Recursion Reports Positive Early Trial Results for Familial Adenomatous Polyposis
Recursion has released early results from its ongoing Phase 1b/2 TUPELO trial evaluating REC-4881, an investigational MEK1/2 inhibitor, as a potential treatment for Familial Adenomatous Polyposis (FAP). FAP is a genetic condition that significantly increases the risk of colorectal cancer. Currently, there are no FDA-approved treatments available for this condition.
The TUPELO study includes a randomized, double-blind, placebo-controlled Phase 1b safety run-in, followed by an open-label Phase 2 efficacy trial, designed to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of REC-4881 in patients with FAP who have undergone colectomy or proctocolectomy. The release notes that eligibility in Phase 2 was amended to ≥55 years to reduce adverse events.
The study is enrolling adults aged 18 and older, with a confirmed APC gene mutation and polyp growth in the duodenum or residual rectum/pouch.
Change in polyp burden at Week 13 among patients receiving REC-4881, as measured in the TUPELO study.
After 13 weeks of treatment with REC-4881 (4 mg once daily), patients showed a median 43% reduction in gastrointestinal polyp burden. Five out of six efficacy-evaluable patients experienced reductions between 31% and 82%, although one patient had a substantial increase in polyp growth. Additionally, half of the patients showed meaningful improvements in their Spigelman stage, a measure of upper GI disease severity.
REC-4881 was identified using Recursion's AI-powered Recursion OS platform, which analyzed cellular models of APC gene loss to uncover disease-relevant mechanisms and potential therapeutic approaches.
Preliminary safety findings were consistent with known profiles for MEK1/2 inhibitors. Among 19 patients across both trial phases, most treatment-related side effects were mild to moderate—commonly rash, diarrhea, and elevated muscle enzymes. Grade 3 side effects occurred in 16% of patients, with no Grade 4 or higher events reported.
Participant enrollment plan for the two-part TUPELO study evaluating REC-4881 in FAP.
Participants were excluded if they had recent use of NSAIDs, corticosteroids, or strong enzyme modulators, or if cancer was detected at screening. Part 1 focused on dose-finding and PK/PD characterization, while Part 2 evaluates polyp burden reduction after 6 months. Some patients may continue into a long-term extension study.
Patient enrollment in the TUPELO trial is ongoing, and Recursion expects to share additional safety and efficacy data in the second half of 2025.
Topics: Clinical Trials
