Recursion Pharmaceuticals, Inc. · NASDAQ:RXRX
Recursion Pharmaceuticals — Investor Presentation (June 2023)
87 slides from Recursion Pharmaceuticals's investor presentation, Jun 13, 2023
Slide 1: Decoding Biology To Radically Improve Lives
Decoding Biology To Radically Improve Lives Early June 2023 GS Recursion
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: Agenda
3 Recursion’s value proposition 4 - 10 How we build maps of biology and chemistry to turn drug discovery into a search problem 11 - 16 How we create value using our maps of biology and chemistry 17 - 18 Pipeline 19 - 63 Partnerships 64 – 67 Data 68 – 69 Value driven by our team and our milestones 70
Slide 4: Recursion's value proposition
Novel oncology program (RBM39) to IND-enabling studies Advancing collaborations in Neuroscience (Roche-Genentech) and Fibrosis (Bayer): $13B in potential milestones across 50+ possible programs plus royalties Entered into agreements to acquire Cyclica and Valence to bolster digital chemistry and gen
Slide 5: Cyclica and Valence acquisition rationale
5 • Enhance the op#miza#on of Recursion’s compounds for efficacy while minimizing liabili#es • Rapidly advance the diversifica#on and discovery of novel chemical ma7er • Enables mechanism of ac#on deconvolu#on and genera#ve chemistry • Enable acceleration of generative design of new molecules, DMPK
Slide 6: Combined capabilities provide the leading full-stack drug discovery solution
@ Recursion Combined capabilities provide the leading full-stack drug discovery solution 9 Recursion. [SCYCLICA Valence BiolOGY phaneice) ‘Tisneurtudamice InVivomics First Lead Candidate Inference Hit toLead Optimization Evaluation IND Preparation ars a°s ais Chemistry Mechanism of Generative Predic
Slide 7: Moore's Law vs Eroom's Law
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 (Transistors per Microprocessor)NMEs per $B spent (inflation adjusted) Moore’s Law: Computing p
Slide 8: Platform-driven versus literature-driven discovery
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. Littl
Slide 9: Failing faster and earlier to spend less and go faster
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 9 Screen — Hit ID — Validated Lead — Advanced Candidate — Development Candidate — Industry Recursion Failing faster and earlier to › › spend les
Slide 10: Pipeline
10 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) FAMILIAL ADENOMATOUS POLYPOSIS (APC; est. 50K) CEREBRAL CAVERNOUS MALFORMATION (CCM; est. 360K1) NEUROFIBROMATOSIS T
Slide 11: How we build maps of biology and chemistry
How we build maps of biology and chemistry to turn drug discovery into a search problem GS Recursion
Slide 12: Mapping multiomic layers of biology
12 Image adapted from D’Orazio, M., et al. Nature Scientific Reports 2022. RNA Level Transcriptomics DNA Level (Popula0on-Scale) Genomics Protein Level Proteomics Metabolites Level Metabolomics Organism Level InVivomics Cell Level Phenotypes Phenomics Built and scaled AspirationalExploratory Like di
Slide 13: Diverse inputs, robotic automation, ML-based analysis
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 Diverse Biological and Chemical Inputs RoboWc AutomaWon at Scale Up to
Slide 14: Whole-genome arrayed CRISPR knock-out map
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 15: JAK/STAT pathway clustered by interaction strength
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… 15 JAK1 TNKS1BP1 PPP1R9B PHF13 SOCS3 PRKCH MEGF8 ASB7 SLC39A1 DOCK9 ZMYM3 FAM49B STK24 YWHAB IL6ST IL6R STA
Slide 16: Integrator complex replication with Genentech maps
Trademarks are the property of their respecRve owners and used for informaRonal purposes only. 16 INTS9 INTS11 INTS4 INTS7 INTS2 INTS8 INTS1 INTS6 C7orf26 INTS10 INTS13 INTS14 IN TS 14 IN TS 13 IN TS 10 C7 or f2 6 IN TS 6 IN TS 1 IN TS 8 IN TS 2 IN TS 7 IN TS 4 IN TS 11 IN TS 9 Phenomics TVN (below
Slide 17: How we create value using our maps
How we create value using our maps of biology and chemistry GS Recursion
Slide 18: Pipeline, partnerships and data strategy
18 Pipeline 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 therapeutic areas requiring large financial commitment and competitive market dynamics Levera
Slide 19: Partnerships, pipeline and data strategy
19 Partnerships Pipeline Data Partnership Strategy Partner in complex therapeutic areas requiring large financial commitment and competitive market dynamics Leverage partner knowledge and clinical development capabilities Build internal pipeline in indications with potential for accelerated path to
Slide 20: Pipeline by therapeutic area and indication
20 PreclinicalLate Discovery Oncology Rare & Other Therapeutic Area Indica>on AXIN1 or APC MUTANT CANCERS (AXIN1 or APC mutant cancers; est. 65K) MYC-DRIVEN ONCOLOGY (MYC; est. 54K4) FAMILIAL ADENOMATOUS POLYPOSIS (APC; est. 50K) CEREBRAL CAVERNOUS MALFORMATION (CCM; est. 360K1) NEUROFIBROMATOSIS TY
Slide 21: 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 22: Large unmet need in CCM
22 • 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 23: CCM patient population
23 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 24: CCM prevalence versus other orphan indications
24 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 >55,00
Slide 25: Novel therapeutic approach: vascular stability hypothesis
25 • 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 o
Slide 26: Identification of REC-994 for CCM
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 Recursion OS in an academic setting, we identified
Slide 27: REC-994 mechanism of action
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 a
Slide 28: Preclinical studies of REC-994 in CCM mouse models
28 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 mou
Slide 29: REC-994 Phase 1 SAD and MAD 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 Moderate Severe 3 1 0 0 0 0 3 0 0 3 0 0 3 1 0 Relationship
Slide 30: REC-994 Phase 2 trial design
30 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,
Slide 31: 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 32: NF2 patient population and no approved therapy
32 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 merl
Slide 33: NF2 meningioma patient numbers
33 • 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 loc
Slide 34: REC-2282 rescues NF2 knockdown cells
34 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 34
Slide 35: REC-2282 HDAC inhibitor mechanism
35 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 syste
Slide 36: REC-2282 preclinical in vivo efficacy
36 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
Slide 37: REC-2282 clinical safety and prior studies
• 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 38: First-in-class HDAC inhibitor for NF2 meningiomas
38 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 inhibitor AR-42 in patients with neurofibromatosis type 2-associ
Slide 39: REC-2282 Phase 2/3 trial design
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 progr
Slide 40: 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 41: FAP patient population
41 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 ma
Slide 42: No approved medical therapy for FAP
42 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 int
Slide 43: REC-4881 rescues APC knockdown phenotype
43 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
Slide 44: REC-4881 MEK inhibitor mechanism
44 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 45: REC-4881 in vivo efficacy in APCmin mice
45 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
Slide 46: REC-4881 Phase 1 healthy volunteer study
46 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 47: REC-4881 Phase 2 trial design
47 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
Slide 48: 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 49: Sustained Wnt signaling in solid tumors
49 • 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 progression and survival1 • AXIN1 or APC mutant solid t
Slide 50: Flexible patient selection strategy and study design
50 • 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 51: REC-4881 rescues APC and AXIN1
AXIN 1 APC 2.5 μM 1.0 μM 0.1 μM 0.2 5μ M 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 regula
Slide 52: In vivo efficacy and next steps
Efficacy found in In Vivo Mice Models … … Led to Significant Progression Free Survival Clinical: AXIN1 or APC -20 0 20 40 60 80 100 Tu m or G ro w th In hi bi tio n (% ) AXIN1 or APC Mutant AXIN1 or APC Wildtype Average TGI: ~70% mutant vs ~49% wildtype Median TGI: ~72% mutant vs ~48% wildtype p = 0
Slide 53: 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 1 Source of Insight Recursion OS
Slide 54: C. difficile infection disease mechanism
54 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 Clostridium difficile Infection. Clinical Gastroent
Slide 55: C. difficile patient population and cost burden
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 5
Slide 56: REC-3964 rescue in HUVEC cells
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. Difficile 56
Slide 57: C. diff toxin mechanism
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 enzymatic domain into the cytosol of the infected cell 2 3
Slide 58: REC-3964 blocks toxin glucosyltransferase
Adapted from Awad, MM. et al. (2014). Clostridium difficile virulence factors: Insights into an anaerobic spore-forming pathogen. Gut Microbes. 5(5), 579-593. Clinical: C. Difficile 3 1 2 4 REC-3964 binds and blocks catalytic activity of the toxin’s innate glucosyltransferase, but not the host's 5 5
Slide 59: REC-3964 restores barrier integrity and survival
ü 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 ü Improved probability of survival beyo
Slide 60: REC-3964 Phase 1 SAD/MAD trial
60 Phase 1 FIH SAD/MAD Trial initiated in Q3 2022 • Enrollment is progressing • In several SAD cohorts and at least one MAD 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 • He
Slide 61: Preclinical programs
Preclinical Programs RBM39 : HR-Proficient Ovarian Cancer Target α : Immunotherapy
Slide 62: RBM39: HR-proficient ovarian cancer
62 CDK13 RBM39 CDK12 2.5μM RBM39 1.0μM 2.5μM 0.1μM 0.25μM 1.0μM REC-65029 0.1μM 0.25μM CDK13 CDK12 REC-65029 Similar Opposite BRCA-proficient ovarian cancer PDX Preclinical: HR-Proficient Ovarian Cancer Identify potential first-in-class tumor-targeted precision therapeutic NCE with novel MOA capable
Slide 63: Target Alpha: immunotherapy
Gene B Gene B REC- 648918 REC-648918 BIRC2 Gene A Gene A BIRC2 63 Similar Opposite (A) CT26 in vivo efficacy Note: (A) Mice harboring CT26 tumors show 60% complete tumor regressions upon treatment with 100 mpk REC-1170035 in combination with 10 mpk anti-PD-1. (B) Flow cytometric analysis of the CT26
Slide 64: Partnerships
64 Partnerships 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 internal pip
Slide 65: Roche-Genentech and Bayer collaboration terms
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 66: Transition to inferential search accelerated program initiation
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 66
Slide 67: Partnership terms
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 68: Partnerships and data strategy
68 Partnerships 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 internal pip
Slide 69: Recursion data universe, RXRX3 and MolRec
69 Recursion Data Universe: >23 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 training large-scale ML models RXRX3: CRISPR knockouts of most of the huma
Slide 70: Value driven by our team and our milestones
Value driven by our team and our milestones GS Recursion
Slide 71: Team and ESG highlights
Advanced degreesEmployees Team Members ~500 43% ESG Highlights ü ESG reporting on Healthcare and Technology Metrics ü 100% of electricity powering our Biohive-1 supercomputer comes from renewable sources ü Learn more about Recursion’s ESG stewardship: www.recursion.com/esg 43% Female Male 54% 1% Non
Slide 72: Strong financials and upcoming milestones
Strong Financials ~$473M in cash at the end of Q1 2023, expect no material change to runway as a result of acquisitions Near-Term • Potential option exercises for partnership programs • Potential option exercises for map building initiatives or data sharing • Potential for additional partnership(s)
Slide 73: Impact
Impact 73
Slide 74: Additional scientific and business context
Additional scientific and business context GS Recursion
Slide 75: AI-native drug discovery asset growth
Images adapted from Jayatunga, M., et al. Nature Reviews Drug Discovery 2022. 75 Top-20 Pharma Companies AI-Native Drug Discovery Companies 705 768 708 602 575 641 686 709 519 439 393 333 0 500 1,000 1,500 2,000 2,500 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 Discovery / Preclinica
Slide 76: Known versus Recursion OS-found pathway relationships
Well-known primary relationships between key members of five pathways: JAK/STAT | SWI/SNF | TGFβ | RAS | Proteasome All primary relationships found by the Recursion OS between key members of five pathways: JAK/STAT | SWI/SNF | TGFβ | RAS | Proteasome 76
Slide 77: Traditional versus Recursion approach
G Recursion Historical tools and the limits of human cognition have led to oversimplifying complex biological systems Traditional vs Recursion The entire genome > single 1 million rget compounds 1 million compounds ti » Se Se Se So Se ge Se ge Se se Se ce Se Se Se Ses v Se Se Se $e Be £0 Be Bo So So
Slide 78: Competitive benchmarking: technology-enabled drug discovery
G Recursion Competitive Benchmarking — Technology Enabled Drug Discovery AbCellera Biologics Exscientia Insitro Schrodinger Recursion. Multiple Large-Scale v Partnerships! v v v v Significant Internally Developed Pipeline of Early v v Y Programs? Multiple Internally Developed Ph2 or Ph3 Clinical Pro
Slide 79: Growth in data and experiments 2018-2022
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. 79 Year 2018 2019 2020 2021 2022 Total Phenomics Experiments (Millions) 8 24 56 115 175 Total Transcriptomics
Slide 80: CRISPR-Cas9 chromosome arm truncations research
• 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 81: COVID-19 predictions and RxRx19 dataset
Drug Prediction Correct? Hydroxychloroquine x ✓ Lopinavir x ✓ Ritonavir x ✓ Remdesivir ✓ ✓ Baricitinib ✓ ✓ Tofacitinib ✓ ✓ Ivermectin x ✓ Fluvoxamine x ✓ Dexamethasone x x 81https://www.biorxiv.org/content/10.1101/2020.04.21.054387v1 • Recursion conducted several AI-enabled experiments in April 2020
Slide 82: Illustrative partnership value inflection points
Program 1 Program 1 Program 1 Program 1 Program 1 Program 1 Program 1 Illustrative example of potential value inflection points Clinical and Approval Milestones Pre-Clinical Milestones Upfront Fee Programs 2 through N Programs 2 through N Programs 2 through N Programs 2 through N Programs 2 through
Slide 83: CCM program summary
Julia – living with CCM 83 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 integrity of the vasculature due to unknown mechanisms PATHOPHYS
Slide 84: NF2 program summary
84 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, AKT, and S6 pathway activation in a Phase 1 PD Study in
Slide 85: FAP program summary
85 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 molecule • Oral dosing • Phase 2 trial initiated in Q3 2022
Slide 86: AXIN1 or APC program summary
86 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 87: C. difficile program summary
87 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
Recursion Pharmaceuticals — Investor Presentation (June 2023) on 6ix