NImmune Biopharma Provides Update on Omilancor Clinical Development Programs in Ulcerative Colitis and Crohn’s Disease

Approvable population of ulcerative colitis (UC) patients for upcoming Phase 3 trials agreed upon with the U.S. Food and Drug Administration (FDA)

Analysis of Phase 2 data using approvable UC patient population for Phase 3 demonstrated statistical significance in the primary endpoint of clinical remission of 26.7% (p=0.01) for the 440 mg dose at 12 weeks and early normalization of fecal calprotectin levels at 2 weeks

Clinical results from a small study of omilancor in biologic naïve and biologic experienced Crohn’s disease patients show a promising clinical efficacy signal

Enrollment in the pivotal global Phase 3 study of omilancor for the treatment of UC anticipated to commence by year-end 2023

NImmune Biopharma ("NImmune”), a late-clinical-stage precision immunology biopharmaceutical company that develops novel biomarker-driven immunoregulatory therapeutics, today announced Phase 2 data on an approvable population of ulcerative colitis (UC) patients and its plans to initiate a registration directed global Phase 3 program for omilancor for the treatment of UC. Omilancor is a wholly-owned, once-daily gut-restricted oral first-in-class LANCL2 therapeutic entering Phase 3 clinical testing in UC patients.

Dr. Josep Bassaganya-Riera, Founder & CEO of NImmune, said, "Following our successful acquisition of the LANCL therapeutic portfolio, we have made meaningful progress in advancing our clinical development programs for omilancor in IBD and NIM-1324 in lupus. Each of our programs remain on track, and now with the original leadership team that developed these medicines from inception we expect to dose the first patient in the global pivotal Phase 3 PACIFY program of omilancor for UC by year-end. Importantly, the omilancor program has taken just over four years since inception to reach Phase 3 initiation, representing significant cost savings compared to traditional drug development timelines. NImmune will continue to address the unmet clinical needs of patients with autoimmune diseases while building substantial and enduring value in lean and capital-efficient ways.”

“We are thrilled to bring omilancor’s best-in-class potential to Phase 3 clinical evaluation. Statistical significance of the approvable primary endpoint of clinical remission using the 440 mg drug formulation provides a robust regulatory path to filing a New Drug Application (NDA) and commercialization of omilancor in UC. We remain highly motivated by the potential for omilancor to be the first-in-class LANCL2 agonist for UC, with immediate follow-on opportunities in Crohn’s disease, psoriasis and additional autoimmune indications."

Phase 2 UC Approvable Population Data

In the approvable UC patient population, clinical remission was induced in 30.4% of omilancor treated patients relative to 3.7% of patients given placebo (Δ = 26.7, p = 0.01), thereby meeting the primary endpoint. Endoscopic remission was induced in 41.7% of patients treated with omilancor relative to 18.6% of patients given placebo (Δ = 23.1, p = 0.07). In patients with elevated baseline FCP, normalization occurred in 43.8% of the omilancor 880 mg group and 40.6% of the omilancor 440 mg group relative to 21.4% of the placebo group after 2 weeks (p = 0.048). PK analysis validated a gut-restricted profile with stable drug levels in stool over the 12-week treatment period and penetration into colonic biopsy tissue with limited systemic exposure. The 440 mg formulation was sufficient to saturate the target and produced target engagement and elicited the downstream immunological changes associated with clinical remission. Omilancor showed 55% lower IL-6 concentrations and 44% lower TNF concentrations after 12 weeks of treatment, consistent with increased levels of regulatory CD4+ T cells and myeloid cells and increased IL-10 expression in remitters (p = 0.036).

Additionally, omilancor exhibited statistically significant decreases in TNF-a expressing myeloid cells (p = 0.037) in the colonic mucosa and statistically significant normalization of fecal calprotectin levels (p = 0.048). Omilancor maintained low Mayo scores following 1 year of treatment, with nearly 90% of patients achieving remission thresholds in stool frequency and rectal bleeding after 36 weeks of open-label treatment.

Omilancor was well tolerated with no trends in adverse event (AE) profile observed and most AEs of mild severity and no dose-limiting toxicities.

In a small clinical trial in biologic naïve and biologic experienced moderate to severe Crohn’s disease patients omilancor showed encouraging efficacy signals in clinical remission at week 12 as measured by the percentage of patients in remission as measured by Crohn’s disease activity (CDAI) less than 150 and PRO-2 remission (abdominal pain equal or less than 1 and loose stools equal or less than 3).

The Global Pivotal Phase 3 Program

PACIFY is a global registration directed double-blind randomized placebo-controlled Phase 3 program of omilancor in active UC patients ranging from mild to severe that aims to enroll 1,378 patients across 250 global clinical sites. Patient identification and selection is anticipated to be aided by a proprietary gene-based biomarker of response to treatment with omilancor developed by the company’s proprietary A.I. biomarker discovery platform in collaboration with the NIMML Institute.

As agreed with the US FDA, the Phase 3 program will consist of two simultaneous trials, PACIFY I and PACIFY II each evaluating the 440 mg once daily oral dose of omilancor versus placebo. PACIFY I aims to randomize 726 active disease UC patients, with 363 patients receiving 440 mg of omilancor and 363 receiving a placebo. PACIFY II aims to randomize 652 active disease UC patients, with 326 patients receiving 440mg of omilancor and 326 patients receiving placebo. Both trials will complete a 12-week induction portion with an approvable primary endpoint of clinical remission. Following the 12-week induction period, PACIFY I patients will continue to a 52-week maintenance portion followed by the opportunity to continue in an Open Label Extension. PACIFY II patients will be offered the opportunity to enroll in the Open Label Extension immediately after completing the 12-week induction period. Top line results from the 12-week induction portion of the global phase 3 program in UC are anticipated within 12-18 months from dosing the first patient.

The primary endpoints will be clinical remission at week 12 and week 52. Attainment of either endpoint can serve as a basis for a New Drug Application (“NDA”). Mucosal healing at week 12 as measured by an endoscopic subscore of 0 or 1 with the Geboes histologic index <3.1 will also be taken.

About Ulcerative Colitis (UC)

UC is a chronic, autoimmune, inflammatory bowel disease that causes inflammation, irritation, and ulcers in the lining of the large intestine (colon) and rectum. Symptoms include abdominal pain, rectal pain and bleeding, bloody stools, diarrhea, fever, weight loss, and malnutrition. Having UC puts a patient at increased risk of developing colon cancer. Diagnosis typically occurs in early adulthood and the disease requires maintenance treatment for the remainder of the patient’s life. UC is estimated to affect over 900,000 patients in the United States and over 1 million patients throughout the rest of the world. With 70% of addressable patients experiencing a second flare within one year and 30% of patients in remission failing to stay in remission for more than one year, there is an unmet medical need in UC for safer and more efficacious therapeutics.

About Omilancor

By activating the LANCL2 pathway and modulating the interactions between immunological and metabolic signals in immune and epithelial cells, omilancor is a first-in-class, oral, once-daily, gut restricted therapeutic designed to create a favorable regulatory microenvironment in the gut, decreasing the production of key inflammatory mediators and increasing anti-inflammatory functions in regulatory T cells (Treg) within the site of inflammation. Omilancor has completed Phase 2 clinical testing in UC patients showing a clinical remission of 30.4% with a placebo-adjusted 12-week clinical remission rate of 26.7% (p=0.01) for the 440 mg dose. Following demonstration of a statistically significant approvable primary endpoint for clinical remission in an approvable active disease patient population, NImmune expects to initiate a global pivotal Phase 3 program (PACIFY I and PACIFY II trials) in UC patients in the second half of 2023.

About NIM-1324

NIM-1324 is an oral, systemically distributed, small-molecule therapeutic candidate which activates LANCL2, a surface membrane-associated receptor that is responsible for modulating key cellular and molecular changes tied to autoimmune diseases. By activating the LANCL2 pathway, NIM-1324 increases the anti-inflammatory capacity and stability of regulatory CD4+ T cells while also supporting the metabolic demands of autophagy in phagocytes. To date, treatment with NIM-1324 has reduced the production of interferon alpha in human peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients and provided protection from clinical disease and tissue pathology in mouse models of lupus and rheumatoid arthritis. Phase 2-ready NIM-1324 completed Phase 1 clinical testing where it met all endpoints and demonstrated a dose proportional change in plasma exposure within the therapeutic range with no accumulation.

About NImmune Biopharma

NImmune is a late-stage precision immunology biopharmaceutical company that develops novel best-in-class biomarker-driven immunoregulatory therapeutics. Underpinned by a discovery platform that utilizes advanced computational modeling, A.I. and bioinformatics coupled with biomedical research capabilities to pioneer innovation in immunoregulatory drug development, NImmune’s business model enables the rapid and capital-efficient clinical development of high conviction drug candidates into New Drug Application (NDA) filing and commercialization. The lead product candidate from NImmune’s internal discovery platform is omilancor, a wholly-owned Phase 3 oral, once-daily, gut-restricted, first-in-class therapeutic targeting LANCL2 for Ulcerative Colitis, with fast follower potential in Crohn’s disease, Psoriasis and other auto-immune diseases. Phase 2 first-in-patient data for omilancor in UC show potential best in class efficacy and safety. Additional information: www.NIMMUNEBIO.COM or contact media@nimmunebio.com.

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