Vedanta Biosciences announced that its microbiome-based therapy VE202 failed to meet the primary endpoint in a Phase 2 study for ulcerative colitis, marking a setback for the company's inflammatory bowel disease program while highlighting the ongoing challenges in developing microbiome-based treatments for IBD.
The randomized, placebo-controlled COLLECTiVE202 study enrolled 114 patients with mild-to-moderate ulcerative colitis across sites in the United States, Europe, and Australia. The trial failed to demonstrate statistical significance for its primary endpoint of Week 8 endoscopic response, defined as a reduction of at least 1 point on the Mayo endoscopic subscore.
Safety Profile Remains Favorable
Despite the efficacy failure, VE202 demonstrated a favorable safety profile throughout the study. Most adverse events were mild or moderate in intensity, with no reports of treatment-related serious adverse events. The therapy was added to patients' stable background ulcerative colitis therapy, with 57 patients receiving VE202 and 57 receiving placebo.
"We are very disappointed that our study did not meet its efficacy endpoints, and our greatest regret is that people living with inflammatory bowel disease will not, for now, have the opportunity to benefit from a new treatment option," said Bernat Olle, Ph.D., Chief Executive Officer of Vedanta Biosciences.
Microbiome Challenges in IBD Treatment
The failure underscores the persistent challenges in translating microbiome science into effective IBD treatments. Dr. Olle acknowledged that while the gut microbiome is a well-recognized driver of IBD, it "remains a facet of the disease untouched by current treatments." He noted that "as a field, we have not yet succeeded in making a meaningful impact for people with IBD through microbiome-based approaches, but every study moves us closer to that goal."
Vedanta plans to share additional analyses of bacterial colonization, histological findings, and immune responses from the COLLECTiVE202 study at upcoming scientific forums to contribute to the broader understanding of microbiome-based IBD interventions.
Strategic Pivot to C. difficile Program
Following the VE202 setback, Vedanta is concentrating resources on its lead program VE303 for preventing recurrent Clostridioides difficile infection (CDI). The company emphasized that ulcerative colitis and CDI are distinct diseases with different underlying biology, and VE202 and VE303 have different bacterial compositions and mechanisms of action.
VE303 has demonstrated more promising results, showing a 30.5% absolute risk reduction compared with placebo and greater than 80% reduction in the odds of CDI recurrence in Phase 2 studies. The therapy is currently being evaluated in RESTORATiVE303, a global registrational Phase 3 study enrolling patients at over 200 sites in 24 countries.
Regulatory Recognition and Market Potential
The VE303 program has received both Fast Track and Orphan Drug designations from the FDA. If approved, VE303 is positioned to become the first live biotherapeutic product for any indication, addressing what the company describes as "a serious health condition with a significant unmet medical need."
Pipeline Development Continues
Beyond VE303, Vedanta is advancing VE707, designed to prevent infections caused by multidrug-resistant organisms. This therapy targets vulnerable populations in oncology, urology, transplantation, and critical care settings, with an IND submission planned for the first half of 2026.
The COLLECTiVE202 study enrolled patients between ages 18 and 75 with mild-to-moderate ulcerative colitis who had not been exposed to any biologic or advanced oral therapies. Secondary endpoints included clinical response and remission, endoscopic improvement and remission, as well as histological assessments and measures of colonization, quality-of-life and inflammatory biomarkers.
Vedanta Biosciences, a PureTech Health founded entity, leverages proprietary capabilities in consortium design and maintains one of the largest libraries of bacteria isolated from the human microbiome. PureTech's ownership stake in Vedanta has been diluted to 4.2% on a fully diluted basis over the course of 2025.
