Recursion’s REC-4881 Shows Polyp Reductions in FAP Trial, With 2027 Study Target

Recursion’s REC-4881 produced polyp reductions across the upper and lower gastrointestinal tract in a Phase Ib/II study of familial adenomatous polyposis (FAP). The signal that stands out is persistence: most assessed patients remained below their baseline polyp burden 12 weeks after stopping treatment. Recursion says it expects to begin its first registrational trial in the second half of 2027, subject to discussions with the FDA.

Reductions persisted after treatment stopped

Updated results from the TUPELO trial (NCT05552755) were presented by Lisa Boardman, MD, a gastroenterologist and Professor of Medicine at Mayo Clinic, at the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer annual meeting in Denver. The study tested REC-4881, an oral therapy, over 12 weeks, followed by 12 weeks off treatment.

After treatment, 13 of 15 patients (87%) had a reduction in total polyp burden, with a median reduction of 47%. About one-third saw reductions of at least 65%. Since the initial data cutoff in November 2025, all four patients added to the study showed a decrease in total burden; two had reductions of 89% and 98%.

At Week 25, 11 of 13 patients (85%) remained below their starting burden. Recursion sees that durability as a possible basis for dosing flexibility, though the small study and short follow-up leave open how long the effect lasts. “Seeing durability over a twelve-week course is certainly encouraging,” said Bryson Katona, MD, PhD, a TUPELO investigator and director of the GI Cancer Genetics Program at the University of Pennsylvania Perelman School of Medicine. “In longer trials we’ll see exactly how long that durability lasts.”

Effects across the GI tract

In the upper GI tract, 12 of 13 patients (92%) had lower polyp burden after 12 weeks, with a median reduction of 55%. Six patients recorded reductions of at least 65%, more than one-third had reductions of at least 75%, and two saw reductions of at least 98%. At Week 13, six of 12 patients improved by at least one Spigelman stage, a measure used to classify duodenal polyposis.

The upper GI response also persisted off treatment: 11 of 12 patients (92%) remained below baseline at Week 25. For six of those 11, the reduction during the off-treatment period was equal to or greater than the reduction measured during treatment.

Lower GI results were also positive. Nine of 11 patients with measurable baseline burden (82%) had a reduction after treatment, with a median decline of 50%; four had reductions of at least 65%. Seven of 10 patients remained below baseline after the 12-week off-treatment period.

The study also tracked larger polyps, defined here as those over 5 mm. Six of eight patients who had these polyps at baseline saw their count fall after treatment, and four had reductions of at least 80%. In two patients, counts dropped from more than 90 larger polyps to one. Both had their larger polyps in the upper GI tract.

A striking responder, with limits to the data

One patient’s total polyp burden fell from 1,344 mm to 32 mm, a 98% reduction. The same patient went from 96 upper GI polyps larger than 5 mm to one. Recursion cautioned that this individual result doesn’t represent the broader study population.

The company also noted a measurement limitation: the trial recorded counts in a largest-size category of greater than 5 mm, but did not collect separate counts for polyps larger than 10 mm. At Week 25, six of the eight patients evaluated for larger polyps were below their baseline count. Most larger polyps at the start of the study were in the upper GI tract.

Safety and the path to a registrational study

No new safety signals were reported in the expanded population, which included adults aged 18 and older. Most treatment-related adverse events were Grade 1 or 2: 21 of 26 patients (80.8%). Four patients (15.4%) had Grade 3 events, and none had Grade 4 or 5 events. Common events included acneiform dermatitis, rash, increased creatine phosphokinase (CPK), diarrhea, and asymptomatic decreases in left ventricular ejection fraction (LVEF), a pattern Recursion said was consistent with MEK1/2 inhibition.

The company described adverse events as manageable, with most resolving within 12 weeks off treatment. Four patients stopped treatment because of Grade 1 or 2 treatment-related events; none discontinued because of a Grade 3 event.

REC-4881 is an oral allosteric inhibitor of MEK1 and MEK2, licensed by Recursion from Takeda Pharmaceutical in 2020 for development in FAP and related oncology areas. Takeda originally developed it as TAK-733 and used Recursion’s AI platform to identify potential areas of oncology application. The licensing deal included a $1.5 million upfront payment, up to $39.5 million in development and regulatory milestone payments, and low-to-mid single-digit royalties on net sales.

FAP is a rare inherited disorder for which care has long relied on frequent endoscopic surveillance and, in many cases, preventive removal of the colon. “We’re still having to send FAP patients for major surgeries and we’re still doing frequent scopes on these patients,” Katona said, describing the continuing need for drug-based prevention. Prevalence estimates vary: Recursion counts more than 50,000 patients across the United States and the EU5, while other estimates place FAP at about one in 6,800 to 31,000 people worldwide and one in 5,000 to 10,000 Americans.

A developing field of FAP drug candidates

REC-4881 is one of several medicines being studied to reduce polyps in FAP. Biodexa Pharmaceuticals is developing eRapa in a Phase III trial under an exclusive global license from Emtora Biosciences, which licensed the drug from the University of Texas Health San Antonio in 2012. eRapa is an oral tablet formulation of rapamycin, also known as sirolimus. Biodexa said last month that it had enrolled 100 patients in the registrational Seranta study (NCT06950385), which has an estimated primary completion date of July 2030.

Tempest Therapeutics is testing TPST-1495, an oral antagonist of the EP2 and EP4 prostaglandin receptors that targets PGE2 signaling in the tumor microenvironment. Its Phase II open-label study (NCT06557733) began in March and is designed to measure changes in small-bowel and colon polyp counts. The study plans to enroll 38 patients, with primary completion estimated for June 30, 2027.

Recursion’s planned second-half 2027 registrational start now gives REC-4881 a development milestone, but the company says timing depends on its FDA discussions and that it will provide further details later this year. The clinical readout came alongside its third-quarter results: revenue tripled year over year to $18.552 million from $5.175 million, while net loss narrowed to $119.036 million from $162.253 million. For the first nine months of 2026, net loss was $367.545 million, down from $536.637 million a year earlier. The next meaningful test for REC-4881 will be whether a larger, longer study confirms that the reductions hold up over time.