Slide 1: Decoding Biology To Radically Improve Lives
Decoding Biology To Radically Improve Lives Early September, 2023
Slide 2: Forward-looking statements
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 pr
Slide 3: Table of Contents
Table of Contents 3 Recursion’s value proposition 6 – 13 How we build maps of biology and chemistry to turn drug discovery into a search problem 14 – 21 How we create value using our maps of biology and chemistry 22 – 77 Pipeline 23 – 73 Partnerships 74 – 75 Data 76 – 77 Value driven by our team and
Slide 4: Pipeline, partnerships and platform updates
Pipeline - Added, accelerated or tightened guidance for clinical studies: • REC-3964 Ph1 C Diff achieved primary objective of assessing safety, tolerability, and PK in Q3, 2023, Ph2 initiation expected in 2024 • REC-994 Ph2 CCM top-line in H2, 2024 • REC-2282 Ph2 NF2 safety & preliminary efficacy in
Slide 5: Bridging Protein and Chemical Space with Massive Protein-Ligand Interaction Prediction
5 ~36 Billion Compounds from the Enamine Real Space ~80,000 predicted binding pockets from ~15,000 human proteins ~2.8 Quadrillion potential protein- ligand interactions computed and stored Recursion partnered with to integrate and optimize MatchMaker (acquired via ) for massive scale GPU-based comp
Slide 6: In Brief: The Recursion Value Proposition
In Brief: The Recursion Value Proposition
Slide 7: Recursion leading a new TechBio sector
Recursion leading a new TechBio sector at the intersection of technology and biology 7Adapted from Scannell, J et al (2012). Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov, 11, 191-200. 0.1 1 10 50B 100M 500K 1K 20201962 1970 1980 1990 2000 2010 Compute Power (Transisto
Slide 8: The Recursion OS today
TranslationCompound OptimizationHit & Target ValidationPatient Connectivity & Novelty Chemical property predictions Compound selection with ML DMPK experiments Phenomic efficacy InVivomic Prioritization & Digital Tolerability InVivomic Efficacy Preclinical assessment Large Language Models to Query G
Slide 9: Leading indicators of efficiency
Data shown is the average of all our programs since late 2017 through 2022. All industry data adapted from Paul, et al. Nature Reviews Drug Discovery. (2010) 9, 203–214 Mapping and navigating the complex systems of biology and chemistry has demonstrated leading indicators of efficiency 9 Screen — Hi
Slide 10: Multi-pronged capital-efficient business strategy
Harnessing value with a multi-pronged capital-efficient business strategy 10 Pipeline Recursion OS Build internal pipeline in indications with potential for accelerated path to approval Pipeline Strategy Precision Oncology Rare Disease Partnerships Data Partnership Strategy Partner in complex therap
Slide 11: Pipeline by indication and phase
PreclinicalLate Discovery Oncology Rare & Other Therapeutic Area Indication AXIN1 or APC MUTANT CANCERS (AXIN1 or APC mutant cancers; est. 65K) MYC-DRIVEN ONCOLOGY (MYC; est. 54K4) CLOSTRIDIOIDES DIFFICILE INFECTION (est. 730K) CEREBRAL CAVERNOUS MALFORMATION (CCM; est. 360K1) NEUROFIBROMATOSIS TYPE
Slide 12: Significant partnerships across biopharma and tech
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
Slide 13: Relatable and scalable data is a key differentiator
13 Relatable and scalable data is a key Recursion differentiator Recursion Data Universe: >25 PB of proprietary biological and chemical data, spanning phenomics, transcriptomics, invivomics, and more • We believe this is one of the largest such datasets fit for the purpose of training large-scale ML
Slide 14: How we build maps of biology and chemistry
How we build maps of biology and chemistry to turn drug discovery into a search problem
Slide 15: Map-based approach to drug discovery
Recursion’s map-based approach is designed to set the standard for drug discovery in the 21st century 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 hyp
Slide 16: The Recursion OS today
TranslationCompound OptimizationHit & Target ValidationPatient Connectivity & Novelty Chemical property predictions Compound selection with ML DMPK experiments Phenomic efficacy InVivomic Prioritization & Digital Tolerability InVivomic Efficacy Preclinical assessment Large Language Models to Query G
Slide 17: Large language models in program ideation
17 TranslationCompound OptimizationHit & Target ValidationPatient Connectivity & Novelty State-of-the-art Large Language Models Rapidly scaling to 1000s of new differentiated program ideas Experiments predict Maps of Biology & Chemistry LLMs evaluate complex opportunities at scale Differentiation &
Slide 18: Hit and target validation
18 TranslationCompound OptimizationHit & Target ValidationPatient Connectivity & Novelty Rapidly scaling to 1000s of new differentiated program ideas Hundreds of compound hits per gene from our Maps >100 programs generated in H1, 2023 Automated data package Distilled insights for rapid decision maki
Slide 19: Compound optimization
19 TranslationCompound OptimizationHit & Target ValidationPatient Connectivity & Novelty Chemical property predictions ML predicted protein-ligand interactions for ~36 billion compounds and ML predictions for new compounds that become part of our library Compound selection with ML Semi-generative an
Slide 20: Translation and InVivomics
20 TranslationCompound OptimizationHit & Target ValidationPatient Connectivity & Novelty InVivomic Prioritization & Digital Tolerability Rat and mouse studies with ML-based selection of optimal compound and dose from videos Preclinical assessment Best options from Compound Optimization Poorly tolera
Slide 21: IND enabling studies and clinical development roadmap
21 IND Enabling StudiesTranslationCompound OptimizationHit & Target ValidationPatient Connectivity & Novelty Chemical property predictions Compound selection with ML DMPK experiments Phenomic efficacy InVivomic Prioritization & Digital Tolerability InVivomic Efficacy Preclinical assessment Large Lan
Slide 22: How we create value using our maps
How we create value using our maps of biology and chemistry
Slide 23: Multi-pronged capital-efficient business strategy
Harnessing value with a multi-pronged capital-efficient business strategy 23 Partnerships Pipeline Recursion OS Data Partnership Strategy Partner in complex therapeutic areas requiring large financial commitment and competitive market dynamics Leverage partner knowledge and clinical development capa
Slide 24: Pipeline by indication and phase
PreclinicalLate Discovery Oncology Rare & Other Therapeutic Area Indication AXIN1 or APC MUTANT CANCERS (AXIN1 or APC mutant cancers; est. 65K) MYC-DRIVEN ONCOLOGY (MYC; est. 54K4) CLOSTRIDIOIDES DIFFICILE INFECTION (est. 730K) CEREBRAL CAVERNOUS MALFORMATION (CCM; est. 360K1) NEUROFIBROMATOSIS TYPE
Slide 25: REC-994 for Cerebral Cavernous Malformations
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
Slide 26: SYCAMORE Clinical Trial: REC-994 for CCM
Julia – living with CCM 26 SYCAMORE Clinical Trial : REC-994 for CCM Phase 2 Fully Enrolled Clinical: CCM Symptomatic US + EU5, >1 million patients worldwide live with these lesions today PREVALENCE & STANDARD OF CARE CAUSE LOF mutations in genes CCM1, CCM2 & CCM3, key for maintaining the structural
Slide 27: Disease Overview: Cerebral Cavernous Malformations
27 • 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
Slide 28: CCM patient population and unmet need
28 Sources: 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 Ca
Slide 29: CCM is an under-appreciated orphan disease
29 Disease Overview : CCM is an Under-Appreciated Orphan Disease 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 fibrosi
Slide 30: Therapeutic Approach to CCM
30 • Symptoms associated with both increased size of lesions, but also inflammation or activation of lesions within the immunoprivileged 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
Slide 31: CCM – Applied prototyping of the Recursion OS
CCM – Applied prototyping of the Recursion OS 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 Using an early version of our Recu
Slide 32: REC-994 Mechanism of Action
Healthy REC-994 – Mechanism of Action 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 ce
Slide 33: Preclinical studies confirm insight
33 Further Confidence : Preclinical Studies Confirm Insight 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 lesi
Slide 34: Clinical studies confirming safety
Further Confidence : Clinical Studies Confirming Safety 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 Mo
Slide 35: SYCAMORE Clinical Trial design
35 SYCAMORE Clinical Trial : REC-994 for CCM Phase 2 Fully Enrolled 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 Outcome Measures Enrollme
Slide 36: REC-2282 for NF2 Mutated Meningiomas
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
Slide 37: POPLAR Clinical Trial: REC-2282 for NF2
37 POPLAR Clinical Trial : REC-2282 for NF2 Part A Underway Clinical: NF2 LOF mutations in NF2 tumor suppressor gene, leading to deficiencies in the tumor suppressor protein merlin PATHOPHYSIOLOGY & REASON TO BELIEVE Efficacy in Recursion OS, cellular, and animal models; suppression of aberrant ERK,
Slide 38: Disease Overview: Neurofibromatosis Type 2
38 Disease Overview : Neurofibromatosis Type 2 (NF2) 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
Slide 39: NF2 Meningiomas patient population
39 Disease Overview : Neurofibromatosis Type 2 (NF2) Meningiomas • 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 C
Slide 40: Insight from OS: REC-2282 Rescued Loss of NF2
40 NF2 knockdown cells Healthy Cells REC-2282 REC-2282 identified as rescuing HUVEC cells treated with NF2 C o n tr o l N F2 s iR N A HUVEC, human umbilical vein endothelial cells; NF2, neurofibromatosis type 2; siRNA, small interfering RNA. Insight from OS : REC-2282 Rescued Loss of NF2 Clinical: N
Slide 41: REC-2282 Mechanism of Action
41 REC-2282 – Mechanism of Action 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;
Slide 42: REC-2282 preclinical in-vivo efficacy
42 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 h an ge in t u m o
Slide 43: Prior studies suggest potential therapeutic benefit
• 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 comm
Slide 44: REC-2282 vs Other HDAC Inhibitors
44 REC-2282 Appears Well Suited for NF2 vs Other HDAC Inhibitors 1 Sborov 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. 2 Collier KA, et al. A phase 1 trial of the histone deacetylase in
Slide 45: POPLAR Clinical Trial design
POPLAR Clinical Trial : REC-2282 for NF2 Part A Underway 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 an
Slide 46: REC-4881 for Familial Adenomatous Polyposis
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
Slide 47: TUPELO Clinical Trial: REC-4881 for FAP
47 TUPELO Clinical Trial : REC-4881 for FAP Phase 2 Underway Clinical: FAP Polyps Found in Colon and Upper GI Tract Inactivating mutations in the tumor suppressor gene APC PATHOPHYSIOLOGY & REASON TO BELIEVE KEY ELEMENTS • Targeting classical FAP patients (with APC mutation) • MEK inhibitor, small m
Slide 48: Disease Overview: Familial Adenomatous Polyposis
48 Disease Overview : Familial Adenomatous Polyposis 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 polyp
Slide 49: FAP Standard of Care
49 Disease Overview : Familial Adenomatous Polyposis – Standard of Care 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 q
Slide 50: REC-4881 rescued phenotypic defects of APC knockdown cells
50 REC-4881 rescued phenotypic defects of cells with APC knockdown 0.1 µM REC-4881 Insight from OS : Rescued Loss of APC, Inhibited Tumor Growth • Compared to thousands of other molecules tested, REC-4881 rescued phenotypic defects substantially better (including better rescue than other MEK inhibit
Slide 51: REC-4881 blocks Wnt mutation induced MAPK signaling
51 Jeon, WJ, et al. (2018). Interaction between Wnt/β-catenin and RAS-ERK pathways and an anti-cancer strategy via degradations of β-catenin and RAS by targeting the Wnt/β-catenin pathway. npj Precision Oncology, 2(5). 3 3 REC-4881 inhibits MEK 1/2 and recovers the destabilization of RAS by the β-Ca
Slide 52: Preclinical reduction in polyp count and dysplasia
52 Further Confidence : Preclinical Studies Confirming Reduction in Polyp Count and High-Grade Dysplasia 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 •
Slide 53: Clinical data generated by Recursion
53 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 • Grou
Slide 54: TUPELO Clinical Trial design
54 TUPELO Clinical Trial : REC-4881 for FAP Phase 2 Underway 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/pouc
Slide 55: REC-4881 for AXIN1 or APC Mutant Cancers
REC-4881 for the Treatment of Solid Tumors with AXIN1 or APC Mutant Cancers Target / MOA MEK Inhibitor Molecule Type Small Molecule Lead Indication(s) Solid Tumors with AXIN1 or APC Mutant Cancers Status Phase 2 Source of Insight Recursion OS
Slide 56: AXIN1 or APC mutant cancers overview
56 LOF mutations in AXIN1 or APC tumor suppressor genes PATHOPHYSIOLOGY & REASON TO BELIEVE Alterations in the WNT pathway are found in a wide variety of tumors and confer poor prognosis and resistance to standard of care Substantial need for developing therapeutics for patients harboring mutations
Slide 57: Disease Overview: AXIN1 or APC Mutant Cancers
57 Disease Overview : AXIN1 or APC Mutant Cancers • 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 or APC leads to sustained Wnt signaling promoting cancer progress
Slide 58: Flexible patient selection strategy and study design
58 • 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 mar
Slide 59: Insight from OS: REC-4881 rescues APC and AXIN1
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 for
Slide 60: Preclinical studies confirming insight
Further Confidence : Preclinical Studies Confirming Insight Clinical: AXIN1 or APC 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. 1 Wong, H., et al. Clin Cancer Res, 2012, 18:14, pp.3846-3855 60 -100 -80 -60 -40 -20 0 20 AXIN1 or APC wildtype
Slide 61: Phase 2 Trial Design: REC-4881 for AXIN1 or APC Mutant Cancers
Phase 2 Trial Design : REC-4881 for AXIN1 or APC Mutant Cancers Expect Phase 2 initiation in Q4, 2023 Outcome Measures Enrollment Criteria • Unresectable, locally advanced, or metastatic cancers • AXIN1 or APC mutation confirmed by NGS (tissue or blood) • CRC patients must be RAS / RAF wildtype • No
Slide 62: REC-3964 for C. Difficile Infection
REC-3964 for the Treatment of C. Difficile Infection Target / MOA Selective C. diff Toxin Inhibitor Molecule Type Small Molecule Lead Indication(s) C. Difficile Infection Status Phase 2 Source of Insight Recursion OS
Slide 63: REC-3964 pathophysiology and key elements
63 Colleen – lived with rCDI C. difficile toxins from colonizing bacterium causes degradation of colon cell junction, toxin transit to bloodstream, and morbidity to host PATHOPHYSIOLOGY & REASON TO BELIEVE Highly recurrent infectious disease with severe diarrhea, colitis, and risk of toxic megacolon
Slide 64: Disease Overview: C. Difficile Infection
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 6
Slide 65: Disease Overview: C. Difficile Infection
65 Disease Overview : C. Difficile Infection (CDI) Disruption of microbiota and colonization of C. diff Release of C. diff toxins Degradation of colon cell junction & toxin transit to bloodstream Clinical: C. Difficile Source: McCollum, D,, Rodriguez, JM . Detection, Treatment, and Prevention of Clo
Slide 66: REC-3964 rescued cells treated with C. difficile toxins
REC-3964 identified as a NCE that demonstrated strong rescue in HUVEC cells treated with C. diff toxin Insight from OS : REC-3964 Rescued Cells Treated with C. Difficile Toxins C. diff toxin B phenotype Healthy Control Disease State Healthy Cells REC-3964 0.1 µM Clinical: C. Difficile 66
Slide 67: REC-3964: Selective Inhibitor of C. Difficile Toxins
REC-3964 : Selective Inhibitor of C. Difficile Toxins Clinical: C. Difficile 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 enzym
Slide 68: REC-3964: Selective Inhibitor of C. Difficile Toxins
Adapted from Awad, MM. et al. (2014). Clostridium difficile virulence factors: Insights into an anaerobic spore-forming pathogen. Gut Microbes. 5(5), 579-593. REC-3964 : Selective Inhibitor of C. Difficile Toxins Clinical: C. Difficile 3 1 2 4 REC-3964 binds and blocks catalytic activity of the toxi
Slide 69: Preclinical studies confirmed Recursion OS insight
Further Confidence : Preclinical Studies Confirmed Recursion OS Insight ✓ 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
Slide 70: Clinical Trial: REC-3964 Phase 1 results
70 Clinical Trial : REC-3964 for C. Difficile Phase 1 study complete Trial Design • Randomized, Double-blind Trial Population • Healthy Participants • SAD (n = 48) • 36 participants treated with REC-3964 • 12 participants treated with placebo • MAD (n = 42) • 34 participants treated with REC-3964 •
Slide 71: Clinical studies confirming safety
MAD Study Placebo (N=8) n ( %) 100 mg (N=10) n ( %) 300 mg (N=8) n ( %) 500 mg (N=8) n ( %) 900 mg (N=8) n ( %) REC-3964 Overall (N=34) n ( %) MAD Overall (N=42) n ( %) Total Number of TEAEs 17 24 5 9 7 45 62 Total Participants with ≥ 1 TEAE 6 ( 75.0) 8 ( 80.0) 4 ( 50.0) 5 ( 62.5) 4 ( 50.0) 21 ( 61.
Slide 72: Planned Phase 2 proof-of-concept development approach
Development Approach • Initial Phase 2 POC study to evaluate REC-3964 in combination with vancomycin • Focus on subjects at risk for CDI with moderate to severe disease planning to receive SOC therapy • Flexibility to assess effects of REC-3964 on both treatment and reduction of recurrence populatio
Slide 73: RBM39: Novel Target for HR-Proficient Ovarian Cancer
RBM39: Novel CDK12-Adjacent Target for HR-Proficient Ovarian Cancer 73 RBM39 CDK12 2.5μM 1.0μM REC-65029 0.1μM 0.25μM CDK13 REC-65029 Similar Opposite BRCA-proficient ovarian cancer PDX Preclinical: HR-Proficient Ovarian Cancer Identify potential first-in-class tumor-targeted precision therapeutic N
Slide 74: Multi-pronged capital-efficient business strategy
74 Partnerships Recursion OS Partnership Strategy Partner in complex therapeutic areas requiring large financial commitment and competitive market dynamics Leverage partner knowledge and clinical development capabilities Fibrosis Other large, intractable areas of biology Neuroscience* Pipeline Build
Slide 75: Significant partnerships across biopharma and tech
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
Slide 76: Capital efficient business strategy
Harnessing value with a capital efficient business strategy 76 Partnerships Recursion OS Partnership Strategy Partner in complex therapeutic areas requiring large financial commitment and competitive market dynamics Leverage partner knowledge and clinical development capabilities Fibrosis Other larg
Slide 77: Data that is relatable and scalable is the differentiator
77 Data that is relatable and scalable is the Recursion differentiator Recursion Data Universe: >25 PB of proprietary biological and chemical data, spanning phenomics, transcriptomics, invivomics, and more • We believe one of the largest biological and chemical datasets fit for the purpose of traini
Slide 78: Value driven by our team and our milestones
Value driven by our team and our milestones
Slide 79: A new kind of team and culture
Advanced degreesEmployees Team Members >550 What it takes to make this happen – a new kind of team and culture >50% ESG Highlights ✓ ESG reporting on Healthcare and Technology Metrics ✓ 100% of electricity powering our Biohive-1 supercomputer comes from renewable sources ✓ Learn more about Recursion
Slide 80: Leadership team and Board of Directors
Trademarks are the property of their respective owners and used for informational purposes only. Our leadership team brings together experience & innovation to lead TechBio 80 Board of Directors Dean Li, MD PHD Co-Founder of RXRX, President of Merck Research Labs Rob Hershberg, MD PHD Co-Founder/CEO
Slide 81: Strong financials and what to watch for
Strong Financials ~$406M in cash at the end of Q2, 2023 (does not include $50M NVIDIA investment) 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
Slide 82: Impact
Impact 82
Slide 83: Additional scientific and business context
Additional scientific and business context
Slide 84: Declining efficiency in drug discovery
Images adapted from Jayatunga, M., et al. Nature Reviews Drug Discovery 2022. The biopharmaceutical industry faces pressure amidst declining efficiency in drug discovery 84 Top-20 Pharma Companies AI-Native Drug Discovery Companies AI-enabled drug discovery efforts have proliferated alongside the de
Slide 85: Building datasets to map relationships across scales
85 We build biological and chemical datasets to map relationships across scales and understand the connectivity of the system Image adapted from D’Orazio, M., et al. Nature Scientific Reports 2022. RNA Level Transcriptomics DNA Level (Population-Scale) Genomics Protein Level Proteomics Metabolites L
Slide 86: Scale of inputs, automation and analysis
50 different human cell types small molecule library, we believe this scale is on par with some large pharma companies hiPSC-derived cells produced since 2022, we believe that we are one of the largest hiPSC- derived cell producers ~1.7 Million ~850 Billion Diverse Biological and Chemical Inputs Rob
Slide 87: Genome-scale mapping
This is a whole-genome arrayed CRISPR knock-out Map generated in primary human endothelial cells Every gene is represented in a pairwise way (each is present in columns and rows) Dark Red indicates phenotypic similarity according to our neural networks while Dark Blue indicates phenotypic anti- simi
Slide 88: JAK / STAT pathway map
One such example – the JAK / STAT pathway clustered by strength of interaction, including both similar genes (red) and opposite genes (blue) Can wade into areas of novel biology and chemistry… 88 JAK1 TNKS1BP1 PPP1R9B PHF13 SOCS3 PRKCH MEGF8 ASB7 SLC39A1 DOCK9 ZMYM3 FAM49B STK24 YWHAB IL6ST IL6R STA
Slide 89: Maps reveal known and novel biology
Maps reveal known and novel biology Trademarks are the property of their respective owners and used for informational purposes only. 89 INTS9 INTS11 INTS4 INTS7 INTS2 INTS8 INTS1 INTS6 C7orf26 INTS10 INTS13 INTS14 IN TS 1 4 IN TS 1 3 IN TS 1 0 C 7 o rf 2 6 IN TS 6 IN TS 1 IN TS 8 IN TS 2 IN TS 7 IN
Slide 90: Competitive Benchmarking — Technology Enabled Drug Discovery
@ Recursion Competitive Benchmarking — Technology Enabled Drug Discovery AbCellera Biologics Exscientia Insitro Schrodinger Recursion. Multiple Large-Scale Vi Partnerships! v v v v Significant Internally Developed Pipeline of Early ae aS f Programs? Multiple Internally Developed vo Ph2 or Ph3 Clinic
Slide 91: Reliable, relatable, scalable data is the differentiator
1 Includes approximately 500,000 compounds from Bayer’s proprietary library. 2 ‘Predicted Relationships’ refers to the number of Unique Perturbations that have been predicted using our maps. Biology and chemistry are complex – data that is reliable, relatable, and scalable is the Recursion different
Slide 92: CRISPR proximity bias revealed using phenomics screens
• Recursion demonstrated that CRISPR-Cas9 editing induces chromosome arm-scale truncations across the genome • Creates a proximity bias in CRISPR screens which can confound some gene-gene relationships • Recursion demonstrated a correction method leveraging public CRISPR-Cas9 knockout screens to mit
Slide 93: COVID-19 research
Drug Prediction Correct? Hydroxychloroquine x ✓ Lopinavir x ✓ Ritonavir x ✓ Remdesivir ✓ ✓ Baricitinib ✓ ✓ Tofacitinib ✓ ✓ Ivermectin x ✓ Fluvoxamine x ✓ Dexamethasone x x COVID-19 research 93https://www.biorxiv.org/content/10.1101/2020.04.21.054387v1 • Recursion conducted several AI-enabled experim
Slide 94: Transformational collaborations provide multiple value inflection points
Program 1 Program 1 Program 1 Program 1 Program 1 Program 1 Program 1 Transformational collaborations provide multiple potential value inflection points Illustrative example of potential value inflection points Clinical and Approval Milestones Pre-Clinical Milestones Upfront Fee Programs 2 through N