Recursion Pharmaceuticals, Inc. · NASDAQ:RXRX
Recursion Pharmaceuticals — Merger or Acquisition (September 2024)
92 slides from Recursion Pharmaceuticals's merger presentation, Sep 3, 2024
Slide 1: Decoding Biology To Radically Improve Lives
September 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 about the proposed combination
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: Phase 2 CCM Clinical Trial Update and Potential Milestones
Phase 2 CCM Clinical Trial Update and Potential Milestones 4
Slide 5: SYCAMORE topline readout: REC-994 for CCM
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 6: Pipeline milestones
Pipeline • CCM: Ph2 in Sep 2024 primary endpoint of safety met, encouraging trends seen in exploratory efficacy • NF2: Ph2 safety & preliminary efficacy expected in Q4 2024 • FAP: Ph2 safety & preliminary efficacy expected in H1 2025 • AXIN1 or APC Mutant Cancers: Ph2 safety & preliminary efficacy e
Slide 7: Partnerships and platform updates
Partnerships • Roche & Genentech: validation program option exercised for 1st validated hit series in oncology, 1st neuroscience phenomap optioned for $30M (part of a structure that could exceed a total of $500M across multiple maps), potential for near-term program and additional map options • Baye
Slide 8: Recursion and Exscientia Combination
Recursion and Exscientia Combination 8
Slide 9: Combination of many complementary factors
Combination of Many Complementary Factors • Pipeline: Diverse portfolio of clinical and near-clinical programs with ~10 clinical readouts over the next ~18 months • Partnerships: Diverse portfolio of transformational partnerships with potential for over $200 million in milestone payments over the ne
Slide 10: Recursion + Exscientia: Pipeline
• Diverse Portfolio of clinical or near-clinical programs • ~10 clinical readouts over the next ~18 months • Complementary therapeutic pipelines with no competitive overlap • Most of these programs, if successful, could have annual peak sales opportunities >$1 billion each • Strategic Focus • Recurs
Slide 11: Combined pipeline and strategic collaborations
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 12: 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 13: 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 14: Exscientia capabilities integrating with Recursion OS
14 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 15: 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 16: Transaction details of Recursion-Exscientia combination
16 Transaction details of Recursion-Exscientia combination Stock Consideration Pro-Forma Ownership Cash Position Management and Board Timing and Approvals • Stock for stock transaction • Exscientia shareholders will receive 0.7729 shares of Recursion Class A common stock for each Exscientia ordinary
Slide 17: 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 18: Recursion Value Proposition and OS
Recursion Value Proposition and OS 18
Slide 19: 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 20: 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 21: 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 22: Recursion OS integrates modules across drug discovery
22 The Recursion OS integrates modules across many diverse steps to industrialize drug discovery and development
Slide 23: Connecting data layers to build multiomic maps
23 We connect data layers to build multiomic digital maps of biology
Slide 24: 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 >250 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 25: 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 26: 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 ADME: Data and scale lead to State of the Art models Estimated 90x throughput over manual approach >750 compound
Slide 27: InVivomics accelerates decision-making in late discovery
DATA GENERATION MODELS InVivomics accelerates decision-making in late discovery • 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
Slide 28: Patient data: path to uncover novel disease drivers
DATA GENERATION MODELS Patient Data: Path to uncover novel disease drivers with Maps >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 ca
Slide 29: 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 30: Recursion's approach
Recursion’s Approach High potential, unexplored Low potential, thoroughly explored Low potential, unexplored High potential, thoroughly explored Our unique approach creates novel opportunities 30
Slide 31: 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 32: Value Creation — Pipeline
Value Creation — Pipeline © Recursion.
Slide 33: 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 34: More than a dozen discovery and research programs
34 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 35: REC-994 for CCM 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 36: 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 37: REC-2282 for NF2 overview
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 38: 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 39: 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 m
Slide 40: TUPELO trial design and update
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 • Polyp
Slide 41: 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 42: LILAC 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 43: ALDER clinical trial: REC-3964 for C. difficile
Clinical: C. difficile ALDER Clinical Trial: REC-3964 for C. Difficile PATHOPHYSIOLOGY & REASON TO BELIEVE ~730,000 Diagnosed US + EU5 patients • Severity of infection varies and can range from mild to severe, requiring colectomy • >29,000 patients die in the US each year from CDI • Cost burden of u
Slide 44: ALDER trial design
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 • Phase 2 initiation expected in Q4 2024, preliminary readout expected by end of 2025 REC-3964 25
Slide 45: RBM39 target insight and preclinical efficacy
Similar Opposite BRCA-proficient ovarian cancer PDX Identify tumor-targeted precision therapeutic NCE with novel MOA capable of potentially treating HR-proficient cancers Inhibition of target RBM39 (previously referred to as Target γ) may mimic the inhibition of CDK12 while mitigating toxicity relat
Slide 46: REC-1245: RBM39 inhibition for HR-proficient cancers
Trial Update Phase 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 minor toxicity / 3 patient cohorts if DLT N = 3-6 Using BOIN design Phase 1B Dose Confirmation
Slide 47: Target Epsilon in fibrotic disease
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 48: Value Creation – Partnerships
Value Creation – Partnerships 48
Slide 49: 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 50: Partnership terms: Bayer, Roche-Genentech, NVIDIA
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 51: Roche-Genentech optioned neuroscience phenomap for $30 Million
Fee Structure Validated Approach Milestone Payment Building Technologies Additional Maps $30 million is part of a fee structure that could exceed a total of $500 million across multiple maps, not inclusive of program milestones Validates Recursion’s scientific approach to mapping biology as well as
Slide 52: Bayer partnership progress
Work initiated Initiated 1st Joint Project which is advancing rapidly towards Lead Series nomination On track to complete 25 unique multi-modal 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
Slide 53: Value Creation – Data Strategy
Value Creation – Data Strategy 53
Slide 54: 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 55: Recursion OS modules
The Recursion OS is a palette of evolving sophisticated modules 55
Slide 56: LOWE demo
[ DEMO ] 56 LOWE puts the Recursion OS at your fingertips via natural language without any coding expertise required
Slide 57: LOWE demo
[ DEMO ] LOWE puts the Recursion OS at your fingertips via natural language without any coding expertise required 57
Slide 58: 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… 58
Slide 59: Culture and Team
Culture and Team © Recursion.
Slide 60: Our People
~43% Female Male ~54% ~1% Non-Binary Parity Pledge Signer gender parity and people of color parity Data shown reflective of Q2 2024, gender statistics include participating individuals have advanced degrees >50% Technology – data science, software engineering, automation, etc. Life Sciences – biolog
Slide 61: Executive team and board of directors
David Mauro, MD PHD Chief Medical Officer Board of Directors Dean Li, MD PHD Co-Founder of RXRX, President of Merck Research Labs Rob Hershberg, MD PHD Co-Founder, CEO, & Chair of HilleVax, Former EVP, CSO, & CBO of Celgene Blake Borgeson, PHD Co-Founder of RXRX Terry-Ann Burrell, MBA CFO & Treasure
Slide 62: Additional Information about Scientific Approach
Additional Information about Scientific Approach 62
Slide 63: 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 64: 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… JAK1 TNKS1BP1 PPP1R9B PHF13 SOCS3 PRKCH MEGF8 ASB7 SLC39A1 DOCK9 ZMYM3 FAM49B STK24 YWHAB IL6ST IL6R STAT3
Slide 65: Active Learning to Increase Knowledge Per Experiment
65 Active Learning to Increase Knowledge Per Experiment
Slide 66: Virtuous Cycles Drive Super-Linear Knowledge Creation
66 Virtuous Cycles Drive Super-Linear Knowledge Creation
Slide 67: Additional Information about Pipeline Programs
Additional Information about Pipeline Programs 67
Slide 68: 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 69: Non-oncology orphan indication comparison
69 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 70: 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 71: REC-994 reduces lesion burden in 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 72: 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 73: 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 74: 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 75: NF2 meningiomas disease overview
75 • 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 76: REC-2282 rescued loss of NF2
76 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 : R
Slide 77: REC-2282: mechanism of action
77 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 78: REC-2282 vs other HDAC inhibitors
78 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 79: REC-4881 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 80: Familial adenomatous polyposis disease overview
80 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 81: Preclinical validation in FAP models
Clinical: FAP Preclinical Validation of Novel OS Insight in Relevant FAP Models 81
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: 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 84: Flexible patient selection strategy and study design
84 • 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 85: REC-4881 phenotypically opposite to APC and AXIN1 KO
85 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 86: 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 87: REC-3964 significantly extended survival over SOC
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 88: 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 89: 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. 3 1 2 4 Clinical: C. difficile REC-3964 : Selective Inhibitor of C. difficile Toxins 89 REC-3964 binds and blocks catalytic activity of the t
Slide 90: REC-3964 Phase 1 trial design and topline
90 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 91: 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 92: 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 • Recursion OS identified RBM39 as a novel target capable of mimicking CDK12 biology independent of CDK13 • Lead molecule h
Recursion Pharmaceuticals — Merger or Acquisition (September 2024) on 6ix