P3534 - Long-Term Upregulation of miR-124 in Blood and Rectal Biopsies of Patients With Moderate-to-severe Ulcerative Colitis Receiving Obefazimod 50mg Daily for 96 weeks

Tuesday, October 24, 2023

10:30 AM – 4:00 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

SS

Sheldon Sloan, MD

Abivax
Paris, Ile-de-France, France

Julien Santo, PhD¹, Aurélien Flatres, PhD¹, Paul Gineste, ², Didier Scherrer, PhD¹, Josianne Nitcheu, PhD², Sheldon Sloan, MD², Hartmut J. Ehrlich, MD², Bruce E. Sands, MD, MS, FACG³, Séverine Vermeire, MD, PhD⁴
¹Abivax, Montpellier, Languedoc-Roussillon, France; ²Abivax, Paris, Ile-de-France, France; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴UZ Leuven, Leuven, Vlaams-Brabant, Belgium

Introduction: Obefazimod is an oral small molecule that has demonstrated long-term efficacy and safety in patients with moderate-to-severe ulcerative colitis (UC) (1,2). Obefazimod is known to modulate inflammation by upregulating a specific anti-inflammatory micro-RNA (miR-124) (3). We examined the long-term effects of obefazimod on miR-124 in blood and rectal biopsies of patients enrolled in a 96-week maintenance study.

Methods: Patients received placebo or obefazimod 25mg, 50mg or 100mg once daily (od) during a 16-week induction phase and, irrespective of their clinical response, could enter an open-label 96-week maintenance phase with obefazimod 50mg od. Absolute quantification (QuantaSoft Pro) of the miR-124 copy number was performed at baseline, weeks 48 and 96 by using droplet digital PCR technology on 115 whole blood samples and 240 rectal biopsy samples. An ANOVA was performed including treatment, time, the interaction between treatment and time, the baseline value as fixed factor and time as repeated effect.

Results: A daily treatment with obefazimod 50 mg significantly upregulated miR-124 over time in blood and rectal tissue at weeks 48 and 96 (p< 0.001 vs. baseline). The miR-124 upregulation was observed in all patients, including those previously receiving placebo during the induction phase.

Discussion: The 96-week efficacy of obefazimod 50mg od in patients with moderate-to-severe UC is associated with a maintained increase in miR-124 expression in blood and rectal tissue.

References:

1. Vermeire S, et al, Lancet Gastroenterol Hepatol 2022, 7 (11): 1024-1035

2. Vermeire et al, J Crohns Colitis 2023. doi: 10.1093/ecco-jcc/jjad067

3. Apolit C, et al, Clin Trans Gastroenterol 2023, 14(4): p e00560

Treatment during the induction phase	Time	Rectal tissue Median fold change from baseline	Blood Median fold change from baseline
Obefazimod 100 mg od	W48	4.8 ^†	128.2 ^†
Obefazimod 100 mg od	W96	7.4 ^†	188.3 ^†
Obefazimod 50 mg od	W48	5.8 ^†	230.1 ^†
Obefazimod 50 mg od	W96	10.3 ^†	244.4 ^†
Obefazimod 25 mg od	W48	4.5 ^†	308.8 ^†
Obefazimod 25 mg od	W96	8.5 ^†	128.5 ^†
Placebo	W48	4.8 ^†	237.0 ^†
Placebo	W96	7.5 ^†	396.8 ^†

†: p< 0.001 vs. baseline ; each timepoint (W48 and W96) is compared to the baseline using a Dunnett adjustment.

Disclosures:

Julien Santo: Abivax – Employee.

Aurélien Flatres: Abivax – Employee.

Paul Gineste: Abivax – Employee.

Didier Scherrer: Abivax – Employee.

Josianne Nitcheu: Abivax – Employee.

Sheldon Sloan: Abivax – Employee.

Hartmut Ehrlich: Abivax – Employee.

Bruce Sands: AbbVie – Consultant. Abivax – Consultant, Speaker’s fees. Adiso Therapeutics – Consultant. Alimentiv – Consultant. Amgen – Consultant. Arena pharmaceuticals – Consultant. Artizan Biosciences – Consultant. Artugen Therapeutics – Consultant. AstraZeneca – Consultant. Bacainn Therapeutics – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Consultant. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support, speaking fees and other support. Calibr – Consultant. Celltrion – Consultant. ClostraBio – Consultant. Connect Biopharm – Consultant. Cytoki Pharma – Consultant. Eli Lilly – Consultant, speaking fees and other support. Enthera – Consultant. Evommune – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant. HMP Acquisition – Consultant. Imhotex – Consultant. Immunic – Consultant. InDex Pharmaceuticals – Consultant. Innovation Therapeutics – Consultant. Inotrem – Consultant. Ironwood Pharmaceuticals – Consultant. Janssen – Grant/Research Support, consulting and speaking fees and other support. Johnson & Johnson – Consultant. Kaleido Biosciences – Consultant. Kallyope – Consultant. Merck – Consultant. MiroBio – Consultant. Morphic Therapeutics – Consultant. MRM Health – Consultant. OSE Immunotherapeutics – Consultant. Pfizer Inc – Consultant, Grant/Research Support, speaking fees and other support. Progenity – Consultant. Prometheus Biosciences – Consultant. Prometheus Laboratories – Consultant. Protagonist Therapeutics – Consultant. Q32 Bio – Consultant. RedHill Biopharma – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Synlogic Operating Company – Consultant. Takeda – Grant/Research Support, consulting and speaking fees and other support. Target RWE – Consultant. Theravance Biopharma – Consultant, Grant/Research Support. TLL Pharmaceutical – Consultant. USWM Enterprises – Consultant. Ventyx Biosciences – Consultant, personal fees and stock options for consulting. Viela Bio – Consultant.

Séverine Vermeire: AbbVie – Consultant, Grant/Research Support. AbolerIS Pharma – Grant/Research Support. AgomAb – Grant/Research Support. Alimentiv – Consultant. Arena Pharmaceuticals – Consultant. AstraZeneca – Consultant. Avaxia Biologics – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant. CVasThera – Consultant, Speakers Bureau. Cytoki Pharma – Consultant, Speakers Bureau. Dr. Falk Pharma – Consultant, Speakers Bureau. Eli Lilly – Consultant, Speakers Bureau. Ferring Pharmaceuticals – Consultant, Speakers Bureau. Galapagos – Consultant, Grant/Research Support, Speakers Bureau. Genentech/Roche – Consultant, Speakers Bureau. Gilead – Consultant, Speakers Bureau. GSK – Consultant, Speakers Bureau. Hospira – Consultant, Speakers Bureau. IMIDomics – Consultant, Speakers Bureau. Janssen Pharmaceuticals – Consultant, Speakers Bureau. Johnson & Johnson – Consultant, Grant/Research Support, Speakers Bureau. Materia Prima – Consultant, Speakers Bureau. MiroBio – Consultant, Speakers Bureau. Morphic – Consultant, Speakers Bureau. MRM Health – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Mundipharma – Consultant, Speakers Bureau. Pfizer – Consultant, Grant/Research Support, Speakers Bureau. ProDigest – Consultant, Speakers Bureau. Progenity – Consultant, Speakers Bureau. Prometheus – Consultant, Speakers Bureau. Robarts Clinical Trials – Consultant, Speakers Bureau. Second Genome – Consultant, Speakers Bureau. Shire – Consultant, Speakers Bureau. Surrozen – Consultant, Speakers Bureau. Takeda – Consultant, Grant/Research Support, Speakers Bureau. Theravance Biopharma – Consultant, Speakers Bureau. Tillotts Pharma – Consultant, Speakers Bureau. Zealand Pharma – Consultant, Speakers Bureau.

Julien Santo, PhD¹, Aurélien Flatres, PhD¹, Paul Gineste, ², Didier Scherrer, PhD¹, Josianne Nitcheu, PhD², Sheldon Sloan, MD², Hartmut J. Ehrlich, MD², Bruce E. Sands, MD, MS, FACG³, Séverine Vermeire, MD, PhD⁴. P3534 - Long-Term Upregulation of miR-124 in Blood and Rectal Biopsies of Patients With Moderate-to-severe Ulcerative Colitis Receiving Obefazimod 50mg Daily for 96 weeks, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.