Recursion Pharmaceuticals, Inc. · NASDAQ:RXRX
Recursion Pharmaceuticals — Investor Presentation (November 2024)
70 slides from Recursion Pharmaceuticals's investor presentation, Nov 20, 2024
Slide 1: Decoding Biology To Radically Improve Lives
NOVEMBER 2024 Decoding Biology To Radically Improve Lives
Slide 2: Forward-looking statements
This presentation of Recursion Pharmaceuticals, Inc. (“Recursion,” “we,” “us,” or “our”) and any accompanying discussion contain statements that are not historical facts may be considered forward-looking statements under federal securities laws and may be identified by words such as “anticipates,” “
Slide 3: Post-Combination portfolio poised for value creation from a unified, AI-powered Operating System
3 Post-Combination portfolio poised for value creation from a unified, AI-powered Operating System 4 Large pharma collaborations ~10 Clinical and pre- clinical programs1 Oncology, Rare diseases, and other High Unmet Need Diseases ~10 Clinical program milestones over the next 18 months2 1 Unified Ope
Slide 4: Pipeline candidates and next anticipated milestones
Candidate Target Indication Preclinical IND-Enabling Phase 1/2 Pivotal / Phase 3 Next Anticipated Milestone REC-6171 CDK7 Advanced Solid Tumors2 • Initial Ph1 monotherapy safety & PK / PD data expected on Dec 9th, 2024 REC-1245 RBM39 Biomarker-Enriched Solid Tumors & Lymphoma • Ph 1 update on dose-e
Slide 5: Robust pipeline of partnered programs
Robust pipeline of partnered programs Therapy Area (Partner) Discovery Hit-to-Lead Lead Optimization Preclinical Clinical Neuroscience Neuroscience Immunology Immunology Other Oncology Oncology Other Oncology Immunology Immunology Immunology Immunology Oncology Oncology Other Immunology Oncology Onc
Slide 6: Unified Recursion OS with First-in-Class & Best-in-Class capabilities
Unified Recursion OS with First-in-Class & Best-in-Class capabilities 6
Slide 7: Unified Recursion OS with First-in-Class & Best-in-Class capabilities
Unified Recursion OS with First-in-Class & Best-in-Class capabilities 7
Slide 8: Unified Recursion OS with First-in-Class & Best-in-Class capabilities
Unified Recursion OS with First-in-Class & Best-in-Class capabilities 8
Slide 9: Multi-pronged capital efficient business strategy
We harness value from the Recursion OS with a multi-pronged capital efficient business strategy Build internal pipeline in indications with potential for advance transformational medicines for patients Pipeline strategy • Oncology • Rare disease • Other areas of high unmet need Partnership strategy
Slide 10: Value Creation: Pipeline
VALUE CREATION Pipeline
Slide 11: Multi-pronged capital efficient business strategy
We harness value from the Recursion OS with a multi-pronged capital efficient business strategy Build internal pipeline in indications with potential for advance transformational medicines for patients Pipeline strategy • Oncology • Rare disease • Other areas of high unmet need Partnership strategy
Slide 12: Pipeline: Oncology
PIPELINE Oncology AG HX
Slide 13: Advanced Solid Tumors (CDK7 Inhibitor): REC-617
• Aberrant CDK7 overexpression common in advanced transcriptionally- addicted solid tumors • Potential to address multiple indications, including post CDK4/6 population patients • Potential Best-in-Class and First-in-Class CDK7 Inhibitor • Designed with reduced transporter interactions to minimize G
Slide 14: Solid Tumors & Lymphoma (RBM39 Degrader): REC-1245
• Molecular glue RBM39 degrader via E3 ligase adaptor DCAF15 • Disrupts RNA splicing to downregulate cell cycle checkpoints, DDR networks, triggering cell stress, apoptosis • Potential First-in-Class RBM39 Degrader • No significant in vitro safety concerns (hERG, CEREP) • Solid tumor and lymphoma pa
Slide 15: B-Cell Malignancies (MALT1 Inhibitor): REC-3565
• Mutations causing constitutive MALT1 protease activity and MALT1-cIAP fusions are aggressive with limited treatment options • Potential to enhance NF-κB inhibition with BTK inhibitors • Reversible allosteric MALT1 inhibitor • Dampens NF-κB signaling which drives survival and proliferation of B-cel
Slide 16: Small-Cell Lung Cancer (LSD1 Inhibitor): REC-4539
• SCLC is a highly progressive disease with 5-year OS ~3% in the extensive stage • Clinical trial enrollment remains NCCN-recommended after 1L chemo/IO, despite advancements with DLL3-targeting BiTEs2 • Potential Best-in-Class LSD1 Inhibitor • Shorter-predicted half-life plus reversible MOA to manag
Slide 17: Pipeline: Rare disease
PIPELINE Rare disease —hd| tt
Slide 18: Cerebral Cavernous Malformation: REC-994
• Reduces lesion number & size in LOF mouse models • Phase 2 primary endpoint of safety and tolerability met • Phase 2 encouraging trends in lesion volume reduction consistent with in vivo POC • No approved therapy • Surgical resection or stereotactic radiosurgery is non curative and not always feas
Slide 19: Familial Adenomatous Polyposis: REC-4881
• No approved therapy • Colectomy during adolescence is standard of care • Patients at significant risk of GI cancer and suffer substantial decrease in quality-of-life • Potential First-in-Disease and Best-in-Class for FAP • Potent, non-competitive, allosteric MEK1/2 inhibitor • Oral 4 mg dose is ph
Slide 20: Hypophosphatasia (ENPP1 Inhibitor): REV102
• Potential First-in-Class and Best-in-Class ENPP1 Inhibitor • Non-immunogenic small molecule offering potentially safer solution than ERT (3-6 injections per week) • Opportunity to significantly reduce costs & treatment burden • Many patients, particularly adults, may have difficulty accessing ERT
Slide 21: Neurofibromatosis Type 2 (HDAC Inhibitor): REC-2282
• No approved therapy • Surgery/RT is standard of care (when feasible)2 • Location may make complete resection untenable, leading to hearing loss, facial paralysis, poor balance and visual difficulty • Potential First-in-Disease and Best-in-Class for NF2 • Potential to rescue disease-inducing effect
Slide 22: Pipeline: Other areas of high unmet need
PIPELINE Other areas of high unmet need
Slide 23: C. difficile (Toxin B Selective Inhibitor): REC-3964
• Limited treatment options for high-risk population with recurrent CDI cases • Ability to address populations not eligible for FMT or microbiome-based therapies • Potential First-in-Class as non-antibiotic oral for rCDI • Highly potent and well-tolerated with no reported DLTs, SAEs or treatment-rel
Slide 24: Idiopathic Pulmonary Fibrosis: REC-4209
• Approved therapies show modest slowing of IPF progression • No improvement in survival (mOS 3-5 years) or quality of life with current treatments • Potential First-in-Class treatment for IPF • Potential for safe and well-tolerated novel treatment • In vitro models suggest capability of reversing t
Slide 25: Value Creation: Partnerships & Data Strategy
VALUE CREATION Partnerships & Data Strategy
Slide 26: Multi-pronged capital efficient business strategy
We harness value from the Recursion OS with a multi-pronged capital efficient business strategy Build internal pipeline in indications with potential for advance transformational medicines for patients Pipeline strategy • Oncology • Rare disease • Other areas of high unmet need Partnership strategy
Slide 27: Partnerships with approximately $450M earned to date
Partnerships with approximately $450M1 earned to date and potential to receive more than $20B2 in additional milestones T E C H P A R T N E R S H I P S $20M upfront with up to $674M in aggregate and with mid-single to low-double digit tiered royalties ONCOLOGY & IMMUNOLOGY $30M upfront and $50M equi
Slide 28: Multi-pronged capital efficient business strategy
We harness value from the Recursion OS with a multi-pronged capital efficient business strategy Build internal pipeline in indications with potential for advance transformational medicines for patients Pipeline strategy • Oncology • Rare disease • Other areas of high unmet need Partnership strategy
Slide 29: We license subsets of data and tools
Recursion OS Preferential access to >20 PBs of real-world, multi-modal oncology data and ability to train causal AI models with utility in target discovery, biomarker development & patient selection. REAL-WORLD DATA ACCESS Access to hundreds of thousands of de-identified records to train causal AI m
Slide 30: LOWE puts the Recursion OS at your fingertips
30 LOWE puts the Recursion OS at your fingertips via natural language without any coding expertise required Note: Large Language Model-Orchestrated Workflow Engine (LOWE) is Recursion’s LLM-based software that can perform complex drug discovery tasks and orchestrate both wet-lab and dry-lab componen
Slide 31: Culture and Team
Culture and Team
Slide 32: Board of Directors and Executive Team
Board of Directors Dean Li, MD PHD Co-Founder of RXRX, President of Merck Research Labs Zavain Dar Co-Founder & Partner of Dimension Rob Hershberg, MD PHD Co-Founder, CEO, & Chair of HilleVax; Former EVP, CSO, & CBO of Celgene Zachary Bogue Co-Founder & Partner of Data Collective Najat Khan, PHD Chi
Slide 33: Our people and ESG highlights
Parity Pledge Signer: Gender parity and people of color parity Technology – data science, software engineering, automation, etc. Life Sciences – biology, chemistry, development, etc. Strategic Operations ~800 employees Our people are the most important ingredient for our mission Community Impact Fou
Slide 34: Appendix: Pipeline Details
APPENDIX Pipeline Details
Slide 35: Pipeline: Oncology
PIPELINE Oncology AG HX
Slide 36: REC-617: CDK7 Inhibitor
Program Status • Potential Best-in-Class and First-in-Class CDK7 inhibitor • Phase 1/2 study in advanced solid tumors ongoing • Initial Phase 1 monotherapy safety, PK/PD update expected at AACR Special Conference in Cancer Research on December 9, 2024 Mechanism of Action • Reversible CDK7 inhibitor
Slide 37: REC-617 robust anti-tumor activity in preclinical models
Category Assay DC Criteria Ph 1 Competitor Ph 1/2 Competitor REC-617 Potency & Selectivity CDK7 IC50 (nM) <10 CDK family selectivity >100-fold HCC70 (breast cancer) IC50 (nM) <100 ADME Caco-2 A2B (efflux) 10⁻⁶ cm/s >5 (<3) Predicted human half- life (hr) <15 Potent tumor regression with minimal IC80
Slide 38: REC-617 Study Design and Next Steps
REC-617 (CDK7 inhibitor): Study Design and Next Steps Development Strategy Part A • Monotherapy Part B • Initial combination with SERD in HR+/HER2- post CDK4/6 inhibitor population • N = 30-60 patients in combination • N will depend on number of disease specific cohorts Primary Endpoint: • Safety an
Slide 39: REC-1245: RBM39 Degrader
Program Status • Potential First-in-Class RBM39 degrader in solid tumors • Phase 1/2 study initiation expected in Q4 2024 • Phase 1 monotherapy update on dose-escalation expected in H1 2026 Mechanism of Action • Molecular glue that degrades RBM39 via E3 ligase adaptor DCAF15 • Disrupts RNA splicing
Slide 40: REC-1245 platform inferred functional similarity between RBM39 and CDK12
Similar Opposite Recursion OS Novel Insight Gene : Gene Relationship: Genetic KO of RBM39 and CDK12 found to be phenotypic similar with neither genes demonstrating a relationship to CDK13 genetic KO Gene : Compound Relationship: REC-1245 demonstrates phenotypic similarity to RBM39 and CDK12 genetic
Slide 41: REC-1245 key preclinical data
Key Preclinical Data1 REC-1245 is highly selective and potent Category Assay DC Criteria REC-1245 Potency / Selectivity RBM39 Degradation DC50 <100 nM CDK12 Kinase No sig. activity In Vitro Safety CEREP Safety Panel No sig. activity hERG IC50 (µM) >30 Pharmacokinetics Oral Bioavailability (%F) >30 R
Slide 42: REC-1245 Study Design and Next Steps
REC-1245 (RBM39 degrader): Study Design and Next Steps Development Strategy Part A • Monotherapy dose-finding Part B • Monotherapy dose- confirmation RP2D Phase 1 Dose Escalation (N~55) Phase 1/2 study design CURRENT STUDY Key Study Characteristics Study objectives: • Safety/Tolerability • RP2D • OR
Slide 43: REC-3565: MALT1 Inhibitor
Program Status • Potential Best-in-Class MALT1 inhibitor • Phase 1 initiation in B-Cell Malignancies (e.g., chronic lymphocytic leukemia), expected Q1 2025 Mechanism of Action • Reversible allosteric MALT1 inhibitor that can dampen NF-κB signaling • Selectively inhibits CLL proliferation with limite
Slide 44: REC-3565 key preclinical data
Key Preclinical Data Category Assay DC Criteria Ph 1 large pharma Ph1 biotech REC-3565 Potency & Selectivity MALT1 IC50 (nM) <100 OCI-Ly3 proliferation IC50 (nM) <400 ADME UGT1A1 IC50 (µM) >10 Caco-2 A2B (efflux) 10⁻⁶ cm/s >5 (<3) REC-3565 has Best-in-Class potential1 Single-agent and synergistic ac
Slide 45: REC-3565 Study Design and Next Steps
REC-3565 (MALT1 inhibitor): Study Design and Next Steps Development Strategy • N ~30 • R/R B-Cell Malignancies • REC-3565 PO QD or BID RD Part A Monotherapy Phase 1 study design Q1 2025 Primary Endpoint: • Safety / tolerability • RD for combination Phase 1 Dose Escalation 45 Trial Update • Trial ini
Slide 46: REC-4539: LSD1 Inhibitor
Program Status • Potential Best-in-Class LSD1 inhibitor • Phase 1 initiation in SCLC expected 1H 2025 Mechanism of Action • Reversible LSD1 inhibitor that can selectively upregulate NOTCH signaling • Promotes differentiation of neuroendocrine cancer cells • Impairs DNA repair pathways sensitizing SC
Slide 47: REC-4539 key preclinical data
Assay DC Criteria Competitor 1 Competitor 2 REC-4539 Brain : Plasma Ratio >0.5 MDCK-MDR1 Efflux Ratio (Pgp) <2 Predicted Human Half-life QD dosing Key Preclinical Data REC-4539 has Best-in-Class potential1 REC-4539 highly efficacious in SCLC xenograft model2 REC-4539 (LSD1 inhibitor): Sufficient CNS
Slide 48: Pipeline: Rare disease
PIPELINE Rare disease —hd| tt
Slide 49: REC-994: Superoxide Scavenger
Program Status • First therapeutic candidate advanced to an industry-sponsored Phase 2 trial • Phase 2 primary endpoint of safety met with similar AE profile across arms • Meeting with FDA anticipated in H2 2025 to discuss plans for additional clinical study Mechanism of Action • Selective, orally b
Slide 50: REC-994 key preclinical data
Lesion size (mm2) Key Preclinical Data1 Reduces lesion number & size in Ccm1 and Ccm22 loss of function (LOF) mouse models REC-994 (Superoxide Scavenger): Preclinical studies showing reduction of lesion burden de-risked the first industry-sponsored Phase 2 study in CCM Identified REC-994 as potentia
Slide 51: REC-994 Phase 2 SYCAMORE topline data
REC-994 (Superoxide Scavenger): Topline Phase 2 data in September demonstrated encouraging signals of efficacy 51 Trial Update • Randomized, double-blind, placebo-controlled Phase 2 study • Primary endpoint of safety and tolerability met September 2024 • Encouraging trends observed in objective MRI-
Slide 52: REC-4881: MEK1/2 Inhibitor
Program Status • First-in-Disease and Best-in-Class potential for the treatment of FAP • Phase 1b safety and futility analysis (polyp burden) anticipated in H1 2025 Mechanism of Action • Loss of APC drives FAP disease progression through aberrant MAPK signaling • REC-4881 is a highly potent, non-com
Slide 53: REC-4881 key preclinical data
Key Preclinical Data1 REC-4881 Decreases Polyp Count and Pre-Cancerous Adenomas • Significantly reduces polyp count at all dose levels, outperforming celecoxib in APCmin/- mouse • Unlike celecoxib, REC-4881 reduces both polyp numbers and % of adenomas • Meaningful efficacy seen at lowest dose tested
Slide 54: REC-4881 Study Design and Next Steps
REC-4881 (MEK1/2 Inhibitor): Study Design and Next Steps Phase 2 Dose Expansion (N=30) REC-4881 Phase 1b Dose Escalation (N≤18) RP2D • Confirmed APC mutation • ≥ 55 years old • Post-colectomy/proctocolectomy • No cancer present • Polyps in upper and lower GI 4mg 8mg 12mg Study Objectives: • Identify
Slide 55: REV102: ENPP1 Inhibitor
Program Status • Potential First-in-Class and Best-in-Class ENPP1 inhibitor for the treatment of patients with HPP • Development candidate nomination expected in Q4 2024 Mechanism of Action • Potent ENPP1 inhibitor is a non-immunogenic small molecule that restores PPi balance • Highly selective ENPP
Slide 56: REV102 in vivo validation and addressable patient opportunity
REV102 (ENPP1 Inhibitor): OS insights validated using in vivo mouse model showing significant difference in restoring HPP biomarker that promotes bone mineralization 56 Data is for REV101 (1st gen tool compound); compound being developed is REV102 L3 Vertebrate (n=5, females) Distal Femur (n=5, male
Slide 57: REC-2282: Pan-HDAC Inhibitor
Program Status • Potential First-in-Disease and Best-in-Class therapy for NF2 mutant meningioma • Data maturing with PFS6 results expected H1 2025 Mechanism of Action • Orally bioavailable, CNS penetrant, and potent pan-HDAC inhibitor • Loss of Merlin (NF2) leads to PI3K signaling and meningioma pro
Slide 58: REC-2282 key preclinical data
REC-2282 S id e E ff e c t S c o r e Disease Score 0 1.0 30 25 35 20 15 10 5 Disease State Healthy Cells REC-2282 (Pan-HDAC Inhibitor): Identified as a unique HDAC inhibitor in Recursion's unbiased screen modeling NF2 loss-of-function + REC-2282 (months) + Normal diet (months) Recursion OS Insight K
Slide 59: REC-2282 Study Design and Next Steps
REC-2282 (Pan-HDAC Inhibitor): Study Design and Next Steps Primary Endpoint: • PFS6 Secondary Endpoint: • Safety, ORR REC-2282 Phase 2 Portion Open-label, 2-arm study 24 Patients Allocated 1:1 40 mg 60 mg • MRI-confirmed progressive meningioma • Sporadic meningioma with confirmed NF2 mutation • Fami
Slide 60: Pipeline: Other areas of high unmet need
PIPELINE Other areas of high unmet need
Slide 61: REC-3964: C. difficile Toxin B Selective Inhibitor
Program Status • First-in-Class therapy for prevention rCDI • First Patient Dosed in the Phase 2 ALDER trial expected in Q4 2024 • Phase 2 update expected in Q1 2026 Mechanism of Action • Highly potent, orally bioavailable C. diff toxin B (TcdB) selective inhibitor • Selectively inhibits catalytic a
Slide 62: REC-3964 key preclinical data
REC-3964 (CDI TcdB Inhibitor): Identified as potential superior inhibitor compared to SOC in in vitro and in vivo preclinical studies Recursion OS Insight Key Preclinical Data1 62 1. N=10 hamsters per group. C. difficile strain 630, Data on File Data on File REC-3964 significantly extended survival
Slide 63: REC-3964 Study Design and Next Steps
Primary Endpoint: • Rate of recurrence Secondary Endpoint: • Additional efficacy measures • Safety / tolerability • PK REC-3964 Phase 2 Open-label, 2-arm study • High-risk of CDI • ≥3 bowel movements in 24 hours • Confirm CDI using EIA (toxin) • No fulminant CDI • No history of chronic diarrheal ill
Slide 64: REC-4209: Target Epsilon
Program Status • First-in-Class therapeutic for treatment of IPF • IND submission expected in 2025 • Phase 1 study in healthy volunteers expected to initiate in 2025 Mechanism of Action • Reversible, orally bioavailable, and potent Target Epsilon inhibitor • Promotes tissue repair and reverses fibro
Slide 65: REC-4209 key preclinical data
Recursion OS Insights1 • REC-4209 at low doses reduces total lung collagen by 45% to 60% versus vehicle mice Control Vehicle 0.03 0.1 0.3 0 1,000 2,000 3,000 4,000 5,000 Total Lung Collagen Lu n g O H P ( u g/ lu n g)Disease State (Fibrocytes) Control State (Pentraxin-2) Normal Lung + REC-4209 Fibro
Slide 66: Appendix: Partnerships & Data Strategy Details
APPENDIX Partnerships & Data Strategy Details
Slide 67: Therapeutic discovery partnerships
67 Trademarks are the property of their respective owners and used for informational purposes only. Exciting scientific collaborations span biopharma, tech & data Therapeutic discovery partnerships • Up to or exceeding $300M in possible program milestones for up to 40 programs • One program and one
Slide 68: Platform, technology, and data partnerships
Computation and ML/AI Real-world data access 68 Trademarks are the property of their respective owners and used for informational purposes only. Exciting scientific collaborations span biopharma, tech & data Platform, technology, and data partnerships • $50M equity investment • Partnership on advanc
Slide 69: OpenPhenom outperforms CellProfiler
OpenPhenom outperforms 'gold standard' CellProfiler package is industry benchmarking tasks 0.95 1.00 1.05 1.10 1.15 1.20 1.25 CellProfiler OpenPhenom Phenom-1 Phenom-2 R e la ti v e R e c a ll I m p ro v e m e n t StringDB Relationship Recall1 Available today under new release Available under commer
Slide 70: Recursion
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