UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): January 13, 2025
(Exact name of registrant as specified in its charter)
| (State or other jurisdiction of incorporation) | (Commission File Number) | (I.R.S. Employer Identification No.) | ||||||||||||
(Address of principal executive offices) (Zip code)
(385 ) 269 - 0203
(Registrant’s telephone number, including area code)
Not Applicable
(Former name or former address, if changed since last report.)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Securities registered pursuant to Section 12(b) of the Act:
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 7.01. Regulation FD Disclosure.
On January 13, 2025, Recursion Pharmaceuticals, Inc. (the “Company”) released an updated investor presentation. The investor presentation will be used at the JP Morgan Healthcare Conference and from time to time in meetings with investors. A copy of the presentation is attached hereto as Exhibit 99.1.
The information furnished in this Item 7.01 (including Exhibit 99.1), shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
| Exhibit Number | Description | ||||
| 99.1 | |||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | ||||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized on January 13, 2025.
| RECURSION PHARMACEUTICALS, INC. | ||||||||
| By: | /s/ Christopher Gibson | |||||||
Christopher Gibson | ||||||||
Chief Executive Officer | ||||||||
Decoding Biology to Radically Improve Lives JANUARY 2025
This presentation of Recursion Pharmaceuticals, Inc. (“Recursion,” “we,” “us,” or “our”) and any accompanying discussion contain statements that are not historical facts may be considered forward-looking statements under federal securities laws and may be identified by words such as “anticipates,” “believes,” “estimates,” “expects,” “intends,” “plans,” “potential,” “predicts,” “projects,” “seeks,” “should,” “will,” or words of similar meaning and include, but are not limited to, statements regarding Recursion’s OS industrializing first- and best-in-class drug discovery; the occurrence or realization of near-or medium-term potential milestones; current and future preclinical and clinical studies, including timelines for enrollment in studies, data readouts, and progression toward IND-enabling and other potential studies; Recursion’s plans to present clinical trial data at medical conference or in publications; the potential size of the market opportunity for our drug candidates; outcomes and benefits from licenses, partnerships and collaborations, including option exercises by partners and the amount and timing of potential milestone payments; the initiation, timing, progress, results, and cost of our research and development programs; advancements of our Recursion OS; the potential for additional partnerships and making data and tools available to third parties; our ability to identify viable new drug candidates for clinical development and the accelerating rate at which we expect to identify such candidates including our ability to leverage the datasets acquired through the license agreement into increased machine learning capabilities and accelerate clinical trial enrollment; and many others. Such forward-looking statements are based on the current beliefs of Recursion’s management as well as assumptions made by and information currently available to them, which are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. Actual outcomes and results may vary materially from these forward- looking statements based on a variety of risks and uncertainties. For a complete discussion of factors that could materially affect our financial results and operations, please refer to Recursion’s most recent Annual Report on Form 10-K, Recursion’s Quarterly Reports on Form 10-Q for the quarterly periods ended March 31, June 30, and September 30, 2024, and the Company’s other filings with the U.S. Securities and Exchange Commission (the “SEC”), which can be accessed at https://ir.recursion.com, or www.sec.gov. All forward-looking statements are qualified by these cautionary statements and apply only as of the date they are made. Recursion does not undertake any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the company’s own internal estimates and research. While the company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while the company believes its own internal research is reliable, such research has not been verified by any independent source. Information contained in, or that can be accessed through our website is not a part of and is not incorporated into this presentation. Cross-trial or cross-candidate comparisons against other clinical trials and other drug candidates are not based on head-to-head studies and are presented for informational purposes; comparisons are based on publicly available information for other clinical trials and other drug candidates. Any non-Recursion logos or trademarks included herein are the property of the owners thereof and are used for reference purposes only. 2 Important information
3 Full-stack Recursion OS is industrializing first-in-class & best-in- class drug discovery
4 Full-stack Recursion OS is industrializing first-in-class & best-in- class drug discovery
5 Full-stack Recursion OS is industrializing first-in-class & best-in- class drug discovery
6 4 Large pharma collaborations 10 Clinical and pre- clinical programs1 Oncology, rare diseases, and other high unmet need diseases ~10 Clinical program milestones over the next 18 months2 1 Unified Operating System (OS) with both first & best-in-class capabilities ~10 Additional advanced discovery programs 10+ Partnered programs ~$450M Upfront and milestone payments earned to-date ~$20B potential milestone payments Oncology, immunology, and other high unmet need diseases 1. Includes preclinical programs (programs expected to enter the clinic within the next 18 months). 2. Program milestones includes data readouts, preliminary data updates, regulatory submissions, trial initiation, etc. Portfolio poised for value creation with waves of new pipeline and partner programs emerging from Recursion OS
VALUE CREATION How the Platform Powers the Portfolio
O T H E R R A R E O N C O L O G Y Candidate Target Indication Preclinical IND-Enabling Phase 1/2 Pivotal / Phase 3 Next Anticipated Milestone REC-617 CDK7 Advanced solid tumors1 • Combination study initiation – 1H25 REC-1245 RBM39 Biomarker-enriched solid tumors & lymphoma • Ph 1 dose-escalation update – 1H26 REC-3565 MALT1 B-cell malignancies • Ph 1 FPD – 1Q25 REC-4539 LSD1 Small-cell lung cancer (SCLC) • Ph 1 FPD – 1H25 REC-994 Superoxide Cerebral cavernous malformations (CCM) • Ph 2 data – ISC3 – February 5th REC-4881 MEK1/2 Familial adenomatous polyposis (FAP) • Ph 1b/2 safety & early efficacy – 1H25 REC-2282 HDAC Neurofibromatosis type 2 (NF2) • PFS6 futility – 1H25 REV1022 ENPP1 Hypophosphatasia (HPP) • IND-enabling studies initiation - 2025 REC-3964 TcdB Prevention of recurrent C. difficile (rCDI) • Ph 2 update – 1Q26 REC-4209 Undisclosed Idiopathic pulmonary fibrosis (IPF) • IND-enabling studies ongoing ~10 advanced discovery programs including a PI3Kα H1047Ri ELUCIDATE POPLAR ALDER TUPELO SYCAMORE EXCELERIZE ENLYGHT DAHLIA 1. Includes non-small cell lung cancer (NSCLC), colorectal cancer, breast cancer, pancreatic cancer, ovarian cancer, head and neck cancer 2. Joint venture with Rallybio 3. International Stroke Conference, late breaking oral abstract 8 Pipeline of ~10 clinical and preclinical technology-enabled programs
9 REC-1245 (RBM39 degrader): A highly selective RBM39 degrader for biomarker-enriched solid tumors and lymphoma REC-1245: RBM39 • Novel approach: Modulation of DDR via RBM39 to potentially avoid on- target toxicities seen with cell cycle checkpoint inhibitors like WEE1, ATR, and CHK1/2 • Efficient R&D Campaign: 18 months from target ID to IND-enabling studies ONCOLOGY Recursion OS: REC-1245 Discovery Our Approach: Unbiased ML-powered phenomap insight to identify novel DDR signature and relate cellular phenotypes
Similar Opposite Recursion OS Novel Insight1 Gene: Gene Relationship: Genetic KO of RBM39 and CDK12 found to be phenotypically similar with neither genes demonstrating a relationship to CDK13 genetic KO Gene: Compound Relationship: REC-1245 demonstrates phenotypic similarity to RBM39 and CDK12 genetic KO but not CDK13, in line with inferred hypothesis REC-1245 10 1. Data on File. ONCOLOGY REC-1245 (RBM39 degrader): Functional similarity between RBM39 and CDK12 suggesting a potential novel approach to DDR modulation
Clinical Updates REC-1245 (RBM39 degrader): Potential first-in-class RBM39 degrader in Phase 1 dose-escalation with first patient dosed 4Q24 11 1. Data on File. 2. N=8 mice per group REC-1245 administered BID PO at doses noted. 3. PD evaluated after 5 days BID oral administration of REC-1245 at doses noted; N=3 mice per group in PD portion ONCOLOGY Compelling dose-dependent antitumor activity correlated with RBM39 degradation in preclinical models1 Product Profile • First-in-class mechanism RNA splicing for targeted tumor control • Highly potent and selective Minimal off-target liabilities identified • Precision based approach Biomarker defined population • First patient dosed 4Q24 • Recruitment active and ongoing • Phase 1 dose-escalation update 1H26 PD: Target Engagement3CDX Model: OVK182
12 REC-617 (CDK7 inhibitor): Precision design for optimizing therapeutic index with CDK7 ONCOLOGY Recursion OS: REC-617 Discovery Our Approach: Generative AI and active learning to optimize molecule design, including non-covalent binding and ADME/PK for rapid absorption REC-617: CDK7 • Recursion Approach: AI-powered precision design with reduced transporter interactions intended to minimize GI adverse events seen with prior molecules in class • Rapid Design Cycle: 136 novel compounds synthesized and under 11 months from hit to candidate ID
REC-617 (CDK7 inhibitor): first-in-human study in solid tumors enrolled a heterogenous and heavily pretreated population 2 mg QD (n=3) • Unresectable, locally recurrent, or metastatic cancer • Progressed following, or intolerant to, available standard of care treatments • ECOG PS 0-1 5 mg QD (n=4) 10 mg QD (n=7) 20 mg QD (n=3) 1 mg BID (n=2) Ongoing Phase 1 Design Ongoing Baseline Demographics • N=19 • Median of 4 prior lines of therapy in advanced setting • Heterogenous population, including: • Colorectal cancer • Breast cancer • Ovarian cancer • NSCLC • Pancreatic cancer Primary: • Monotherapy safety and recommended Phase 2 dose (RP2D) Key Secondary: • Pharmacokinetics Exploratory: • Preliminary antitumor activity (RECIST v1.1) • Pharmacodynamics: POLR2A gene expression in blood Endpoints ONCOLOGY 13
REC-617 (CDK7 inhibitor): REC-617 achieves dose dependent PK/PD and strong target modulation in the clinic 14 1. Papadopoulos KM, et al. ENA (2020) PK/PD Summary • Dose-Linear PK: REC-617 exceeds CDK7 IC80 with rapid absorption (Tmax 0.5–2h) and short t½ (5–6h) • Robust Target Engagement: Early POLR2A 3-4x modulation suggests ~80–90% target engagement1 • Rapid Transient Modulation: Quick, time-limited target engagement with POLR2A normalization in 24h • BID Evaluation: Twice-daily dosing under investigation ONCOLOGY
REC-617 (CDK7 inhibitor): REC-617 offers a competitive and unique profile that potentially improves the therapeutic index 15 Key Differentiation • Data suggests superior target coverage for REC- 6171 compared to two clinical CDK7 inhibitors • REC-617 is more rapidly absorbed (earlier Tmax) compared to reported PK from two CDK7 inhibitors2,3 suggesting a reduction in localized GI residence time • A shorter half-life would allow for flexible target modulation, which may improve the therapeutic index in the clinic 1. CDK7 IC80 reflects biochemical in vitro potencies on file 2. Coombes, RC, Nat Comms (2023) 3. Papadopoulos KM, et al. ENA (2020) ONCOLOGY 0 4 8 12 16 20 24 0.01 0.1 1 10 100 Time (hr) F r e e P la s m a C o n c e n tr a ti o n / I C 8 0 CDK7 IC80 Coverage REC-617 20 mg QD SY-5609 3 mg QD3 Samuraciclib 360 mg QD2
REC-617 (CDK7 inhibitor): Durable monotherapy PR observed in a metastatic ovarian cancer patient after 4 prior lines of therapy 16 1. By RECIST 1.1. Response evaluation criteria in solid tumors, PR: decrease of more than 30% in the sum of the longest diameters of target lesions + no new lesions + no progression of non target lesions Baseline Week 16 Para-aortic LN Para-aortic LN Clinical Updates • Continue dose escalation (QD & BID) • Initiate combination study in 1H25 • Leverage new tech and clinical data partnerships for patient stratification One confirmed, durable partial response (PR)1 • Partial response (-34%) achieved at Week 16 • Meaningful reduction of tumor markers • Response ongoing after 6+ months treatment Early data indicates favorable safety profile • Maximum tolerated dose (MTD) not reached ONCOLOGY ~44% ~68%
REC-994 (superoxide scavenger): A safe and well tolerated superoxide scavenger for the treatment of Cerebral Cavernous Malformation (CCM) 17 RARE DISEASE Recursion OS: REC-994 Discovery • Met primary endpoint of safety/tolerability in Phase 2 study • Time- and dose- dependent trends in reduced lesion volume and hemosiderin ring size compared to placebo • 80% of Phase 2 patients continued to LTE • Full results to be presented at ISC as a late-breaking oral abstract on February 5, 2025 REC-994 (superoxide) Our Approach: Unbiased phenotypic screen to identify cellular and structural changes associated with CCM2 loss, a pathogenic mutation in CCM
REC-4881 (MEK1/2 inhibitor): Modeling FAP-relevant biology to discover REC-4881, a potential best-in-class MEK1/2 inhibitor 18 RARE DISEASE • 4 mg QD dose is pharmacologically active and well-tolerated • Differentiated ADME profile may enhance exposures at the site of GI adenomas • FTD (US) and ODD (US,EU) • Ph 1b/2 safety and early efficacy data expected in 1H25 Recursion OS: REC-4881 Discovery REC-4881 (MEK 1/2) Our Approach: Unbiased phenotypic screen to identify cellular and structural changes associated with APC loss, the driving genetic mutation in FAP
REV102 (ENPP1 inhibitor): Identified novel chemical space to enable the design of a potential first-in-class and best-in-class therapy for HPP 19 RARE DISEASE Our Approach: Generative AI-powered fragment-based screen to achieve selectivity and improve physiochemical properties compared to prior molecules in the class • Structurally distinct vs competitor ENPP1 inhibitors • Dose-dependent normalizations in PPi and other disease relevant markers observed in genetic models of HPP • Suitable for chronic dosing with no significant in vitro safety concerns • IND-enabling studies to start in 2025 Recursion OS: REV102 Discovery REV102 (ENPP1)
OTHER REC-3964 (CDI TcdB inhibitor): A safe and well tolerated C. difficile toxin B selective inhibitor for the prevention of recurrent C. difficile (rCDI) Our Approach: Unbiased ML-aided conditional phenotypic drug screen in human cells to identify novel mechanisms that rescue the effect of C. diff. toxin B treatment • Potential first-in-class non-antibiotic oral toxin B selective inhibitor for prevention of rCDI • Well-tolerated with no treatment-related discontinuations or SAEs in Phase 1 • Recruitment ongoing with Phase 2 update expected in 1Q26 • 30+ new trial sites identified using RWD/ML REC-3964 (TcdB)Recursion OS: REC-3964 Discovery 20
Partnership Pipeline Pipeline
• $20M upfront | >$650M deal value • Focused on three projects in oncology & immunology ONCOLOGY & IMMUNOLOGY • $80M upfront + investment | ~$1.5B total value • Focusing on up to seven programs in oncology ONCOLOGY • $100M upfront | >$5B total value • Focusing on up to 15 novel small molecule candidates across oncology & immunology ONCOLOGY & IMMUNOLOGY • $150M upfront | Up to $300M per program for 40 programs • Identifying novel targets and small molecules, with the potential to advance up to 40 programs in neuroscience & a GI oncology indication. NEUROSCIENCE & ONCOLOGY 22 Recursion OS 1. Upfront and milestone payments from these therapeutic partnerships Note: Total deal value may include program milestones (for development, commercialization and net sales) and tiered royalties on net sales Pharma partnerships with approximately $450M1 earned to date and potential to receive more than $20B in additional milestones
23 PARTNERSHIPS Multiple whole-genome phenomaps with chemical perturbations completed in disease relevant cell types First validated hit series now in hit-to-lead Additional near-term program options World's first neuro-specific whole- genome arrayed CRISPR KO phenomap optioned for $30M Target validation packages underway Additional neuroscience phenomap options Additional near-term program options GI Oncology Neuroscience Capture Data Query Maps Interrogate Biological Mechanisms Select cell type to profile 1 Pheno-map Transcripto-map Recursion to capture >17M images per cell type gRED to generate scRNA-seq data for whole genome CRISPR ● Validation ● Target Deconvolution ● Hit to Lead & Lead Op Pheno- transcripto map (neuro only) Expose cells to perturbations 2 Capture multi- modal data 3 Build (ML) and query maps 4 Target & drug discovery 5
PARTNERSHIPS 24 Oncology and Inflammation Three programs have advanced through initial milestones; aggregate 2024 milestones of $15m for two programs Expansion of collaboration with internally-discovered program Identification of new targets and initiation of multiple new programs Advance additional programs into lead optimization
25 Full-stack Recursion OS is industrializing first-in-class & best-in- class drug discovery
MICRO Pathway Model MESO Largest fit-for-purpose dataset of perturbative biology and multiple FMs make Recursion a leader Protein Model Increasingly commoditized – We partner with builders of frontier models for early access Atomistic Model Recursion AI + Compute + Exscientia QM/MD = Recipe for leadership 26 Full-stack Recursion OS is industrializing first-in-class & best-in- class drug discovery
Business Updates
Board of Directors Dean Li, MD PHD Co-Founder of RXRX, President of Merck Research Labs Zavain Dar Co-Founder & Partner of Dimension Rob Hershberg, MD PHD Co-Founder, CEO, & Chair of HilleVax; Former EVP, CSO, & CBO of Celgene Zachary Bogue Co-Founder & Partner of Data Collective Najat Khan, PHD Chief R&D Officer & Chief Commercial Officer Franziska Michor, PHD Chair at Dana-Farber Cancer Institute & Professor at Harvard University Executive Team Ben Mabey Chief Technology Officer Kristen Rushton Chief Operations Officer David Mauro, MD PHD Chief Medical Officer Matt Kinn Chief Business Officer Najat Khan, PHD Chief R&D Officer & Chief Commercial Officer Erica Fox Chief People & Impact Officer David Hallett, PHD Chief Scientific Officer Lina Nilsson, PHD SVP, Head of Platform Blake Borgeson, PHD Co-Founder of RXRX Note: Trademarks are the property of their respective owners and used for informational purposes only.28 Chris Gibson, PHD Co-Founder, & Chief Executive Officer Chris Gibson, PHD Co-Founder & Chief Executive Officer Our leadership brings together experience & innovation to advance TechBio Ben Taylor Chief Financial Officer & President Recursion UK Nathan Hatfield Chief Legal Officer
Deeply focused on maximizing return post business-combination 29 1. As of September 30, 2024, pro forma for the combined entity, cash and cash equivalents includes short-term bank deposits Status • Hosted successful in-person multi-day onboarding event in London • Low post-close regrettable turnover • Senior-leadership teams combined and operating • Company-wide processes and platforms review underway with focus on highest impact operations • Integration of EXAI precision design platform into Recursion OS underway Next steps • 90-day goals update at YE24 earnings • Actively progressing with combination synergies - additional guidance to be provided in 2Q25 Pro Forma Cash1: $752 million
Positioned for a catalyst-rich 2025 30 Pipelines REC-994 (Superoxide Scavenger) in CCM Late breaker oral presentation (Phase 2) at International Stroke Conference Feb 5th, 2025 REC-3565 (MALT-1i) in B-cell malignancies Phase 1 first patient dosed 1Q25 REC-617 (CDK7i) in advanced solid tumors Initiation of combination studies 1H25 REC-4881 (MEK1/2i) in FAP Phase 1b/2 safety and early efficacy data 1H25 REC-2282 (HDACi) in NF2 PFS6 futility analysis 1H25 REC-4539 (LSD-1i) in SCLC Phase 1 first patient dosed 1H25 REC-617 (CDK7i) in advanced solid tumors Additional Phase 1 data from ELUCIDATE 2H25 Advancement of discovery programs including a PI3Kα H1047Ri FY25 Partnerships Potential for additional phenomap options Potential for multiple new project initiations Potential for multiple programs optioned by partners Platform Updates on early clinical development AI build in Recursion OS Updates on industry-leading foundation models at multiple biological levels Integration of technology and autonomous workflows to support best- and first-in-class programs
Appendix
Culture and Team
Parity Pledge Signer: Gender parity and people of color parity Technology – data science, software engineering, automation, etc. Life Sciences – biology, chemistry, development, etc. Strategic Operations ~800 employees Community Impact Founding Partner, Life Science Accelerator Founding Member, Life Science Collective ESG Highlights Learn more about Recursion’s ESG stewardship: www.recursion.com/esg Milpitas, California Salt Lake City, Utah Toronto, Ontario Montréal, Québec London, England Oxford, England New York, New York Headquartered in Salt Lake City, Utah with other primary locations in: • Milpitas, California • New York, New York • Toronto, Ontario • Montréal, Québec • London, England • Oxford, England 34 Our people are the most important ingredient for our mission
Pipeline Details APPENDIX
Oncology PIPELINE
Program Status • Potential Best-in-Class and First-in-Class CDK7 inhibitor • Phase 1/2 study in advanced solid tumors ongoing • Initial Phase 1 monotherapy safety, PK/PD update presented at AACR Special Conference in Cancer Research held on December 9, 2024 Mechanism of Action • Reversible CDK7 inhibitor that targets both cell cycle progression and transcriptional regulation Thesis & Differentiation • Non-covalent binding and improved selectivity to decrease off- target toxicity • 8-10 hours of therapeutic coverage at IC80 with a short half-life to reduce on-target toxicity • Rapid absorption and permeability at lowest possible dose Unmet Need1 • Multiple cancer indications that have the potential to address ~185,000 patients annually • R/R solid tumors including breast, NSCLC, ovarian, pancreatic, colorectal, and head & neck 37 1. Advanced solid tumors including breast, NSCLC, ovarian, pancreatic, colorectal and head & neck. US and EU5 treatable incidence, 2022. Recursion Approach • AI-powered precision design to optimize PK/PD to maximize potential therapeutic index • 136 novel compounds synthesized to candidate ID REC-617: CDK7 Inhibitor A precision designed highly selective CDK7 inhibitor for Relapsed and/or Refractory (R/R) Solid Tumors
Assay DC Criteria Ph 1 Competitor Ph 1/2 Competitor REC-617 CDK7 IC50 (nM) <10 CDK family selectivity >100-fold HCC70 (breast cancer) IC50 (nM) <100 Caco-2 A2B (efflux) 10⁻⁶ cm/s >5 (<3) Predicted human half-life (hr) <15 Potent tumor regression with minimal IC80 exposureREC-617 has Best-in-Class potential1 Designed to avoid efflux transporter substrate to minimize GI adverse events Key Preclinical Data 38 1. Data on File. 2. Besnard et al, AACR (2022). 3. PK studies conducted in CD1 mice, single-dose administration. >10 hr IC80 results in significant body weight loss Meets or exceeds criteria Minor deviation Major deviation Development Candidate (DC) Criteria: • CDK7 IC50: green <10nM; yellow 10-30nM; red >30nM • CDK7 selectivity: green >100-fold; yellow 30-100-fold; red <30-fold • HCC70 IC50: green <100nM; yellow 100-500nM; red >500 nM • Caco-2 A2B (efflux): green >5(<3); yellow >1.5 (<10); red <1.5 (>30) • Half-life: green <15, yellow <24, red >24 • REC-617 demonstrates potent tumor regression with less than 10 hours of exposure above IC80 to optimize benefit-risk CDX Model: OVCAR32 Mouse PK3 REC-617: Robust antitumor activity demonstrated in disease relevant preclinical tumor models Initial clinical safety and PK/PD presented at AACR Special Congress in December 2024
Development Strategy Part A • Monotherapy Part B • Initial combination with SERD in HR+/HER2- post CDK4/6 inhibitor population • N = 30-60 patients in combination • N will depend on number of disease specific cohorts Primary Endpoint: • Safety and Tolerability • Recommended Dose RP2D Phase 1 Dose Escalation (N≤60) Phase 1/2 study design CURRENT STAGE Primary Endpoint: • ORR 39 Trial Update • Phase 1 monotherapy preliminary safety and PK/PD data update presented at AACR Special Conference in Cancer Research in December 2024 • Continue dose escalation (QD & BID) • Initiate combination study in 1H25 • Leverage new tech and clinical data partnerships for patient stratification REC-617 Competitive Profile • Potential Best-in-Class CDK7 inhibitor • Reduced risk of off-target toxicity • Highly selective & potent REC-617 (CDK7 inhibitor): Study Design and Next Steps
Program Status • Potential First-in-Class RBM39 degrader in solid tumors • First patient dosed in 4Q24 • Phase 1 monotherapy update on dose-escalation expected in 1H26 Mechanism of Action • Molecular glue that degrades RBM39 via E3 ligase adaptor DCAF15 • Disrupts RNA splicing to downregulate cell cycle checkpoints and DDR networks Thesis & Differentiation • RBM39 phenotypically mimics CDK12 and is distinct from CDK13 in Recursion OS • Novel approach to target DDR biology via RBM39 avoids on-target toxicities associated with cell cycle checkpoint inhibitors (e.g., CDK12, WEE1, ATR, ATM, PLK1) • Selective RBM39 degrader with minimal ITGA2 liability to limit thrombocytopenia Unmet Need1 • >100,000 patients with solid tumor or lymphoma experience disease progression while on frontline therapies • Potential to be used as a single agent or in combination with chemo/IO 40 1. Internal company estimates. Assumes US+EU5 addressable incidence with biomarker-enriched solid tumors and other select histologies. 2. Paul et al, Nat Rev Drug Discov (2010) Recursion Approach • Unbiased ML-aided genomics screen to identify biological signature and relate cellular phenotypes • Progressed REC-1245 from target biology to IND-Enabling studies in under 18 months (vs. 42 months in industry2) REC-1245: RBM39 Degrader A highly selective RBM39 degrader for Biomarker-Enriched Solid Tumors and Lymphoma
Similar Opposite Recursion OS Novel Insight Gene: Gene Relationship: Genetic KO of RBM39 and CDK12 found to be phenotypic similar with neither genes demonstrating a relationship to CDK13 genetic KO Gene: Compound Relationship: REC-1245 demonstrates phenotypic similarity to RBM39 and CDK12 genetic KO but not CDK13, in line with inferred hypothesis REC-1245 41 1. Data on File. REC-1245 (RBM39 degrader): Platform inferred a functional similarity between RBM39 and CDK12 biology suggesting a novel approach to potential DDR modulation
Key Preclinical Data1 REC-1245 is highly selective and potent1 Assay DC Criteria REC-1245 RBM39 Degradation DC50 <100 nM CDK12 Kinase No sig. activity CEREP Safety Panel No sig. activity hERG IC50 (µM) >30 Oral Bioavailability (%F) >30 REC-1245 has compelling efficacy and PK/PD in preclinical models 42 1. Data on File. 2. N=8 mice per group in TV portion. REC-1245 administered BID PO. 3. PD evaluated after 5 days BID oral of REC-1245 at doses noted ; N=3 mice per group in PD portion Meets or exceeds criteria Minor deviation Major deviation • REC-1245 shows significant monotherapy regressions • Dose-dependent antitumor activity correlates with PD CDX Model: OVK182 PD: Target Engagement3 REC-1245 (RBM39 degrader): Robust efficacy/PK/PD in biomarker-positive disease relevant preclinical tumor models – Phase 1 initiated in 4Q24
Development Strategy Part A • Monotherapy dose-finding Part B • Monotherapy dose- confirmation RP2D Phase 1 Dose Escalation (N~55) Phase 1/2 study design CURRENT STUDY Key Study Characteristics Study objectives: • Safety/Tolerability • RP2D • ORR Eligibility: • Select histologies including a biomarker population and R/R lymphomas 43 Trial Update • First patient dosed in 4Q24 • Trial active and enrolling at 5 US sites REC-1245 Competitive Profile • Highly potent, potential First-in-Class RBM39 degrader (<100nM DC50) • No significant in vitro safety concerns (CEREP, hERG) • No significant activity in CDK12 kinase assay • Minimal ITGA2 liability to limit thrombocytopenia • High oral bioavailability DAHLIA: Study of REC-1245 in Participants with Unresectable, Locally Advanced, or Metastatic Cancer REC-1245 (RBM39 degrader): Study Design and Next Steps
Program Status • Potential Best-in-Class MALT1 inhibitor • Phase 1 initiation in B-Cell Malignancies (e.g., chronic lymphocytic leukemia), expected 1Q25 Mechanism of Action • Reversible allosteric MALT1 inhibitor that can dampen NF-κB signaling • Selectively inhibits CLL proliferation with limited impact on T-Cell viability Thesis & Differentiation • Low UGT1A1 liability with potential for reduced risk of hyperbilirubinemia • Potential for reduced liver toxicity and enhanced efficacy in combination with BTK and BCL2 inhibitors • Low predicted human clearance and high oral bioavailability Unmet Need1 • Current monotherapy treatments in B-cell malignancies not curative and prone to resistance • ~41,000 patients with R/R B-cell malignancies (treatable in US and EU5) – targeting CLL combination therapy 44 *Formerly EXS73565. 1. Cerner Enviza Treatment Architecture Reports 2023, rounded to nearest 1,000 patients per year. Recursion Approach • AI powered precision- designed novel molecule using molecular dynamics and hotspot analysis • 344 novel compounds synthesized to candidate ID • Maintain selectivity and deliver a candidate with lower predicted safety risk in the clinic REC-3565*: MALT1 Inhibitor A precision designed selective MALT1 inhibitor for B-Cell Malignancies
Key Preclinical Data Assay DC Criteria Ph 1 large pharma Ph1 biotech REC-3565 MALT1 IC50 (nM) <100 OCI-Ly3 proliferation IC50 (nM) <400 UGT1A1 IC50 (µM) >10 Caco-2 A2B (efflux) 10⁻⁶ cm/s >5 (<3) REC-3565 has Best-in-Class potential1 Single-agent and synergistic activity in vivo2 • OCI-Ly10 and Rec-1 cells are sensitive to both MALT1i and zanubrutinib in vitro • Administration of REC-3565 as a single agent showed tumor growth regression • Durable tumor growth regression observed when REC-3565 was combined with zanubrutinib Development Candidate (DC) Criteria: • MALT1 IC50 nM: green <100 nM; yellow >100-<300 nM; red>300 nM • OCI-Ly3 IC50 nM: green <400 nM; yellow >400-<1000 nM; red>1000 nM • UGT1A1 IC50 uM: green >10 uM; yellow <10->1 uM; red<1 uM • Caco-2 A2B (efflux): green >5(<3); yellow >1-<5(>3-<10); red <1(>10) 45 1. Data on File. 2. Payne et al. ENA, (2024) Meets or exceeds criteria Minor deviation Major deviation CDX Model: OCI-Ly102 70% Of mice in combination arm (REC-3565 + zanu) had no palpable tumors 10-days post last dose REC-3565 (MALT1 inhibitor): Minimal UGT1A1 liability vs competitors and significant tumor regression observed in vivo with Phase 1 initiation anticipated in 1Q25
Development Strategy • N ~30 • R/R B-Cell Malignancies • REC-3565 PO QD or BID RD Part A Monotherapy Phase 1 study design Q1 2025 Primary Endpoint: • Safety / tolerability • RD for combination Phase 1 Dose Escalation 46 Trial Update • Trial initiation expected 1Q25 REC-3565 Competitive Profile • Low predicted human clearance and high oral bioavailability • No unexpected in vitro or in vivo safety concerns identified • Well tolerated in rat/dog dose range finding (DRF) studies • GLP-tox studies completed with suitable no- observed-adverse-effect level (NOAEL) enabling clinical trials REC-3565 (MALT1 inhibitor): Study Design and Next Steps
Program Status • Potential Best-in-Class LSD1 inhibitor • Phase 1 initiation in SCLC expected 1H25 Mechanism of Action • Reversible LSD1 inhibitor that can selectively upregulate NOTCH signaling • Promotes differentiation of neuroendocrine cancer cells • Impairs DNA repair pathways sensitizing SCLC cells to immune checkpoint inhibitors Thesis & Differentiation • LSD1 inhibitor designed to be reversible and brain penetrant • Shorter-predicted half life versus competitors to manage on-target toxicity • Highly selective to reduce off-target toxicity • Preclinical data shows therapeutic exposures have minimal effects on platelets, suggesting potential reduced risk of thrombocytopenia Unmet Need1 • >45,000 patients with treatable Stage III/IV SCLC • Limited treatment options post progression on frontline therapies 47 1. EvaluatePharma Epidemiology 2023 (US and EU5) Recursion Approach • Precision design using active learning to select most information rich compounds • 414 novel compounds synthesized to candidate ID • Used multiparameter optimization to design a unique candidate combining reversibility with CNS penetration REC-4539: LSD1 Inhibitor A precision designed unique LSD1 inhibitor with CNS penetrance
Assay DC Criteria Competitor 1 Competitor 2 REC-4539 Brain: Plasma Ratio >0.5 MDCK-MDR1 Efflux Ratio (Pgp) <2 Predicted Human Half-life QD dosing Key Preclinical Data REC-4539 has Best-in-Class potential1 REC-4539 highly efficacious in SCLC xenograft model2 Development Candidate (DC) Criteria: • Brain:plasma ratio: green >0.5; red <0.5 • MDCK-MDR1 efflux ratio (Pgp): green <2; yellow >2-<10; red >10 • Predicted half-life: green <24 hours; yellow 24-48h hours; red >48 hours 48 1. Data on File. 2. Payne et al. AACR (2023). 3. Data on File Trial Update • Phase 1 First Patient Dosed in SCLC expected 1H25 Meets or exceeds criteria Minor deviation Major deviation • Dose-dependent regression • Well-tolerated with limited impact on platelet levels CDX Model: H14172 Plasma ProGRP3 REC-4539 (LSD1 inhibitor): Sufficient CNS exposures vs competitors and compelling dose-response demonstrated in vivo with Phase 1 initiation anticipated in 1H25
Rare disease PIPELINE
Program Status • First therapeutic candidate advanced to an industry-sponsored Phase 2 trial • Phase 2 primary endpoint of safety met with similar AE profile across arms • Meeting with FDA anticipated in 2H25 to discuss plans for additional clinical study Mechanism of Action • Selective, orally bioavailable, redox-cycling nitroxide • Promotes the metabolism of ROS to reduce oxidative stress within cells • Stabilizes endothelial barrier function Thesis & Differentiation • Develop the first oral therapy for the treatment of symptomatic CCM • Target the underlying genetic mechanisms that drive the disease pathophysiology of CCM Unmet Need1 • ~360,000 symptomatic CCM patients with no approved therapies – ~63,000 patients harboring brainstem lesions and elevated bleeding risk – ~36,000 patients with cavernoma-related epilepsy2,3 50 1. Prevalence for hereditary and sporadic symptomatic population, Internal company estimates. 2. Smith ER. N Engl J Med (2024). 3. Horne MA, et al. Lancet Neuro, (2016). Recursion Approach • Unbiased ML-aided phenotypic drug screen to identify effective therapeutics driving CCM • In vivo POC demonstrated lesion reductions that were also observed in the Ph2 trial REC-994: Superoxide Scavenger A safe and well tolerated superoxide scavenger for the treatment of Cerebral Cavernous Malformation (CCM)
Lesion size (mm2) Key Preclinical Data1 Reduces lesion number & size in Ccm1 and Ccm22 loss of function (LOF) mouse models Identified REC-994 as potential rescue molecule in phenotype associated with CCM2 loss of function Recursion OS Insight 51 1. Gibson et al, Circulation (2015) and Data on File. 2. Data not shown Ccm1 LOF Model REC-994 (Superoxide Scavenger): Preclinical studies showing reduction of lesion burden de-risked the first industry-sponsored Phase 2 study in CCM
52 Trial Update • Randomized, double-blind, placebo-controlled Phase 2 study • Primary endpoint of safety and tolerability met September 2024 • Encouraging trends observed in objective MRI-based exploratory efficacy measures observed • Time- and dose-dependent trends in reduced lesion volume and hemosiderin ring size compared to placebo • 80% of Phase 2 study participants remain on the long-term extension phase of the study Next Steps • Meeting with FDA to define regulatory path and Phase 2/3 study under development • Data to be presented at a late breaking oral abstract session at the International Stroke Conference on Feb 5, 2025 SYCAMORE – CCM: Part 1: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Two Doses of REC-994; Part 2: A Long-Term Blinded Extension Clinical Trial to Evaluate Long-Term Safety Tolerability and Efficacy of REC-994 REC-994 (Superoxide Scavenger): Topline Phase 2 data in September demonstrated encouraging signals of efficacy
Program Status • First-in-Disease and best-in-class potential for the treatment of FAP • Phase 1b safety and futility analysis (polyp burden) anticipated in 1H25 Mechanism of Action • Loss of APC drives FAP disease progression through aberrant MAPK signaling • REC-4881 is a highly potent, non-competitive, allosteric MEK1 and MEK2 inhibitor • Selectively blocks the activation of ERK (MAPK pathway) Thesis & Differentiation • Develop the first oral therapy for the treatment of FAP • Target underlying genetic mechanisms that drive the FAP disease progression • Preferential distribution to GI tissues vs competitors which may enable greater activity at lower doses Unmet Need1 • No approved systemic therapies and significant unmet need for ~50,000 FAP patients beyond colectomy – Includes ~7,0002 advanced duodenal polyposis patients in the US at high-risk of developing cancer 53 1. US + EU5 diagnosed prevalence of FAP (adult and pediatric), Internal company estimates. 2. US addressable patients ≥ 55 years old. Recursion Approach • Unbiased ML-aided phenotypic drug screen in human cancer cells • Validated findings in vivo demonstrating significant reductions in polyps and adenomas REC-4881: MEK1/2 Inhibitor A highly selective and potent MEK1/2 inhibitor for chemoprevention of Familial Adenomatous Polyposis (FAP)
Key Preclinical Data1 REC-4881 decreases polyp count and pre-cancerous adenomas • Significantly reduces polyp count at all dose levels, outperforming celecoxib in APCmin/- mouse • Unlike celecoxib, REC-4881 reduces both polyp numbers and % of adenomas • Meaningful efficacy seen at lowest dose tested (1mg/kg) – suggests potential for therapeutic activity at reduced systemic exposures Recursion OS Insight S id e E ff e c t S c o r e 30 25 20 15 10 0 0.5 1.0 1.5 Disease Score REC-4881 0.3 µM Healthy Cells Disease State • AI/ML extracts morphological features to distinguish “diseased” vs. “healthy” states • Compounds co-treated with APC siRNA for 24 hours to find hits that reverse disease state back to healthy in a concentration-dependent manner REC-4881 suppresses disease-inducing effects of APC mutations 54 1. Data on File Mean Polyps Per Group % Pre-Cancerous Polyps REC-4881 (MEK1/2 Inhibitor): Highly selective and potent molecule demonstrated superior in vivo efficacy versus celecoxib
Phase 2 Dose Expansion (N=30) REC-4881 Phase 1b Dose Escalation (N≤18) RP2D • Confirmed APC mutation • ≥ 55 years old • Post-colectomy/proctocolectomy • No cancer present • Polyps in upper and lower GI 4mg 8mg 12mg Study Objectives: • Identify RP2D • Safety/tolerability • Reduction in polyp burden at week 12 Development Strategy Phase 1b/2 study design 55 TUPELO-FAP: Evaluate The Efficacy, Safety, Pharmacokinetics, And Pharmacodynamics Of REC-4881 in Patients With Familial Adenomatous Polyposis (FAP) Trial Update • Futility – reduction in polyp burden; assessed after 10 evaluable patients at the RP2D • Ph 1b/2 safety & early efficacy data – 1H25 REC-4881 Competitive Profile • Early PD data indicates 4 mg dose is pharmacologically active and well-tolerated • Fast Track Designation in FAP granted by FDA in 2022 • ODD in US and EU Key Eligibility REC-4881 (MEK1/2 Inhibitor): Study Design and Next Steps
Program Status • Potential first-in-class and best-in-class ENPP1 inhibitor for the treatment of patients with HPP • IND enabling studies expected to initiate in 2025 Mechanism of Action • Potent ENPP1 inhibitor is a non-immunogenic small molecule that restores PPi balance • Highly selective ENPP1 inhibitor with low nM potency Thesis & Differentiation • ENPP1 inhibition is a genetically validated target in HPP models • Potential for first oral disease-modifying therapy (compared to multiple weekly injections) without dose-limiting adverse events • Non-immunogenic small molecule approach offering potentially safer solution than enzyme replacement therapy (ERT) • REV102 offers a more tolerable and affordable option to ERTs Unmet Need1 • ~7,800 diagnosed prevalence of HPP across US and EU5 • Many patients, particularly adults, may have difficulty accessing ERT • Those who can access ERT face high treatment burden and tolerability hurdles • Opportunity to significantly reduce costs and treatment burden 56 1. HPP prevalence at birth. Mornet et al, 2020. 2. Joint Venture with Rallybio Recursion Approach2 • Precision designed for both high potency and a lifetime of chronic dosing • Structurally distinct differences vs competitor ENPP1 inhibitors • Maintain selectivity and deliver a candidate with high oral bioavailability in the clinic REV102: ENPP1 Inhibitor A safe and highly selective ENPP1 inhibitor for hypophosphatasia (HPP)
57 Data is for REV101 (1st gen tool compound); compound being developed is REV102 L3 Vertebrate (n=5, females) Distal Femur (n=5, males) Significant market opportunity addressing the unmet need across patient subtypes T o d a y Severe form Moderate- and mild form Potential for REV102 ENPP1i to become standard-of-care for juvenile-onset HPP patients and expand the market significantly with improved diagnosis Perinatal/ Infantile Onset (10%) Mild form 82.5% Add REV102 to TNSALP replacement for perinatal / infantile onset and other highly symptomatic patients Diagnosed juvenile-onset patients not actively treated (72%) REV102 Addressable Patient Opportunity Highly sympto- matic Juvenile Onset (18%) ENPP1i monotherapy candidates: 72% ENPP1 + TNSALP replacement combination candidates: 28% w / E N P P 1 i Diagnosed Prevalence of ~2.2k Diagnosed Prevalence of ~5.6k Potential Monotherapy Candidates with prevalence of up to 1/508 Undiagnosed population with non- specific symptoms What’s Next • Initiate IND-enabling studies in 2025 Market Opportunity1 Bone morphometry 2D analysis of trabecular bones Key Preclinical Data2 PPi lowered by ~30% in adult HPP mice when treated with REV101 Plasma levels of PPi After 100-day dosing WT Mouse Model Adult-onset HPP model REV101-TreatedControlControl REV101-TreatedWildtypeControl REV101-TreatedWildtype Estimated diagnosed prevalence hypophosphatasia patients in US 1. EvaluatePharma and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868366/, https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-019-2420-8, Trinity Market Research 2021. 2. Narisawa et al. ASBMR (2024) REV102 (ENPP1 Inhibitor): OS insights validated using in vivo mouse model showing significant difference in restoring HPP biomarker that promotes bone mineralization
Program Status • Potential first-in-disease and best-in-class therapy for NF2 mutant meningioma • Data maturing with PFS6 results expected 1H25 Mechanism of Action • Orally bioavailable, CNS penetrant, and potent pan-HDAC inhibitor • Loss of Merlin (NF2) leads to PI3K signaling and meningioma proliferation REC-2282 indirectly facilitates AKT dephosphorylation by disrupting the PP1-HDAC interaction Thesis & Differentiation • Develop the first therapeutic for NF2 meningioma • Highly selective molecule with favorable brain exposure and reduced risk of cardiac toxicity Unmet Need1 • No approved therapy for ~33,000 NF2 meningioma patients beyond surgery • Surgery only feasible in a limited number of patients and carries high rate of recurrence2 58 1. US + EU5 treatable incidence for all NF2-driven meningiomas. 2. Rogers et al. J Neurosurg, (2015) Recursion Approach • Unbiased ML-aided phenomap insight and drug screen in human cells • Identify effective therapeutics that rescue disease-inducing effects of NF2 loss REC-2282: Pan-HDAC Inhibitor CNS-penetrating pan-HDAC inhibitor for the first oral therapeutic to treat Neurofibromatosis Type 2 (NF2)
REC-2282 S id e E ff e c t S c o r e Disease Score 0 1.0 30 25 35 20 15 10 5 Disease State Healthy Cells + REC-2282 (months) + Normal diet (months) Recursion OS Insight Key Preclinical Data1 59 1. Data on File Prevents growth & regrowth of NF2-deficient meningioma model in mice REC-2282 demonstrates concentration-dependent reversal of NF2 loss REC-2282 (Pan-HDAC Inhibitor): Identified as a unique HDAC inhibitor in Recursion's unbiased screen modeling NF2 loss-of-function
Primary Endpoint: • PFS6 Secondary Endpoint: • Safety, ORR REC-2282 Phase 2 Portion Open-label, 2-arm study 24 Patients Allocated 1:1 40 mg 60 mg • MRI-confirmed progressive meningioma • Sporadic meningioma with confirmed NF2 mutation • Familial NF2 meningioma • Have documented progression with past 24 months 60 POPLAR-NF2: Efficacy and Safety of REC-2282 in Patients With Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas Development Strategy Phase 2/3 study design Trial Update • Phase 2 Data maturing • Futility analysis (PFS6) expected in 1H25 REC-2282 Competitive Profile • Orally bioavailable and CNS penetrant • Fast Track Designation in NF2 granted by FDA in 2021 • ODD in US and EU Key Eligibility REC-2282 (Pan-HDAC Inhibitor): Study Design and Next Steps
Other areas of high unmet need PIPELINE
Program Status • First-in-class therapy for prevention rCDI • First patient dosed in the Phase 2 ALDER trial in 4Q24 • Phase 2 update expected in 1Q26 Mechanism of Action • Highly potent, orally bioavailable C. diff toxin B (TcdB) selective inhibitor • Selectively inhibits catalytic activity of bacterial glucosyltransferase Thesis & Differentiation • Develop the first non-antibiotic oral therapy that is safe and convenient • Selectively targets bacterial toxin while sparing the host to minimize adverse events • Preclinical efficacy demonstrates superiority in survival versus bezlotoxumab Unmet Need1 • ~175,000 cases of rCDI with limited treatment options for high-risk population • Ability to address populations not eligible for FMT or microbiome-based therapies 62 Recursion Approach • Unbiased ML-aided conditional phenotypic drug screen in human cells • Identified novel mechanisms that mitigated the effect of C. diff. toxin B treatment 1. Incidence of addressable US cases of recurrent CDI, Shields et al., Anaerobe (2016) REC-3964: C. difficile Toxin B Selective Inhibitor Non-antibiotic selective toxin-inhibitor for the prevention of recurrent C. difficile infection (rCDI)
Recursion OS Insight Key Preclinical Data1 63 1. N=10 hamsters per group. C. difficile strain 630, Data on File REC-3964 significantly extended survival vs. bezlotoxumab alone at the end of treatment (p<0.001, log rank test) REC-3964 potently inhibits Toxin B with some activity against Toxin A, while bezlotoxumab is specific to Toxin B Healthy Control C. diff toxin B phenotype REC-3964 (CDI TcdB Inhibitor): Identified as potential superior inhibitor compared to SOC in in vitro and in vivo preclinical studies
Primary Endpoint: • Rate of recurrence Secondary Endpoint: • Additional efficacy measures • Safety / tolerability • PK REC-3964 Phase 2 Open-label, 2-arm study • High-risk of CDI • ≥3 bowel movements in 24 hours • Confirm CDI using EIA (toxin) • No fulminant CDI • No history of chronic diarrheal illness due to other causes REC-3964 250 mg orally BID REC-3964 500 mg orally BID Observational R 2:1:1 N=80 Patients with confirmed CDI Vancomycin Orally for 14 days Patients with symptom resolution 64 Development Strategy Phase 2 study design Trial Update • First Patient Dosed in 4Q24 • Program update expected 1Q26 REC-3964 Competitive Profile • Highly potent, orally bioavailable • Potential first-in-class therapy for prevention of rCDI • First non-antibiotic oral therapy Key Eligibility REC-3964 (CDI TcdB Inhibitor): Study Design and Next Steps
Program Status • First-in-class therapeutic for treatment of IPF • IND enabling studies ongoing Mechanism of Action • Reversible, orally bioavailable, and potent Target Epsilon inhibitor • Promotes tissue repair and reverses fibrosis by potentially modulating TGF-ß Thesis & Differentiation • Develop a novel preferred treatment option that is safe and well-tolerated • In vitro models suggest capability of reversing the fibrotic process driving IPF progression Unmet Need1 • ~130,000 patients with IPF in the US • Approved therapies show modest slowing of IPF progression • No improvement in survival (mOS 3-5 years) or quality of life with current treatments 65 Recursion Approach • Unbiased ML-powered phenomap drug screen in human cells • Identify novel mechanisms that reversed the differentiation of fibrocytes 1. Global Data, Internal company estimates on IPF prevalence, Collard et al., Chest (2014) REC-4209: Target Epsilon Highly potent and potential First-in-Class medicine for the treatment of Idiopathic Pulmonary Fibrosis (IPF)
Recursion OS Insights1 • REC-4209 at low doses reduces total lung collagen by 45% to 60% versus vehicle mice Control Vehicle 0.03 0.1 0.3 0 1,000 2,000 3,000 4,000 5,000 Total Lung Collagen Lu n g O H P ( u g/ lu n g)Disease State (Fibrocytes) Control State (Pentraxin-2) Normal Lung + REC-4209 Fibrotic Lung IC50 = 104nM Key Preclinical Data2 66 1. Data on File 2. Groups (n=10 per group; n=6 in control) compared against Vehicle. ****p<0.0001; one-way ANOVA with Tukey’s multiple comparison test. Data reflects mean ± 95% CI REC-4209 mg/kg (PO, BID) + Bleomycin What’s Next • IND-enabling studies ongoing **** In Vitro Fibrocyte Rescue Assay REC-4209 (Target Epsilon): Identified as a novel mechanism in Recursion's screen with compelling preclinical efficacy demonstrated in bleomycin lung fibrosis mouse model
Partnerships & Data Strategy Details APPENDIX
68 Trademarks are the property of their respective owners and used for informational purposes only. • Up to or exceeding $300M in possible program milestones for up to 40 programs • One program and one map already optioned • Mid- to high-single digit tiered royalties on net sales • $30M upfront and $50M equity investment • Increased per program milestones which may be up to $1.5B in aggregate for up to 7 oncology programs • Low- to mid-single digit royalties on net sales • Recursion owns all algorithmic improvements • First beta-user of LOWE • $100M upfront with the potential of $5.2B in total milestones plus high-single digit to mid-teen tiered royalties • Up to 15 novel small molecule candidates across oncology and immunology • New discovery stage program added identified and initially advanced by Exscientia in Dec. 2023 • 3 programs advanced through initial milestones • $20M upfront at initiation for three projects with up to $674M in discovery, development, regulatory and sales-based milestones • Mid-single to low-double digit tiered royalties Announced Dec. 2021 Announced Jan. 2022 Announced Sept. 2023 Announced Sept. 2020 Updated Nov. 2023 Exciting scientific collaborations span biopharma, tech & data Therapeutic discovery partnerships
Computation and ML/AI Real-world data access 69 Trademarks are the property of their respective owners and used for informational purposes only. • $50M equity investment • Partnership on advanced computation (e.g., foundation model development) • Priority access to compute hardware or DGXCloud Resources • BioHive-2: helped design and build next generation supercomputer • Includes exploring generative AI capabilities (including Gemini models) and driving improved search and access with BigQuery • Scaled compute resources, improved management of petabytes of RX data, and continued data privacy and security support • OpenPhenom S/16 model available on Google Cloud • Preferential access to >20 PBs of real-world, multi- modal oncology data, including DNA & RNA sequencing and clinical outcome data for >100,000 patients • Ability to train causal AI models with utility in target discovery, biomarker development & patient selection • Opportunity to accelerate clinical trial enrollment through broad clinical network • Access to hundreds of thousands of de-identified records, including Helix’s Exome+(R) genomics & longitudinal health data, to train causal AI models and design biomarker & patient stratification strategies across broad disease areas • Utilizes Recursion’s predicted protein-ligand interactions for ~36B compounds from Enamine’s REAL Library • Aim to generate enriched screening libraries & co- brand customer offerings Cheminformatics and chemical synthesis Announced July 2023 Announced Oct. 2024 Announced Nov. 2023 Announced May 2024 Announced Dec. 2023 Exciting scientific collaborations span biopharma, tech & data Platform, technology, and data partnerships
