Recursion researchers at work. Recursion said it expects to launch its first registrational trial in the second half of this year for its lead candidate REC-4881 based on talks with the FDA, after the oral familial adenomatous polyposis (FAP) therapy generated positive mid-stage clinical data. [Recursion]
Recursion said it expects to launch its first registrational trial in the second half of this year for its lead candidate REC-4881 based on talks with the FDA, after the oral familial adenomatous polyposis (FAP) therapy generated positive mid-stage clinical data.
Most patients treated with REC-4881 showed reductions in both the number of larger, higher-risk polyps and in lower GI polyp burden, according to updated data from the Phase Ib/II TUPELO trial (NCT05552755). That data was 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 (CGA-IGC) Annual Meeting, being held through Wednesday in Denver.
“REC-4881 is reducing the larger polyps that often drive much of the surgery for these [FAP] patients, across the GI tract from a single oral therapy,” Najat Khan, PhD, Recursion’s president and CEO, said in a statement. “This is a lifelong disease with no approved pharmacologic therapies, and REC-4881 is the clearest proof point yet of what we built Recursion to do.”
Recursion said its anticipated second half 2027 timing for a registrational trial will depend on its talks with the FDA, with additional details set to be provided later this year.
Recursion announced the REC-4881 data after the close of markets on Monday. The news appeared to make little impression on investors, as Recursion shares stayed all but flat Tuesday as of 12:55 pm ET, inching up 0.1% to $3.84, a penny above yesterday’s closing price.
Licensed from Takeda
REC-4881 is a first-in-class, oral allosteric inhibitor of MEK1 and MEK2 that Recursion is developing through a global licensing agreement with Takeda Pharmaceutical signed in 2020 and covering FAP and related areas of oncology. Recursion agreed to pay Takeda $1.5 million upfront, up to $39.5 million in payments tied to achieving development and regulatory milestones, plus low-to-mid single-digit royalties on net sales of products containing the drug by Recursion, its affiliates, or sublicensees.
Takeda initially developed the drug as TAK-733 and used Recursion’s artificial intelligence (AI) platform to uncover targeted areas of oncology where the drug could be effective.
For FAP, a rare genetic disorder, the standard of care has long consisted of lifelong active endoscopic surveillance and eventual prophylactic surgical removal of the colon.
“People have been doing research in the chemoprevention space in FAP for decades, and at least in the United States, we still don’t have an agent that is FDA approved,” stated Bryson Katona, MD, PhD, TUPELO study investigator and director of the GI Cancer Genetics Program, University of Pennsylvania Perelman School of Medicine. “We’re still having to send FAP patients for major surgeries and we’re still doing frequent scopes on these patients. The need for effective chemoprevention in FAP is very large, and it’s only going to increase over time as the number of FAP patients continues to increase.”
Estimates of prevalence FAP vary widely. While Recursion has counted >50,000 FAP patients in the United States and EU5 (France, Germany, Italy, Spain, and the United Kingdom), other institutions have shared figures showing FAP to affect approximately one in 6,800 to 31,000 individuals worldwide, including about one in 5,000 to 10,000 Americans.
Recursion is among biopharmas working to develop treatments for FAP.
One FAP treatment is already in Phase III study—eRapa™, which since 2024 has been developed by Biodexa Pharmaceuticals under an exclusive global license from Emtora Biosciences, which licensed eRapa from the University of Texas (UT) Health San Antonio in 2012, when Emtora was known as Rapamycin Holdings.
eRapa is an oral tablet formulation of the mTOR inhibitor rapamycin (sirolimus), sold in generic versions; Pfizer ceased selling the branded version, Rapamune®, in 2023. Last month, Biodexa said it had enrolled 100 patients in its registrational Phase III Seranta trial (NCT06950385) of eRapa, which has an estimated primary completion date of July 2030.
Also in clinical trials for FAP is Tempest Therapeutics’ TPST-1495, a first-in-class oral small molecule selective dual EP2 and EP4 prostaglandin receptor antagonist targeting prostaglandin E2 (PGE2) signaling in the tumor microenvironment. In March, Tempest launched a Phase II open label trial (NCT06557733) designed to assess how well TPST-1495 reduces the number of polyps in the small bowel and colon in patients with FAP. The study’s estimated enrollment is 38 patients with primary completion expected June 30, 2027.
Recursion’s TUPELO trial was designed to study polyp burden reduction after 12 weeks on REC-4881 (4mg once daily) and again after 12 weeks off-treatment. Following 12 weeks of treatment, Recursion said, 87% of patients (13 of 15) had a reduction in total polyp burden after 12 weeks of treatment, with a 47% median reduction. Approximately one in three patients achieved reductions of ≥65%.
Since the initial November 2025 data cut, all four patients added to the study showed a reduction in total polyp burden, including two patients with 89% and 98% reduction, respectively. At Week 25, after 12 weeks off treatment, 85% of patients (11 of 13) remained below baseline.
Recursion reasons that the persistence of polyp burden reduction below baseline in most patients studied may allow for dosing flexibility.
‘Certainly encouraging’
“Seeing durability over a twelve-week course is certainly encouraging. In longer trials we’ll see exactly how long that durability lasts, but I think it is a very encouraging first sign for this drug,” Katona said.
Within the upper GI tract, 92% of patients (12 of 13) had reductions in polyp burden after 12 weeks of treatment, with a 55% median reduction. Nearly half (six of 13) achieved reductions of ≥65%, more than one in three achieved ≥75%, and two patients achieved reductions of ≥98%. Half (six of 12) improved by at least one Spigelman stage at Week 13, while 92% (11 of 12) remained below baseline at Week 25, after 12 weeks off-treatment, and six of 11 had equal or greater reductions during the off-treatment period than during treatment.
Within the lower GI tract, nine of 11 patients (82%) with measurable polyp burden at baseline had reductions after 12 weeks of treatment, with a 50% median reduction, and four of 11 achieved reductions of 65% or more. At Week 25, after 12 weeks off-treatment, seven of 10 patients remained below baseline.
Six of eight patients that showed polyps greater than 5 mm at baseline had reductions in the number of these polyps after 12 weeks of treatment. Four achieved reductions of ≥80%, including two whose larger-polyp counts fell from more than 90 polyps to one. In both of those patients, all of the larger polyps were in the upper GI tract.
One patient, 98% reduction
The highest responder was a patient who went from 1,344 mm of total polyp burden to 32 mm, a 98% reduction, and from 96 upper GI polyps >5 mm to one. Recursion cautioned that the patient was not representative of the overall population.
The company also cautioned that the study collected its polyp counts using >5 mm as the largest size category; separate counts for polyps >10 mm were not collected.
Six of the eight patients assessed at Week 25 were below their baseline count after 12 weeks off treatment. Most of the larger polyps at baseline were in the upper GI, Recursion said.
No new safety signals were observed as of the data cutoff in the expanded patient population, which includes patients 18 and older. Most treatment-related adverse events (TRAE), according to recursion, were Grade 1 or 2 (21 of 26 patients, 80.8%). The highest-grade TRAE was Grade 3 in four patients (15.4%), and there were no Grade 4 or 5 TRAEs.
The most common TRAEs were consistent with MEK1/2 inhibition, including dermatitis acneiform, rash, CPK increase, diarrhea, and asymptomatic LVEF decrease. Adverse events were manageable, and most resolved within 12 weeks off treatment. Four patients were discontinued for Grade 1 or 2 TRAEs, with no discontinuations for a Grade 3 event.
Recursion announced the clinical data along with third quarter earnings that showed a reduced quarterly net loss year over year. Recursion ended the third quarter with a net loss of $119.036 million, compared to a net loss of $162.253 million for Q3 2025, on revenue that tripled to $18.552 million from $5.175 million. For Q1-Q3 2026, Recursion cut its net loss to $367.545 million from $536.637 million a year ago.
