Slide 1: REC-4881 Phase 1b/2 Trial in FAP: Updated Safety and Efficacy
Ongoing Phase 1b/2 Trial of the Allosteric MEK1/2 Inhibitor REC-4881 as Monotherapy in Familial Adenomatous Polyposis (FAP): Updated Safety and Efficacy December 8, 2025
Slide 2: Forward-looking statements disclaimer
This presentation discusses an investigational product whose safety and efficacy have not been established. This document contains information that includes or is based upon “forward-looking statements” within the meaning of the Securities Litigation Reform Act of 1995, including, without limitation
Slide 3: From platform discovery to positive clinical data in FAP
From platform discovery to positive clinical data: REC-4881’s emerging potential for treatment of familial adenomatous polyposis High Unmet Need in FAP • >50,000 patients in US/EU5 • Lifelong surveillance and life altering surgeries • No approved pharmacotherapy Safety Data Update • Most common TRAE
Slide 4: Recursion momentum: pipeline advancements and partnership value
4 Recursion momentum: Delivering pipeline advancements and partnership value in total cash inflows achieved across all our partnerships and collaborations >$500 million ✓ 6 Phenomaps: 4 GI oncology, 2 neuroscience ✓ 1 program initiated in GI onc indication ✓ 4 milestones achieved in 18 months ✓ Port
Slide 5: Recursion OS 2.0: novel insights, precision design, optimized trials
Design Workflow Automated ADMET Automated Chemistry Automated Biology 3D Protein & Atomistic Models Molecular Property Prediction & Design Scientific Agents Nomination Workflow Scientific Agents Transcriptomics Assay & Models ML-based Patient Connectivity (RWD) LLMs & Graphs MOA Deconvolution Scaled
Slide 6: REC-4881: in-licensed from Recursion OS V0.1, now leveraging V2.0
Causal AI Patient Selection & RWD Clinical Trial Design AI-powered Recruitment REC-4881: In-licensed based on novel insights from Recursion OS V0.1; now leveraging V2.0 platform to advance clinical development 9 Design Workflow Automated ADMET Automated Chemistry Automated Biology 3D Protein & Atomi
Slide 7: REC-4881: in-licensed from Recursion OS V0.1, now leveraging V2.0
REC-4881: In-licensed based on novel insights from Recursion OS V0.1; now leveraging V2.0 platform to advance clinical development 9 Design Workflow Automated ADMET Automated Chemistry Automated Biology 3D Protein & Atomistic Models Molecular Property Prediction & Design Scientific Agents Transcript
Slide 8: Natural history RWE: quantifying FAP disease progression
8 Natural history RWE: Quantifying FAP disease progression to contextualize TUPELO program and inform regulatory path 1. Supported by multiple guidances including: U.S. Food and Drug Administration. Rare Diseases: Natural History Studies for Drug Development (Draft Guidance for Industry) [Internet].
Slide 9: Natural history RWE: quantifying FAP disease progression
9 Natural history RWE: Quantifying FAP disease progression to contextualize TUPELO program and inform regulatory path 1. Supported by multiple guidances including: U.S. Food and Drug Administration. Rare Diseases: Natural History Studies for Drug Development (Draft Guidance for Industry) [Internet].
Slide 10: Fireside chat: Today's speakers
Fireside chat: Today’s speakers 10 Elizabeth Bruckheimer, PhD VP of Clinical Development Recursion • Highly accomplished executive with ≥20 years of industry experience, directing all phases of drug development from preclinical to clinical execution • Former VP and CSO Panbela Therapeutics / Cancer
Slide 11: REC-4881 Program
REC-4881 Program Elizabeth Bruckheimer, PhD | VP, Clinical Development
Slide 12: Disease context: FAP with no approved pharmacotherapies
Disease context: FAP is a rare disease characterized by extensive polyps in the GI tract, with no approved pharmacotherapies • Orphan disease caused by autosomal dominant inactivating mutations in APC1 • One of the most clinically significant hereditary colorectal cancer syndromes • Majority of pati
Slide 13: Patient journey: FAP lifelong continuum of disease progression
Patient journey: FAP is a lifelong continuum of disease progression and intervention, driven by chronic polyp growth 13 Note: There is a high degree of variability in SOC across practices and/or regions 1. Vasen HFA et al. Optimizing the timing of colorectal surgery in patients with Lynch syndrome:
Slide 14: ClinTech insights: real-world EHR data on FAP progression
ClinTech insights: Real-world US electronic health records and physician notes highlight disease progression in FAP patients Note: all reported rates are adjusted for variable follow up time. Data analysis includes unstructured physician notes and structured components of EHRs such as billing codes
Slide 15: Platform insight: MEK1/2 inhibition as APC-rescue mechanism
Platform insight: Unbiased AI-driven phenotypic discovery identified MEK1/2 inhibition as a novel APC-rescue mechanism, positioning REC-4881 for FAP • Platform screened thousands of compounds in APC mutant rescue assays • REC-4881 strongly clusters with APC rescue signature, indicating reversal of A
Slide 16: REC-4881 profile: precision MEK1/2 inhibitor for FAP
REC-4881 profile: A precision MEK1/2 inhibitor uniquely suited to the biology and anatomy of FAP 16 • APC loss-of-function drives FAP through hyperactivation of Wnt/β- catenin and MAPK signaling, leading to uncontrolled adenoma formation • REC-4881 selectively blocks ERK activation (MAPK pathway)—a
Slide 17: Preclinical data: REC-4881 reduced polyps in APCmin/+ models
Preclinical data: REC-4881 reduced total polyps and high-grade adenomas in APCmin/+ FAP models APCmin/+ Mouse Model of FAP • Significant reduction in polyp count, outperforming celecoxib at clinically relevant exposures3 • Decreases both polyp number and pre- cancerous adenomas % Pre-Cancerous Polyp
Slide 18: Ongoing Phase 1b/2 Updated Results & Natural History Analysis
Ongoing Phase 1b/2 Updated Results & Natural History Analysis
Slide 19: Phase 2: REC-4881-201 study design & objectives
Phase 2: REC-4881-201 study design & objectives Note: REC-4881 Ph 2 was also tested N=2 patients in 8 mg QD. One patient was excluded due to: less than 75% drug exposure (N=1) and the other patient was excluded due to having zero polyp burden at baseline (N=1) 1. After analysis in Phase 1b, the elig
Slide 20: Phase 2: Baseline demographics and clinical characteristics
Phase 2: Baseline demographics and clinical characteristics 20 Characteristic Ph 2 REC-4881 4 mg (N=14 safety evaluable)2 Age, years 61.9±4.8 Sex, n (%) Female 8 (57.1) Male 6 (42.9) Race, n (%) White 14 (100) FAP Disease Primary Site, n (%)3 Duodenum 11 (78.6) Rectum/Pouch 3 (21.4) Spigelman Stage
Slide 21: Phase 1b and Phase 2: summary of adverse events
Phase 1b and Phase 2: REC-4881 summary of adverse events 21 Note: For 8 mg (N=2, only 1 efficacy evaluable), N=1 (50%) exhibited Grade 2 TRAEs (rash), no Grade 3 TRAEs 1. For 4 mg, N=5 patients in Phase 1b and N=14 patients in Phase 2 were dosed; safety data cutoff date of 2025-11-25 2. Decrease was
Slide 22: Rapid polyp burden reductions on treatment, 75% responding
22 3 months on-treatment: Rapid polyp burden reductions with REC- 4881, 75% of patients responding Percent (%) change from baseline calculates the change between post-resection value from screening visit to the pre-resection value at Week 13/EOT visit. Subjects with absolute value of 0 at baseline a
Slide 23: Durable polyp burden reductions off-treatment, 82% responding
23 After 3 months off-treatment: Durable polyp burden reductions with REC-4881, with 82% of patients responding Note: Polyp burden defined as the sum of all diameters of polyps in the GI 1. Non-responder with 233% increase – polyp burden increased from 3mm to 10mm due to one polyp growth at Week 25
Slide 24: Durable reductions in polyp burden through Week 25
24 3 months on and 3 months off-treatment: REC-4881 produces durable reductions in polyp burden through Week 25 Note: Percent (%) change from baseline calculates the change between post-resection value from screening visit to the pre-resection value at Week 13/EOT visit and Week 25/EOT. Efficacy Eva
Slide 25: Natural history analysis: polyp burden increase in ~87%
Natural history analysis: ~87% show polyp burden increase, while ~10% remained stable, highlighting the disease progression of FAP 25 Annualized % change in polyp burden in a natural history cohort Amsterdam University Medical Center FAP registry (N=55) Natural History Study Summary Each bar represe
Slide 26: Spigelman stage: downstaging in 40% of patients
Week 13 Spigelman stage: REC-4881 produced Spigelman downstaging in 40% of patients, reflecting UGI disease improvement 26 AUMC: Amsterdam University Medical Center Note: N=10 efficacy evaluable for UGI; 2 patients lacked UGI anatomy. Spigelman Stage can be confounded by sampling errors 1. Patient d
Slide 27: Summary and Next Steps
Summary and Next Steps ® Recursion,
Slide 28: Phase 1b/2 data review and next steps (I/II)
REC-4881: Phase 1b/2 data review and next steps (I/II) 28 REC-4881 Potential First-in-Disease and Best-in-Class First Clinical Validation for Recursion OS Platform Platform-Generated Novel Mechanistic Insight → First Clinical Proof • First clinical validation of the Recursion OS • Recursion’s phenot
Slide 29: Rapid and durable reductions in polyp burden at 4 mg
REC-4881: Phase 1b/2 data review and next steps (I/II) 29 Rapid and Durable Reductions in Polyp Burden at 4 mg • Safety consistent with MEK inhibitors; low rate of Grade 3 events; no Grade 4/5 • Rapid and substantial clinical activity with 43% median reduction in 3 months; 75% of patients responded
Slide 30: Phase 1b/2 data review and next steps (II/II): path forward
REC-4881: Phase 1b/2 data review and next steps (II/II) 30 Path Forward • Expanding population from ≥55 to ≥18 years old and further optimizing dosing schedule • Engage FDA (1H 2026) to define registration path informed by leveraging data generated thus far along with RWE assessments • Continue foll
Slide 31: Thank you to all trial patients, families and sites
31 Thank you to all the trial patients and their families and clinical trial sites
Slide 32: Fireside Chat
Fireside Chat Najat Khan, PhD | Chief R&D Officer and Commercial Officer, Incoming CEO Jessica Stout, DO | Asst Clinical Professor, University of Utah Al Cohen, MD, FACS, FASCRS | Former Chief of Colorectal Service, Memorial Sloan-Kettering Cancer Center David Mauro, MD, PhD | Chief Medical Officer
Slide 33: Fireside chat: Today's speakers
Fireside chat: Today’s speakers 33 Najat Khan Chief R&D Officer and Commercial Officer, Incoming CEO • Former Chief Data Science Officer & SVP, Global Head of R&D Strategy, Portfolio & Operations at Johnson & Johnson Innovative Medicine • Former Partner & Senior Principal at Boston Consulting Group,
Slide 34: Appendix
© Recursion.
Slide 35: REC-4881 safety at 4 mg dose
Event, n (%) REC-4881 Ph 1b and 2 4 mg (N=19 safety evaluable)1 Any TEAE related to study drug (TRAE) 18 (94.7) Grade 4/5 TRAE 0 Grade 3 TRAE 3 (15.8) Discontinuation due to TRAE 4 (21.1) Dose interruption due to TRAE 2 (10.5) Dose modification due to TRAE 0 REC-4881 Safety 4 mg dose: Safety profile
Slide 36: Change in total polyp burden at Week 13
Percent (%) change from baseline calculates the change between post-resection value from screening visit to the pre-resection value at Week 13/EOT visit. Subjects with absolute value of 0 at baseline are not displayed. Note: Polyp burden defined as the sum of all diameters of polyps in the GI 1. Fol
Slide 37: Change in total polyp burden at Week 25
REC-4881 4mg dose level % change from baseline in total polyp burden at Week 25 (12 weeks off therapy) % c h a n g e f ro m b a s e li n e Percent (%) change from baseline calculates the change between post-resection value from screening visit to the pre-resection value at Week 25/EOT visit. Note: P
Slide 38: Fireside Chat Q&A
Fireside Chat Q&A KOL Topic Question Jessica Current Treatment & Unmet Need As a gastroenterologist managing complex FAP patients, can you tell us a bit about your patients’ journey? What are the most significant unmet clinical needs for your patients in your opinion? Data Interpretation From your p
Slide 39: REC-4881 preliminary efficacy: 43% median reduction
©2025 Mayo Foundation for Medical Education and Research | slide-39 REC-4881 PRELIMINARY EFFICACY PRELIMINARY RESULTS 43% MEDIAN REDUCTION IN TOTAL POLYP BURDEN ON 4 MG REC-4881 • 6 patients on 4 mg efficacy evaluable1 • 100% (n=6) received at least 75% of treatment • 43% median reduction in total p
Slide 40: Reductions in polyp burden across upper and lower GI tract
©2025 Mayo Foundation for Medical Education and Research | slide-40 REC-4881 PRELIMINARY EFFICACY PRELIMINARY RESULTS REDUCTIONS IN POLYP BURDEN SEEN ACROSS UPPER AND LOWER GI TRACT Upper GI Burden • 6 patients efficacy evaluable1 • 58% median reduction in UGI polyp burden • 50% patients with >1-poi
Slide 41: Proof of concept of AI-based target selection in rare disease
©2025 Mayo Foundation for Medical Education and Research | slide-41 Proof of Concept of an AI based target selection and drug development in a rare disease with unmet need Preliminary REC-4881 safety • Generally well-tolerated in early analysis • TRAEs in 4 mg patients1 : rash (45.5%), dermatitis ac
Slide 42: Preliminary efficacy: reduction in Spigelman stage
©2025 Mayo Foundation for Medical Education and Research | slide-42 REC-4881 Preliminary Efficacy PRELIMINARY RESULTS: 50% OF PATIENTS ON 4 MG REC- 4881 DEMONSTRATED A REDUCTION IN SPIGELMAN STAGE* 42 Subject ID Polyp Burden Screening -> W13 (CfB%) Polyp Count Screening -> W13 (CfB%) Spigelman Stage