Recursion Pharmaceuticals has announced promising preliminary results from its ongoing Phase 1b/2 TUPELO clinical trial evaluating REC-4881 for familial adenomatous polyposis (FAP), showing significant polyp reduction in treated patients. The data will be presented at the upcoming Digestive Disease Week (DDW) meeting on May 4, 2025, in San Diego.
The preliminary results revealed that efficacy-evaluable patients experienced a median reduction of more than 30% in total polyp burden after just 12 weeks of treatment with REC-4881, an orally bioavailable, non-ATP-competitive allosteric small molecule MEK 1/2 inhibitor.
"We are pleased that DDW has recognized the importance of our data in addressing the unmet needs of the FAP patient population, where no FDA-approved therapies currently exist," said Najat Khan, PhD, Chief R&D Officer and Chief Commercial Officer at Recursion.
Disease Background and Unmet Need
Familial adenomatous polyposis is a rare hereditary autosomal dominant colorectal cancer predisposition syndrome caused by mutations in the APC gene. The condition affects approximately 50,000 people across the United States, France, Germany, Italy, Spain, and the United Kingdom. Patients with FAP develop hundreds to thousands of precancerous polyps in the colon and rectum, with nearly 100% progressing to colorectal cancer if left untreated.
Currently, there are no FDA-approved pharmacological treatments for FAP. The standard of care involves surgical interventions such as colectomy or proctocolectomy, which significantly impact patients' quality of life.
Trial Design and Safety Profile
The Phase 1b/2 TUPELO trial is evaluating REC-4881 as a potential treatment for patients with FAP who have already undergone colectomy or proctocolectomy. This multicenter, open-label study assesses the efficacy, safety, and pharmacokinetics of REC-4881 in this patient population.
According to the data cut-off from February 7, 2025, 13 patients received 4 mg of REC-4881 once daily. The safety profile showed that 84.6% of patients experienced at least one treatment-related adverse event (TRAE), with rash or dermatitis acneiform being the most commonly reported side effect, primarily Grade 1 or 2 in severity.
AI-Driven Drug Discovery
What sets REC-4881 apart is how it was discovered. The compound was identified through Recursion's AI-powered Recursion OS platform, which analyzed cellular models of APC gene loss—the root cause of FAP—to uncover potential therapeutic interventions.
"MEK 1/2 inhibition for the potential treatment of FAP was identified through our AI-powered Recursion OS platform, which analyzed cellular models of APC gene loss to uncover a potential first-in-disease treatment," explained Dr. Khan. "We look forward to sharing our preliminary findings in our upcoming DDW presentation in May."
Regulatory Status and Future Directions
The U.S. Food and Drug Administration has granted REC-4881 both Fast Track and Orphan Drug designations, while the European Commission has also awarded it Orphan Drug designation. These designations acknowledge the significant unmet medical need in FAP and could expedite the development and review process.
The upcoming presentation at DDW will include new results from a later data cut-off, providing a more comprehensive picture of REC-4881's efficacy and safety profile. Dr. N. Jewel Samadder from Mayo Clinic Comprehensive Cancer Center will present the findings during the Research Forum session on Hereditary GI cancer syndromes.
Expert Perspective
While not directly quoted in the preliminary data release, the selection of Dr. Samadder as the presenter highlights the clinical significance of these findings. As a specialist from Mayo Clinic Comprehensive Cancer Center, his involvement underscores the potential impact of REC-4881 on clinical practice for FAP management.
The TUPELO trial represents a significant step forward in addressing the unmet needs of FAP patients, potentially offering the first pharmacological intervention that could reduce polyp burden and potentially delay or prevent the need for invasive surgical procedures.
As the trial progresses, the medical community will be watching closely to see if these preliminary results are sustained over longer treatment periods and in larger patient populations, potentially changing the treatment paradigm for this devastating hereditary condition.
