Agomab Therapeutics announced positive topline results from its landmark STENOVA Phase 2a clinical trial, marking a significant milestone in the development of treatments for fibrostenosing Crohn's disease (FSCD). The study of ontunisertib (AGMB-129), an investigational oral gastrointestinal-restricted ALK5 inhibitor, successfully achieved its primary safety endpoint in 103 participants after 12 weeks of treatment.
Trial Design and Primary Results
The STENOVA study represents the first-in-indication, first-in-class trial for FSCD, a condition affecting approximately 46% of Crohn's disease patients. Part A of the randomized, double-blind, placebo-controlled study enrolled 103 participants across the USA, Canada, and six European countries. Patients received either 100mg once daily or 200mg twice daily of ontunisertib, or placebo, for 12 weeks on top of standard care including anti-inflammatory biologics.
"As a first-in-indication, first-in-class trial, STENOVA is a landmark study that demonstrates the feasibility of recruiting and conducting a clinical investigation in patients with Fibrostenosing Crohn's Disease," commented Florian Rieder, MD, Vice-Chair Department of Gastroenterology, Hepatology and Nutrition at Cleveland Clinic. "The STENOVA data represent a major contribution to the development of registrational endpoints in the field."
Safety Profile and Pharmacokinetics
The trial achieved its primary endpoint with a favorable safety profile supporting further clinical development. The severity and incidence of adverse events were similar among all treatment arms, including placebo. Notably, there were no signs of treatment-related cardiac toxicity, no pro-inflammatory effects, and no concerning signals in safety laboratories, vital signs, or physical examinations.
Secondary endpoint analysis revealed that ontunisertib demonstrated high local exposure in the gastrointestinal tract with minimal systemic exposure. These pharmacokinetic results confirmed the gut-restricted profile of ontunisertib in FSCD patients, consistent with prior data in healthy participants.
Efficacy Signals and Mechanism of Action
Positive trends were observed across several exploratory clinical endpoints, including the Simple Endoscopic Score of Crohn's disease (SES-CD) and Magnetic Resonance Enterography (MRE) parameters. These findings support ontunisertib's potential dual anti-inflammatory and anti-fibrotic mode of action through ALK5/TGF-β pathway inhibition.
The study also evaluated novel FSCD-specific endpoints such as the Stricturing Patient Reported Outcome (S-PRO) score, contributing valuable data for future registrational endpoint development in this underserved patient population.
Extended Safety Data and Future Plans
In the ongoing open-label extension study, ontunisertib continues to demonstrate a generally favorable safety and tolerability profile, with participants receiving 200mg twice daily for up to 36 weeks total. Eligible participants from the double-blind phase can continue treatment for up to an additional 48 weeks.
"We are very pleased with the STENOVA results announced today. The trial recruited faster and enrolled more patients than originally anticipated, underscoring the strong investigator support and patient interest," said Philippe Wiesel, Chief Medical Officer at Agomab. "The data demonstrate that ontunisertib has the potential to safely target the key fibrotic TGFβ/ALK5 pathway in a gut-restricted fashion."
Addressing Unmet Medical Need
Fibrostenosing Crohn's disease represents a significant unmet medical need, with no approved pharmacological therapies currently available. The condition causes gastrointestinal tract fibrosis, resulting in stricture formation and intestinal obstructions, most frequently in the terminal ileum. These strictures lead to obstructive symptoms, dietary changes, malnutrition, and often require surgical intervention.
Ontunisertib's design specifically targets ALK5 (TGF-β RI) in the gastrointestinal tract, with rapid first-pass metabolism in the liver preventing clinically relevant systemic exposure. This approach potentially delivers an improved safety profile compared to systemically available inhibitors in this class. The drug has received U.S. FDA Fast Track Designation.
Agomab plans to discuss the STENOVA results with regulatory authorities and prepare for a Phase 2b study, while also planning to present detailed results at a future scientific conference.
