Recursion’s REC-4881 Shows Early Efficacy And Tolerability In Patients With Familial Adenomatous Polyposis

Recursion Pharmaceuticals has shared promising preliminary safety and efficacy results from its ongoing Phase 1b/2 TUPELO trial of REC-4881, an investigational MEK1/2 inhibitor aimed at treating Familial Adenomatous Polyposis (FAP), a rare and inherited disorder. The data were presented as a late-breaking oral session at Digestive Disease Week 2025 in San Diego. FAP leads to the formation of numerous gastrointestinal polyps and carries a near-100% lifetime risk of colorectal cancer, yet no FDA-approved therapies currently exist.

"For patients with FAP, who face increased risk of colorectal and small bowel cancer and a lifetime of invasive interventions, the preliminary polyp burden reduction at a median of >43% seen with REC-4881 1 in just three months of treatment is highly encouraging. These early results offer a much-needed glimpse of hope for this underserved population," said Dr. Jewel Samadder, Gastroenterologist at Mayo Clinic and Principal Investigator of TUPELO.

In the open-label Phase 2 portion of the study, REC-4881 (4 mg once daily) led to a median 43% reduction in polyp burden after 13 weeks among six efficacy-evaluable patients, with 83% experiencing meaningful reductions. This compares favorably to other investigational agents, which have shown 20–30% reductions over more extended periods. Half of the patients also reduced the Spigelman stage, a measure of disease severity, though one patient experienced notable disease progression.

"For patients with FAP, who currently lack FDA-approved treatment options, Recursion's AI-powered Recursion OS platform identified a promising approach through MEK 1/2 inhibition. By analyzing cellular models of APC gene loss, we uncovered a potential first-in-disease treatment. We are excited to share our preliminary findings," said Najat Khan, PhD, Chief R&D Officer and Chief Commercial Officer at Recursion. 

From a safety standpoint, among the 19 patients across both trial phases, REC-4881 showed a tolerable safety profile consistent with other MEK1/2 inhibitors. Most treatment-related adverse events (TRAEs) were mild or moderate, including rash and diarrhoea, with no Grade 4 or higher events reported. Only three patients discontinued the study, and treatment changes were uncommon. The results support continued development of REC-4881 as a potential first-in-class treatment for FAP.