Agomab aligns with FDA on Phase 2b NOV-ERA design for FSCD

Agomab Therapeutics has announced the design of its NOV-ERA Phase 2b study evaluating ontunisertib in fibrostenosing Crohn's disease (FSCD), confirming regulatory alignment with the US Food and Drug Administration on key elements including a novel primary endpoint. The Antwerp-based company expects to dose the first participants in the second half of 2026.

The trial protocol has cleared central Institutional Review Board approval in the US and received a green light from Health Canada. Agomab has also submitted Clinical Trial Applications in the European Union, Asia Pacific, and other territories. The study can begin enrolling once all remaining regulatory and ethics approvals are in place.

Study design and endpoints

NOV-ERA is a randomised, double-blind, placebo-controlled, dose-ranging, multicentre trial targeting up to 320 adult patients globally. Participants will be randomised in a 1:1:1:1 ratio across three dose levels of ontunisertib (400 mg, 200 mg and 100 mg, all administered twice daily) and matching placebo. The treatment period runs for 52 weeks, preceded by a six-week screening window.

The primary endpoint is the proportion of patients achieving endoscopic passability of the ileal index stricture at Week 24, assessed by the Simple Endoscopic Score for Crohn's Disease (SES-CD) narrowing score. This endpoint was agreed with the FDA and is described by the company as novel for the indication. Secondary endpoints include endoscopic passability at Week 52, changes in magnetic resonance enterography imaging, total SES-CD scores, and patient-reported outcome measures using the S-PRO 2.0 severity questionnaire, as well as time to FSCD-related events such as surgery or endoscopic balloon dilation.

Philippe Wiesel, Chief Medical Officer at Agomab, said the study "breaks new ground as the first Phase 2b study in FSCD" and that the data will inform dose selection and pivotal endpoints for a potential registrational programme.

Ontunisertib is an oral small-molecule inhibitor of ALK5 (also known as TGF-beta receptor I), engineered to act selectively within the gastrointestinal tract. Rapid hepatic first-pass metabolism is intended to limit systemic exposure, which the company argues could reduce the safety liabilities associated with systemic TGF-beta inhibition. The candidate holds FDA Fast Track Designation.

Market context and competitive landscape

FSCD represents a substantial and poorly served patient population. Agomab estimates that approximately 46% of people with Crohn's disease develop fibrotic strictures, yet no pharmacological therapy has regulatory approval specifically for this complication. Current management relies on corticosteroids and biologics that address inflammatory activity but show limited impact on established fibrosis, with surgery or endoscopic balloon dilation used when obstruction becomes symptomatic.

The broader intestinal fibrosis space has attracted growing pharmaceutical interest as the limitations of inflammation-targeting biologics in structural disease become clearer. Several companies are exploring anti-fibrotic strategies in inflammatory bowel disease, including TGF-beta pathway modulation and anti-integrin approaches, though the clinical validation work remains early. Agomab's GI-restricted design differentiates its approach from systemically available ALK5 inhibitors, which have historically encountered cardiovascular and other off-target safety signals. Whether the restricted pharmacology translates into a meaningfully cleaner safety profile in a 52-week, 320-patient study will be one of the key readouts investors and regulators will scrutinise closely. The NOV-ERA primary readout at Week 24 is therefore likely to generate significant attention within the GI drug development community.