P0862Continued efficacy improvement beyond the induction period with once-daily obefazimod: week 8 to week 48 outcomes from the Phase 2b open-label maintenance study in patients with moderately to severely active ulcerative colitis, stratified by prior advanced-therapy exposure

Abstract Background Obefazimod (obe) is an investigational, oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and is currently in Phase 3 clinical trials for the treatment of patients (pts) with moderately to severely active ulcerative colitis (UC) 1. Obe showed efficacy in pts with UC at week 8 (W8) in a Phase 2b, double-blind, placebo (PBO)-controlled, induction trial and the subsequent open-label maintenance (OLM) study 2. Similar to the ongoing Phase 3 ABTECT program, the Phase 2b program enrolled pts with inadequate response, loss of response, or intolerance to conventional treatments and/or advanced therapies AT (biologics/JAK inhibitors) with no upper limit AT exposure. Here, we report results from the Phase 2b OLM study focusing on patient subgroups aligned with the population enrolled in the ongoing Phase 3 Maintenance trial, specifically the proportion of W8 obe-treated clinical responders (W8CR) achieving efficacy endpoints by prior AT experience. This analysis reflects the population enrolled in the ongoing Phase 3 ABTECT maintenance trial NCT05535946. Methods In the Phase 2b induction trial, pts were randomized to PBO or obe (25mg, 50mg Obe-50 or 100mg QD) for 16 weeks, and, irrespective of their clinical response, could enter the optional OLM study with Obe-50. For this post-hoc analysis, endpoints including clinical remission, endoscopic improvement/remission and histo-endoscopic mucosal improvement (HEMI) were assessed at W48 among W8CR, stratified by prior AT experience (AT-experienced vs. AT-naïve). Results Of the 217 pts who participated in the OLM, 74.7% (162/217) received Obe during induction. Among Obe-treated pts, 63.6% (103/162) were W8CR, of whom 60.2% (62/103) were AT-naïve and 39.8% (41/103) were AT-experienced. Among W8CR pts, the proportion achieving clinical remission increased from W8 to W48 irrespective of prior AT experience: AT-naïve from 45.2% (28/62) to 77.4% (48/62) (net increase of + 20 pts); AT-experienced: from 31.7% (13/41) to 51.2% (21/41) (net increase of + 8 pts)(Table). Most efficacy endpoints showed increased proportions of pts meeting efficacy criteria at W48 versus W8, regardless of prior AT experience. Conclusion Obe-treated pts who achieved clinical response at W8 demonstrated continued improvement across all efficacy endpoints at W48, including clinical remission, independent of prior AT experience. Since both the Phase 2 and 3 studies enrolled similar populations of both AT-naïve and AT-experienced pts (including pts who failed prior AT), these findings provide relevant context for the ongoing Phase 3 maintenance trial. References: 1. Vermeire S, et al. J Crohns Colitis. 2023; 17: 1689-1697 2. Vermeire S, et al. The Lancet Gastroenterology 7: 1024-1035 Conflict of interest: Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda Atreya, Raja: RA has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, Arena Pharmaceuticals, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr Falk Pharma, Galapagos, Gilead, GlaxoSmithKline, InDex Pharmaceuticals, Johnson & Johnson, Lilly, Materia Prima, Merck Sharpe & Dohme, Pfizer, Roche Pharma, Takeda Pharma, Viatris. Dubinsky, Marla C: Personal Fees: Consultant or Advisory Board: Abbvie, Abivax, Astra Zeneca, BMS, Celltrion, Gilead, Genentech, Janssen, Johnson and Johnson, Lilly, Merck, Pfizer, Prometheus Biosciences, Sanofi, Spyre, Target RWE, Takeda Other: Shareholder, Co-founder, Board of Directors of Trellus Health Co-Founder Mi Test Health Sands, Bruce E: Grant: Janssen, Bristol Myers Squibb, Pfizer Personal Fees: Abivax SA Abbvie Adiso Therapeutics Agomab Therapeutics Alimentiv Amgen AnaptysBio AstraZeneca Biora Therapeutics Boehringer-Ingeleim Bristol Myers Squibb Celltrion, Inc. ClostraBio Cytoki Pharma EcoR1 Capital Eli Lilly and Company Enthera Equilium, Inc. Ensho Therapeutics Evommune Ferring Galapagos Genentech, Inc. Gilead Sciences GlaxoSmithKline Gossamer Bio Imhotex Immunyx Pharma Ltd. Index Pharmaceuticals Innovation Pharmaceuticals Janssen Janssen Biotech Janssen Pharmaceutica NV Janssen Research & Development, LLC Janssen Scientific Affairs, LLC Janssen-Cilag PTY, Ltd. Johnson & Johnson Kaleido Kallyope Kyowa Kirin, Inc. Merck & Co. Microba Microbiotica Limited Mirador Therapeutics Morphic Therapeutic MRM Health NV Palisade Therapeutics Pfizer, Inc. Prometheus Biosciences Prometheus Laboratories Protagonist Therapeutics, Inc. Q32 Bio Sanofi Sorriso Therapeutics Surrozen Takeda Target RWE Teva TLL Pharmaceutical Tr1x Union Therapeutics Ventyx Biosciences Non-financial Support: Janssen, Pfizer, Lilly, Takeda, Bristol Myers Squibb Other: Stock/Stock Options from Ventyx Biosciences Dulai, Parambir: Grant: Takeda, Janssen, Pfizer, Abbvie, Polymedco, Buhlmann, Prometheus Personal Fees: Takeda, Janssen, Pfizer, Abbvie, Polymedco, Buhlmann, Prometheus Cataldi, Fabio: Employee of Abivax Jacobstein, Doug: Employee of Abivax Rabbat, Chris: Employee of Abivax Shan, Kevin: Employee of Abivax Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx.