Recursion Pharmaceuticals has announced the dosing of the first patient in its Phase 2 clinical trial evaluating REC-3964, a potential first-in-class oral small molecule for the treatment of recurrent Clostridioides difficile infection (rCDI). This milestone marks a significant step in addressing the growing public health challenge posed by rCDI, which affects up to 175,000 individuals in the U.S. annually and incurs approximately $2 billion in healthcare costs.
A Novel Approach to a Persistent Problem
C. difficile infection is a bacterial disease that leads to diarrhea and colitis, and can be life-threatening. Current standard treatments, primarily antibiotics, often disrupt the gut microbiome, leading to recurrence rates of 20-30% after initial treatment, increasing to 40% after the first recurrence and 45-65% after two or more recurrences. REC-3964 offers a novel, non-antibiotic approach by selectively inhibiting the glucosyltransferase activity of toxin B produced by C. difficile, thus sparing the healthy gut microbiome.
REC-3964: Mechanism and Preclinical Data
REC-3964 is the first new chemical entity developed using Recursion's operating system. Unlike broad-spectrum antibiotics, REC-3964 precisely targets the bacterial toxin while minimizing impact on healthy tissue. Preclinical studies presented at the 6th Edition of the World Congress on Infectious Diseases demonstrated REC-3964's superiority over bezlotoxumab in a human disease-relevant C. difficile hamster model. Phase 1 studies in healthy volunteers also showed that REC-3964 was well-tolerated, with no serious adverse events (SAEs).
The Phase 2 ALDER Trial
The Phase 2 ALDER clinical trial is a multi-center, randomized study designed to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of REC-3964 at doses of 250 mg or 500 mg. The trial will include an observation-only arm and enroll approximately 80 individuals across the U.S. and Europe. The primary endpoint is the reduction of C. difficile recurrence after initial cure with vancomycin. Participants will receive treatment with REC-3964 for 28 days.
Management Commentary
"There’s a significant unmet need for new treatment options for patients with C. diff. infection that are easier to use and more cost-effective," said Chris Gibson, Ph.D., Co-Founder and CEO of Recursion. Najat Khan, Ph.D., Chief Commercial Officer and Chief R&D Officer at Recursion, added, "For these patients and their families, the need for safe, effective, non-antibiotic treatment options is critical."
Impact and Future Directions
With approximately 29,000 deaths annually in the U.S. attributed to C. difficile infection, and recurrence rates posing a significant challenge, REC-3964 represents a promising new approach. The results of the Phase 2 ALDER trial will provide critical insights into the potential of REC-3964 to address this unmet medical need and reduce the burden of rCDI on patients and the healthcare system.
