Preliminary Phase 1b/2 Data for REC-4881 in Familial Adenomatous Polyposis (FAP) Demonstrates Reduced Polyp Burden

Core Insights - Recursion announced preliminary safety and efficacy results from its Phase 1b/2 TUPELO trial of REC-4881, an investigational MEK1/2 inhibitor for Familial Adenomatous Polyposis (FAP) [1][5] Company Overview - Recursion is a clinical-stage TechBio company focused on decoding biology to improve lives, utilizing its Recursion OS platform to analyze biological and chemical datasets [23] - The company has received Fast Track and Orphan Drug designations from the U.S. FDA for REC-4881, which is aimed at treating FAP, a rare inherited disorder [2] Clinical Trial Details - The TUPELO trial is evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of REC-4881 in patients with FAP [6][8] - The Phase 1b portion was a randomized, double-blind, placebo-controlled safety run-in, while the ongoing Phase 2 portion is open-label [7][8] Efficacy Results - As of March 17, 2025, REC-4881 treatment led to a preliminary median 43% reduction in polyp burden at Week 13 among six efficacy-evaluable patients [3][10] - Five out of six patients (83%) experienced reductions in polyp burden ranging from 31% to 82%, while one patient showed a 595% increase from baseline [3][10] - Three of six patients (50%) achieved a ≥1-point reduction in Spigelman stage, indicating improvement in disease severity [11] Safety Profile - Among 19 safety-evaluable patients, 79% experienced at least one treatment-related adverse event (TRAE), with the majority being Grade 1 or 2 [4][16] - The most frequent TRAEs included acneiform rash, diarrhea, and decreased left ventricular ejection fraction (LVEF) [4][17] - Grade 3 TRAEs occurred in 16% of patients, with no Grade ≥4 events reported [4][18] Next Steps - Patient enrollment in the TUPELO trial is ongoing, with additional efficacy and safety analyses anticipated in the second half of 2025 [21]