Recursion Begins Phase 2 Trial for AI-Developed Non-Antibiotic Treatment for Recurrent C. diff. Infection

Recursion, an AI-driven drug discovery company, has dosed the first patient in its Phase 2 ALDER trial for REC-3964, an oral small molecule for the treatment of recurrent Clostridioides difficile (C. diff.) infection. REC-3964 is the first non-antibiotic small molecule developed entirely using Recursion’s proprietary platform, RecursionOS.

Background:

• C. diff. infections affect over 730,000 people annually across the U.S. and EU5, causing about 29,000 deaths in the U.S. each year.
• Recurrent C. diff. cases are a growing concern, with up to 175,000 cases in the U.S. per year.
• Antibiotic treatments, the current standard of care, wipe out both harmful and beneficial gut bacteria, leading to recurrence in 20-30% of cases.
• The healthcare cost associated with recurrent C. diff. averages $11,000 per case, amounting to approximately $2 billion annually in the U.S.

See also: The Time for Breakthroughs in Antibiotic Discovery

What is REC-3964:

• REC-3964 is a first-in-class, orally bioavailable, non-antibiotic small molecule that inhibits the glucosyltransferase activity of toxin B produced by C. diff., without disturbing healthy gut bacteria.
• Developed through Recursion's AI-driven platform, RecursionOS, REC-3964 offers a targeted treatment option for recurrent C. diff., addressing a critical unmet need for microbiome-sparing therapies.
• Preclinical studies presented at the World Congress on Infectious Diseases showed that REC-3964 outperformed bezlotoxumab, a monoclonal antibody, in a disease-relevant hamster model of C. diff. infection.
• In Phase 1 trials, REC-3964 demonstrated safety and tolerability, with no serious adverse events (SAEs) reported.

The ALDER Phase 2 Trial:

• The trial will enroll approximately 80 participants across the U.S. and Europe.
• The study will evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of REC-3964 at doses of 250 mg or 500 mg, alongside a placebo-controlled observation arm.
• Participants will receive REC-3964 for 28 days to assess its effectiveness in preventing recurrent C. diff. infections after initial treatment with vancomycin.

Chris Gibson, Ph.D., Co-Founder and CEO of Recursion:

“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. We are encouraged by the progress of REC-3964, the first new chemical entity from our platform to advance to Phase 2 clinical trials, and now, to the first patient dosed.”

Christian John Lillie, Co-Founder and CEO of the Peggy Lillis Foundation:

“We are so pleased to learn that our partner Recursion has initiated its ALDER trial. All new therapies that can be added to the known standard of care have the potential to decrease the physical and emotional suffering of recurrent C. diff. on patients and the significant burden to the health care system.”

RecursionOS is a platform that integrates advanced infrastructure, including automated lab robotics and data capture tools, to support large-scale drug discovery. It processes over 23 petabytes of biological and chemical data through a scalable technology stack. The system includes the Recursion Data Universe, housing multimodal datasets such as phenomic, transcriptomic, and proteomic data, and the Recursion Map, a set of tools designed to analyze this data and provide insights for research teams. Tools like PhenoMap and Scaffold Shopper help identify biological relationships and assist in optimizing drug candidates through in silico methods.

Photo credit: okskaz

Topics: Clinical Trials