AGMB-129 is an oral small molecule GI-restricted inhibitor of ALK5 (or TGFβR1) intended for the treatment of Fibrostenosing Crohn’s Disease (FSCD). TGFβ is a master regulator of fibrosis and preliminary clinical data supports targeting the pathway in fibrotic indications. AGMB-129 is specifically designed to inhibit ALK5 in the GI-tract. Rapid first-pass metabolism in the liver prevents clinically relevant systemic exposure, delivering an improved safety profile over other inhibitors in its class. Fibrostenosing complications occur in nearly 50% of Crohn’s disease patients and are the leading cause of bowel resection surgery. Yet, there are no approved specific therapies for FSCD.

AGMB-129 successfully completed a Phase 1 study in 2022. The Phase 1 study included single ascending dose (SAD), multiple ascending dose (MAD) and food- effect (FE) stages, as well as an additional stage for the assessment of local drug exposure in terminal ileal mucosa, where the Fibrostenosing strictures in FSCD patients are most often located. A total of 81 healthy subjects were randomized to receive either single or multiple daily oral doses of AGMB-129, or matching placebo.

AGMB-129 was well-tolerated at all doses tested. The incidence and intensity of adverse events were similar across all dose cohorts including the placebo cohort. No drug-related safety signal or dose- limiting toxicities were identified. The favorable safety profile from the Phase 1 study supports the evaluation of AGMB-129 in a global Phase 2a study in patients with FSCD. Plasma PK analyses showed no clinically relevant systemic exposure, whereas biopsies of the ileum showed high local concentrations of AGMB-129, confirming that the GI-restriction mechanism can operate efficiently in humans.

AGMB-129 is currently being investigated in the STENOVA Global Ph2a study in Fibrostenotic Crohn’s Disease (NCT05843578)

AGMB-129 has received FDA Fast Track Designation