• REC-3964 is Recursion’s first new chemical entity developed using the RecursionOS.
• REC-3964 represents a novel, non-antibiotic approach with a unique mechanism of action that binds and blocks catalytic activity of the toxin's innate glucosyltransferase in order to inhibit the toxin produced by C. diff. in the gastrointestinal tract.
• There are up to 175,000 cases of recurrent C. diff. each year and more than 29,000 patients die in the U.S. from C. diff. annually. Rates of recurrent C. diff. have increased significantly in recent years, representing a major public health challenge.

Recursion (NASDAQ: RXRX), a leading clinical stage TechBio company decoding biology to radically improve lives, announced that the first patient has been dosed in its Phase 2 clinical trial of REC-3964, a potential first-in-class, oral small molecule and new chemical entity for the treatment of recurrent Clostridioides difficile infection. C. diff is a toxin producing bacteria that causes diarrhea and colitis, and can be life threatening. Up to 730,000 cases are estimated to occur in the U.S. and EU5 annually, and the infection is responsible for an estimated 29,000 deaths in the U.S. each year. Recursion’s study will initially address the recurrent C. diff. (up to 175,000 cases in the United States per year) population, which costs the healthcare system approximately two billion dollars per year.

Increasing cases of recurrent C. diff. infections pose significant public health challenges. Antibiotics, the standard treatment for C. diff. infections, disturb the gut microbiome due to their non-selective nature. Despite initial success, antibiotics fail to prevent recurrence in 20-30% of primary cases. Further, the risk of subsequent recurrence rises to 40% after the first and 45-65% after two or more.

REC-3964 is the first novel small molecule developed through Recursion’s Operating System, and selectively inhibits the glucosyltransferase activity of toxin B produced by C. diff in the gastrointestinal tract, offering a unique mechanism of action. Unlike antibiotics, which disrupt the gut microbiome, REC-3964 precisely targets the bacterial toxin while sparing healthy tissue, potentially minimizing adverse events. It is being studied as part of a treatment regimen to prevent recurrent C. diff infections, a leading cause of antibiotic-associated diarrhea that can lead to significant morbidity and mortality.

Presented at the 6th Edition of World Congress on Infectious Diseases, preclinical studies demonstrated its superiority over bezlotoxumab in a human disease-relevant C. diff. hamster model. Additionally, Phase 1 studies in healthy volunteers showed REC-3964 was well tolerated with no serious adverse events (SAEs), underscoring its potential safety and tolerability.

“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. “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. We look forward to continuing to advance this trial to help patients in need and drive down billions in costs to the healthcare system for treatment.”

Christian John Lillie, Co-Founder and CEO of the Peggy Lillis Foundation, shared: "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.”

“Patients with C. diff face significant challenges, with 20-30% of initial infections recurring after standard treatment and a 40% chance of further recurrence, often leading to severe complications and a diminished quality of life,” said Najat Khan, Ph.D., Chief Commercial Officer and Chief R&D Officer at Recursion. “For these patients and their families, the need for safe, effective, non-antibiotic treatment options is critical. REC-3964 offers a novel, targeted approach by selectively inhibiting the bacterial toxin while sparing the host. With encouraging preclinical data and strong tolerability demonstrated in Phase 1 studies, it’s particularly rewarding to see the first drug developed using the RecursionOS and advancing to Phase 2 trials.”

The Phase 2 ALDER clinical trial is a multi-center randomized study to investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of REC-3964 at doses of either 250 mg or 500 mg for the reduction of C. diff. and will include an observation only arm. Approximately 80 individuals will ultimately be enrolled in the study across the U.S. and Europe.