Agomab Announces Positive Topline Phase 2a Interim Results for AGMB-129 in Fibrostenosing Crohn’s Disease
Agomab Therapeutics NV (“Agomab”), a biotechnology company focused on developing innovative treatments for fibrotic diseases, has announced positive interim results from its ongoing STENOVA Phase 2a clinical trial evaluating AGMB-129. The trial is investigating AGMB-129, an oral, gastrointestinal (GI)-restricted small molecule inhibitor of ALK5 (also known as TGF-β RI), as a potential treatment for Fibrostenosing Crohn’s Disease (FSCD). The interim analysis includes data from 44 patients who have completed the treatment phase of the study.
Fibrostenosing Crohn’s Disease (FSCD) is a severe manifestation of Crohn’s disease characterized by fibrosis and strictures in the intestines, leading to complications such as bowel obstructions and the need for surgical intervention. Despite significant advances in biologic therapies for Crohn’s disease, no approved treatments specifically target the fibrotic complications that occur in approximately 50% of patients. Agomab’s AGMB-129 is designed to address this critical unmet medical need by inhibiting ALK5, a key driver of fibrosis in the gastrointestinal tract.
STENOVA Phase 2a Clinical Trial Overview
The STENOVA trial is a randomized, double-blind, placebo-controlled Phase 2a study designed to assess the safety, tolerability, and pharmacokinetics of AGMB-129 in FSCD patients. The study is being conducted at multiple clinical centers across the United States, Canada, and Europe, with a total enrollment goal of 90 patients. Participants are randomized to receive one of two doses of AGMB-129 or a placebo for 12 weeks in combination with their existing standard of care, which may include biologic therapies.
The primary endpoints of the STENOVA trial focus on evaluating the safety and tolerability of AGMB-129 in patients with FSCD. Secondary endpoints include assessments of pharmacokinetics, target engagement at the site of ileal strictures through transcriptomics, and preliminary efficacy measures.
According to Agomab, the interim analysis demonstrated that AGMB-129 met all primary and secondary endpoints, indicating a favorable safety and pharmacokinetic profile. These findings support the drug’s mechanism of action and its potential to provide a much-needed therapeutic option for FSCD patients.
Positive Interim Results and Future Outlook
Dr. Philippe Wiesel, Chief Medical Officer at Agomab Therapeutics, expressed enthusiasm about the promising interim results, stating, “The positive interim data for the STENOVA Phase 2a clinical trial represent a significant milestone for this program. We look forward to presenting the detailed results at a scientific conference in the near term.”
In addition to the double-blind treatment phase, Agomab has initiated an open-label extension (OLE) study, allowing patients who have completed the 12-week trial to continue receiving AGMB-129 for an additional 48 weeks. The OLE study will provide valuable long-term safety and efficacy data, further supporting the development of AGMB-129 as a potential treatment for FSCD.
About AGMB-129 and Its Mechanism of Action
AGMB-129 is an oral small-molecule inhibitor of ALK5, a receptor involved in the TGF-β signaling pathway, which plays a key role in fibrosis. The drug is designed to be GI-restricted, meaning it acts primarily within the intestines, thereby reducing the risk of systemic side effects. This targeted approach is made possible by AGMB-129’s rapid first-pass metabolism in the liver, which prevents significant systemic exposure while ensuring high local drug concentrations in the ileum, the region of the small intestine most commonly affected by FSCD.
The potential benefits of AGMB-129’s localized inhibition of ALK5 include:
- Reduced Fibrosis: By blocking TGF-β signaling, AGMB-129 may help prevent or reduce fibrotic scarring in the intestines.
- Lower Risk of Systemic Side Effects: Unlike systemically available ALK5 inhibitors, AGMB-129’s GI-restricted activity minimizes the likelihood of adverse effects in other organs.
- Improved Safety Profile: Early-phase clinical studies have demonstrated that AGMB-129 is well-tolerated, with no clinically significant systemic exposure.
Regulatory Designations and Future Development Plans
Recognizing the high unmet medical need for effective FSCD treatments, the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to AGMB-129. This designation is intended to facilitate the development and expedite the regulatory review of drugs that address serious conditions with limited treatment options.
Following the completion of the STENOVA trial, Agomab plans to advance AGMB-129 into a larger Phase 2b study to further evaluate its safety and efficacy. Additionally, the company aims to explore biomarker-driven strategies to identify patients who may benefit the most from AGMB-129 therapy.
The Burden of Fibrostenosing Crohn’s Disease
Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract that affects millions of people worldwide. While many patients respond well to anti-inflammatory and immunosuppressive therapies, approximately half will develop fibrostenotic complications over time. These complications result in the formation of intestinal strictures, which can cause severe symptoms such as abdominal pain, bowel obstructions, and malnutrition.
Currently, treatment options for FSCD are limited to endoscopic dilation or surgical resection, both of which carry significant risks and do not prevent stricture recurrence. The development of targeted antifibrotic therapies like AGMB-129 represents a major step forward in addressing this unmet medical need and improving patient outcomes.
About Agomab
Agomab is focused on achieving disease modification by modulating inflammation and fibrosis in chronic indications such as Fibrostenosing Crohn’s Disease and Idiopathic Pulmonary Fibrosis. We do this by targeting biologically validated pathways, including Transforming Growth Factor β, and by applying specialized capabilities in organ-restricted small molecules. With a differentiated clinical pipeline across several fibrotic disorders, end-to-end research and development capabilities, a proven track-record and a strong investor base, Agomab is building a transformational company with the aim to have a real impact on patients.
