Recursion doses first patient in Phase 2 trial of REC-3964 for recurrent C. difficile infection

Recursion, a clinical-stage biopharmaceutical company, has initiated a Phase 2 clinical trial for REC-3964, an innovative oral small molecule designed to treat recurrent Clostridioides difficile (C. diff) infections. This marks a significant milestone as REC-3964 is the first new chemical entity developed using Recursion’s advanced technological platform, RecursionOS.

C. diff is a harmful bacterium causing severe diarrhea and colitis, leading to considerable morbidity and mortality. In the U.S. and EU5, the annual cases are estimated at around 730,000, with about 29,000 deaths in the U.S. alone. Recurrent infections are particularly challenging, with up to 175,000 cases annually in the U.S., costing the healthcare system approximately two billion dollars each year.

Standard antibiotic treatments for C. diff disrupt the gut microbiome and often fail to prevent recurrence. About 20-30% of primary C. diff cases recur after initial treatment, with the risk of further recurrence rising significantly. After one recurrence, there is a 40% chance of another, and this risk increases to 45-65% after multiple recurrences.

REC-3964 operates through a unique mechanism by selectively inhibiting the glucosyltransferase activity of toxin B, produced by C. diff in the gastrointestinal tract. This approach is distinct from antibiotics as it targets the bacterial toxin without disrupting the beneficial gut microbiome, potentially reducing adverse effects. REC-3964 aims to prevent the recurrence of C. diff infections, which are a major cause of antibiotic-associated diarrhea.

In preclinical studies, REC-3964 demonstrated superior efficacy compared to bezlotoxumab in a disease-relevant C. diff hamster model. It was also well tolerated in Phase 1 trials involving healthy volunteers, showing no serious adverse events. These findings highlight the potential safety and effectiveness of REC-3964.

Chris Gibson, Ph.D., Co-Founder and CEO of Recursion, emphasized the urgent need for new treatment options for C. diff infections that are easier to use and more cost-effective. He expressed optimism about REC-3964's progress, stating that this is the first new chemical entity from Recursion’s platform to advance to Phase 2 trials, with the first patient already dosed. He anticipates that this trial will help patients in need and reduce healthcare costs.

Christian John Lillie, CEO of the Peggy Lillis Foundation, expressed satisfaction with Recursion's progress in initiating the ALDER trial. He noted that new therapies like REC-3964 could significantly alleviate the physical and emotional suffering of patients with recurrent C. diff and reduce the burden on the healthcare system.

Najat Khan, Ph.D., Chief Commercial Officer and Chief R&D Officer at Recursion, highlighted the significant challenges faced by C. diff patients, including high recurrence rates and severe complications. She stressed the critical need for safe and effective non-antibiotic treatment options. REC-3964 offers a targeted approach by selectively inhibiting the bacterial toxin while preserving the host’s health. With promising preclinical data and a strong safety profile demonstrated in Phase 1 studies, it is gratifying to see this drug advancing to Phase 2 trials.

The Phase 2 ALDER clinical trial is a multi-center randomized study investigating the safety, tolerability, pharmacokinetics, and efficacy of REC-3964. The trial involves doses of either 250 mg or 500 mg and includes an observation-only arm. Approximately 80 participants will be enrolled across the U.S. and Europe. The study aims to evaluate the reduction of recurrent C. diff infections after initial treatment with vancomycin, with participants receiving REC-3964 for 28 days.

Recursion continues to push the boundaries of biomedical innovation, leveraging its RecursionOS platform to develop groundbreaking treatments and improve patient outcomes. The company's efforts are a significant step toward addressing the public health challenges posed by recurrent C. diff infections.