How much weight can a 15-patient, open-label study carry? That is the central question behind the Recursion REC-4881 Phase 2 results, announced on 2 November 2026. In the TUPELO Phase 1b/2 study, 13 of 15 adults with familial adenomatous polyposis (FAP) had a lower total polyp burden after 12 weeks of the investigational oral MEK1/2 inhibitor REC-4881, with a median reduction of 47%. This article appraises the evidence, including the safety data, the design limits and what a registrational trial would need to show. REC-4881 is not approved, and this is news reporting and not medical advice.
Recursion REC-4881 Phase 2 results: evidence at a glance
- Design: open-label, single-arm Phase 1b/2 (NCT05552755), post-colectomy adults, 4 mg once daily for 12 weeks and 12 weeks off treatment.
- Efficacy population: 15 patients for total polyp burden, 8 for larger polyps; safety population: 26.
- Main result: 13 of 15 had a reduction in total polyp burden; the median was 47%.
- Durability signal: 11 of 13 evaluable patients (85%) were still below baseline at Week 25, 12 weeks after the last dose.
- Safety: Grade 3 treatment-related events in 4 of 26 patients (15%) and none at Grade 4 or 5.
Design strengths and limits in the Recursion REC-4881 Phase 2 results
Every participant received the drug, and there was no placebo or concurrent control. Open-label design can inflate perceived benefit, particularly for outcomes that involve a reader judging endoscopic findings. The company reports the groups as small and the data as preliminary, and it warns that they may not predict later-stage results. Only 12 weeks of treatment have been studied, so the durability of any effect on treatment is unknown. The efficacy cohort of 15 includes four patients added after a November 2025 data cut, and the safety cohort of 26 mixes 5 Phase 1b and 21 Phase 2 patients.
What was measured in the Recursion REC-4881 Phase 2 results
FAP is caused by changes in the APC gene and leads to many polyps in the bowel and upper digestive tract; the National Cancer Institute gives background. The study measured total polyp burden, which in the company’s example is expressed in millimetres, in the upper and lower digestive tract separately, plus counts of polyps larger than 5 millimetres. In the upper tract the Spigelman stage, a clinical grading of duodenal polyp severity, was also tracked.
- Upper tract: 12 of 13 had a reduction, median 55%; 6 of 12 improved by at least one Spigelman stage at Week 13.
- Lower tract: 9 of 11 with measurable burden had a reduction, median 50%.
- Larger polyps: 6 of 8 had fewer, and 4 had reductions of at least 80%; two patients went from more than 90 polyps over 5 millimetres to one.
Comparison with natural history in the Recursion REC-4881 Phase 2 results
Recursion analysed a registry of about 200 FAP patients held with Amsterdam University Medical Center. Among 47 who matched the trial criteria, polyp burden rose over time: by a mean of 33% a year in the upper tract (35 patients) and 88% a year in the lower tract (28 patients). This helps explain why a reduction is notable, but it is a company analysis of an external group. Without randomisation, differences in patient selection, timing and measurement can bias such comparisons.
Safety profile in the Recursion REC-4881 Phase 2 results
Of 26 treated patients, 21 (81%) had a worst treatment-related event of Grade 1 or 2, 4 (15%) of Grade 3, and one had none. Commonly reported events were acne-like dermatitis, rash, raised creatine phosphokinase, diarrhoea and an asymptomatic decrease in left ventricular ejection fraction. Four patients stopped for Grade 1 or 2 events. The company says most effects resolved within 12 weeks off treatment and that no new safety signals appeared in the expanded adult population. For a therapy that may need long courses in people with an inherited condition, cardiac and skin monitoring and cumulative toxicity will be central questions. This is general reasoning and not a finding from the study.
The heart and skin findings behind the Recursion REC-4881 Phase 2 results
MEK inhibitors act on a signalling pathway found in many tissues, so effects on skin and on cardiac function are recognised features of the class. A decrease in ejection fraction that causes no symptoms is still something clinicians monitor, usually with repeat echocardiograms. How often the effect occurred and how large it was are not given in the material we reviewed.
Regulatory status and the Recursion REC-4881 Phase 2 results
The FDA has granted REC-4881 Orphan Drug and Fast Track designations; the FDA explains Fast Track as a process to speed development of drugs for serious conditions, and it does not imply approval or efficacy. Recursion expects to begin a registrational trial in the second half of 2027, pending ongoing FDA discussions, and will give more detail later in 2026. A key design question is the primary endpoint: whether polyp burden itself, a clinical event such as the need for surgery, or cancer outcomes will be accepted. The company has not stated the agreed endpoint.
REC-1245 in the Recursion REC-4881 Phase 2 results announcement
The same release reported Phase 1 data for REC-1245, an investigational oral degrader of the splicing factor RBM39. With a data cut-off of 21 August 2026, there were two confirmed partial responses in endometrial cancer and one unconfirmed partial response in hepatocellular carcinoma among heavily pretreated patients, all at 45 mg daily or higher; 11 of 12 patients at those doses had disease control. Among 10 patients at 45 mg there were no dose-limiting toxicities, and fatigue and anaemia each occurred in 30%. Early-phase responses in a handful of patients do not establish efficacy.
Where AI fits in the Recursion REC-4881 Phase 2 results
Recursion says its AI foundation models identified REC-4881 through phenotypic screening. The trial results do not test that claim. They test whether the drug lowers polyp burden. For related coverage of AI-linked drug deals see our report on AstraZeneca’s AI deal with insitro, and for another Phase 2 readout reported with attention to limits see our report on Cardurion’s tovinontrine results.
Market context from Acumen Research and Consulting
Acumen Research and Consulting’s AI in Oncology Market report values that global segment at USD 0.9 billion in 2022 and projects USD 10.5 billion by 2032, a CAGR of 28.5% for 2023 to 2032, with North America at about 46% in 2022. By our own calculation, the stated endpoints imply about 27.8% a year, so the report’s CAGR and forecast do not fully agree. It was published in July 2024 and covers AI in cancer care generally, not FAP or Recursion, so use it only as indicative context.
Questions clinicians and researchers may ask about the Recursion REC-4881 Phase 2 results
Does lower polyp burden translate into fewer cancers or surgeries? Is intermittent dosing possible? Do effects last? How should cardiac monitoring work? See more in our pharmaceutical section.
Timeline of the Recursion REC-4881 Phase 2 results
- November 2025: earlier data cut.
- 15 October 2026: upper digestive tract results announced.
- 2 November 2026: expanded results presented at the annual meeting of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer.
- Second half of 2027: registrational trial expected to start.
General background: current care for FAP
Management combines surveillance, endoscopic removal of polyps and surgery. Removing duodenal polyps carries risks such as bleeding and perforation, and advanced disease may need major surgery, according to the company. No drug therapy is approved, per the company and a trial investigator quoted in its announcement.
Our analysis of the Recursion REC-4881 Phase 2 results
In our assessment, the Recursion REC-4881 Phase 2 results are a credible early signal of biological activity in a disease with few options, but they cannot show clinical benefit. The next step must separate drug effect from chance and show durable, safe benefit.
What is not disclosed about the Recursion REC-4881 Phase 2 results
- The primary endpoint and total enrolment of the study.
- Severity and frequency of the ejection fraction changes.
- The registrational endpoint agreed with the FDA, if any.
Risks and caveats
This article relies on the company’s announcement and public trial registry. Data are preliminary, and subgroup counts are small. A single patient with a 98% reduction is not representative, as the company notes. This is not medical advice.
What to watch next
- Registrational trial design.
- Longer follow-up and cardiac safety data.
- Peer-reviewed publication.
FAQ
Is the study randomised?
No. It is open-label and single-arm.
How many patients were analysed?
15 for total polyp burden and 26 for safety.
Does a lower polyp count mean lower cancer risk?
That was not tested in this study.
How we reported this: we relied on the company’s announcement of 2 November 2026, ClinicalTrials.gov, regulator and health-agency pages and the Acumen Research and Consulting report cited above. Our calculations are labelled. Last updated 3 November 2026. This is news reporting and not advice.
