Recursion Pharmaceuticals (RXRX) investor relations material

Disease background and unmet need

• Familial adenomatous polyposis (FAP) is a rare, hereditary colorectal cancer syndrome affecting over 50,000 individuals in the US and EU5, with a near 100% lifetime risk of colorectal cancer if untreated and no approved pharmacotherapies.

• Patients face lifelong surveillance, repeated surgeries, and significant quality of life impacts, as current management relies on surgery and endoscopic procedures that do not halt disease progression.

• There is a significant unmet need for therapies that slow disease progression, reduce polyp burden, and improve patient outcomes.

Mechanism, discovery, and preclinical insights

• REC-4881 is a potent, selective allosteric MEK1/2 inhibitor identified via an AI-driven phenotypic platform as a targeted therapy for FAP, redirecting a previously deprioritized oncology compound.

• The drug blocks ERK activation, suppresses cell proliferation, and reverses APC loss-of-function phenotypes in disease models.

• Preclinical studies in APCmin/+ mouse models showed significant, dose-dependent reductions in total polyps and high-grade adenomas, outperforming celecoxib.

Study design and patient population

• The ongoing open-label Phase 1b/2 TUPELO trial evaluates REC-4881 (4 mg QD) in FAP patients post-colectomy/proctocolectomy, with measurable upper and lower GI polyps and no active cancer.

• Primary objectives include safety, tolerability, PK/PD, and efficacy, measured as percent change in polyp burden after 12 weeks on and 12 weeks off treatment.

• The majority of patients had duodenal disease, with a median baseline polyp burden of 132 mm; 14 patients were safety evaluable, and 12 efficacy evaluable in Phase 2.