Recursion Pharmaceuticals (Recursion) announced preliminary data for its drug candidate REC-4881, a MEK1/2 inhibitor, on May 4, 2025, at Digestive Disease Week (DDW). This data, from the ongoing Phase 1b/2 TUPELO study in Familial Adenomatous Polyposis (FAP), indicated a preliminary median 43% reduction in polyp burden at the week 13 assessment in a cohort of six patients in the Phase 2 open-label study. Five of these six patients (83%) experienced polyp reductions ranging from 31% to 82%, though one patient showed a substantial increase from baseline. The early safety profile was reported as generally consistent with other MEK1/2 inhibitors, with most treatment-related adverse events being Grade 1 or 2.1
Recursion has stated that "Additional data in FAP from TUPELO" is expected in the second half of 2025 (2H25), with specific mention of "Additional safety and efficacy data from TUPELO in FAP in December".1
The impact of this additional 2H25 data on the previously reported 43% polyp reduction results could be significant for several reasons:
- Increased Patient Numbers: The initial 43% median reduction was based on a very small sample size of six patients.1 The forthcoming data will likely include more patients, providing a more statistically robust and representative view of REC-4881's efficacy across a larger population. A larger dataset can either reinforce the initial positive trend, reveal greater variability in response, or potentially alter the median reduction if the new patients respond differently.
- Longer-Term Follow-up: The May 4, 2025, data primarily focused on the 13-week assessment.1 The 2H25 data may include longer follow-up periods for the initial cohort and new patients, offering crucial insights into the durability of the polyp reduction and the long-term safety profile of REC-4881. One report noted that at week 25, two out of two patients on a specific regimen maintained a durable reduction, suggesting longer-term data is being collected.2
- Refined Safety Profile: With more patients and extended exposure to the drug, the additional data will further characterize the safety profile. This could confirm the manageable nature of adverse events observed so far or identify any less common but potentially more severe side effects.
- Confirmation or Divergence: The new data will be critical in confirming whether the promising early results in a small group can be replicated in a larger cohort. If the expanded data set continues to show similar or improved efficacy, it would strengthen confidence in REC-4881's potential. Conversely, if the expanded data shows a less favorable response, the overall interpretation of the drug's benefit might be adjusted.
In summary, the additional 2H25 data will move beyond the preliminary findings to provide a more comprehensive and statistically sound understanding of REC-4881's efficacy and safety in treating FAP. This will be crucial for assessing the drug's overall potential and guiding its further clinical development.
