Agomab Unveils Design for First-Ever Phase 2b Trial in Fibrostenosing Crohn's Disease with Oral ALK5 Inhibitor Ontunisertib
核心洞察
Agomab Therapeutics (搜索) announced the design of the NOV-ERA Phase 2b study, the first Phase 2b trial in fibrostenosing Crohn's disease (搜索) (FSCD), with FDA alignment on key elements including a novel primary endpoint of endoscopic passability.
The randomized, placebo-controlled, dose-ranging trial will enroll up to 320 adult patients globally and evaluate three dose levels of ontunisertib (搜索), with first participants expected to be dosed in the second half of 2026.
Approximately 46% of Crohn's disease patients develop FSCD with fibrotic strictures causing obstructive symptoms, yet no approved pharmacological therapies currently exist for this condition.
Agomab Therapeutics (搜索) NV, a clinical-stage biopharmaceutical company focused on fibro-inflammation, today announced the design of its upcoming NOV-ERA Phase 2b study evaluating ontunisertib (搜索), an investigational oral gastrointestinal (GI)-restricted small molecule inhibitor of ALK5 (搜索), for the potential treatment of fibrostenosing Crohn's disease (搜索) (FSCD). The announcement, made from the company's headquarters in Antwerp, Belgium, marks a significant milestone as the first Phase 2b study ever conducted in FSCD, a condition that affects approximately 46% of Crohn's disease patients and for which no approved pharmacological therapies exist.
The company has achieved regulatory alignment with the U.S. Food and Drug Administration (FDA) on key elements of the NOV-ERA study design, including the novel primary efficacy endpoint of endoscopic passability at Week 24 as assessed by the Simple Endoscopic Score for Crohn's Disease (SES-CD) narrowing score. The protocol has been submitted to the FDA and has cleared central Institutional Review Board (IRB) approval in the U.S., while also receiving approval from Health Canada. Clinical Trial Applications have been submitted in multiple countries globally, including in the European Union and Asia Pacific territories.
"The NOV-ERA study breaks new ground as the first Phase 2b study in FSCD, an area of high unmet medical need, and will inform dose selection and pivotal endpoints," said Philippe Wiesel, MD, Chief Medical Officer of Agomab. "The submission of the study protocol to key regulatory agencies is a crucial milestone in the late-stage development of ontunisertib (搜索) in FSCD. We are now focused on completing operational preparations and look forward to initiating patient enrollment in the coming months."
Study Design and Endpoints
The NOV-ERA study is a randomized, double-blind, placebo-controlled, dose-ranging, multicenter Phase 2b trial designed to assess the efficacy and safety of ontunisertib (搜索) in participants diagnosed with symptomatic FSCD. The trial is expected to enroll up to 320 adult patients globally. Eligible participants must have at least one naive or anastomotic endoscopically non-passable ileal stricture, confirmed by a centrally read SES-CD.
Participants will be randomized in a 1:1:1:1 ratio to receive ontunisertib (搜索) at one of three dose levels — 400 mg, 200 mg, or 100 mg — or matching placebo, administered twice daily. The trial structure includes a 6-week screening period, a 52-week treatment period, and a 2-week follow-up period.
The primary endpoint is the proportion of patients achieving endoscopic passability of the ileal index stricture at Week 24. Key secondary endpoints include the proportion of participants achieving endoscopic passability at Week 52, change from baseline in Magnetic Resonance Enterography (MRE) imaging features of the index stricture at Weeks 24 and 52, change from baseline in total SES-CD, the proportion of participants with endoscopic response and remission, change from baseline in the Patient-Reported Outcome questionnaire for stricturing Crohn's disease (S-PRO 2.0) severity score, and time to an FSCD-related event including surgery and endoscopic balloon dilation. These endpoints are designed to inform the selection of potential registrational endpoints for ontunisertib (搜索) in FSCD.
Mechanism of Action and Unmet Need
Ontunisertib (搜索) (AGMB-129) is specifically designed to inhibit ALK5 (搜索), also known as TGF-β (搜索) RI, within the GI tract. TGF-β is recognized as a major driver of fibrosis, the pathological process underlying stricture formation in FSCD. The molecule's rapid first-pass metabolism in the liver prevents clinically relevant systemic exposure, a design feature that may offer an improved safety profile compared to systemically available inhibitors in this class. Ontunisertib has received U.S. FDA Fast Track designation.
Fibrostenosing Crohn's disease (搜索) represents a substantial unmet medical need. Crohn's disease is a chronic progressive disease of the gastrointestinal tract, and fibrotic strictures — most frequently occurring in the terminal ileum — can cause obstructive symptoms leading to dietary change, malnutrition, and the need for surgery. Despite the significant patient burden, there are currently no approved pharmacological therapies for FSCD.
The company expects to initiate the NOV-ERA study following receipt of applicable regulatory and ethics approvals and plans to dose the first participants in the second half of 2026. Ontunisertib (搜索) remains investigational and has not been approved by any regulatory authority; its efficacy and safety have not been established.