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 25, 2023
(Exact name of registrant as specified in its charter)
| (State or other jurisdiction of incorporation) | (Commission File Number) | (I.R.S. Employer Identification No.) | ||||||||||||
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(385 ) 269 - 0203
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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 8.01. Other Events.
On January 25, 2023, Recursion Pharmaceuticals, Inc. released an updated investor presentation. The investor presentation will be used at its Download Day presentation and from time to time in meetings with investors. A copy of the presentation is attached hereto as Exhibit 99.1.
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 25, 2023.
| RECURSION PHARMACEUTICALS, INC. | ||||||||
| By: | /s/ Christopher Gibson | |||||||
Christopher Gibson | ||||||||
Chief Executive Officer | ||||||||
Breakfast (8:30 – 9:30 AM) Welcome Tina Larson, President & COO R. Martin Chavez PhD, Chairman State of Recursion Chris Gibson PhD, Co-Founder & CEO Recursion OS Imran Haque PhD, VP of Data Science Lina Nilsson PhD, VP of Product Pre-Clinical Opportunities Laura Schaevitz PhD, SVP and Head of Research Tours & Demos Ben Mabey, Chief Technology Officer Lunch (12:00 – 1:00 PM) Welcome Back Heather Kirkby, Chief People Officer Dean Li MD PhD, Co-founder and Board Member Clinical Programs Shafique Virani MD, Chief Business Officer and Interim Chief Medical Officer Partnerships Matt Kinn, SVP of Business Development Financials & Potential Milestones Michael Secora PhD, Chief Financial Officer Closing Chris Gibson PhD, Co-Founder & CEO Zavain Dar, Board Member Reception, Tours & Demos (3:30 – 4:30 PM)
Welcome Remarks Tina M. Larson President and COO of Recursion Download Day 2023
Welcome Remarks R. Martin Chavez PhD Chairperson of Recursion Download Day 2023
Download Day 2023 State of Recursion Chris Gibson PhD Co-Founder / CEO
This presentation and any accompanying discussion and documents contain information that includes or is based upon "forward-looking statements" within the meaning of the Securities Litigation Reform Act of 1995. These forward-looking statements are based on our current expectations, estimates and projections about our industry and our company, management's beliefs and certain assumptions we have made. The words “plan,” “anticipate,” “believe,” “continue,” “estimate,” “expect,” “intend,” “may,” “will” and similar expressions are intended to identify forward-looking statements. Forward-looking statements made in this presentation include statements about Recursion's use of the proceeds from its private placement, the initiation, timing, progress, results, and cost of our research and development programs and our current and future preclinical and clinical studies, the potential size of the market opportunity for our drug candidates, our ability to identify viable new drug candidates for clinical development and the accelerating rate at which we expect to identify such candidates, our expectation that the assets that will drive the most value for us are those that we will identify in the future using our datasets and tools, and many others. Forward-looking statements made in this presentation are neither historical facts nor assurances of future performance, are subject to significant risks and uncertainties, and may not occur as actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. For a discussion of factors that could affect our business, please refer to the "Risk Factors" sections in our filings with the U.S. Securities and Exchange Commission, including our most recent Quarterly Report on Form 10-Q and our Annual Report on Form 10-K. This presentation does not purport to contain all the information that may be required to make a full analysis of the subject matter. We undertake no obligation to correct or update any forward- looking statements, 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. Any non-Recursion logos or trademarks included herein are the property of the owners thereof and are used for reference purposes only. 6
7 0.1 1 10 20201962 1970 1980 1990 2000 2010 NMEs per $B spent (inflation adjusted) Eroom’s Law: Drug discovery is becoming slower and more expensive over time Recursion Founded Adapted from Scannell et al and Our World in Data
8 0.1 1 10 50B 100M 500K 1K 20201962 1970 1980 1990 2000 2010 Compute Power (Transistors per Microprocessor)NMEs per $B spent (inflation adjusted) Moore’s Law: Computing power becomes faster and less expensive over time Eroom’s Law: Drug discovery is becoming slower and more expensive over time Adapted from Scannell et al and Our World in Data Recursion Founded
9Adapted from Scannell et al and Our World in Data 0.1 1 10 50B 100M 500K 1K 20201962 1970 1980 1990 2000 2010 Compute Power (Transistors per Microprocessor)NMEs per $B spent (inflation adjusted) Moore’s Law: Computing power becomes faster and less expensive over time Eroom’s Law: Drug discovery is becoming slower and more expensive over time Opportunity Recursion Founded
10 Hypothesis 1: In biology, structure suits function; by applying sophisticated analysis techniques to images of human cells, a new scale of biological insight can be unlocked
11 Hypothesis 2: By industrializing a small number of extraordinarily data-rich assays using automation and computation, biology and chemistry can be mapped and navigated, turning drug discovery into an efficient search problem
Machine Learning and Automation 12
Machine Learning and Automation 13
Traditional discovery pipeline Ideal discovery pipeline Broaden the funnel of potential target hypotheses & therapeutic starting points Identify failures earlier in the research cycle when they are relatively inexpensive, to rapidly narrow the neck of the funnel Accelerate delivery of high- potential drug candidates to the clinic 14
Preliminary data shown is the average of all our programs since late 2017. All industry data adapted from Paul, et al. Nature Reviews Drug Discovery. (2010) 9, 203–214 Screen — Hit ID — Validated Lead — Advanced Candidate — Development Candidate — Industry Recursion Failing faster and earlier to › › spend less › Co st to IN D ($ M ) 25 — 20 — 15 — 10 — 5 — 0 — Industry 40 — 30 — 20 — 10 — 0 — › and go faster 100 80 60 51 80% 75% 85% 100 64 25 64% 39% 62% 12 50% St ag e Ti m e to V al id at ed Le ad (m o) Recursion Industry Recursion 8 Industry Recursion 15
Initiated 5 clinical trials in 2022 (3 Ph2, 2 Ph1) • Includes Ph1 FAP study completed by Recursion Novel oncology programs (Target Alpha, Target Gamma) nearing IND-enabling studies Advancing collaborations in Fibrosis (Bayer) and Neuroscience (Roche-Genentech) • $13B in potential milestones across 50+ possible programs plus royalties Planning a 6th clinical trial to initiate (Ph1b/2) We believe that we have built one of the largest proprietary & relatable in-vitro biological and chemical datasets on Earth • >21 petabytes of data and >3 trillion searchable relationships 16
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Strong Financials ~$550M in cash and cash equivalents at the end of 2022 with potential for increased revenue in the near term Pipeline • Guidance on top-line readout for Ph2 CCM program • Guidance on interim Ph2 safety readout for NF2 program • Guidance on Ph1 C diff readout • Trial update on Ph2 FAP program • Guidance on Ph1b/2 AXIN1/APC trial start • Target disclosure for Project Gamma 18 Partnerships • Update on Bayer collaboration including state of partnered pipeline • Update on Roche/Genentech collaboration Platform • Announcement of RXRX3 and MolRec dataset releases
Our Mission: Decode Biology to Radically Improve Lives
Impact
RecursionOS® Lina Nilsson PhD Vice President, Product Download Day 2023 Imran Haque PhD Vice President, Data Science
Platforms drive discovery. Unbiased & target agnostic Literature drives discovery. Informs target-based hypotheses Data are our fuel. Shape our hypotheses Data are an exhaust. Limited to testing hypotheses Virtuous cycles of atoms & bits. Iterative feedback accelerates learning Linear process. Little cross-program learning or iteration Industrialized to scale. Automation & standardization Bespoke processes. Low-dimensional assays & biomarkers 22 Connected data across programs. Relatable high-dimensional data Disparate data generation. Siloed to individual programs and diseases
Machine Learning and Automation 23
Biological Tools Automation Tools Computational Tools 24
25 Proprietary high-dimensional data Biological Tools >500 Billion High-quality neurons produced in-house in 2022 using completely novel techniques. Model and manipulate disease biology
26 Automation Tools >19PB Proprietary high-dimensional data Create scalable, repeatable and reliable laboratory processes 2.2 Million Wet-lab experiments per week Up to
Computational Tools Extract, organize and analyze highly structured data >21 Petabytes Proprietary high-dimensional data
28Image adapted from D’Orazio, M., et al. Nature Scientific Reports 2022. RNA Level Transcriptomics DNA Level (Population-Scale) Genomics Protein Level Proteomics Metabolates Level Metabolomics Organism Level Invivomics Cell Level Phenotypes Phenomics Built and scaled AspirationalExploratory
Maps of Biology & Chemistry Imran Haque Vice President, Data Science Download Day 2023
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35 Traditional target-based screens A single target 1 million compounds
36 1 million compounds The entire genome
Machine Learning and Automation 37
Model diseases with diverse biological and chemical tools Detect and analyze subtle changes using ML algorithms Combine datasets to reveal known & novel relationships in our Maps of Biology Capture holistic and high-dimensional snapshots of cellular states 38
Multiple high-dimensional datasets validate and expand the total biological understanding of the disease model and hits 39
40 Relationships revealed in our maps become ‘hits’ for potential programs 1 Up to Transcriptome profiles every week Transcriptomic assays validate a hypothesis with additional high-dimensional, unbiased data 2 Detects more relationships between disease-relevant genes and each compound 3 Disease component gene set 1 Di se as e co m po ne nt g en e se t 2 Internal Myotonic Dystrophy Program
Digital animal studies build high- dimensional signatures of animal behavior and health 41
42 Traditional Animal Studies Recursion’s Digital Animal Studies
an im al Gr ou p 1 Gr ou p 2 Gr ou p 3 Time 43 • Limited data generation • Low-dimensional assays • Influenced by human intervention • Time-consuming • Expensive Traditional Animal Studies Recursion’s Digital Animal Studies • Continuous data generation • High-dimensional assays • Unbiased • Faster • Cost-effective
44 ~2 months Real-time <1 week 1 year 1 week 6-8 weeks Recursion Disease Induction Liability InVivomics Digital Tolerability
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46 Our approach will improve the efficiency of the DMTA chemistry cycle, reducing the number of cycles, shrinking the time required, and increasing throughput for each cycle. The Impact: Reduce time to candidate selection from months to weeks Make Test Design Analyze Automated Microsynthesis Automated DMPK Testing Facility Digital Chemistry Platform Digital Chemistry Platform
47 Digital Chemistry Platform Design Multi-objective generative chemistry MOGFNs outperform other benchmarked algorithms in numerous multi-objective settings in chemistry. rxrx.ai/neurips-2022 Multi-Objective GFlowNets
48 Foundation models for low-data prediction MolE achieves #1 or #2 performance on 14 of 22 Therapeutics Data Commons ADMET tasks, including all distribution and metabolism tasks, and #1 in 9 of 22. rxrx.ai/neurips-2022 Analyze Digital Chemistry Platform MolE: a molecular foundation model for drug discovery
49 Test Automated DMPK Testing Facility Automated DMPK Testing Recursion proprietary DMPK module designed to test up to 500 compounds / week on three critical DMPK assays, to drive programs and fuel machine learning.
50 Automated Microsynthesis MakeRobotic Synthesis Automation of chemical synthesis will enable broader SAR and faster turnaround time for active learning cycles.
Scalable Reliable Relatable 51
Pre-clinical Opportunities Laura Schaevitz PhD Senior Vice President, Head of Research Download Day 2023
53 Human Genes Hu m an G en es
… Challenging biology Patient genetics Complex genetic screens … Complex datasets Undruggable targets Recovery of function 54
Target Alpha: Potential first-in-class NCE with novel MOA to enhance anti-PD-(L)1 response
1. Cancer.gov 2. Haslam, A.; et al. JAMA Netw Open. 2019, 2, e192535. 2. Valentin,J.; et al. Journal of Oncology, Volume 2021, Article ID 5524685. 3. Ghisoni,E.; et al. European Journal of Cancer 149, 2021, 153; 4. Evaluate Pharma 1.9M US patients diagnosed with cancer in 20221 Recursion’s Goal Pre-clinical: Target α Minimize peripheral inflammatory side effects High proportion of treatment-limiting IRAE (Ex: 46%-melanoma3) No response in 88% of patients 44% eligible for checkpoint immunotherapy2 (2022 est. spend: $48 Billion4) Increase immune clearance of tumors 56
1 Manguso et al., 2017, Lawson et al., 2020 Evaluation of 110 sensitization and resistance markers from public pooled CRISPR screens1 in the Recursion Map Identification of novel dual-targeting checkpoint modifier Pre-clinical: Target α BIRC2 BIRC2 family Gene A Gene A inhibitor (250 nM) Gene A Gene B Identification of an unexpected, druggable gene similar to BIRC2 New target identified for annotated Gene A inhibitor 1 2 3 Monitor local immune engagement: Show immune-based clearance and associated cytokines Measure peripheral inflammation: Show reduced inflammatory risk 57
Potentiation of immunotherapy Immunological memory Pre-clinical: Target α In vivo response: tumor clearance1.9M US patients diagnosed with cancer in 20221 High proportion of treatment-limiting IRAE (Ex: 46%-melanoma3) No response in 88% of patients 44% eligible for checkpoint immunotherapy2 (2022 est. spend: $48 Billion4) 581. Cancer.gov 2. Haslam, A.; et al. JAMA Netw Open. 2019, 2, e192535. 2. Valentin,J.; et al. Journal of Oncology, Volume 2021, Article ID 5524685. 3. Ghisoni,E.; et al. European Journal of Cancer 149, 2021, 153; 4. Evaluate Pharma
Pre-clinical: Target α Total CD45+ M2 Macrophages LAG3+ CD8 In vivo response: tumor clearance1.9M US patients diagnosed with cancer in 20221 High proportion of treatment-limiting IRAE (Ex: 46%-melanoma3) No response in 88% of patients 44% eligible for checkpoint immunotherapy2 (2022 est. spend: $48 Billion4) 591. Cancer.gov 2. Haslam, A.; et al. JAMA Netw Open. 2019, 2, e192535. 2. Valentin,J.; et al. Journal of Oncology, Volume 2021, Article ID 5524685. 3. Ghisoni,E.; et al. European Journal of Cancer 149, 2021, 153; 4. Evaluate Pharma
Pre-clinical: Target α IFN-ɣCXCL10 In vivo response: cytokine 1.9M US patients diagnosed with cancer in 20221 High proportion of treatment-limiting IRAE (Ex: 46%-melanoma3) No response in 88% of patients 44% eligible for checkpoint immunotherapy2 (2022 est. spend: $48 Billion4) 601. Cancer.gov 2. Haslam, A.; et al. JAMA Netw Open. 2019, 2, e192535. 2. Valentin,J.; et al. Journal of Oncology, Volume 2021, Article ID 5524685. 3. Ghisoni,E.; et al. European Journal of Cancer 149, 2021, 153; 4. Evaluate Pharma
1. Cancer.gov 2. Haslam, A.; et al. JAMA Netw Open. 2019, 2, e192535. 2. Valentin,J.; et al. Journal of Oncology, Volume 2021, Article ID 5524685. 3. Ghisoni,E.; et al. European Journal of Cancer 149, 2021, 153; 4. Evaluate Pharma Pre-clinical: Target α IFN-ɣCXCL10 In vivo response: cytokine 1.9M US patients diagnosed with cancer in 20221 No response in 88% of patients 44% eligible for checkpoint immunotherapy2 (2022 est. spend: $48 Billion4) High proportion of treatment-limiting IRAE (Ex: 46%-melanoma3) 61
Medicinal chemistry efforts deployed to improve potency1 Cellular and biochemical assays show clear SAR2 Phenotype maintained as NCE progress3 Pre-clinical: Target α Core 1 CR O -b as ed u ni va ria te re ad ou ts Target Phenotype Compound 1B Compound 1C Compound 1A Compound 1A Compound 1B Compound 1C Compound 1A Compound 1B Compound 1C 62
Core 2Core 1 Dramatic improvement in cellular activity could easily redirect chemistry efforts Pre-clinical: Target α CR O -b as ed u ni va ria te re ad ou ts Compound 1A Compound 1A Compound 1B Compound 1B Compound 1C Compound 1C Target Phenotype Compound 1B Compound 1C Compound 1A Compound 2B Compound 2B Compound 2A Compound 2A 63
Core 2Core 1 Dramatic improvement in cellular activity could easily redirect chemistry efforts Map-detected a divergent phenotype Pre-clinical: Target α CR O -b as ed u ni va ria te re ad ou ts Compound 1A Compound 1B Compound 1C Compound 2A Compound 2B Target Phenotype Compound 1B Compound 1C Compound 1A Compound 2BCompound 2A Compound 1A Compound 1B Compound 1C Compound 2BCompound 2A 64
Compound 2A Compound 2B Target Phenotype Compound 1B Compound 1C Compound 1A Despite activity in target and cellular assays, the compound series generated a clearly separate phenotype 1 Synthesis efforts immediately realigned on original series core2 New series annotated as CDK9 inhibitor by map inference and confirmed by biochemical assay3 Immediately-deprioritized series CDK9 Compound 2A at multiple concentrations Pre-clinical: Target α 65
Pre-clinical: Target α 66 Unbiased discovery of an exciting dual targeting compound that appears to both enhance anti-PD1 response, while also decreasing peripheral inflammation 1 Recursion OS augmented our medicinal chemistry team enabling efficient optimization efforts on a molecule with essential polypharmacology 2
Target Gamma: Novel CDK12-adjacent target, RBM39, for potentially treating HRD-negative ovarian cancer
Platinum-Sensitive Ovarian Cancer Patients HRD BRCAMUT BRCAWT mPFS (PARP vs. Placebo): 22 mo (HR, 0.40; 95% CI, 0.27-0.62) 20 mo (HR, 0.50; 95% CI, 0.31-0.83) 50% HRP 8 mo (HR, 0.68; 95% CI, 0.49-0.94) 50% 65%35% NCT02655016, N=733 patients with newly diagnosed, advanced ovarian cancer who responded to frontline platinum-based chemotherapy 2:1 to receive niraparib (n = 487) or placebo (n = 246). Niraparib is the only approved PARP in Ovarian cancer patients with HRP disease HRD: Homologous Recombination Repair Deficient HRP: Homologous Recombination Repair Proficient Data from cohort analysis of Phase 3 PRIMA trial for niraparib Pre-clinical: Target γ 68
• CDK12 has been advanced as a target to improve response in the HR-proficient setting • Selective inhibition of CDK12 over other CDKs, especially CDK13, is very challenging • Inhibition of target RBM39 (for example, with REC-65029) may mimic inhibition of CDK12 while mitigating toxicity due to CDK13 inhibition RBM39 CDK12 2.5μM 1.0μM REC-65029 0.1μM 0.25μM CDK13 REC-65029 Pre-clinical: Target γ Similar Opposite 69
Vehicle Olaparib REC-65029 REC-65029 +olaparib Increase in rate to CR, durability in combinationTumor volume Pre-clinical: Target γ Vehicle Olaparib REC-65029 REC-65029 +olaparib OV0273 PDX – REC-65029 dosed at 85 mg/kg PO, BID, olalparib dosed at 90mg/kg PO QD; ** p<0.01 **** p<0.0001 relative to vehicle HR-proficient ovarian cancer PDX 70
Pre-clinical: Target γ REC-0065029 is tolerated at an efficacious dose 1 Digital tolerability uncovers safety concern for REC- 1170204 at an efficacious dose 2 REC-1321245 demonstrates improved tolerability at efficacious doses 3 71
72 Target Alpha and Gamma reaching IND-enabling studies in 2023 Continuing to augment our digital chemistry and predictive capabilities (property assessment, DMPK, ADMET, etc.) Continuing to drive potential first-in-disease or first-in-class programs at greater automation and scale Pre-clinical 72
RxRx3 Dataset & MolRec Application Ben Mabey Chief Technology Officer Download Day 2023
RxRx3: Phenomics Map of Biology • Spans CRISPR knockouts of most of the human genome, ~17k genes • 1,600 FDA approved and commercially available bioactive compounds at 8 concentrations and tens of thousands of control images • 2.2 million images and deep learning embeddings of HUVEC cells, over 100TB • Recursion’s 5th major public dataset release, • 100 times larger than our previous datasets combined 74
75 Compound-specific data viewable in MolRec ™ ADMET & More >250K Transcriptomics Experiments InVivomics Video Data Phenomics Data Spanning 175 million Experiments and 48 Human Cell Types RxRx3
MolRec™ is a simplified version of one of Recursion’s internal compound intelligence tools • A demo/freemium app to illustrate what can be done with this data. This is not our flagship internal Map App. • We are providing this tool for basic exploration of compound/compound and compound/gene relationships across ~1,600 FDA approved and commercially available bioactive compounds • All plots and driven by this single dataset highlighting the power and flexibility of our phenomics-based platform 76
The majority of the genes (~16k) are anonymized / blinded to facilitate a "sneak peek" 77
• Offer a glimpse of the power of Recursion’s internal data and tools to pique the interest of potential partners • Provide the largest dataset of its kind to date to enrich the field and foster the next generation of computational biologists • Discover new methods and bright talent that we can bring in house 79
Clinical Programs Shafique Virani MD Chief Business Officer & Interim Chief Medical Officer Download Day 2023
Partnership strategy Discovery Partnerships Partner in complex therapeutic areas requiring large financial commitment and competitive market dynamics Leverage partner knowledge and clinical development capabilities 81 Fibrosis Other large, intractable areas of biology Neuroscience *and a single oncology indication Internal Pipeline - Rare Genetic Diseases Internal Pipeline Build wholly-owned pipeline in indications with potential for accelerated path to approval Pipeline strategy Precision Oncology Rare Disease
PreclinicalLate Discovery Oncology Rare & Other All populations defined above are US and EU5 incidence unless otherwise noted. EU5 is defined as France, Germany, Italy, Spain and UK. (1) Our program has the potential to address a number of indications driven by MYC alterations, totalling 54,000 patients in the US and EU5 annually. We have not finalized a target product profile for a specific indication. (2) Our program has the potential to address a number of indications in this space. (3) Prevalence for hereditary and sporadic symptomatic population. (4) Annual US and EU5 incidence for all NF2-driven meningiomas. Therapeutic Area Indication AXIN1/APC MUTANT CANCERS (AXIN1/APC mutant cancers; est. 32K) CANCER IMMUNOTHERAPY TARGET BETA (Multiple; 15K2) MYC-DRIVEN ONCOLOGY (MYC; est. 54K1) HR-PROFICIENT OVARIAN CANCER TARGET GAMMA (HR-proficient ovarian cancer; 13K) FAMILIAL ADENOMATOUS POLYPOSIS (APC; est. 50K) CANCER IMMUNOTHERAPY, TARGET DELTA (Multiple; 88K2) CEREBRAL CAVERNOUS MALFORMATION (CCM; est. 360K3) NEUROFIBROMATOSIS TYPE 2 (NF2; est. 33K4) CLOSTRIDIUM DIFFICILE COLITIS (est. 730K) More than a dozen early discovery and research programs in oncology, neuroscience, inflammation & immunology, and rare disease CANCER IMMUNOTHERAPY TARGET ALPHA (Multiple; 72K2) Phase 1 Phase 2 Phase 3 Partnership Programs MULTIPLE PROGRAMS ADVANCING SIMULTANEOUSLY 82 82
REC-994 for the Treatment of Symptomatic Cerebral Cavernous Malformations (CCM) Target / MOA Superoxide Scavenger Molecule Type Small Molecule Lead Indication(s) Cerebral Cavernous Malformations Status Phase 2 Designation(s) US & EU Orphan Drug Source of Insight Recursion OS
84 • Large unmet need for a novel nonsurgical treatment • Vascular malformations (cavernomas) in the brain and spinal cord • High-risk for hemorrhage creates “ticking time bomb” • Progressive increase in CCM size and number over time in those with familial disease • Debilitating symptoms, including intractable seizure, intracerebral hemorrhage, focal neurological deficits Description “Historically, cavernomas have been managed primarily with observation, surgical resection, and occasionally radiotherapy. However, for a number of reasons, many patients with cavernomas must endure a life with neurologic symptoms” - Ryan Kellogg, MD, Investigator at the University of Virginia 84 Clinical: CCM
85 Non-oncology Orphan Indication Product U.S. + EU5 Prevalence Cerebral cavernous malformation (CCM) REC-994 (Recursion) >1,800,000 (Symptomatic: ~360,000) Idiopathic pulmonary fibrosis (IPF) Esbriet (pirfenidone) >160,000 Cystic fibrosis (CF) VX-669/ VX-445 + Tezacaftor + Ivacaftor - Vertex >55,000 Spinal muscular atrophy (SMA) SPINRAZA (nusinersen) >65,000 Clinical: CCM Source: Angioma Alliance ; Flemming KD, et al . Population-Based Prevalence of Cerebral Cavernous Malformations in Older Adults: Mayo Clinic Study of Aging. JAMA Neurol. 2017 Jul 1;74(7):801-805. doi: 10.1001/jamaneurol.2017.0439. PMID: 28492932; PMCID: PMC5647645 ; Spiegler S, et al Cerebral Cavernous Malformations: An Update on Prevalence, Molecular Genetic Analyses, and Genetic Counselling. Mol Syndromol. 2018 Feb;9(2):60-69. doi: 10.1159/000486292. Epub 2018 Jan 25. PMID: 29593473; PMCID: PMC5836221; Maher T, et al Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir Res. 2021 Jul 7;22(197). Doi: 10.1186/s12931-021-01791-z. PMID: 34233665. DRG 2022 Solutions, Report: Epidemiology, Cystic Fibrosis. CDC: SMA 85
86 Source: Angioma Alliance ; Flemming KD, et al . Population-Based Prevalence of Cerebral Cavernous Malformations in Older Adults: Mayo Clinic Study of Aging. JAMA Neurol. 2017 Jul 1;74(7):801-805. doi: 10.1001/jamaneurol.2017.0439. PMID: 28492932; PMCID: PMC5647645 ; Spiegler S, et al Cerebral Cavernous Malformations: An Update on Prevalence, Molecular Genetic Analyses, and Genetic Counselling. Mol Syndromol. 2018 Feb;9(2):60-69. doi: 10.1159/000486292. Epub 2018 Jan 25. PMID: 29593473; PMCID: PMC5836221. ~360,000 Patient Population – Large and Diagnosable No Approved Medical Therapy • >1 million patients worldwide live with these lesions today • Caused by loss of function mutation in one of three genes: CCM1 (60%), CCM2 (20%), and CCM3 (20%) • Inherited autosomal dominant mutation in 30-40%; or sporadic • US symptomatic population is more than 5 times larger than other rare diseases like Cystic Fibrosis (>31k patients) and Spinal Muscular Atrophy (>33k patients) • No approved drugs for CCM and no other potential therapeutic in industry-sponsored clinical development • Most patients receive no treatment or only symptomatic therapy • Surgical resection or stereotactic radiosurgery not always feasible because of location of lesion and is not curative Julia – living with CCM Clinical: CCM Symptomatic US + EU5 patients 86
87 • Symptoms associated with both increased size of lesions, but also inflammation or activation of lesions within the immunopriviledged environment of the brain • Lesions arise from the capillary bed and are not high-pressure (e.g. the lesion growth is unlikely to be primarily driven by the law of Laplace) • The Recursion Vascular Stability Hypothesis: • Eliminating the lesions may not be required for significant patient benefit • Slowing or halting the growth of the lesions while mitigating lesion leakiness and endothelial cell activation to halt the feed-forward inflammatory reaction may mitigate some symptoms and be beneficial to patients Novel therapeutic approach 87 Clinical: CCM
Clinical: CCM Storkebaum, et al. Cerebrovascular disorders: molecular insights and therapeutic opportunities. Nature Neuroscience, 2011 88
Clinical: CCM Gibson, et al. Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Circulation, 2015 89
Clinical: CCM siCTRL siCCM2 Gibson, et al. Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Circulation, 2015 90
Clinical: CCM Gibson, et al. Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Circulation, 2015 siCTRL siCCM2 siCCM2 + Simvastatin siCCM2 + Cholecalciferol siCCM2 + REC-994 To the human eye, Simvastatin looks like the only potential rescue in this panel. However, we already know that at the doses tested it did not rescue the translational animal model… …but according to a basic machine-learning classifier trained on images, cholecalciferol, REC-994 and other molecules show image-based rescue. 91
92 Source:: Data above from Gibson, et al. Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Circulation, 2015 or Recursion internal data (Ccm1 mouse model) Preclinical Studies: REC-994 reduces lesion burden and ameliorates vascular defects in genetic mouse models of CCM Vascular permeability is a clinically relevant feature of CCM lesions REC-994 stabilizes the integrity of vasculature against challenges to permeability Clinical: CCM Reduces lesion number and size in Ccm1 and Ccm2 LOF mouse models1 Completely rescues acetylcholine-induced vasodilation defect2 Rescues dermal permeability defect in CCM2 mice3 Lesion size (mm2) Ccm1 LOF Model ecKO + REC-994 WT ecKO % V as od ila tio n Acetylcholine [Log M] 92 Lesion size (mm2) Ccm2 LOF Model * * * DMSO control REC-994 Ccm2 WT Ccm2 ecKO De rm al P er m ea bi lit y (A bs or pt io n, A U ) *
Healthy REC-994 ImpactCCM Clinical: CCM • Endothelial cell activation • Smooth muscle proliferation • Leukocyte adhesion • Platelet aggregation By regulating SOD2, CCM1 (KRIT1) & CCM2 suppress: CCM1 or CCM2 loss of function leads to activated endothelium: • Decreased cell-cell junctional integrity and increased monolayer permeability • Impaired vasodilation • Cavernous angioma formation Dosing of REC-994 restores normal function: • Normalized ROS balance • Restores quiescent endothelial cell state • Stabilizes endothelial barrier function Adapted from REC-994 Investigator Brochure 93
REC-994 Phase 1 Studies - well-tolerated with no dose-dependent adverse events in SAD and MAD Clinical: CCM MAD Study Placebo 50 mg 200 mg 400 mg 800 mg Total Number of TEAEs Total Subjects with ≥ one TEAE 5 4 0 0 10 3 4 3 15 4 Severity Mild Moderate Severe 3 1 0 0 0 0 3 0 0 3 0 0 3 1 0 Relationship to Study Drug None Unlikely Possibly Likely Definitely 3 1 0 0 0 0 0 0 0 0 0 1 0 2 0 2 1 0 0 0 1 2 0 1 0 Total Number of SAEs Total Subject with ≥ one TEAE Discontinued Study Drug Due to AE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Source: REC-994 for the Treatment of Symptomatic Cerebral Cavernous Malformation (CCM) Phase 1 SAD and MAD Study Results. Oral Presentation at Alliance to Cure Scientific Meeting. 2022 Nov 17 94
95 Phase 2 trial initiated in Q1 2022 Source: https://www.clinicaltrials.gov/ct2/show/NCT05130866?term=recursion&draw=2&rank=3; https://www.SycamoreCCM.com/ Screening & Randomization 1:1:1 Treatment Follow-up Enroll 60 400mg 200mg Placebo 12 Months Treatment Period Visits: Days 1 & 2 Months 1, 3, 6, 9 & 12 Extension study • Enrollment is progressing • Top-line data expected 2H 2024 Outcome Measures Enrollment Criteria • MRI-confirmed CCM lesion(s) • Familial or sporadic • Symptoms directly related to CCM • Primary: Safety and tolerability • Adverse events & symptoms • Secondary: Efficacy • Clinician-measured outcomes (CGI and PGI) • Imaging of CCM lesions – number, size & rate of change • Impact of acute stroke (mRS, NIHSS) • Patient reported outcomes (SMSS, PROMIS-29, CCM HI, symptom questionnaires) • Exploratory: Biomarkers Trial Update Clinical: CCM 95
REC-2282 for the Treatment of Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas Target / MOA HDAC Inhibitor Molecule Type Small Molecule Lead Indication(s) NF2 Mutated Meningiomas Status Phase 2/3 Designation(s) Fast Track; US and EU Orphan Drug Source of Insight Recursion OS
97 Source: https://rarediseases.org/rare-diseases/neurofibromatosis-2 Patient Population – Large and Diagnosable No Approved Medical Therapy • Rare autosomal dominant tumor syndrome resulting from biallelic inactivation of the NF2 gene which leads to deficiencies in the tumor suppressor protein merlin • NF2 can be inherited or spontaneous (>50% of patients represent new mutations); up to 1/3 are mosaic • CNS manifestations: meningiomas and vestibular schwannomas; mean age at presentation: ~20 years • No approved drugs for NF2 • Surgery is standard of care (when feasible) • Location may make complete resection untenable, leading to hearing loss, facial paralysis, poor balance and visual difficulty Ricki – living with NF2 Clinical: NF2 97
98 • Threatens mortality; if amenable, surgical excision is primary intervention • Many patients have multiple meningiomas that exhibit heterogenous behavior and asynchronous growth • Stasis or shrinkage of tumor could improve prognosis Clinical: NF2 ● Most tumors are benign and slow growing but location in CNS leads to serious morbidity or mortality ● Prognosis is adversely affected by early age at onset, a higher number of meningiomas and having a truncating mutation ~29,500 Patients who have Meningiomas that Harbor NF2 Mutations (Sporadic) ~3,500 NF2 Patients have Meningiomas (Familial) >66,000 Patients have Meningiomas Treatable US + EU5 patients ~33,000 Intracranial Meningioma Source: Pemov, et al. Comparative clinical and genomic analysis of neurofibromatosis type 2-associated cranial and spinal meningiomas. Nature. 2020 Jul 28;10(12563). Doi: https://doi.org/10.1038/s41598-020-69074-z; NORD 98
99 NF2 knockdown cells Healthy Cells REC-2282 REC-2282 identified as rescuing HUVEC cells treated with NF2 Co nt ro l N F2 si RN A HUVEC, human umbilical vein endothelial cells; NF2, neurofibromatosis type 2; siRNA, small interfering RNA. Clinical: NF2 99
100 AKT, protein kinase B; eIF4F, eukaryotic initiation factor 4F; HDAC, histone deacetylase; mTor, mammalian target of rapamycin; mTORC1; mammalian target of rapamycin complex 1; NF2, neurofibromatosis type 2; PI3K, phosphoinositide 3-kinase; PP1, protein phosphate 1; Ras, reticular activating system. Clinical: NF2 Orally Bioavailable, CNS-penetrating, Small Molecule HDAC Inhibitor NF2 encodes for the protein Merlin and negatively regulates mTOR signaling 1 1 2 3 Loss of Merlin leads to increased signaling in the PI3K/AKT/mTOR pathway 2 Oncogenic mTOR signaling arrested with HDAC inhibitors 3 Cell proliferation and survival Normal cell proliferation and survival Cell proliferation and survival Constitutive activation is independent of extracellular factors and does not respond to biochemical signals that would normally regulate activity 100
101 REC-2282 preclinical studies demonstrated clear in-vivo efficacy in multiple NF2 tumor types Shrinks vestibular schwannoma xenografts in nude mice Prevents growth & regrowth of NF2- deficient meningioma model in mice Vehicle % Change tumor vol. REC-2282 % Change tumor vol. % c ha ng e in tu m or v ol um e fr om b as el in e M RI % c ha ng e in tu m or v ol um e fr om b as el in e M RI Clinical: NF2 https://link.springer.com/article/10.1007/s00280-020-04229-3 1 2 0% 10% 30% 60% -20% -40% 20% 40% 50% -10% -30% -50% 0% 10% -20% -40% -10% -30% -50% 101
• Evaluable Patients: CNS Solid Tumors: NF2 N=5; Non-CNS Solid Tumors: N=10 • PFS: CNS solid tumors = 9.1 months; Non-CNS solid tumors = 1.7 months • Best overall response = SD in 8/15 patients (53%; 95% CI 26.6–78.7) • Longest duration of follow-up without progression: > 27 months (N=1) • Most common AEs: cytopenia, fatigue, nausea 0 1 2 3 4 5 6 7 8 9 10 Overall Non-CNS solid tumors CNS solid tumors Months Progression-Free Survival 9.1m 1.7m 3.6m Clinical: NF2 Well understood clinical safety ... Multiple investigator-initiated studies in oncology indications Lengthy human clinical exposure in NF2 – multiple patients on drug for several years Well-characterized side effect profile … with a drug-like profile Established and scalable API manufacturing process Multiple cGMP batches of 10mg and 50mg tablets have been manufactured Excellent long-term stability 102
103 1Sborov DW, et al. A phase 1 trial of the HDAC inhibitor AR-42 in patients with multiple myeloma and T- and B-cell lymphomas. Leuk Lymphoma. 2017 Oct;58(10):2310-2318. 2Collier KA, et al. A phase 1 trial of the histone deacetylase inhibitor AR-42 in patients with neurofibromatosis type 2-associated tumors and advanced solid malignancies. Cancer Chemother Pharmacol. 2021 May;87(5):599-611. 3 Prescribing Information of Vorinostat/Belinostat/Romidepsin respectively Clinical: NF2 REC-2282 Would be First-In-Class HDAC Inhibitor for Treatment of NF2 Meningiomas 103
Phase 2/3 trial initiated in Q2 2022 Outcome Measures Enrollment Criteria • MRI-confirmed progressive meningioma • Either of the below • Sporadic meningioma with confirmed NF2 mutation • Confirmed diagnosis of NF2 disease • Primary: Safety and tolerability • Progression-free survival • Time to progression • Duration of response • Overall response rate https://clinicaltrials.gov/ct2/show/NCT05130866 Clinical: NF2 Interim Analysis Go/No-go to Ph3 PFS Safety/Tolerability PK Enroll 20 40mg 60mg 6 Months Tx Period 20 Months Tx Period Extension Study Cohort A Final Data Screening & Randomization 1:1 Treatment Follow-up Agreement on Phase 3 registration plans FDA Mtg Phase 2 (Cohort A) Enroll 60 Phase 3 (Cohort B) 26 Months Tx Period Extension Study Interim Analysis At 50% of events For Sample size re-estimation (i.e., adaptive design) • Enrollment is progressing • Interim safety analysis expected 2024 Trial Update 104
REC-4881 for the Treatment of Familial Adenomatous Polyposis (FAP) Target / MOA MEK Inhibitor Molecule Type Small Molecule Lead Indication(s) Familial Adenomatous Polyposis Status Phase 2 Designation(s) Fast Track; US and EU Orphan Drug Source of Insight Recursion OS
106 Patient Population – Easily Identifiable Clinical: FAP ~50,000 Diagnosed US + EU5 patients • Autosomal dominant tumor predisposition syndrome caused by a mutation in the APC gene • Classic FAP (germline mutation) : • Hundreds to thousands of polyps in colon and upper GI tract • Extraintestinal manifestations (e.g. desmoid tumors) • 100% likelihood of developing colorectal cancer (CRC) before age 40, if untreated Polyps Found in Colon and Upper GI Tract 106https://www.hopkinsmedicine.org/health/conditions-and-diseases/familial-adenomatous-polyposis
107 No Approved Medical Therapy • Standard of care: colectomy during adolescence (with or without removal of rectum) • Post-colectomy, patients still at significant risk of polyps progressing to GI cancer • Significant decrease in quality-of-life post-colectomy: continued endoscopies and surgical intervention Polyps on mucosal membrane of colon Cross section of colon and rectum Multiple polyps in the colon Sigmoidoscope Scope view Clinical: FAP “Despite progress with surgical management, the need for effective therapies for FAP remains high due to continued risk of tumors post-surgery” - Niloy Jewel Samadder, MD, Mayo Clinic https://www.hopkinsmedicine.org/health/conditions-and-diseases/familial-adenomatous-polyposis 107
108 REC-4881 rescued phenotypic defects of cells with APC knockdown 0.1 µM REC-4881 • Compared to thousands of other molecules tested, REC-4881 rescued phenotypic defects substantially better (including better rescue than other MEK inhibitors) for APC specific knockdown • Findings validated in tumor cell lines and spheroids grown from human epithelial tumor cells with APC mutation • 1,000x more selectivity in tumor cell lines with APC mutation • Inhibited growth and organization of spheroids APC knockdown cellsHealthy Cells Clinical: FAP 108
109 Goitre et al., PLoS ONE, 2010. 3 3 REC-4481 inhibits MEK 1/2 and recovers the destabilization of RAS by the β-Catenin destruction complex, restoring the cell back to a Wnt-off like state 2 1 Orally Bioavailable, Small Molecule MEK Inhibitor Disease State REC-4881 Impact Clinical: FAP 109
110 APC, adenomatosis polyposis coli; ERK, extracellular signal-regulated kinase; FAP, familial adenomatous polyposis. Clinical: FAP ↓ High-Grade Dysplasia 2• In-vivo efficacy in APCmin mouse model • Apcmin = FAP disease model • Mice treated once daily for 8 weeks After 8 weeks of treatment: ↓ Polyp Count1 1 2 To ta l P ol yp C ou nt (+ /- SE M ) H ig h G ra de A de no m as (% ) 110
111 Note: AE, adverse event; MEK, mitogen-activated protein kinase; NHV, normal healthy volunteer; pERK, phosphorylated extracellular signal-regulated kinase; SAE, serious adverse event. REC-4881-101: Single-center, double-blind, placebo- controlled, dose-escalation study in healthy volunteers • Group 1 (n=13): Food effect crossover (REC-4881 4 mg/PBO [fed/fasted]), followed by single dose REC-4881 8 mg/PBO [fed] • Group 2 (n=12): Matched single ascending dose (REC- 4881 4 mg/PBO; REC-4881 8 mg/PBO; REC-4881 12 mg/PBO) Accomplished Clinical: FAP Recursion formulation yields exposures comparable to Takeda No food effect Dose proportional increases in exposure Similar to C20001 study, observed pERK inhibition (i.e. target engagement) at 8 mg and 12 mg doses Acceptable safety profile 111
112 Clinical: FAP Phase 2 trial initiated in Q3 2022 Outcome Measures Enrollment Criteria • Confirmed APC mutation • Post-colectomy/proctocolectomy • No GI cancer present • Polyps in either duodenum (including ampulla of Vater) or rectum/pouch • Primary: • Part 1: PK • Part 2: % Change from Baseline in Polyp Burden • Secondary: • Part 1: Safety & Tolerability • Part 2: PK; PD; Change from Baseline in Polyp Number, Histological grade, disease scoring • Exploratory: • Part 1: PD • Part 2: Time to first occurrence of FAP- related event; Change from baseline in extent of Desmoid Disease Part 2 • Recent protocol amendments aimed at accelerating quality and pace of the trial Trial Update Screening & Randomization 1:1:1:1 Treatment Follow-up Enroll N = 34/arm 4mg 8mg Placebo 6 Months Treatment Period Extension study 12mg *Option to drop an active dose arm after Interim Analysis of the first 16 participants (blinded safety and PK/PD data review only) Part 1 Option to roll into Part 2… Multiple Dose (4mg or PBO) Single Dose (4mg or PBO) Enroll N = 7 (5:2 active/placebo) https://clinicaltrials.gov/ct2/show/NCT05552755 112
REC-4881 for the Treatment of Solid Tumors with AXIN1/APC Mutant Cancers Target / MOA MEK Inhibitor Molecule Type Small Molecule Lead Indication(s) Solid Tumors with AXIN1/APC Mutant Cancers Status Phase 1b/2 Source of Insight Recursion OS
114 • Sustained Wnt signaling is a frequent driver event found across a wide variety of solid tumors • Dysregulation of β-catenin destruction complex due to inactivating mutations in AXIN1/APC leads to sustained Wnt signaling promoting cancer progression and survival1 • AXIN1/APC mutant solid tumors are considered clinically aggressive and resistant to standard treatments 1Bugter, J.M., et al. Nat Rev Cancer, 2021, 21, pp.5-21 Gross morphology of HCC tumor Clinical: AXIN1/APC “Nothing in HCC has immediate therapeutic relevance and the most common mutations are TERT, TP53, and Wnt (CTNNB1/AXIN1/APC) and combined these alterations define almost 80% of patients and are not targetable” - KOL, Clinical Investigator, Texas 114
115 • AXIN1 and APC genes covered by commercially available NGS panels and liquid biopsy detection assays • FDA guidance supports utility of ctDNA as patient selection for the detection of alterations for eligibility criteria and as a stratification factor for trials enrolling marker-positive and marker-negative populations4 • Multiple tumor types will inform study design and patient selection Flexible Patient Selection Strategy and Study Design 1Represents higher of either AXIN1 or APC alteration frequency; obtained from cbioportal.org. 2Represents 2L prevalance estimates; obtained from DRG. 3HCC treatable population includes potential 1L treatment regimen. 4 https://www.fda.gov/media/158072/download Tumor Type Alteration Frequency1 Treatable Population2,3 (US+EU5) LUAD 11% 10,000 HCC 12% 7,600 Prostate 11% 5,600 Bladder 8% 3,700 Esophageal 7% 2,000 Endometrial 12% 1,500 PDAC 2% 1,000 Ovarian 1% 350 TNBC 2% 200 Preclinical data with REC-4881 at clinically relevant exposures in HCC and Ovarian PDX mouse models gives confidence to pursue other mutant cancer types Clinical: AXIN1/APC 115 ~32,000
REC-4881 Dosage Hypothesis: Rescue of AXIN1 may impact tumor progression and/or restore checkpoint sensitivity in cancers driven by AXIN1 loss Recursion Differentiation: REC-4881 rescues tumor suppressor genes APC and AXIN1 • APC and AXIN1 are negative regulators of Wnt signaling • Both proteins form part of the B-catenin destruction complex. Strong clustering suggests map recapitulation of this biology Clinical: AXIN1/APC Heat map from Recursion OS Similar Opposite 116
Note: REC-4881 dosed at 3 mg/kg QD for up to 21 days. 3 mice per treatment per model (3 x 3 x 3) design Efficacy found in In Vivo Mice Models … … Led to Significant Progression Free Survival p = 0.0009 AXIN1/APC mutant p = 0.23 AXIN1 / APC wildtype Clinical: AXIN1/APC Pr ob ab ili ty o f p ro gr es sio n- fr ee (b y tu m or d ou bl in g) Pr ob ab ili ty o f p ro gr es sio n- fr ee (b y tu m or d ou bl in g) 117
118 Finalize design of a Phase 1b/2 biomarker-enriched trial Initiate Phase 1b/2 trial in select tumor types in early 2024 Identify suitable partners for genetic testing capabilities Evaluate REC-4881 in combination with targeted and/or immune modulating agents Clinical: AXIN1/APC 118
REC-3964 for the Treatment of Clostridium Difficile Infection Target / MOA Selective C. diff Toxin Inhibitor Molecule Type Small Molecule Lead Indication(s) Clostridium Difficile Infection Status Phase 1 Source of Insight Recursion OS
120 Disruption of microbiota and colonization of C. diff Release of C. diff toxins Degradation of colon cell junction & toxin transit to bloodstream Clinical: C. diff Source: McCollum, D,, Rodriguez, JM . Detection, Treatment, and Prevention of Clostridium difficile Infection. Clinical Gastroenterology and Hepatology 2012 Mar 19. https://doi.org/10.1016/j.cgh.2012.03.008 120 1 2 3
Source, CDC *NAAT = Nucleic Acid Amplification Test; **rCDI = recurrent CDI • RCDI** occurs in 20-30% of patients treated with standard of care • 40% of those patients will continue to recur with 2+ episodes • >29,000 patients die in the US each year from CDI • Cost burden of up to $4.8bn annually 121 Patient Population – Large, Diagnosable and Easy to Identify Large, Unmet Need with Significant Cost Burden • Symptoms caused by clostridium difficile tissue-damaging toxins released in the colon • Patients who experience >3 unformed stools are diagnosed via NAAT* for toxin gene or positive stool test for toxins • Patients who are at highest risk are those on antibiotics, and frequently visit hospitals or are living in a nursing home • More than 80% of cases occur among patients age 65 or older Clinical: C. diff ~730,000 Diagnosed US + EU5 patients Colleen – lived with rCDI 121
REC-3964 identified as a NCE that demonstrated strong rescue in HUVEC cells treated with C. diff toxin C. diff toxin B phenotype Healthy Control Disease State Healthy Cells REC-3964 0.1 µM Clinical: C. diff 122
Clinical: C. diff The glucosyltransferase locks Rho family GTPases in the inactive state C.diff toxins bind to cell surface receptors and trigger endocytic event 1 Autocatalytic cleavage event releases C.diff toxin's glucoyltransferase enzymatic domain into the cytosol of the infected cell 2 3 3 1 2 Inactivation of Rho GTPases alters cytoskeletal dynamics, induces apoptosis, and impairs barrier function which drives the pathological effects of C.diff infection 4 4 REC-3964 is Recursion’s 1st Small Molecule NCE to Reach the Clinic 123Adapted from Awad et al. 2014
Adapted from Awad et al. 2014 Clinical: C. diff 3 1 2 4 REC-3964 binds and blocks catalytic activity of the toxin’s innate glucosyltransferase, but not the host's 5 5 REC-3964 is Recursion’s 1st Small Molecule NCE to Reach the Clinic 124
REC-3964 restores gut epithelial barrier integrity, which when disrupted causes inflammation and diarrhea REC-3964 rescues barrier integrity with increasing concentrations REC-3964 improved probability of survival in a hamster model of C. difficile infection Improved probability of survival beyond treatment completion Clinical: C. diff Healthy Monolayer (100%) Toxin-Damaged Monolayer (0%) REC-3964 Concentration (Log μM) Re si st an ce (n or m al iz ed % ) 125
126 Phase 1 FIH SAD/MAD Trial initiated in Q3 2022 • Enrollment is progressing • In several SAD cohorts and at least one MD cohort, REC-3964 has been extremely safe and well tolerated • Complete safety and PK data readout expected 2H 2023 Trial Design • Randomized, Double-blind Trial Population • Healthy Subjects • SAD (n = 56) • MAD (n = 50) Primary Objectives Assess the safety & tolerability of SAD and MAD of REC-3964 Evaluate the PK profile of REC-3964 after single and multiple doses Clinical: C. diff Trial Update 126
Download Day 2023 Partnerships Matt Kinn Senior Vice President of Business Development
Partnership strategy Discovery Partnerships Partner in complex therapeutic areas requiring large financial commitment and competitive market dynamics Leverage partner knowledge and clinical development capabilities 128 Fibrosis Other large, intractable areas of biology Neuroscience *and a single oncology indication Internal Pipeline - Rare Genetic Diseases Internal Pipeline Build wholly-owned pipeline in indications with potential for accelerated path to approval Pipeline strategy Oncology Rare Disease
Fibrosis Neuroscience *and a single oncology indication • $30M upfront and $50M equity investment • Up to or exceeding $1.2B in milestones for up to or exceeding 12 programs • Mid single-digit royalties on net sales • Recursion owns all algorithmic improvements • $150M upfront and up to or exceeding $500M in research milestones and data usage options • Up to or exceeding $300M in possible milestones per program for up to 40 programs • Mid to high single-digit tiered royalties on net sales • Recursion owns or co-owns all algorithmic improvements (Announced Sep 2020; Expanded Dec 2021) (Announced Dec 2021) Trademarks are the property of their respective owners and used for informational purposes only. 129
Early DiscoveryScreening Brute Force (commenced 2020) Inferential Search (commenced 2022) Approach Late Discovery Transition to Inferential Search has accelerated new program initiation in 2022 Active Paused / Terminated Pre-programs 131
100% of projects to be sourced from inferential search in 2023 ~100 fibrosis-relevant genes ready for further study >500,000 Phenoprints Mapped 2 PB of data generated 40 million experiments performed 8 Projects initiated; 4 in 2022
Fibrosis Neuroscience *and a single oncology indication • $30M upfront and $50M equity investment • Up to or exceeding $1.2B in milestones for up to or exceeding 12 programs • Mid single-digit royalties on net sales • Recursion owns all algorithmic improvements • $150M upfront and up to or exceeding $500M in research milestones and data usage options • Up to or exceeding $300M in possible milestones per program for up to 40 programs • Mid to high single-digit tiered royalties on net sales • Recursion owns or co-owns all algorithmic improvements (Announced Sep 2020; Expanded Dec 2021) (Announced Dec 2021) Trademarks are the property of their respective owners and used for informational purposes only. 133
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Financials & Milestones Michael Secora PhD Chief Financial Officer Download Day 2023
136 • Cash and cash equivalents • Currently projecting ~$550M at the end of 2022 • Operating costs and expenses • Currently projecting ~$275-295M in 2022 • Based on current operations, we project relatively flat operating costs and expenses in the near term • Revenue • Currently projecting ~$30-45M in 2022 • Potential for increased revenue in the near-term from the following sources: • Potential partnership option exercises • Potential additional partnership(s) • Revenue recognition from existing partnerships Condensed Consolidated Statements of Operations (Unaudited, in thousands) 2022 2021 2022 2021 Revenue Operating revenue $ 13,053 $ 2,500 $ 26,005 $ 7,500 Grant revenue 107 34 162 145 Total revenue $ 13,160 $ 2,534 $ 26,167 $ 7,645 Operating costs and expenses Cost of revenue $ 15,409 - $ 37,435 - Research and development 40,836 33,246 111,716 86,979 General and administrative 19,488 15,690 61,761 38,481 Total operating expenses $ 75,733 $ 48,936 $ 210,912 $ 125,460 Loss from operations ($62,573) ($46,402) ($184,745) ($117,815) Other income (loss), net 2,128 (1,026) 2,761 (3,731) Net loss ($60,445) ($47,428) ($181,984) ($121,546) Three months ended September 30 Nine months ended September 30
Trademarks are the property of their respective owners and used for informational purposes only. 2014 2016 2017 2018 2019 2020 2021 2022 2023 Recursion Founded Series A: $15M Series B: $60M Series C: $122M Series D: $239M $30M Bayer Upfront IPO: $502M $150M Roche/GNE Upfront PIPE: $150M 2015
Advanced degreesEmployees Team Members ~500 43% ESG Highlights Inaugural ESG report in 2022 – reporting on Healthcare and Technology Metrics 100% of electricity powering our Biohive-1 supercomputer comes from renewable sources 43% Female Male 55% 1% Non-Binary Parity Pledge Signer - gender parity and people of color parity Life Sciences –biology, chemistry, development, etc. Technology –data science, software engineering, automation, etc. Strategic Operations Community Impact Committed to ESG Excellence Founding Partner, Life Science Accelerator Founding Member, Life Science Collective 138 Data shown reflective of Q4 2022 and Recursion’s 2022 ESG report
TINA LARSON President & COO Executive Team HEATHER KIRKBY, MBA Chief People Officer BEN MABEY Chief Technology Officer Trademarks are the property of their respective owners and used for informational purposes only. 139 KRISTEN RUSHTON, MBA SVP of Business Operations MICHAEL SECORA, PHD Chief Financial Officer CHRIS GIBSON, PHD Co-Founder & CEO SHAFIQUE VIRANI, MD FRCS Chief Business Officer & Interim CMO NATHAN HATFIELD, JD MBA SVP and Head of Legal LAURA SCHAEVITZ, PHD SVP and Head of Research Board of Directors DEAN LI, MD/PHD Co-Founder of RXRX, President of Merck Research Labs ROB HERSHBERG, MD/PHD Co-Founder/CEO/Chairman of HilleVax, Former EVP/CSO/CBO of Celgene BLAKE BORGESON, PHD Co-Founder of RXRX TERRY-ANN BURRELL, MBA CFO & Treasurer, Beam Therapeutics ZAVAIN DAR Co-Founder & Partner of Dimension R. MARTIN CHAVEZ, PHD Chairman of RXRX, Board Member of Alphabet, Vice-Chairman of 6th Street, Former CFO/CIO of GS ZACHARY BOGUE, JD Co-Founder & Partner of Data Collective CHRIS GIBSON, PHD Co-Founder & CEO
Strong Financials ~$550M in cash and cash equivalents at the end of 2022 with potential for increased revenue in the near term Near-Term • Potential option exercises for partnership programs • Potential option exercises for map building initiatives or data sharing • Potential for additional partnership(s) in large, intractable areas of biology and / or technological innovation • Ph1 clinical trial readout for Clostridium difficile Colitis program expected 2H 2023 • Potential for additional INDs and clinical starts, including Ph1b/2 trial initiation for AXIN1/APC program • Potential for consolidation of technologies, talent and assets to accelerate the Recursion OS Medium-Term • Multiple POC readout(s) for AI-discovered programs • NF2 interim safety analysis expected 2024 • CCM top-line data expected 2H 2024 • Potential for additional INDs and clinical starts • Potential option exercises for partnership programs • Potential option exercises for map building initiatives or data sharing • Potential additional partnership(s) in large, intractable areas of biology and / or technological innovation • Recursion OS moves towards autonomous map building and navigation with digital and micro-synthetic chemistry Upcoming Potential Milestones 140
Machine Learning and Automation 141
Q&A Chris Gibson PhD & Recursion Executive Team Download Day 2023
Closing Remarks Download Day 2023 Zavain Dar Director of Recurison