P0922Impact of obefazimod treatment on histologic and combined histologic-endoscopic outcomes in patients with moderately to severely active ulcerative colitis: results from the ABTECT-1 and ABTECT-2 Phase 3, double-blind, placebo-controlled induction trials

Abstract Background Obefazimod (Obe) is an oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and has been studied in two Phase 2 induction trials and subsequent open-label maintenance studies 1-3 in patients (pts) with moderately to severely active ulcerative colitis (UC). In Phase 3 ABTECT-1 NCT05507203 and ABTECT-2 NCT05507216 8-week induction trials, Obe achieved clinically meaningful improvements in clinical, endoscopic and histologic endpoints. UC treatment goals are shifting from symptomatic treatment (i.e. clinical remission) to achieving mucosal healing 4. Here we report proportions of pts that met endoscopic, histologic and combined histologic-endoscopic outcomes in ABTECT trials. Methods The multicenter, randomized, double-blind, placebo-controlled ABTECT trials enrolled pts with moderate-to-severe UC (modified Mayo score (MMS)≥ 5, rectal bleeding sub-score (RBS) ≥ 1 and centrally read endoscopic score≥2) who had inadequate response, loss of response, or intolerance to at least one prior therapy including corticosteroids, immunosuppressants, biologics, S1P receptor modulators and/or JAK inhibitors, with no limit on the number of prior advanced therapy inadequate responses. Pts were randomized 2:1:1 to Obe 50 mg QD (Obe-50), Obe 25 mg QD (Obe-25) or placebo (PBO) for 8 weeks. Rectal or sigmoidal biopsies from the most affected segment were collected during endoscopy at screening and Week 8 (W8) to evaluate treatment effect of Obe vs PBO on histopathology scores using the Geboes index. Endoscopic improvement/remission, histologic improvement (Geboes histologic score ≤3.1)/remission (Geboes histologic score 2.0), histo-endoscopic mucosal improvement (HEMI; endoscopic sub-score ≤1 and Geboes Index score ≤3.1) and remission (HEMR; endoscopic sub-score= 0 and Geboes histologic score 2.0), and endoscopic improvement histological remission (EIHR; endoscopic sub-score ≤1 and Geboes Index score 2.0) were evaluated using non-responder imputation (NRI) for pts with missing outcome at W8 and pts reporting any intercurrent event prior to W8. Results 1272 pts were randomized and treated in the two ABTECT trials. In a pooled analysis, higher proportions of pts receiving either Obe-25 or Obe-50 versus PBO achieved all endoscopic and histologic endpoints (endoscopic improvement: Obe-25-PBO difference=21.9%; Obe-50-PBO difference=26.6% - histologic improvement: Obe-25-PBO difference=19.6%; Obe-50-PBO difference=22.8%), and combined endoscopic-histologic with nominal significance, including the most stringent endpoint of HEMR (Table 1). Conclusion In ABTECT induction trials, Obe treatment led to clinically meaningful improvements in endoscopic, histologic, and combined histologic-endoscopic endpoints at W8. References: 1. Vermeire S, et al. J Crohns Colitis. 2023; 17: 1689-1697 2. Vermeire S, et al. Gastroenterology 2021; 160: 2595-2598 3. Vermeire S, et al. The Lancet Gastroenterology 7: 1024-1035 4. Kobayashi T, et al. Nat Rev Dis Primers. 2020 Sep 10;6(1):74 doi: 10.1038/s41572-020-0205-x Conflict of interest: Magro, Fernando: Fernando Magro served as speaker and received honoraria from Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, Vifor. Sands, Bruce E: Grant: Janssen, Bristol Myers Squibb, Pfizer Personal Fees: Abivax SA Abbvie Aclaris Therapeutics, Inc. Adiso Therapeutics Agomab Therapeutics Alfasigma SpA Alimentiv Amgen AMT AnaptysBio Arena Pharmaceuticals Artizan Biosciences AstraZeneca Biora Therapeutics Boehringer-Ingeleim Bristol Myers Squibb Calibr Celltrion, Inc. ClostraBio Connect Biopharm Cytoki Pharma EcoR1 Capital Eli Lilly and Company Enthera Equilium, Inc. Evommune Ferring Fresenius Kabi Galapagos Genentech, Inc. Gilead Sciences GlaxoSmithKline Gossamer Bio Imhotex Immunic 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 Kyowa Kirin, Inc. Merck & Co. Microba Microbiotica Limited MiroBio Morphic Therapeutic MRM Health NV Pfizer, Inc. Progenity Prometheus Biosciences Prometheus Laboratories Protagonist Therapeutics, Inc. Q32 Bio Surrozen Synlogic Operating Company, Inc. Takeda Target RWE Televant Teva Branded Pharmaceutical Products R&D TLL Pharmaceutical VectivBio AG Ventyx Biosciences Non-financial Support: Janssen, Pfizer, Lilly, Takeda, Bristol Myers Squibb Other: Stock/Stock Options from Ventyx Biosciences 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 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 Cataldi, Fabio: Employee of Abivax Jacobstein, Doug: Employee of Abivax Rabbat, Chris: Employee of Abivax Shan, Kevin: Employee of Abivax Harlacher, Luciana: Speaker fee from Johnson & Johnson, AbbVie, and Takeda. Conducts clinical trials for Johnson & Johnson, AbbVie, Takeda, Ventyx, Abivax, BMS, Lilly, MSD, and Sanofi. Scaldaferri, Franco: Consultancy fee/board for Janseen, Takeda, Pfizer, MSD, Sandoz, Galapagos, Celltrion, Ferring, Abbvie, Lilly, Alfasigma, Abivax D’Haens, Geert: Grant: Pfizer, BMS, Johnson and Johnson, Abbvie, Alimentiv BV, Eli Lilly, Takeda, Prometheus Laboratories Personal Fees: Abbvie, Abivax,