Recursion Phase 2 Trial Shows Promising Outcomes For FAP

KUALA LUMPUR, Dec 9 (Bernama) -- Recursion, a clinical-stage techbio company, has 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).

FAP is a hereditary colorectal cancer syndrome that, if untreated, can progress to colorectal cancer before the age of 40.

According to the company in a statement, an unbiased phenotypic screen of thousands of compounds using 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 artificial intelligence (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.

Recursion in-licensed REC-4881 from Takeda and redirected the compound—originally evaluated clinically in solid tumours—as a mechanistically aligned therapeutic candidate for FAP. REC-4881 is now the first MEK1/2 inhibitor studied clinically for this condition.

In the Phase 2 portion of the study, REC-4881 demonstrated rapid and durable reductions in polyp burden, with a 43 per cent median reduction in evaluable patients after 12 weeks of treatment, and 75 per cent of evaluable patients had a reduction in polyp burden.

Importantly, the effect persisted well beyond the dosing period, with 82 per cent of evaluable patients (nine of 11) maintaining reductions at week 25—12 weeks after completing therapy—with a 53 per cent median decrease from baseline. These outcomes are notable compared with real-world natural history data, which show untreated FAP patients generally experience increases in polyp burden over the same period.

Recursion plans to expand the trial population to include patients aged 18 and older, optimise dosing schedules, and engage with the Food and Drug Administration (FDA) in the first half of next year to define a potential registration pathway.

-- BERNAMA