Agomab doses first patient in Phase 2b NOV-ERA fibrotic Crohn's trial
Agomab Therapeutics has dosed the first patient in NOV-ERA, its Phase 2b study of ontunisertib in symptomatic fibrostenosing Crohn's disease (FSCD), marking a significant step in what the Antwerp-based company describes as the first targeted anti-fibrotic programme specifically designed for this indication.
The randomised, double-blind, placebo-controlled trial will enrol approximately 320 adult patients across multiple international sites. Participants will receive one of three twice-daily oral doses of ontunisertib (400 mg, 200 mg, or 100 mg) or placebo over a 52-week treatment period. The primary endpoint is endoscopic passability of the ileal index stricture at Week 24, a clinically meaningful measure of whether the narrowed bowel segment has opened sufficiently to permit passage of an endoscope.
Trial design and scientific rationale
Ontunisertib is an oral, small-molecule inhibitor of ALK5, also known as TGF-beta receptor I. TGF-beta signalling is a well-established driver of fibrosis across multiple organ systems, and Agomab has engineered ontunisertib to act specifically within the gastrointestinal tract. Rapid first-pass hepatic metabolism is intended to limit systemic exposure, potentially conferring a cleaner safety profile compared with non-restricted ALK5 inhibitors. The compound holds FDA Fast Track Designation.
The NOV-ERA design builds directly on STENOVA, Agomab's Phase 2a study, which generated positive efficacy signals and, through its open-label extension, demonstrated long-term tolerability at the 400 mg twice-daily dose. That extension data underpinned the decision to include the highest dose arm in the Phase 2b programme.
Philippe Wiesel, Chief Medical Officer of Agomab, said: "FSCD is associated with progressive bowel damage and a substantial burden for patients; yet there are currently no approved therapies that specifically address the fibrotic component of the disease."
The milestone also triggers a €7 million payment to former shareholders of Origo Biopharma, acquired by Agomab in 2021 for up to €20 million in development and regulatory milestones. Including a €3 million payment made in 2025, a total of €10 million has now become payable under that arrangement.
Market context and competitive landscape
FSCD is a distinct and poorly served subset of Crohn's disease characterised by progressive bowel wall fibrosis and stricture formation. Current management relies on endoscopic balloon dilation or surgical resection to relieve obstruction; neither approach addresses the underlying fibrotic pathology or meaningfully alters disease course. Biologics approved for Crohn's disease, including anti-TNF agents and anti-integrins, are not designed to reverse established fibrosis, leaving a clear gap that Agomab is targeting.
The TGF-beta pathway has been pursued in fibrosis research across hepatology, pulmonology, and gastroenterology for several years, but the challenge of delivering systemic TGF-beta inhibition without off-target cardiovascular and immunological effects has limited progress. Agomab's GI-restricted approach is intended to sidestep those concerns and represents a design strategy that, if validated in NOV-ERA, could attract considerable partnership interest from larger gastroenterology franchises.
Key secondary endpoints in NOV-ERA include time to FSCD-related events such as bowel surgery and endoscopic dilation, changes in MRI enterography features, and patient-reported outcome scores using the S-PRO 2.0 instrument. Agomab has stated that the endpoints are chosen to inform a potential registrational trial design, suggesting a Phase 3 submission could follow if results are positive. Primary data at Week 24 are therefore the near-term catalyst for the programme.