Recursion Targets H2 2027 Pivotal Trial After REC-4881 Cuts FAP Polyps 47%

Recursion plans to launch its first registrational trial for REC-4881 in the second half of 2027, following FDA discussions and Phase Ib/II data showing a 47% median reduction in total polyp burden in familial adenomatous polyposis (FAP) patients after 12 weeks of treatment.

The updated TUPELO trial results (NCT05552755), presented by Lisa Boardman, MD, a gastroenterologist and professor of medicine at Mayo Clinic, at the CGA-IGC Annual Meeting in Denver, showed 87% of patients (13 of 15) achieved reductions in total polyp burden. Roughly one in three hit reductions of 65% or more.

"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," Recursion president and CEO Najat Khan, PhD, 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."

The market barely reacted. Recursion shares inched up 0.1% to $3.84 by 12:55 pm ET Tuesday, a penny above Monday's close, after the announcement landed post-market Monday.

How durable is the effect?

REC-4881 is a first-in-class oral allosteric MEK1/MEK2 inhibitor, licensed from Takeda in 2020 under a deal that cost Recursion $1.5 million upfront, up to $39.5 million in milestone payments, and low-to-mid single-digit royalties on net sales. Takeda originally developed the compound as TAK-733; Recursion used its AI platform to identify FAP and related oncology indications.

At Week 25 — after 12 weeks off treatment — 85% of patients (11 of 13) remained below baseline polyp burden. Since the initial November 2025 data cut, all four added patients showed reductions, including two with 89% and 98% reductions. Recursion suggests the persistence may permit flexible dosing.

"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," said Bryson Katona, MD, PhD, a TUPELO investigator who directs the GI Cancer Genetics Program at the University of Pennsylvania's Perelman School of Medicine.

What did the tract-by-tract data show?

Patients took 4mg once daily. Results split by region:

• Upper GI: 92% of patients (12 of 13) improved, with a 55% median reduction; six of 12 improved by at least one Spigelman stage at Week 13, and 92% (11 of 12) stayed below baseline at Week 25.
• Lower GI: nine of 11 patients (82%) with measurable baseline burden improved, a 50% median reduction; four of 11 hit 65%-plus.
• Larger polyps (>5mm): six of eight patients with such polyps at baseline saw counts fall; four dropped 80% or more, including two patients whose counts collapsed from more than 90 polyps to one.

The top responder went from 1,344mm of total polyp burden to 32mm — a 98% cut — and from 96 upper GI polyps over 5mm to one. Recursion cautioned this patient was not representative. The company also flagged a method limit: the study capped its largest polyp-size category at >5mm and did not collect separate counts for polyps over 10mm.

Safety held up. Of 26 patients, 80.8% (21) had Grade 1 or 2 treatment-related adverse events; four had Grade 3, with no Grade 4 or 5 events. Common events matched MEK1/2 inhibition — dermatitis acneiform, rash, CPK increase, diarrhea, asymptomatic LVEF decrease — and mostly resolved within 12 weeks off treatment. Four patients discontinued over Grade 1 or 2 events; none over Grade 3.

Who else is chasing FAP?

No FDA-approved FAP drug exists; standard care means lifelong endoscopic surveillance and eventual prophylactic colon removal. Katona noted researchers have pursued chemoprevention "for decades" without an approval, while patient numbers keep growing. Prevalence estimates vary widely: Recursion counts more than 50,000 patients in the US and EU5, while other institutions cite roughly one in 6,800 to 31,000 people worldwide, and one in 5,000 to 10,000 Americans.

Competitors are advancing. Biodexa's eRapa, an oral rapamycin formulation licensed from Emtora Biosciences, has enrolled 100 patients in its Phase III Seranta trial (NCT06950385), with primary completion estimated July 2030. Tempest Therapeutics launched a 38-patient Phase II trial of TPST-1495 (NCT06557733) in March, targeting June 2027 primary completion.

Recursion also reported Q3 earnings alongside the data: a net loss of $119.036 million, down from $162.253 million a year earlier, on revenue that tripled to $18.552 million from $5.175 million. Nine-month net loss narrowed to $367.545 million from $536.637 million.

The company says the H2 2027 registrational timing remains contingent on ongoing FDA discussions, with further details expected later this year.