The Company has the right
and option to terminate the royalty stream payable to CFFTI by
making a one-time payment to CFFTI of a specified amount.
In December 2003, the Company and CFFTI amended the agreement to
provide the Company with an interest-bearing advance against a
future milestone. This $1,500,000 advance was paid to the
Company in January 2004 and is included in long-term deferred
revenue on the consolidated balance sheet. The advance,
including interest at an annual rate of 15%, will be deducted
from the milestone at the time the milestone is earned. In
addition to the amounts deducted from the future milestone, and
in the event ALTU-135
is approved, the Company will pay to CFFTI an amount equal to
the advance in addition to the amounts otherwise owed to CFFTI.
If the milestone is not achieved or
ALTU-135 is not
approved, the Company has no obligation to CFFTI as a result of
this amendment.
Dr. Falk Pharma GmbH The Companys
collaborator, Dr. Falk Pharma GmbH, or Dr. Falk, has
asserted that there is a third-party foreign patent with claims
that may be relevant to
ALTU-135 and,
therefore, that the Company breached a representation in its
agreement with Dr. Falk and may be liable for damages under the
agreement. The Company does not believe that it breached its
agreement and is in discussions with Dr. Falk to resolve
this matter. The Company also believes that if this patent were
asserted against it, it is likely that the Company would not be
found to infringe any valid claim of the patent relevant to its
development and commercialization of
ALTU-135. The Company
cannot predict the outcome of this matter with certainty.
|
|
10. |
Research and Development Arrangements and Significant
Customers |
The Company has entered into collaborative arrangements with
corporate partners to provide research and development
activities relating to the partners products and
internally developed products. In connection with these
arrangements, the Company has granted licenses, or the right to
obtain certain licenses, to technology developed by the Company.
In return for such grants, the Company will receive payments
upon the achievement of certain milestones and royalties.
The Company recorded revenue greater than 10% of total revenue
from the following customers:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Year Ended | |
|
|
December 31, | |
|
|
| |
|
|
2002 | |
|
2003 | |
|
2004 | |
|
|
| |
|
| |
|
| |
Customer:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Dr. Falk
|
|
|
* |
% |
|
|
38 |
% |
|
|
43 |
% |
|
CFFTI
|
|
|
36 |
|
|
|
11 |
|
|
|
43 |
|
|
Pfizer, Inc.
|
|
|
* |
|
|
|
16 |
|
|
|
* |
|
|
GlaxoSmithKline
|
|
|
10 |
|
|
|
* |
|
|
|
* |
|
|
|
* |
Revenue derived from this customer was less than 10% of the
Companys total revenue for the applicable period. |
F-17
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
|
|
11. |
Redeemable Preferred Stock |
Redeemable Preferred Stock In connection with
the 1999 reorganization of the Company, 450,000 shares of
redeemable preferred stock, par value $.01 per share (the
Redeemable Preferred Stock), were issued to Vertex
with a value of $3,100,000. Vertex has no stockholder voting
rights with respect to these shares other than specified rights
relating to the terms of the shares, and is entitled to receive
dividends at an annual rate of $0.50 per share. Such
dividends are not to be declared, paid or set aside for payment
until all accrued but unpaid dividends on the Series B and
C convertible preferred stock shall have been paid. Dividends
are cumulative whether or not declared by the Board of Directors
and have been accrued in the amount of approximately $1,106,000
and $1,331,000 at December 31, 2003 and 2004, respectively.
The Redeemable Preferred Stock is redeemable at the option of
Vertex on or after December 31, 2010 at a price of
$10.00 per share plus accrued and unpaid dividends. Upon
liquidation, Vertex is entitled to receive, on parity with the
holders of the Series A Convertible Preferred Stock
(Series A Preferred Stock) and prior to any
payment with respect to the common stock, $10.00 per share
plus accrued but unpaid dividends.
Series B Convertible Preferred Stock In
December 2001, the Company completed a private placement of
11,773,609 shares of its Series B Convertible
Preferred Stock (Series B Preferred Stock) and
warrants to purchase an additional 1,154,546 shares of the
Series B Preferred Stock at approximately $4.31 per
share. Net proceeds to the Company were approximately
$46,180,000 (net of issuance costs of $4,620,000). The warrants
are exercisable immediately and expire no later than
December 7, 2008. The fair value of the warrants on the
date of issuance was approximately $2,730,000. Accordingly,
approximately $2,730,000 of the net proceeds received from the
sale of the Series B Preferred Stock was allocated to the
warrants and recorded as an increase to additional paid-in
capital.
The Series B Preferred Stock is convertible into common
stock at any time at the option of the holder, initially on an
approximate 0.44-for-1 basis, and subject to mandatory
conversion upon the closing of an initial public offering at a
price of at least $14.86 per share and with net proceeds to the
Company of at least $50.0 million, or a Qualified Public
Offering. The holders of the Series B Preferred Stock have
voting rights equivalent to the number of shares of common stock
into which their shares of Series B Preferred Stock convert
and are entitled to receive dividends at a rate of 6% of the
purchase price per annum. Dividends are cumulative whether or
not declared by the Board of Directors and have been accrued in
the amount of approximately $6,718,000 and $9,766,000 at
December 31, 2003 and 2004 respectively. Upon completion of
a Qualified Public Offering, all accrued but unpaid dividends on
the Series B Preferred Stock will convert into common stock
at the then-current fair market value.
The Company shall redeem the Series B Preferred Stock and
the Series C Convertible Preferred Stock
(Series C Preferred Stock described
below) at any time on or after December 31, 2010 upon
written notice from the holders of at least 55% of the
then-outstanding shares of Series B Preferred Stock and
Series C Preferred Stock, on an as-converted basis, voting
together as a single class of stock, at a price equal to
approximately $4.31 per share plus accrued but unpaid
dividends. Such redemption would be pari passu and in preference
to the redemption of any other shares of the Companys
capital stock, including the Series A Preferred Stock and
Redeemable Preferred Stock. For as long as 35% of the total
number of shares of Series B Preferred Stock is
outstanding, the holders of the Series B Preferred Stock
are entitled to elect two members of the Board of Directors, and
for so long as 35% of the total number of shares of
Series B Preferred Stock and Series C Preferred Stock
remain outstanding, the holders of
F-18
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
Series B Preferred Stock and Series C Preferred Stock
retain final approval authority over mergers, acquisitions,
sales of assets, and certain other corporate transactions.
Upon liquidation, the holders of the Series B Preferred
Stock are entitled to receive, after and subject to the payment
in full of all amounts required to be distributed to holders of
the Series C Preferred Stock, but prior to any payment with
respect to the holders of the Redeemable Preferred Stock,
Series A Preferred Stock or common stock, an amount equal
to approximately $4.31 per share plus accrued but unpaid
dividends. After the payment of all preferential amounts
required to be paid on liquidation to the holders of the
Series B Preferred Stock, and any other class or series of
stock ranking senior or on parity with the Series B
Preferred Stock, the Redeemable Preferred Stock and the
Series A Preferred Stock, holders of the Series B
Preferred Stock will also share in the remaining assets with
holders of the common stock and Series C Preferred Stock on
a pro-rata basis, assuming conversion into common stock.
However, the aggregate amount paid to the holders of the
Series B Preferred Stock shall not exceed approximately
$8.63 plus accrued but unpaid dividends.
Series C Convertible Preferred Stock In
May 2004, the Company completed a private placement of
11,819,959 shares of Series C Preferred Stock and
warrants to purchase an additional 2,600,400 shares of
Series C Preferred Stock at approximately $4.31 per
share. Net proceeds to the Company were approximately
$50,364,000 (net of issuance costs of $636,000). The warrants
are exercisable immediately and expire no later than
May 21, 2011. The fair value of the warrants on the date of
issuance was approximately $8,717,000. Accordingly,
approximately $8,717,000 of the net proceeds received from the
sale of the Series C Preferred Stock was allocated to the
warrants and recorded as an increase to additional paid-in
capital.
The Series C Preferred Stock is convertible into common
stock at any time at the option of the holder, initially on an
approximate 0.44-for-1 basis, and subject to mandatory
conversion upon the closing of a Qualified Public Offering. The
holders of the Series C Preferred Stock have voting rights
equivalent to the number of shares of common stock into which
their shares of Series C Preferred Stock convert and are
entitled to receive dividends at a rate of 9% of the purchase
price per annum. Dividends are cumulative whether or not
declared by the Board of Directors and have been accrued in the
amount of approximately $2,817,000 at December 31, 2004.
Upon completion of a Qualified Public Offering, all accrued but
unpaid dividends on the Series C Preferred Stock will
convert into common stock at the then-current fair market value.
At any time after December 31, 2010, the holders of 55% of
the outstanding shares of Series C Preferred Stock and
Series B Preferred Stock, on an as-converted basis, voting
together as a single class of stock, will be entitled to require
the Company to redeem all outstanding shares of Series C
Preferred Stock and Series B Preferred Stock at a price
equal to approximately $4.31 per share plus accrued but
unpaid dividends. Such redemption would be pari passu and in
preference to the redemption of any other shares of the
Companys capital stock, including the Series A
Preferred Stock and Redeemable Preferred Stock.
Upon liquidation, the holders of the Series C Preferred
Stock are entitled to receive, prior to any payment with respect
to the holders of the common and other preferred stocks, an
amount equal to approximately $4.31 per share plus accrued
but unpaid dividends. After the payment of all preferential
amounts required to be paid on liquidation to the holders of the
Series C Preferred Stock, and any other class or series of
stock ranking senior or on parity with the Series C
Preferred Stock, the Series B Preferred Stock, the
Redeemable Preferred Stock and the Series A Preferred
Stock, the holders of the Series C Preferred Stock will
also share in the remaining assets with holders of the common
stock and
F-19
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
holders of the Series B Preferred Stock on a pro-rata
basis, assuming conversion into common stock. However, the
aggregate amount paid to the holders of the Series C
Preferred Stock shall not exceed approximately $8.63 plus
accrued but unpaid dividends.
|
|
12. |
Stockholders Deficit |
Series A Convertible Preferred Stock
Also in connection with the 1999 reorganization of the Company,
the Company issued 87,500 shares of its Series A
Preferred Stock to Vertex for a total value of $897,000. The
Series A Preferred Stock is convertible into common stock
at any time at the option of the holder initially on an
approximate 4.36-for-1
basis and is subject to mandatory conversion upon completion of
a Qualified Public Offering. The holders of the Series A
Preferred Stock have voting rights equivalent to the number of
shares of common stock into which their shares of Series A
Preferred Stock convert and are not entitled to receive
dividends. Upon liquidation, holders of Series A Preferred
Stock are entitled to receive, prior to any payment with respect
to the holders of common stock, $0.05 per share.
Common Stock Warrants The Company has issued
common stock warrants in connection with certain debt and equity
financings and the execution of a research and development
collaboration.
Debt Financings The following table
summarizes information about outstanding common stock warrants
issued in connection with debt financings as of
December 31, 2004:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Number | |
|
Exercise | |
|
|
Year Granted |
|
Outstanding | |
|
Price | |
|
Expiration Date | |
|
|
| |
|
| |
|
| |
2004
|
|
|
3,934 |
|
|
$ |
9.88 |
|
|
|
August 31, 2009 to December 17, 2009 |
|
2003
|
|
|
2,300 |
|
|
|
9.79 |
|
|
|
February 12, 2008 to October 27, 2008 |
|
|
|
|
1,208 |
|
|
|
9.79 |
|
|
|
February 19, 2010 to April 17, 2010 |
|
2002
|
|
|
1,820 |
|
|
|
9.79 |
|
|
|
September 27, 2009 to October 28, 2009 |
|
|
|
|
3,994 |
|
|
|
9.79 |
|
|
|
April 4, 2007 to September 27, 2007 |
|
2001
|
|
|
2,180 |
|
|
|
9.79 |
|
|
|
February 22, 2008 |
|
2000
|
|
|
11,915 |
|
|
|
9.79 |
|
|
|
October 20, 2007 |
|
|
|
|
682 |
|
|
|
68.79 |
|
|
|
May 24, 2005 |
|
|
|
|
1,017 |
|
|
|
7.86 |
|
|
|
January 18, 2005 |
|
1999
|
|
|
43,610 |
|
|
|
6.88 |
|
|
|
June 21, 2006 |
|
|
|
|
|
|
|
|
|
|
|
Total
|
|
|
72,660 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
All warrants are immediately exercisable commencing on the date
of grant.
The fair value of the warrants issued to all lenders was
approximately $13,000, $8,000, and $7,000 in 2002, 2003 and
2004, respectively. The fair value of the warrants has been
offset against the carrying value of the debt and is being
amortized to interest expense over the life of the debt.
Equity Financings In 2001, the Company issued
warrants for the purchase of 170,585 shares of common stock
at an exercise price of $9.79 per share to an investment
banking firm in connection with the placement of the
Series B Preferred Stock. The warrants are exercisable at
any time prior to their expiration date of December 7,
2006. The fair value of the warrants on the date of issuance was
approximately $220,000, which was recorded as an increase to
additional paid-in capital and as part of the issuance costs of
the related preferred stock.
F-20
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
In connection with the 1999 reorganization, the Company issued
warrants to Vertex for the purchase of 436,109 shares of
common stock at an exercise price of $.11 per share and
warrants to purchase 1,962,494 shares of common stock
at exercise prices ranging from $5.73 to $11.47 per share.
The fair value of the warrants on the date of issuance was
approximately $2,574,000.
In connection with the sale of the Series B Preferred Stock
in 2001, Vertex agreed to modify certain terms of the
reorganization agreement. In addition, Vertex exercised warrants
and purchased 436,109 shares of the Companys common
stock for $50,000. As consideration for agreeing to and
executing the modifications to facilitate the sale of the
Series B Preferred Stock, the exercise prices of the
1,962,494 warrants were reduced to $5.64 per share.
The incremental fair value of the 1,962,494 warrants,
repriced at $5.64 per share, amounted to approximately
$420,000 and is included in noncash contract modification
expense in the 2001 consolidated statement of operations. The
warrants are exercisable at any time prior to their expiration
date of February 1, 2009.
Collaboration with CFFTI The
174,443 warrants issued in connection with the strategic
alliance agreement with CFFTI (see Note 6) expire on
February 22, 2013. Of the total, 100,479 are exercisable
after February 21, 2008 and 73,964 are exercisable after
February 21, 2011, or earlier upon certain triggering
events. The triggering events include matters related to
achievement of a certain milestone, product development
progress, and an initial public offering of the Companys
common stock.
Certain terms of the agreement were amended in connection with
the sale of the Series B Preferred Stock. As consideration
for entering into the amendments, the Company issued a warrant
to CFFTI for the purchase of an additional 87,221 shares of
its common stock at $0.02 per share. The new warrant vested
immediately and expires on September 26, 2011. The fair
value of the new warrant amounted to $340,260 and is included in
noncash contract modification expense in the 2001 consolidated
statement of operations.
The Company had no provision for income taxes in 2002, 2003, and
2004 due to its net operating losses.
The significant components of deferred taxes were as follows at
December 31:
|
|
|
|
|
|
|
|
|
|
|
2003 | |
|
2004 | |
|
|
| |
|
| |
Net operating loss carryforwards
|
|
$ |
8,339,000 |
|
|
$ |
17,092,000 |
|
Tax credit carryforwards
|
|
|
1,093,000 |
|
|
|
1,338,000 |
|
Deferred revenue
|
|
|
5,146,000 |
|
|
|
4,247,000 |
|
Capitalized research and development
|
|
|
1,319,000 |
|
|
|
1,579,000 |
|
Other
|
|
|
433,000 |
|
|
|
648,000 |
|
|
|
|
|
|
|
|
Net deferred tax assets
|
|
|
16,330,000 |
|
|
|
24,904,000 |
|
Valuation allowance
|
|
|
(16,330,000 |
) |
|
|
(24,904,000 |
) |
|
|
|
|
|
|
|
Net deferred tax balance
|
|
$ |
|
|
|
$ |
|
|
|
|
|
|
|
|
|
The Company has established a full valuation reserve against the
net deferred tax assets due to the uncertainty of earning
sufficient taxable income and, accordingly, has not given
recognition to these tax assets in the accompanying consolidated
financial statements. The Company has federal net operating loss
F-21
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
(NOL) carryforwards of approximately $42,744,000 and
tax credits of $617,000, and state NOLs of $42,638,000 and state
tax credits of $720,000, which may be subject to limitation
under the Internal Revenue Code (the Code) in the
event of a change of ownership. The net operating loss
carryforwards expire starting in 2005 for state purposes and
2020 for federal purposes.
Stock Option Plans On February 7, 2002,
the Company ceased granting options under the 1993 Plan and
adopted the 2002 Plan. Under the 1993 Plan and the 2002 Plan,
the total number of shares issuable upon the exercise of
outstanding stock options or available for future grant, to
employees, directors, and consultants, at December 31,
2004, was 2,257,719 shares. On January 27, 2005, the
Board of Directors authorized an additional 654,164 shares
available for future grant. All option grants are nonstatutory
(nonqualified) stock options except option grants to
employees (including officers and directors) intended to qualify
as incentive stock options under the Code. Incentive stock
options may not be granted at less than the fair market value of
the Companys common stock on the date of grant, as
determined in good faith by the Board of Directors at its sole
discretion. Nonqualified stock options may be granted at an
exercise price established by the Board of Directors at its sole
discretion. Vesting periods are generally four years and are
determined by the Board of Directors or a delegated
subcommittee. Granted options and awards generally may be
exercised immediately, but the shares purchased are subject to
restrictions on transfer until vested. At December 31,
2004, the Company had no such shares outstanding.
In the event of termination of an employee or the business
relationship with a nonemployee, the Company may repurchase all
unvested shares from the optionee at the original issue price.
Options granted under the 1993 and 2002 Plans expire no more
than 10 years from the date of grant.
F-22
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
A summary of the stock option activity under the 1993 and 2002
Plans is as follows:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Average | |
|
|
|
|
Exercise | |
|
|
Shares | |
|
Price | |
|
|
| |
|
| |
Balance January 1, 2002 (126,391 options vested)
|
|
|
710,377 |
|
|
$ |
4.33 |
|
|
Granted
|
|
|
509,430 |
|
|
|
3.92 |
|
|
Exercised
|
|
|
(13 |
) |
|
|
5.02 |
|
|
Canceled
|
|
|
(37,146 |
) |
|
|
3.78 |
|
|
|
|
|
|
|
|
Balance December 31, 2002 (320,075 options
vested)
|
|
|
1,182,648 |
|
|
|
4.17 |
|
|
Granted
|
|
|
496,642 |
|
|
|
3.92 |
|
|
Exercised
|
|
|
(2,650 |
) |
|
|
1.22 |
|
|
Canceled
|
|
|
(78,110 |
) |
|
|
4.13 |
|
|
|
|
|
|
|
|
Balance December 31, 2003 (599,985 options
vested)
|
|
|
1,598,530 |
|
|
|
4.10 |
|
|
Granted
|
|
|
1,047,626 |
|
|
|
3.92 |
|
|
Exercised
|
|
|
(29,745 |
) |
|
|
2.82 |
|
|
Canceled
|
|
|
(498,811 |
) |
|
|
4.15 |
|
|
|
|
|
|
|
|
Balance December 31, 2004 (826,570 options
vested)
|
|
|
2,117,600 |
|
|
|
4.01 |
|
|
Granted (unaudited)
|
|
|
1,263,192 |
|
|
|
3.94 |
|
|
Exercised (unaudited)
|
|
|
(102,335 |
) |
|
|
2.89 |
|
|
Canceled (unaudited)
|
|
|
(244,346 |
) |
|
|
3.92 |
|
|
|
|
|
|
|
|
Balance September 30, 2005 (unaudited)
(1,151,937 options vested)
|
|
|
3,034,111 |
|
|
$ |
4.04 |
|
|
|
|
|
|
|
|
In computing stock-based compensation to employees for the years
ended December 31, 2002, 2003, and 2004, the Company has
assumed risk-free interest rates in the range of 2.6% to 4.4% in
2002, 1.8% to 2.9% in 2003, and 2.4% to 3.9% in 2004. The
Company assumed an expected average option life of four years,
no dividends, and no volatility for 2002 and 2003. The Company
assumed an expected average option life of five years, no
dividends, and no volatility for 2004.
The weighted-average fair value of employee and nonemployee
options granted at exercise prices equal to fair market value
during 2002, 2003 and 2004 was $0.20, $0.18 and $0.28,
respectively. The weighted-average fair value of employee and
nonemployee options granted at exercise prices below fair market
value during 2002 was $1.20. There were no options granted below
fair market value during 2003 and 2004.
Included in options outstanding for each year presented are
13,192 options granted to consultants during 1999 to 2002. Such
options provide for 25% vesting each year. Compensation expense
is estimated based on fair value of the award until the final
measurement date, which is the earlier of performance completion
or vesting. Accordingly, the total amount of compensation
expense to be recognized for stock options granted to
consultants will increase or decrease over the
vesting/performance period based on changes in the fair value of
such stock options. The Company recorded total noncash
compensation
F-23
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
expense relating to consultants options of approximately
$11,000, $3,000 and $1,000 in the years ended December 31,
2002, 2003 and 2004, respectively, based on the fair value of
these options as calculated using the Black-Scholes
option-pricing model.
At December 31, 2004, there were 140,119 available for
future grant under the 2002 Plan.
The following table summarizes information about stock options
outstanding:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
December 31, 2004 | |
| |
|
|
Weighted- | |
|
|
|
|
Average | |
|
|
|
|
Remaining | |
|
Number | |
|
|
Exercise | |
|
Number | |
|
Contractual | |
|
Vested and | |
|
|
Price | |
|
Outstanding | |
|
Life (Years) | |
|
Exercisable | |
|
|
| |
|
| |
|
| |
|
| |
|
|
$ |
0.11 |
|
|
|
11,895 |
|
|
|
4.8 |
|
|
|
11,895 |
|
|
|
|
0.23 |
|
|
|
327 |
|
|
|
2.0 |
|
|
|
327 |
|
|
|
|
0.92 |
|
|
|
39,904 |
|
|
|
3.0 |
|
|
|
39,904 |
|
|
|
|
2.29 |
|
|
|
654 |
|
|
|
5.2 |
|
|
|
654 |
|
|
|
|
3.44 |
|
|
|
14,391 |
|
|
|
5.6 |
|
|
|
14,391 |
|
|
|
|
3.92 |
|
|
|
1,946,466 |
|
|
|
8.8 |
|
|
|
658,966 |
|
|
|
|
7.25 |
|
|
|
80,849 |
|
|
|
6.0 |
|
|
|
80,849 |
|
|
|
|
8.60 |
|
|
|
23,114 |
|
|
|
6.4 |
|
|
|
19,584 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
$ |
0.11-$8.60 |
|
|
|
2,117,600 |
|
|
|
8.5 |
|
|
|
826,570 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
15. |
Employee Benefit Plans |
401(k) Retirement Plan Employees of the
Company are eligible to participate in the Companys 401(k)
retirement plan. Participants may contribute up to 60% of their
annual compensation to the plan, subject to statutory
limitations. The Company may declare discretionary matching
contributions to the plan. Matching contributions were
approximately $138,000, $213,000 and $241,000 for the years
ended December 31, 2002, 2003 and 2004, respectively.
Deferred Compensation Plan During 2001, the
Company adopted the Deferred Compensation Plan (the
Plan) for certain officers and key employees. The
Plan is an unfunded, nonqualified deferred compensation
arrangement in which participants may elect to defer bonus
compensation.
F-24
ALTUS PHARMACEUTICALS INC. AND SUBSIDIARY
NOTES TO CONSOLIDATED
FINANCIAL STATEMENTS (Continued)
FOR THE YEARS ENDED DECEMBER 31, 2002, 2003 AND 2004
(Information as of September 30, 2005 and for the Nine
Months Ended
September 30, 2004 and 2005 is unaudited)
|
|
16. |
Selected Quarterly Financial Data (Unaudited) |
The following table presents unaudited quarterly financial data
for the Company. The Companys quarterly results of
operations for these periods are not necessarily indicative of
future results of operations.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Basic and | |
|
|
|
|
|
|
|
|
Diluted | |
|
|
|
|
|
|
|
|
Net Loss | |
|
|
|
|
|
|
Net Loss | |
|
Attributable | |
|
|
|
|
|
|
Attributable | |
|
to Common | |
|
|
|
|
|
|
to Common | |
|
Stockholders | |
(In thousands, except per share data) |
|
Revenue | |
|
Net Loss | |
|
Stockholders | |
|
Per Share | |
|
|
| |
|
| |
|
| |
|
| |
Year Ended December 31, 2004
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
First Quarter
|
|
$ |
1,072 |
|
|
$ |
(4,649 |
) |
|
$ |
(5,873 |
) |
|
$ |
(3.49 |
) |
|
Second Quarter
|
|
|
948 |
|
|
|
(3,647 |
) |
|
|
(5,529 |
) |
|
|
(3.27 |
) |
|
Third Quarter
|
|
|
1,056 |
|
|
|
(5,141 |
) |
|
|
(7,880 |
) |
|
|
(4.61 |
) |
|
Fourth Quarter
|
|
|
1,154 |
|
|
|
(7,520 |
) |
|
|
(10,263 |
) |
|
|
(5.98 |
) |
Nine Months Ended September 30, 2005
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
First Quarter
|
|
|
1,484 |
|
|
|
(7,099 |
) |
|
|
(9,805 |
) |
|
|
(5.71 |
) |
|
Second Quarter
|
|
|
1,118 |
|
|
|
(7,817 |
) |
|
|
(10,540 |
) |
|
|
(6.12 |
) |
|
Third Quarter
|
|
|
4,125 |
|
|
|
(4,193 |
) |
|
|
(6,933 |
) |
|
|
(4.01 |
) |
Basic and diluted net loss per common share are identical since
common equivalent shares are excluded from the calculation as
their effect is antidilutive.
|
|
17. |
Subsequent Events (Unaudited) |
On May 9, 2005, the Board of Directors increased the number
of shares of common stock available for grant under the 2002
Plan by 566,942 shares.
On October 17, 2005, the Company filed a registration
statement with the Securities and Exchange Commission to
register shares of the Companys common stock in connection
with a proposed initial public offering.
On November 18, 2005, the Company terminated its deferred
compensation plan.
On January 10, 2006, the Company effected a 1-for-2.293
reverse stock split. All share and per share amounts in the
consolidated financial statements have been retroactively
adjusted for all periods presented to give effect to the reverse
stock split, including reclassifying an amount equal to the
reduction in par value to additional paid-in-capital.
F-25
Through
and including February 20, 2006 (25 days after the
date of this prospectus), all dealers that buy, sell or trade
our common stock, whether or not participating in this offering,
may be required to deliver a prospectus. This delivery
requirement is in addition to the obligation of dealers to
deliver a prospectus when acting as underwriters and with
respect to their unsold allotments or subscriptions.
7,000,000 Shares
Common Stock
PROSPECTUS
January 26, 2006