Recursion Pharmaceuticals, Inc. · NASDAQ:RXRX
Recursion Pharmaceuticals — Investor Presentation (December 2023)
97 slides from Recursion Pharmaceuticals's investor presentation, Dec 20, 2023
Slide 1: Decoding Biology To Radically Improve Lives
Decoding Biology To Radically Improve Lives December 2023
Slide 2: Disclaimers
2 Disclaimers 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, es
Slide 3: Virtuous cycles of atoms and bits
3 Real (atoms) Digital (bits) 1 Profile Systems Capture high-dimensional data to create a digital record of reality (things, places, preferences, etc.) Data Aggregate and organize data to create digital maps of reality Algorithms Navigate digital maps to predict novel relationships, then try them in
Slide 4: Our approach breaks down the data roadblocks in traditional biopharma
4 Trademarks are the property of their respective owners and used for informational purposes only. Reproducibility Crisis Multiple studies have shown that the vast majority of published academic literature cannot be recapitulated Analog Standard The fax machine is alive and well in medicine, while i
Slide 5: Recursion OS: wet lab, data and compute
Improved and scaled clinical pipeline Recursion OS Profile Systems: We have built and continue to scale among the world’s most prolific automated wet labs 5 Data: Each week we digitize millions of our own experiments across multiple layers of biology from cell to animal ALGORITHMS: We own and operat
Slide 6: A leap forward in our vision
Updates reinforce Recursion’s position as a leader at the intersection of scaled biology and compute • 5-year partnership providing access to multi-modal data for >100k oncology patients • Ability to build causal AI models to tune Recursion OS • More precisely aim clinical programs towards right pat
Slide 7: Update 1: Tempus Partnership
Update 1: Tempus Partnership
Slide 8: Recursion to partner with Tempus
+ • $160M paid by Recursion to Tempus in cash or equity, at our election, in increasing annual increments over five years, beginning with $22M of equity to be issued later this year • Expected to accelerate model deployment, linking molecular data with outcomes • Expected to enhance program translat
Slide 9: Another potential virtuous cycle with patient data
Creating another potential virtuous cycle: Recursion will direct biological exploration by the Recursion OS based on scaled patient data as well as drive programs into the clinic with biomarker and patient stratification insights at an unparalleled pace 20PB+ of data immediately available to Recursi
Slide 10: Comprehensive set of biological data layers
10 Partnership will create among the most comprehensive set of biological data layers in the industry Image adapted from D’Orazio, M., et al. Nature Scientific Reports 2022 RNA Level (Cell and Population-Scale) Transcriptomics DNA Level (Population-Scale) Genomics Protein Level Proteomics Organism L
Slide 11: Recursion Data Universe
11 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 models in biology • RXRX3: CRISPR knockouts of most of the hu
Slide 12: Preferential access to multi-modal data
12 Collaboration provides preferential access to multi-modal data to enhance precision medicine, translation and trial design TranslationCompound OptimizationHit & Target ValidationPatient Connectivity & Novelty Chemical property predictions Compound selection with ML DMPK experiments Phenomic effic
Slide 13: Update 2: Supercomputer Expansion
Update 2: Supercomputer Expansion
Slide 14: BioHive-1 expansion with H100s
Computational Tools Expand BioHive-1 from: • 320 A100s… …to include an additional • 504 H100s With operations beginning H1 2024 Likely to be the highest performing compute cluster owned and operated by any biopharma company on earth and among the top 50 compute clusters on the Top500 list 14
Slide 15: Scaled data and accelerated computing advance biological ML
The combination of scaled data generation and accelerated computing is a key to advancing biological ML World’s largest phenomic foundation model for biology (PHENOM-1) 15 Increasingly powerful foundation models for chemistry Orchestration with custom LLMs to minimize toil and bias from discovery at
Slide 16: Update 3: Bayer Partnership Transformation
Update 3: Bayer Partnership Transformation
Slide 17: Updated Bayer collaboration in precision oncology
17 Update of existing collaboration to exploit Recursion OS advancements and align with Bayer’s strategic interest in precision oncology Go-forward collaboration • Re-aligned focus to deliver on Bayer strategic objectives in oncology • Up to 7 new Projects anticipated • >1.5x increase in per program
Slide 18: In Brief: The Recursion Value Proposition
In Brief: The Recursion Value Proposition
Slide 19: Leading a new TechBio sector
Recursion leading a new TechBio sector at the intersection of technology and biology 19Adapted 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 (Transist
Slide 20: The Recursion OS today
20 The Recursion OS today: Industrializing drug discovery to transform BioTech into TechBio TranslationCompound OptimizationHit & Target ValidationPatient Connectivity & Novelty Chemical property predictions Compound selection with ML DMPK experiments Phenomic efficacy InVivomic Prioritization & Dig
Slide 21: 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 21 Screen — H
Slide 22: Multi-pronged capital-efficient business strategy
Harnessing value with a multi-pronged capital-efficient business strategy 22 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 23: Our pipeline reflects the scale and breadth of our approach
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. 54K5) CLOSTRIDIOIDES DIFFICILE INFECTION (est. 730K) CEREBRAL CAVERNOUS MALFORMATION (CCM; est. 360K1) NEUROFIBROMATOSIS TYPE
Slide 24: Significant scientific collaborations in TechBio
Significant scientific collaborations in TechBio across biopharma and tech Trademarks are the property of their respective owners and used for informational purposes only. 24 Undruggable oncology targets • $30M upfront and $50M equity investment • Increased per program milestones which may be up to
Slide 25: 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 26: The Recursion OS today
26 The Recursion OS today: Industrializing drug discovery to transform BioTech into TechBio TranslationCompound OptimizationHit & Target ValidationPatient Connectivity & Novelty Chemical property predictions Compound selection with ML DMPK experiments Phenomic efficacy InVivomic Prioritization & Dig
Slide 27: LLMs query global knowledge for program ideation
27 27 TranslationCompound OptimizationHit & Target ValidationPatient Connectivity & Novelty State-of-the-art LLMs query global knowledge for program ideation & evaluation Rapidly scaling to 1000s of new differentiated program ideas Large language models (LLMs) evaluate complex opportunities at scale
Slide 28: Rapidly scaling to 1000s of new program ideas
28 28 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 ma
Slide 29: Compound optimization with ML and automation
29 29 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
Slide 30: InVivomics and preclinical assessment
30 30 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 tol
Slide 31: LLM-based orchestration and autonomous exploration
31 Recursion OS LLM-based orchestration and autonomous exploration LLMs query global knowledge for program ideation & evaluation Combined models and tools will enable automated generation of novel, patient-specific hypotheses Custom AI Chemist LLM minimizes human toil and bias approaching later-stag
Slide 32: Virtuous cycles leading to first-in-disease development
32 Our virtuous cycles of atoms and bits are already leading to first-in-disease development and beyond
Slide 33: SYCAMORE: REC-994 for CCM
Julia – living with CCM 33 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 34: SYCAMORE Clinical Trial: REC-994 for CCM
34 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 Enrollmen
Slide 35: POPLAR: REC-2282 for NF2
35 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 36: POPLAR Clinical Trial: REC-2282 for NF2
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 and
Slide 37: TUPELO: REC-4881 for FAP
37 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 38: TUPELO Clinical Trial: REC-4881 for FAP
38 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/pouch
Slide 39: REC-4881 for AXIN1 or APC mutant cancers
39 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 40: Phase 2 trial design for AXIN1 or APC mutant cancers
Expect Phase 2 initiation in late Q4 2023 or early Q1 2024 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 MEK inhibitor treatment within 2 months of
Slide 41: REC-3964 for C. difficile infection
41 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 42: REC-3964 Phase 1 results
42 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 43: Planned Phase 2 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 44: RBM39 for HR-proficient ovarian cancer
RBM39: Novel CDK12-Adjacent Target for HR-Proficient Ovarian Cancer 44 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 45: Value driven by our team and our milestones
Value driven by our team and our milestones
Slide 46: 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 47: Our leadership team and board
Our leadership team brings together experience & innovation to lead TechBio 47 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
Slide 48: Strong financial position and what to watch
Strong Financial Position ~$387M in cash at end of Q3 2023 Near-Term • Potential option exercises for map building initiatives • Potential for additional partnership(s) in large, intractable areas of biology such as CV/Met • Potential additional option exercises for partnership programs • Ph2 initia
Slide 49: Impact
Impact 49
Slide 50: 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 50 Top-20 Pharma Companies AI-Native Drug Discovery Companies AI-enabled drug discovery efforts have proliferated alongside the de
Slide 51: Map-based approach versus traditional 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 52: Scale of biological and chemical inputs and automation
~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 ~1 Trillion Diverse Biological and Chemical Inputs Rob
Slide 53: 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 54: JAK/STAT pathway in the maps
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… 54 JAK1 TNKS1BP1 PPP1R9B PHF13 SOCS3 PRKCH MEGF8 ASB7 SLC39A1 DOCK9 ZMYM3 FAM49B STK24 YWHAB IL6ST IL6R STA
Slide 55: 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. 55 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 56: Massive protein-ligand interaction predictions
56 ~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 com
Slide 57: 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 58: Reliable, relatable, scalable data differentiates Recursion
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 59: 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 60: COVID-19 research: Recursion OS predicted 9 of 10 trials
Drug Prediction Correct? Hydroxychloroquine x ✓ Lopinavir x ✓ Ritonavir x ✓ Remdesivir ✓ ✓ Baricitinib ✓ ✓ Tofacitinib ✓ ✓ Fostamatinib ✓ ✓ Ivermectin* x ✓ Fluvoxamine x ✓ Dexamethasone x x COVID-19 research: Recursion OS correctly predicted 9 of 10 clinical trials 60https://www.biorxiv.org/content/
Slide 61: 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 62: Disease Overview: Cerebral Cavernous Malformations
62 • 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 63: CCM patient population and no approved therapy
63 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 64: CCM is an under-appreciated orphan disease
64 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 65: Therapeutic approach to CCM
65 • 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 66: 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 67: 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 68: Preclinical studies confirm insight
68 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 69: REC-994 Phase 1 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 70: 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 71: Disease Overview: Neurofibromatosis Type 2
71 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 72: NF2 meningiomas patient population
72 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 73: REC-2282 rescued loss of NF2
73 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 74: REC-2282 mechanism of action
74 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 75: REC-2282 preclinical in-vivo efficacy
75 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 76: 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 77: REC-2282 versus other HDAC inhibitors
77 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 78: 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 79: Disease Overview: Familial Adenomatous Polyposis
79 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 80: FAP standard of care
80 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 81: REC-4881 rescued APC knockdown defects
81 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 82: REC-4881 blocks Wnt mutation induced MAPK signaling
82 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 83: Preclinical reduction in polyp count and dysplasia
83 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 84: Clinical data generated by Recursion
84 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 85: 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 86: Disease Overview: AXIN1 or APC mutant cancers
86 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 87: Flexible patient selection strategy and study design
87 • 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 88: REC-4881 dosage hypothesis and insight from OS
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 89: 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 89 -100 -80 -60 -40 -20 0 20 AXIN1 or APC wildtype
Slide 90: 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 91: 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 9
Slide 92: Disease Overview: C. difficile infection
92 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 93: REC-3964 rescued cells treated with C. diff 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 93
Slide 94: 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 95: 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 96: 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 97: REC-3964 MAD study 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.
Recursion Pharmaceuticals — Investor Presentation (December 2023) on 6ix