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: Third-party data and additional information
Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the company’s own internal estimates and research. While the company believes these third-party sources to be reliable as of the date of th
Slide 4: Q3 Highlights
Q3 Highlights 4
Slide 5: Advancing Multiple Clinical Programs
Pipeline • CCM: Ph2 top-line readout met primary endpoint of safety with encouraging time-dependent trends seen in exploratory efficacy, preparations for FDA meeting and Ph2/3 trial underway • NF2: Ph2 update expected in Q4 2024 • FAP: Ph2 safety & preliminary efficacy expected in H1 2025 • AXIN1 or
Slide 6: Partnerships and Platform highlights
Partnerships • Roche & Genentech: 1st neuroscience phenomap optioned for $30M (part of a structure that could exceed a total of $500M across multiple maps), validation program option exercised for 1st validated hit series in oncology, potential for near-term program and additional map options • Baye
Slide 7: Recursion and Exscientia Combination
Recursion and Exscientia Combination 7
Slide 8: Combination of Many Complementary Factors
Combination of Many Complementary Factors • Pipeline: Diverse portfolio of more than ten clinical and near- clinical programs advancing simultaneously • Partnerships: Diverse portfolio of transformational partnerships with the potential for over $200 million in milestone payments over the next 2 yea
Slide 9: Combined pipeline
In addition, 4 large strategic collaborations (e.g., Roche, Bayer, Sanofi, Merck KGaA) with 10 programs already optioned across oncology and immunology Note: Over a dozen discovery programs in combined pipeline, including ENPP1 inhibitor in collaboration with Rallybio, which is expected to achieve d
Slide 10: Recursion + Exscientia: Partnerships
• Diverse Portfolio of transformational partnerships with leading large pharma companies • 10 programs already optioned across oncology and immunology • Combined company expects potential additional milestone payments of ~$200 million over the next 2 years from current partnerships • Potential for >
Slide 11: Recursion + Exscientia: Platform
• Core Strengths • Recursion: scaled biology exploration and translational capabilities primarily focused on first-in- disease opportunities • Exscientia: precision chemistry design and small molecule automated synthesis primarily focused on best-in-class opportunities • Assembles a full-stack platf
Slide 12: Complementary capabilities integrating with Recursion OS
12 Complementary capabilities through combination with Exscientia labelled in orange. Overview of areas where Exscientia’s capabilities can immediately integrate and complement the Recursion OS upon close
Slide 13: Summary of complementary factors
Platform Strength Scaled exploration and mapping of biological relationships Precision chemistry design and molecular synthesis Internal Pipeline First-in-class products in oncology, rare disease, infectious disease Best-in-class products in oncology, inflammation, immunology Large Pharma Partnershi
Slide 14: Transaction details of Recursion-Exscientia combination
14 Transaction details of Recursion-Exscientia combination Stock Consideration • Stock for stock transaction • Exscientia shareholders will receive 0.7729 shares of Recursion Class A common stock for each Exscientia ordinary share, subject to rounding for fractional shares Pro-Forma Ownership • Recu
Slide 15: Exscientia: '617 CDK7 inhibitor
Exscientia: ‘617 precision designed to have best-in-class properties Precision designed to maximize therapeutic index allowing for optimized combinations and potentially better efficacy • Selectivity, reversibility & efflux design properties limit potential toxicities to widen therapeutic index • CD
Slide 16: Recursion Value Proposition and OS
Recursion Value Proposition and OS 16
Slide 17: Formula for mapping and navigating complex systems
There is a formula for mapping and navigating complex systems using technology Digital (bits) Data Aggregate and organize data to create digital maps of reality 2 2 Real (atoms) 1 Profile Systems Capture high-dimensional data to create a digital record of reality (things, places, preferences, etc.)
Slide 18: Data roadblocks make mapping biology difficult
Data roadblocks make mapping and navigating biology difficult 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 in biopharma, study results from CROs
Slide 19: Recursion OS
Algorithms We own and operate one of the fastest supercomputers on earth, allowing us to train LLMs & FMs fit for the purpose of drug discovery Profile Systems We have built and continue to scale among the world’s most prolific automated wet labs Data Each week we digitize millions of our own experi
Slide 20: Recursion OS integrates modules to industrialize drug discovery
20 The Recursion OS integrates modules across many diverse steps to industrialize drug discovery and development
Slide 21: Multiomic digital maps of biology
21 We connect data layers to build multiomic digital maps of biology
Slide 22: Phenomics: Foundation models improve at detecting biology
Phenomics: Foundation models improve at detecting biology Brightfield to capture dynamics DATA GENERATION MODELS 25.7% increase in expressed gene knock-outs detected >300 million experiments >50 human cell types >1 trillion neurons generated 2 w e e k s Parameters B io lo gi ca l r ec al l Recall of
Slide 23: Transcriptomics: Multimodal data scales validation and mapping
Transcriptomics: Multimodal data scales validation and mapping >1M samples sequenced 1st genome-scale transcriptomic map DATA GENERATION MODELS 90% Ability to predict compounds that failed later disease-relevant assays in internal tests 60% Ability to predict compounds that passed later disease-rele
Slide 24: ADME: Data and scale lead to State of the Art models
1.25 1.00 0.75 0.50 0.25 0.00 -0.25 10⁶ 10⁷ 10⁸ 10⁹ Generalized performance over all 22 TDC ADMET datasets Number of parameters N o rm a liz e d p e rf o rm a n c e DATA GENERATION MODELS Estimated 90x throughput over manual approach >750 compounds per week Our single generalizable model improves wi
Slide 25: InVivomics accelerates decision-making in late discovery
DATA GENERATION MODELS • Machine learning enables scale by extracting signals from video and temperature sensors • Applied across breadth of Recursion portfolio • Designed to select the right molecule at the right dose before entering efficacy studies >1,000 digital mouse cages 150 digital rat cages
Slide 26: Patient Data: Path to uncover novel disease drivers
DATA GENERATION MODELS >20 PB of real-world multi-modal oncology data Hundreds of thousands of unique de-identified patient records across diverse therapeutic areas Combining Recursion maps of biology with patient clinical data unlocks causal modeling to find novel targets 26 Patient Data: Path to u
Slide 27: Failing faster and earlier to spend less and go faster
Screen — Hit ID — Validated Lead — Advanced Candidate — Development Candidate — Industry Recursion Failing faster and earlier to › › spend less › C o st t o IN D ( $ M ) › and go faster 100 80 60 51 80% 75% 85% 100 55 18 55% 32% 62% 7 37% St ag e Ti m e t o V al id at ed L e ad ( m o ) 4 Industry Re
Slide 28: Our unique approach creates novel opportunities
Recursion’s Approach High potential, unexplored Low potential, thoroughly explored Low potential, unexplored High potential, thoroughly explored 28 Our unique approach creates novel opportunities
Slide 29: Multi-pronged capital efficient business strategy
We harness value from the Recursion OS with a multi-pronged capital efficient business strategy 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
Slide 30: Value Creation — Pipeline
Value Creation — Pipeline © Recursion.
Slide 31: Pipeline Strategy
Build internal pipeline in indications with potential for accelerated path to approval Pipeline Strategy Precision Oncology Rare Disease Pipeline Partnerships Data *Includes a single oncology indication from our Roche and Genentech collaboration. We harness value from the Recursion OS with a multi-p
Slide 32: More than a dozen discovery and research programs
32 More than a dozen discovery and research programs in oncology or with our partners – first program optioned by Roche-Genentech in GI-oncology All populations defined above are US and EU5 incidence unless otherwise noted. EU5 is defined as France, Germany, Italy, Spain, and UK. (1) Prevalence for
Slide 33: REC-994 for CCM: Topline Readout in September 2024
SYCAMORE is the first industry-sponsored Phase 2 trial for CCM Topline Readout September 2024 • Primary endpoint of safety and tolerability met • Encouraging trends in objective MRI-based exploratory efficacy measures demonstrated - reduced lesion volume and hemosiderin ring size in patients at the
Slide 34: REC-994 for CCM program overview
PATHOPHYSIOLOGY & REASON TO BELIEVE PREVALENCE & STANDARD OF CARE CAUSE KEY ELEMENTS Symptomatic US + EU5, >1 million patients worldwide live with these lesions today LOF mutations in genes CCM1, CCM2 & CCM3, key for maintaining the structural integrity of the vasculature due to unknown mechanisms E
Slide 35: SYCAMORE Clinical Trial: REC-994 for CCM Phase 2
Outcome Measures Enrollment Criteria • MRI-confirmed CCM lesion(s) • Familial or sporadic • Symptoms directly related to CCM • Primary: Safety and tolerability • Secondary: Efficacy • Exploratory: Biomarkers Trial Update 400mg 200mg Placebo Visits: Days 1 & 2 Months 1, 3, 6, 9 & 12 Enroll ~60 Extens
Slide 36: REC-2282 for NF2
PATHOPHYSIOLOGY & REASON TO BELIEVE PREVALENCE & STANDARD OF CARE CAUSE KEY ELEMENTS LOF mutations in NF2 tumor suppressor gene, leading to deficiencies in the tumor suppressor protein merlin Efficacy signal in Recursion OS, cellular, and animal models; suppression of aberrant ERK, AKT, and S6 pathw
Slide 37: POPLAR Trial: REC-2282 for NF2
Clinical: NF2 POPLAR Trial: REC-2282 for NF2 Part A Fully Enrolled Phase 2/3 trial initiated in Q2 2022 Outcome Measures Key Enrollment Criteria • MRI-confirmed progressive meningioma • Sporadic meningioma with confirmed NF2 mutation • Familial NF2 meningioma • Have documented progression with past
Slide 38: TUPELO Clinical Trial: REC-4881 for FAP
Clinical: FAP TUPELO Clinical Trial: REC-4881 for FAP Phase 2 Underway Polyps Found in Colon and Upper GI Tract PATHOPHYSIOLOGY & REASON TO BELIEVE PREVALENCE & STANDARD OF CARE CAUSE KEY ELEMENTS Inactivating mutations in the tumor suppressor gene APC • Targeting classical FAP patients (with APC mu
Slide 39: TUPELO Clinical Trial design
Clinical: FAP TUPELO Clinical Trial: REC-4881 for FAP Phase 2 Underway Source: Evaluate REC-4881 in Patients With FAP (TUPELO) Part 2 Enrollment Commenced Outcome Measures Key Enrollment Criteria • Confirmed APC mutation • ≥ 55 years old • Post-colectomy/proctocolectomy • No cancer present • Polyps
Slide 40: LILAC Clinical Trial: REC-4881 for AXIN1 or APC mutant cancers
Clinical: AXIN1 or APC LILAC Clinical Trial: REC-4881 for AXIN1 or APC mutant cancers PATHOPHYSIOLOGY & REASON TO BELIEVE PREVALENCE & STANDARD OF CARE CAUSE KEY ELEMENTS LOF mutations in AXIN1 or APC tumor suppressor genes Treatable US + EU~104,000 Substantial need for developing therapeutics for p
Slide 41: LILAC Clinical Trial design
Clinical: AXIN1 or APC LILAC Clinical Trial: REC-4881 for AXIN1 or APC mutant cancers FPI achieved Q1 2024 Outcome Measures Enrollment Criteria • Unresectable, locally advanced, or metastatic cancers • ≥ 55 years old • AXIN1 or APC mutation confirmed by NGS (tissue or blood) • CRC patients must be R
Slide 42: ALDER Clinical Trial: REC-3964 for recurrent C. difficile
Clinical: C. difficile ALDER Clinical Trial: REC-3964 for Prevention of Recurrent C. Difficile PATHOPHYSIOLOGY & REASON TO BELIEVE ~175,000 Addressable recurrent US patients • Severity of infection varies and can range from mild to severe, requiring colectomy • >29,000 patients die in the US each ye
Slide 43: ALDER Clinical Trial: POC Phase 2
ALDER Clinical Trial: POC Phase 2 REC-3964 in Patients at High Risk of C. Difficile Recurrence Trial Update Clinical: C. difficile Screening Randomization & Treatment • Phase 1 and DDI studies completed • Proof-of-concept Phase 2 first patient dose occurred in Q4 2024 • Preliminary readout expected
Slide 44: REC-1245: RBM39 Degrader
Identify tumor-targeted precision therapeutic NCE with novel MOA capable of potentially treating biomarker-enriched solid tumors and lymphoma Inhibition of target RBM39 may mimic the inhibition of CDK12 while mitigating toxicity related to CDK13 inhibition REC-1245 target engagement assays demonstra
Slide 45: Planned Phase 1/2 study of REC-1245
Trial Update Part 1A Dose Finding (Accelerated Titration BOIN) N=30 Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4+ Single patient, accelerated titrations until pharmacologically active dose (PAD) or toxicity / 3 patient cohorts if DLT N = 3-6 Using BOIN design Part 1B Dose Confirmation N=20 Do
Slide 46: Target Epsilon fibrosis program
Healthy StateDiseased State Reversal of Fibrocyte Differentiation Assay Identify a therapeutic NCE with a novel MOA capable of reversing disease- related fibrotic processes Recursion-generated hits show concentration-dependent rescue in a disease relevant human PBMC assay and phenomimic genetic KO o
Slide 47: Value Creation – Partnerships
Value Creation – Partnerships 47
Slide 48: Partnership Strategy
Partnership Strategy Partner in complex therapeutic areas requiring large financial commitment or competitive arbitrage Leverage partner knowledge and clinical development capabilities Undruggable Oncology Other large, intractable areas of biology (e.g., CV/Met) Neuroscience* Pipeline Partnerships D
Slide 49: Partnership terms: Bayer, Roche-Genentech, Tempus
Undruggable oncology targets • $30M upfront and $50M equity investment • Increased per program milestones which may be up to $1.5B in aggregate for up to 7 oncology programs • Mid single-digit royalties on net sales • Recursion owns all algorithmic improvements • First beta-user of LOWE Neuroscience
Slide 50: Roche-Genentech optioned neuroscience phenomap for $30 Million
Fee Structure $30 million is part of a fee structure that could exceed a total of $500 million across multiple maps, not inclusive of program milestones Validated Approach Validates Recursion’s scientific approach to mapping biology as well as Recursion’s ability to deliver on success-based data opt
Slide 51: Bayer partnership in undruggable oncology
Work initiated Initiated 1st Joint Project which is advancing rapidly towards Lead Series nomination Delivered multiple oncology data packages in Q3 Nov 2023 Focus on Oncology Q2 Bayer is the 1st beta-user of LOWE (Recursion’s LLM Orchestrated Workflow Engine) Recursion is delivering value across it
Slide 52: Value Creation – Data Strategy
Value Creation – Data Strategy 52
Slide 53: Data Strategy
Pipeline Partnerships License subsets of data and key tools Direct generation of new data internally to maximize pipeline and partnership value-drivers Data Strategy Licensing Augment Recursion OS Data We harness value from the Recursion OS with a multi-pronged capital efficient business strategy *I
Slide 54: Recursion OS is a palette of evolving modules
The Recursion OS is a palette of evolving sophisticated modules 54
Slide 55: LOWE demo
[ DEMO ] 55 LOWE puts the Recursion OS at your fingertips via natural language without any coding expertise required
Slide 56: LOWE demo
[ DEMO ] LOWE puts the Recursion OS at your fingertips via natural language without any coding expertise required 56
Slide 57: Discovery User Interface
The Recursion OS is now more than a collection of point solutions accessible to expert users …it is increasingly integrated and accessible via a Discovery User Interface that can be used by any of our scientists from the comfort of their laptop… 57
Slide 58: Culture and Team
Culture and Team © Recursion.
Slide 59: Our People
~43% Female Male ~55% ~1% Non-Binary Parity Pledge Signer gender parity and people of color parity Data shown reflective of Q3 2024, gender statistics include participating individuals have advanced degrees >50% Technology – data science, software engineering, automation, etc. Life Sciences – biolog
Slide 60: 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 Chris Gibson, PHD Co-Founder & CEO Tina Marriott President & COO Executiv
Slide 61: Additional Information about Scientific Approach
Additional Information about Scientific Approach 61
Slide 62: 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 63: 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… JAK1 TNKS1BP1 PPP1R9B PHF13 SOCS3 PRKCH MEGF8 ASB7 SLC39A1 DOCK9 ZMYM3 FAM49B STK24 YWHAB IL6ST IL6R STAT3
Slide 64: Active Learning to Increase Knowledge Per Experiment
64 Active Learning to Increase Knowledge Per Experiment
Slide 65: Additional Information about Pipeline Programs
Additional Information about Pipeline Programs 65
Slide 66: REC-994 for CCM program overview
Clinical: CCM REC-994 for CCM • First therapeutic candidate advanced to an industry-sponsored Phase 2 trial (SYCAMORE) for CCM • Partnered with leading KOLs at University of Rochester to develop a CCM PRO instrument for clinical trials • Putative MOA decreases ROS and oxidative stress to rescue path
Slide 67: Non-oncology orphan indication prevalence comparison
67 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 68: CCM – Applied prototyping of the Recursion OS
siCTRL siCCM2 siCCM2 + Simvastatin siCCM2 + Cholecalciferol siCCM2 + REC-994 Using an early version of our Recursion OS in an academic setting, we identified about 39 molecules out of 2,100 screened that according to a machine learning classifier rescued a complex unbiased phenotype associated with
Slide 69: REC-994 preclinical studies in CCM mouse models
Clinical: CCM 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) • REC-994 stabilizes the integrity of vasculature against challenges to permeability •
Slide 70: REC-994: Mechanism of Action
Healthy REC-994 ImpactCCM • Endothelial cell activation • Smooth muscle proliferation • Leukocyte adhesion • Platelet aggregation By regulating SOD2, CCM1 (KRIT1) & CCM2 suppress: CCM1 or CCM2 loss of function leads to activated endothelium: • Decreased cell-cell junctional integrity and increased m
Slide 71: REC-994 Phase 1 studies safety
REC-994 Phase 1 Studies - well-tolerated with no dose-dependent adverse events in SAD and MAD MAD Study Placebo 50 mg 200 mg 400 mg 800 mg Total Number of TEAEs Total Subjects with ≥ one TEAE 5 4 0 0 10 3 4 3 15 4 Severity Mild Moderate Severe 3 1 0 0 0 0 3 0 0 3 0 0 3 1 0 Relationship to Study Drug
Slide 72: REC-2282 program overview
Program Overview First-in-disease opportunity in NF2 with HDAC inhibitor Clinical Updates Near-term Catalysts Commercial Opportunity IP & Exclusivity • Orally bioavailable small molecule inhibitor of class I and class IIB HDACs in Phase 2/3 (POPLAR) trial • Unique MOA that disrupts PP1-HDAC interfac
Slide 73: NF2 Disease Overview: Meningiomas
73 • 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 ~27,000 Patients who have Meningiomas that Harbor NF2 Mutations
Slide 74: Insight from OS: REC-2282 Rescued Loss of NF2
74 Clinical: NF2 NF2 knockdown cells Healthy Cells REC-2282 HUVEC, human umbilical vein endothelial cells; NF2, neurofibromatosis type 2; siRNA, small interfering RNA. Prevents growth & regrowth of NF2- deficient meningioma model in mice + REC-2282 (months) + Normal diet (months) Insight from OS: RE
Slide 75: REC-2282: Mechanism of Action
75 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 76: REC-2282 vs other HDAC inhibitors for NF2
76 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 77: REC-4881 for FAP program overview
First-in-disease opportunity in FAP with a MEK 1/2 inhibitor • Orally bioavailable, small molecule non-ATP competitive allosteric inhibitor of MEK 1/2 in Phase 1b/2 (TUPELO) • REC-4881 appears more active versus approved MEK inhibitors in disease relevant preclinical models • Fast Track Designation
Slide 78: Disease Overview: Familial Adenomatous Polyposis
78 Patient Population ~50,000 Diagnosed US + EU5 patients • Autosomal dominant tumor predisposition syndrome caused by a mutation in the APC gene • Classic FAP (germline mutation): • Hundreds to thousands of polyps in colon and upper GI tract • Extraintestinal manifestations (e.g., desmoid tumors) •
Slide 79: Preclinical Validation in Relevant FAP Models
Clinical: FAP Preclinical Validation of Novel OS Insight in Relevant FAP Models 79
Slide 80: MoA: REC-4881 Blocks Wnt Mutation Induced MAPK Signaling
80 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 81: REC-4881 for AXIN1 or APC program overview
Program Overview Clinical Updates Near-term Catalysts Commercial Opportunity IP & Exclusivity Clinical: AXIN1 or APC First-in-disease opportunity in AXIN1 or APC mutant cancers with a MEK 1/2 inhibitor • Orally bioavailable, small molecule non-ATP competitive allosteric inhibitor of MEK 1/2 in Phase
Slide 82: Flexible Patient Selection Strategy and Study Design
82 • 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 83: REC-4881 phenotypically opposite to APC and AXIN1 KO
83 Clinical: AXIN1 or APC REC-4881 is phenotypically opposite to the genetic KO of APC and AXIN1 providing a novel mechanism that may restore the disease state modeled by the loss of these genes AXIN1 APC 2.5 µm 1.0 µm 0.25 µm 0.1 µm REC 4881 Significantly greater antitumor activity in mutant models
Slide 84: REC-3964 program overview
Program Overview Clinical Updates Near-term Catalysts Commercial Opportunity IP & Exclusivity Potential first-in-class small molecule for prevention of rCDI • Orally bioavailable, small molecule C. difficile toxin inhibitor and the first NCE developed by Recursion • Differentiated MOA selectively ta
Slide 85: Insight from OS: REC-3964 Rescued Cells
Disease State Healthy Cells REC-3964 0.1 µM Clinical: C. difficile • REC-3964 potently inhibits toxin B with residual activity against toxin A, while bezlotoxumab is specific to toxin B. • Significant difference in probability of survival vs bezlotoxumab alone at the end of treatment (p<0.001, log-r
Slide 86: REC-3964: Selective Inhibitor of C. difficile Toxins
Clinical: C. difficile CDI toxins bind to cell surface receptors and trigger endocytic event 1 Autocatalytic cleavage event releases CDI toxin's glucosyltransferase enzymatic domain into the cytosol of the infected cell 2 The glucosyltransferase locks Rho family GTPases in the inactive state 3 Inact
Slide 87: REC-3964: Selective Inhibitor of C. difficile Toxins
3 1 2 4 Clinical: C. difficile REC-3964: Selective Inhibitor of C. difficile Toxins 87 REC-3964 binds and blocks catalytic activity of the toxin’s innate glucosyltransferase, but not the host's 5 5 REC-3964 is Recursion’s 1st Small Molecule NCE to Reach the Clinic Adapted from Awad, MM. et al. (2014
Slide 88: REC-3964 Phase 1 trial design and topline
88 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 • 8 participants treated with placebo Primary Objectives ✓ Assess th
Slide 89: REC-3964 MAD study adverse events
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 90: REC-1245 program overview
Program Overview Clinical Updates Near-term Catalysts Commercial Opportunity IP & Exclusivity Potential first-in-class molecular glue degrader for biomarker selected population • REC-1245 demonstrates RBM39 degradation to modulate DDR without impacting CDK12 across multiple cell lines • REC-1245 dem