S1095 Obefazimod in Patients With Moderate-to-Severe Ulcerative Colitis: Efficacy and Safety Analysis From the 96-Week Open-Label Maintenance Phase 2b Study

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Introduction: Obefazimod is an oral small molecule that modulates inflammation by upregulating a specific anti-inflammatory micro-RNA (miR-124). Obefazimod has demonstrated safety and efficacy in patients with moderate-to-severe ulcerative colitis (UC) in the randomized, placebo-controlled, phase 2b induction study (1). This analysis presents data at week 96 after subjects enrolled in the open-label (OL) maintenance study. Methods: Patients received placebo or obefazimod 25mg, 50mg or 100mg once daily (od) during the 16-week induction Phase 2b and, irrespective of their clinical response, could enter the optional OL 96-week maintenance study with obefazimod 50mg od. A total of 217 patients were enrolled into this study from January 13, 2020 onwards. Patients were followed monthly (first year) or every three months (2nd year) for safety and efficacy. Non-responder imputation (NRI) was used for missing efficacy data. Results: Of 222 patients who completed the phase 2b induction study, 217 (97.7%) were enrolled in the OL maintenance study. 30/217 (13.8%) subjects dropped out prior to week 48, 6 subjects did not qualify the second year of treatment (non-responders) and 17/181 (9.4%) subjects dropped out between week 48 and week 96. All dropouts were considered as treatment failures for this analysis. 164 subjects completed the second year of treatment. Main efficacy results are presented in Table 1 below. Among the 168 patients with no clinical remission after week 16 induction, 81 (48.2 %) achieved de novo clinical remission at week 96 of the OL maintenance study. Among the 49 patients with clinical remission after induction, 33 (67.3 %) maintained remission at week 96. In total, 149 /217 subjects (68.7 %) reported at least one treatment emergent adverse events (TEAE) over 2 years of treatment. TEAEs leading to study discontinuation were reported in 17 subjects (7.8 %) and serious adverse events (SAEs) were reported in 18 subjects (8.3 %). The most frequent TEAEs (≥ 5 %) were COVID-19 (14.3 %), headache (11.5%), ulcerative colitis (7.8 %) and nasopharyngitis (6.9 %). No new safety risks were identified over these 96 weeks. Conclusion: Results from this 96-week analysis of the OL maintenance Phase 2b study confirmed long-term efficacy of obefazimod 50 mg od, with durable clinical remission, as well as a favorable long-term safety profile. Reference: 1. Vermeire S, et al. Lancet Gastroenterol Hepatol 2022, 7 (11): 1024-1035. Table 1. - Main efficacy results Criteria Definition All patients (NRI)N=217 Clinical remission MMS : stool frequency sub-score ≤1, RBS = 0 and endoscopic sub-score ≤1 52.5% Endoscopic improvement Endoscopic sub-score ≤1 59.0% Endoscopic remission Endoscopic sub-score = 0 35.9% Clinical response Decrease from baseline in the MMS ≥ 2 points and ≥30% from baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1 72.8% MMS: Modified Mayo score ; NRI: Non-responder imputation; RBS: rectal bleeding sub-score.

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