In the 12-week randomized Part A of the Phase 2a STENOVA study (n=103), ontunisertib met its primary endpoint with an overall safety and tolerability profile comparable to placebo across both dose arms (100 mg QD and 200 mg BID). Pharmacokinetic data showed high local gastrointestinal exposure with minimal systemic levels, aligning with the drug’s gut-restricted design. Exploratory signals trended positive on endoscopic disease activity (SES-CD) and magnetic resonance enterography parameters, while an ongoing open-label extension through 36 weeks continues to support a favorable safety profile.
The core development is Agomab’s first-in-indication readout in fibrostenosing Crohn’s disease (FSCD), a setting with no approved pharmacologic therapies and persistent reliance on endoscopic dilation and surgery. Part A was randomized, double-blind, and placebo-controlled, layered on top of standard of care, including anti-inflammatory biologics, and included U.S., Canadian, and European sites. Secondary measures included pharmacokinetics and transcriptomic target engagement in mucosal biopsies, with the latter analysis ongoing. The company plans regulatory discussions to shape a Phase 2b program and intends to present fuller data at an upcoming meeting. Ontunisertib holds an FDA Fast Track designation.
Strategically, Agomab is pursuing a fibrosis-first thesis in a population where inflammation control has not addressed stricture biology. Targeting TGFβ/ALK5 has long been constrained by systemic toxicity; a GI-restricted small molecule is a deliberate attempt to retain anti-fibrotic activity while avoiding off-target liabilities. Equally notable is the operational precedent: STENOVA demonstrates that protocolized imaging, biopsy-based pharmacodynamics, and symptom measures in symptomatic ileal strictures can be executed at scale across regions. That feasibility matters as the FDA and EMA expect sponsors to move beyond generic Crohn’s metrics and develop FSCD-relevant outcome measures.
The implications cut across stakeholders. For sites, this trial model requires strong imaging infrastructure, central reads, and endoscopy coordination, plus capabilities for biopsy-based transcriptomics—an operational lift that favors tertiary centers and specialized IBD networks. CROs and vendors can expect demand for standardized MRE acquisition/reading and validation work around FSCD-specific PROs like the S-PRO instrument. For sponsors, the signal lowers perceived execution risk in an area long viewed as clinically important but methodologically difficult, and it encourages investment in fibrosis programs that can run on top of existing biologic regimens. Regulators are likely to focus on endpoint maturation—linking imaging and PRO changes to meaningful reductions in obstruction, dilation, or surgery—while maintaining scrutiny on systemic exposure and class-related toxicities over longer durations.
Next, the Phase 2b blueprint will need to stretch beyond 12 weeks to capture tissue remodeling and stricture dynamics, finalize dose selection, and anchor a primary endpoint that regulators accept for FSCD. A composite of imaging-based structure metrics with symptom and functional readouts is a plausible path, but it will require rigorous centralization and reproducibility. Key risks include translating “positive trends” into statistically robust effects, avoiding attenuation in a background of potent biologics, and sustaining minimal systemic exposure as duration increases. Watch for the pending target engagement analyses, longer-term OLE outcomes through 48 weeks, the choice of imaging quantitation strategy and central reading model, and whether future protocols enrich for specific structure phenotypes or baseline lengths. If the Phase 2b study can convert feasibility and pharmacology into a clinically persuasive, durable structure benefit, ontunisertib could define the regulatory and operational template for FSCD drug development.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
