- REC-4881 (4 mg QD) achieved rapid clinical activity, with 75% of evaluable patients showing reductions in total polyp burden and a 43% median reduction after 12 weeks of treatment (n=12)
- After 12 weeks off therapy (week 25 of the study), 82% of evaluable patients (9 of 11) maintained a durable reduction in total polyp burden, with a 53% median reduction observed from baseline
- Natural history analysis showed that 87% of untreated FAP patients - who resembled the inclusion criteria of TUPELO - had annualized polyp-burden increase, 10% remained stable, and 3% showed modest decrease—underscoring the disease’s progressive trajectory (n=55)
- 40% of patients (4 out of 10) achieved a ≥1-point improvement in Spigelman stage—a clinically meaningful measure of upper GI disease severity to assess surveillance and clinical management
- REC-4881 (4 mg QD) has a safety profile consistent with MEK1/2 inhibition, with the majority of treatment-related adverse events being Grade 1 or 2, Grade 3 events occurring in 15.8% of the safety-evaluable patients, and no Grade ≥4 TRAEs reported to date
- First clinical validation of the Recursion OS, demonstrating how unbiased phenotypic and mechanistic insights—such as MEK1/2 rescue of APC loss-of-function—can translate to novel, differentiated therapeutics for diseases like FAP with no approved therapy and high prevalence of >50,000 patients in US and EU5
- Next steps: Engage the FDA in the 1H26 to define a potential registration pathway, and in parallel, expand the population from ≥55 to ≥18 years old, and further optimize dosing schedule
SALT LAKE CITY, Dec. 08, 2025 (GLOBE NEWSWIRE) -- Recursion (Nasdaq: RXRX), a clinical-stage TechBio company decoding biology to radically improve lives, today announced positive Phase 1b/2 data from the ongoing TUPELO trial of REC-4881, an investigational allosteric MEK1/2 inhibitor for familial adenomatous polyposis (FAP).
Through an unbiased phenotypic screen of thousands of compounds, the earliest version of the Recursion OS identified selective MEK1/2 inhibition as a highly specific mechanism capable of reversing APC loss-of-function signatures. Using high-content cellular phenomics driven by AI, REC-4881 emerged as one of the strongest phenotypic rescue hits, reverting APC-deficient cells toward a healthy state and suppressing ERK/MAPK hyperactivation downstream of APC loss. Guided by this AI-driven insight, Recursion in-licensed REC-4881 from Takeda and redirected REC-4881—originally evaluated clinically in solid tumors—as a mechanistically aligned therapeutic candidate for FAP. REC-4881 is now the first MEK1/2 inhibitor ever studied clinically for this disease.
“The durable polyp burden reduction demonstrated by REC-4881—especially the sustained effect seen at Week 25, 12 weeks after completing therapy—is highly encouraging for the FAP community,” said Jessica Stout, D.O., Assistant Clinical Professor, University of Utah School of Medicine, and Principal Investigator of the TUPELO study. “Given the near-100% lifetime risk of colorectal cancer and the absence of any approved medical therapies, patients today often face a lifetime of intensive surveillance and life-altering surgeries. These Phase 2 results provide a meaningful basis for hope and support the potential for REC-4881 to offer a much-needed non-surgical option for this debilitating, life-long disease.”
“These Phase 2 results mark a meaningful validation of the Recursion OS,” said Chris Gibson, Ph.D., Co-Founder and CEO of Recursion. “An unbiased phenotypic insight from our platform and driven by AI—linking MEK1/2 inhibition to APC loss-of-function biology—has now translated into rapid, substantial, and durable reductions in polyp burden in patients. This is a powerful example of how even the earliest versions of the Recursion OS can uncover therapeutic opportunities in diseases with no approved pharmacotherapy options. And since this discovery, we’ve only added to the breadth, depth, and power of the Recursion OS; we believe this is the first of many potential medicines that will advance as our flywheel of discovery accelerates.”
In the Phase 2 portion of the study, REC-4881 demonstrated rapid and durable reductions in polyp burden, with 43% median reduction in evaluable patients after 12 weeks of treatment. 75% of evaluable patients had a reduction in polyp burden in this same period. Importantly, the effect persisted well beyond the dosing period: 82% of evaluable patients (9 of 11) maintained reductions at Week 25—12 weeks after stopping therapy—with a 53% median decrease from baseline. These results are especially meaningful when considered alongside real-world natural history analyses showing that untreated FAP patients are expected to experience increases when left untreated.
“This program reflects a full validation cycle of the Recursion OS: an unbiased phenotypic signal identifying MEK1/2 inhibition as a rescue mechanism for APC loss-of-function, followed by mechanistic confirmation, clinical translation, and now encouraging human data in a disease with no approved medical therapies,” said Najat Khan, Ph.D., Chief R&D and Commercial Officer and incoming President and CEO. “REC-4881, an allosteric MEK1/2 inhibitor, represents a first precision-medicine approach for the causal biology of FAP. In TUPELO, we are seeing rapid, substantial, and durable reductions in polyp burden — including sustained benefit after patients stop therapy. Equally important, our ClinTech and real-world data capabilities have been instrumental in guiding this program — from refining eligibility to contextualizing a single-arm dataset with a first-of-its-kind natural history study.”
About FAP
FAP is one of the most clinically significant hereditary colorectal cancer syndromes and is caused by inactivating mutations in the APC gene, leading to the growth of hundreds to thousands of gastrointestinal polyps and a near 100% risk of developing colorectal cancer before the age of 40 if left untreated. With no approved pharmacotherapies, excisions followed sequentially by debilitating, life altering surgeries remain the only option to remove polyps and polyp burdened organs, typically involving colectomy in the early 20s. While this procedure removes immediate colon cancer risk, it does not address the underlying disease biology and does not prevent future polyp formation. Patients will continue to develop polyps in the rectum or upper GI tract, with approximately 50% of patients requiring subsequent life-altering surgical procedures to manage the persistent disease. Current treatment approaches lead to substantial long-term loss of quality of life, affecting continence, fertility, and long-term gastrointestinal function in relatively young patients. Approximately 90% of FAP patients go on to develop duodenal adenomas, with 6% eventually undergoing a high-morbidity risk duodenectomy to control polyp growth. FAP affects an estimated >50,000 individuals across the US and EU5 (France, Germany, Italy, Spain, and the UK).