• In the Phase 2 open-label study, REC-4881 (4 mg QD) led to a median 43% reduction (n=6 patients) in polyp burden at the Week 13 assessment at time of data cutoff.
• Five of six patients (83%) experienced reductions in polyp burden ranging from 31% to 82%, however, one patient showed a substantial increase from baseline.
• At Week 13, 50% of patients (3 out of 6) achieved ≥1-point improvement in Spigelman stage, a measure of upper GI disease severity.
• The early safety profile of REC-4881 was generally consistent with that of prior MEK1/2 inhibitors; among 19 patients across Phase 1b and 2, most treatment-related adverse events were Grade 1 or 2, with Grade 3 events in 16% of patients and no Grade ≥4 TRAEs reported to date.

 Recursion (Nasdaq: RXRX), a clinical-stage TechBio company decoding biology to radically improve lives, today announced preliminary safety and efficacy results from its ongoing Phase 1b/2 TUPELO trial of REC-4881, an investigational, allosteric MEK1/2 inhibitor in development for Familial Adenomatous Polyposis (FAP). These data were presented in a late-breaking oral presentation at Digestive Disease Week (DDW) 2025 in San Diego, California.

FAP is a rare, inherited disorder caused by mutations in the APC gene, leading to the growth of hundreds to thousands of gastrointestinal polyps and a near 100% lifetime risk of colorectal cancer if left untreated. Despite this significant burden, there are currently no FDA-approved treatments. FAP affects an estimated 50,000 individuals across the US and EU5 (France, Germany, Italy, Spain, and the UK). REC-4881 has received Fast Track and Orphan Drug designations from the U.S. FDA, as well as Orphan Drug designation from the European Commission.

As of the March 17, 2025 data cutoff in the open-label Phase 2 portion of the TUPELO trial, treatment with REC-4881 (4 mg QD) led to a preliminary median 43% reduction to date in polyp burden at the Week 13 assessment among six efficacy-evaluable patients. Other investigational agents in separate studies have reported 20-30% polyp burden reduction in 6 months¹. Five of the six patients (83%) experienced reductions in polyp burden ranging from 31% to 82%, while one patient (17%) showed a substantial increase of 595% from baseline. Additionally, three of six patients (50%) achieved a ≥1-point reduction in Spigelman stage; one patient had no change, one progressed from Stage II to IV, and one had no baseline stage but was classified as Stage II at Week 13.

Across the combined Phase 1b and ongoing Phase 2 cohorts (n=19 safety-evaluable patients), REC-4881 demonstrated an early safety profile generally consistent with that of prior MEK1/2 inhibitors. Seventy-nine percent (15 of 19) of patients experienced at least one treatment-related adverse event (TRAE), the majority of which were Grade 1 or 2 in severity. Grade 3 TRAEs occurred in 16% of patients, with no Grade ≥4 events reported to date. In Phase 1b, the most frequent TRAEs (≥20%) were acneiform rash, diarrhea, and decreased left ventricular ejection fraction (LVEF), while in Phase 2, the most common events were acneiform rash, blood creatine phosphokinase (CPK) increase, and diarrhea. Overall, treatment modifications were infrequent, with 3 of 19 patients discontinuing treatment, 1 patient each requiring dose interruption or modification.

"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 ¹in just three months of treatment is highly encouraging," said Dr. Jewel Samadder, Gastroenterologist at Mayo Clinic and Principal Investigator of TUPELO, "These early results offer a much-needed glimpse of hope for this underserved population."

"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," said Najat Khan, PhD, Chief R&D Officer and Chief Commercial Officer at Recursion. "By analyzing cellular models of APC gene loss, we uncovered a potential first-in-disease treatment and are excited to share our preliminary findings."