Relay Therapeutics, Inc. · NASDAQ:RLAY
Relay Therapeutics — 40th Annual J.P. Morgan Healthcare Conference (January 2022)
43 slides from Relay Therapeutics's conference presentation, Jan 10, 2022
Slide 1: 40th Annual J.P. Morgan Healthcare Conference Company Presentation
40th Annual J.P. Morgan Healthcare Conference Company Presentation January 2022 Exhibit 99.1
Slide 2: Disclaimer
Disclaimer This presentation contains forward-looking statements and information about our current and future prospects and our operations and financial results, which are based on currently available information. All statements other than statements of historical facts contained in this presentatio
Slide 3: Relay Tx – Patient-Driven, Growth-Oriented
Relay Tx – Patient-Driven, Growth-Oriented Clear Focus Validated Targets Therapeutic Areas Modalities Small molecules Oncology Genetic diseases Challengers Innovators New Breed of Biotech EXPERIMENTATION COMPUTATION Validated Approach PI3KαPAN RLY-2608 FGFR2 RLY-4008 SHP2 RLY-1971 The more we do, th
Slide 4: Relay Tx – Created by the Nexus of Unstoppable Forces and Data
Relay Tx – Created by the Nexus of 3 Unstoppable Forces and Data INTEGRATION Improving Experimental insight Increasing Genomic data 1990 Increasing Computational power Data Data Data Increasing efficiency and effectiveness of drug discovery Motion-Based Drug Design™
Slide 5: The Dynamo Platform – Integrating Experimentation with Computation
The Dynamo™ Platform – Integrating Experimentation with Computation Chemical biology insights Deep structural understanding Physics-based simulations AI / ML Dynamo™️ Platform EXPERIMENTATION COMPUTATION NMR and HDX-MS Data-constrained molecular dynamics Cryo-EM Ambient temp. X-Ray crystallography I
Slide 6: The Dynamo Platform – Experimentation
The Dynamo™ Platform – Experimentation EXPERIMENTATION Chemical biology insights Deep structural understanding Tools Cryo-EM Ambient Temp X-Ray Crystallo-graphy People and Functions Target Mechanistics Nanoscale Chemistry Time-resolved Biophysics Protein Engineering Etc. Experience 2016 Today 3 clin
Slide 7: The Dynamo Platform – Computation
The Dynamo™ Platform – Computation COMPUTATION Physics-based simulations AI / ML Tools Swimming Simulations Virtual Screens Experience 2016 Today 3 clinical assets in 5 years People and Functions Automated Chemical Design Force Field Development Quantum Mechanics Free Energy Methods Etc.
Slide 8: The Dynamo Platform – The Power of Experimentation + Computation
The Dynamo™ Platform – The Power of Experimentation + Computation Chemical biology insights Deep structural understanding Physics-based simulations AI / ML Dynamo™️ Platform EXPERIMENTATION COMPUTATION 5+ earlier stage programs in pipeline 2 therapeutic areas The more we do, the better we get 3 clin
Slide 9: Relay Tx – Our 3-Step Drug Discovery Process
Chemical biology insights Deep structural understanding Physics-based simulations AI / ML Dynamo™️ Platform EXPERIMENTATION COMPUTATION Relay Tx – Our 3-Step Drug Discovery Process Long Time Scale MD Examples of tools used: Examples of tools used: FEP Simulation ML-DEL Screen Virtual Screens Underst
Slide 10: Relay Tx – Our Current Focus
z Relay Tx – Our Current Focus Current Focus Modalities Therapeutic Areas Small molecules Oncology Genetic diseases SHP2 FGFR2 Validated Targets Challenger programs Innovator programs PI3Kα -- Rapid path to clinical POC Clear patient selection strategy Amenable to Relay Tx’s Dynamo™️ platform Increa
Slide 11: Relay Tx – We Have Validated Our Approach and Built Significant Advantage
Relay Tx – We Have Validated Our Approach and Built Significant Advantage PI3KαPAN RLY-2608 Motion-Based Hypothesis Pre-Clinical Validation Clinical Progress The more we do, the better we get SHP2 RLY-1971 Opportunity Size Annual US patient # Note: Patient #’s refer to total annual number of US pati
Slide 12: Relay Tx – Our Extensive Precision Medicines Pipeline
Innovators FGFR2 RLY-4008 Mutant + WT 8-20K PI3Kα franchise PI3KαPAN RLY-26081 RLY-2608 Pan-mutant allosteric inhibitor 50-156K PI3KαSPECIFIC H1047R-specific RLY-1047R H1047R allosteric inhibitor 15-48K PI3KαOTHER Additional Other novel mutant selective mechanisms To be announced Other oncology 3 pr
Slide 13: Relay Tx – What to Expect
Relay Tx – What to Expect Execution focus underpins value creation RLY-2608 (PI3KαPAN) RLY-4008 (FGFR2) To be disclosed in 1H 2022 Next target in pipeline RLY-1971 (SHP2) $617M Cash, cash equivalents and investments as of the end of Q3 2021 $381M Net proceeds from follow-on offering in October 2021
Slide 14: The Dynamo Platform – Evolving with Landscape of Leading Edge Techniques
The Dynamo™ Platform – Evolving with Landscape of Leading Edge Techniques Automated chemical design Protein structure prediction (AlphaFold) ML directed free energy calculations Active learning Long-time scale MD Quantitative DEL Generating data to build pharmacokinetic ML models High-throughput and
Slide 15: Relay Tx Programs
Relay Tx Programs
Slide 16: FGFR2 – Highlights from RLY-4008 Interim Clinical Data Disclosure
FGFR2 – Highlights from RLY-4008 Interim Clinical Data Disclosure (Oct 2021) Robust inhibition of FGFR2 with promising initial tolerability data Safety and Tolerability Early evidence of tumor regressions across several tumor and alteration types (with 3 out of 6 fusion positive cholangiocarcinoma F
Slide 17: FGFR2 – Validated Target Present in Several Tumor Types
FGFR2 – Validated Target Present in Several Tumor Types Fusions Amplifications Mutations FGFR2 Annual Cases (US, comprehensive) FGFR2-altered cancers remain a high unmet medical need Pancreatic Breast Endometrial Skin Melanoma Stomach Lung Bladder CUP Ovarian ~5K-15K patients in the US per year1 ~3K
Slide 18: FGFR2 – Selective Inhibitor Required to Address Large Unmet Medical Need
FGFR2 – Selective Inhibitor Required to Address Large Unmet Medical Need A selective inhibitor of FGFR2 with broad activity against acquired resistance mutations is necessary to address significant unmet need in patients with FGFR2-altered tumors Compound Company Stage FGFR2 Selective Response Rate
Slide 19: FGFR2 – Standard Approach to Discovery Has Had Limited Success
FGFR2 – Standard Approach to Discovery Has Had Limited Success Standard Approach FGFR1 FGFR2
Slide 20: FGFR2 – Increasing Experimental Resolution Reveals New Opportunities
FGFR2 – Increasing Experimental Resolution Reveals New Opportunities FGFR1 FGFR2 Down Up Down Up Down Up Down Up Down Up Up Up Down Down Down Up Exploiting the dynamic difference between FGFR1 and FGFR2 enabled Relay Tx to design a selective FGFR2 inhibitor We predicted that a segment of FGFR1 would
Slide 21: FGFR2 – RLY-4008 Is Potentially the First Highly Selective and Irreversible FGFR2 Inhibitor
FGFR2 – RLY-4008 Is Potentially the First Highly Selective and Irreversible FGFR2 Inhibitor Pan-FGFR Inhibitors RLY-4008 AZD4547 Erdafitinib Pemigatinib Futibatinib FGFR2 Note: Single experiment that tested each compound run at 500nM against 468 targets in the absence of ATP and without preincubatio
Slide 22: FGFR2 – RLY-4008 First-in-Human (FIH) Study Design
FGFR2 – RLY-4008 First-in-Human (FIH) Study Design Orally dosed; BID and QD schedules explored using the Bayesian Optimal Interval Escalation (BOIN) design; Starting dose was 50 mg BID Key Objectives: MTD/RP2D, safety, pharmacokinetics, biomarkers (ctDNA, tumor markers), preliminary anti-tumor activ
Slide 23: FGFR2 – RLY-4008 FIH Study: Parallel Bayesian Dose Optimization Ongoing
FGFR2 – RLY-4008 FIH Study: Parallel Bayesian Dose Optimization Ongoing Preliminary data as of 09-Sept-2021 Dose reductions 2020 2021 SEP OCT NOV DEC JAN FEB MAR APR MAY JUN JUL AUG SEP Dose cohort enrollment periods – Bayesian dose optimization with enrichment (ongoing) DLT rate Deprioritized 6/7 (
Slide 24: FGFR2 – RLY-4008 FIH Study: RLY-4008 QD Safety Profile
Presumed FGFR2- related AEs Off-target AEs Other AEs FGFR2 – RLY-4008 FIH Study: RLY-4008 QD Safety Profile Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference (QD schedule n=32); Bemarituzumab ASCO 2021 Presentation – notes corneal AEs are defined by Standardised
Slide 25: FGFR2 – RLY-4008 Induced Radiographic Tumor Regression in FGFR Inhibitor-Naïve Patients
FGFR2 – RLY-4008 FIH Study: RLY-4008 Induced Radiographic Tumor Regression in FGFR Inhibitor-Naïve FGFR2-Fusion+ Cholangiocarcinoma Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference *Confirmed PR; #Tumor resection after data cut off. FGFRi, fibroblast growth fact
Slide 26: FGFR2 – RLY-4008 Exhibited Activity in Pan-FGFR Inhibitor Resistant Cholangiocarcinoma
FGFR2 – RLY-4008 FIH Study: RLY-4008 Exhibited Activity in Pan-FGFR Inhibitor Resistant FGFR2-Fusion Cholangiocarcinoma Regardless of FGFR2 Resistance Mutations Preliminary data as of 09-Sept-2021 Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference Note: (N550, N54
Slide 27: FGFR2 – RLY-4008 Showed Tumor Regression in FGFR2 Mutations and Amplifications
FGFR2 – RLY-4008 FIH Study: RLY-4008 Showed Radiographic Tumor Regression in FGFR2 Oncogenic Mutations and in FGFR2 Amplifications *Confirmed PR with increased tumor reduction after data cut; ^PR pending confirmation. 1. Based on Company’s review of presented meeting abstracts and published studies
Slide 28: FGFR2 – RLY-4008 First-in-Human (FIH) Study Design
FGFR2 – RLY-4008 First-in-Human (FIH) Study Design Orally dosed; BID and QD schedules explored using the Bayesian Optimal Interval Escalation (BOIN) design; Starting dose was 50 mg BID Key Objectives: MTD/RP2D, safety, pharmacokinetics, biomarkers (ctDNA, tumor markers), preliminary anti-tumor activ
Slide 29: FGFR2 – Highlights from RLY-4008 Interim Clinical Data Disclosure
FGFR2 – Highlights from RLY-4008 Interim Clinical Data Disclosure (Oct 2021) Robust inhibition of FGFR2 with promising initial tolerability data Safety and Tolerability Early evidence of tumor regressions across several tumor and alteration types (with 3 out of 6 fusion positive cholangiocarcinoma F
Slide 30: PI3Kα Opportunity Is Among the Largest Ever for Precision Oncology
PI3Kα Opportunity Is Among the Largest Ever for Precision Oncology Sources: FoundationInsights® database; SEER; Alpelisib – FDA prescribing label 1. Annual incidence of solid tumors with KRAS G12C, PI3K H1047R, PI3K H1047X, PI3K E542X + E545X alterations; 2. Head & Neck Squamous Cell Carcinoma; 3. C
Slide 31: PI3Kα – Existing Inhibitors Establish POC, but Have Limited Therapeutic Window
PI3Kα – Existing Inhibitors Establish POC, but Have Limited Therapeutic Window Compound/ Company Stage Mutant Selective Regimen Response Rate % of Patients with Hyperglycemia % of Patients with GI Toxicity % of Patients Discontinued or Dose Reduced Alpelisib Approved No Monotherapy (Dose Escalation)
Slide 32: PI3Kα – Relay Tx Has a Unique Understanding of PI3Kα
PI3Kα – Relay Tx Has a Unique Understanding of PI3Kα PI3Kα Franchise PI3KαPAN RLY-2608* Pan-mutant selective allosteric inhibitor PI3KαSPECIFIC H1047R-specific allosteric inhibitor PI3KαOTHER Other PI3Kα allosteric programs Relay Tx has a unique understanding of PI3Kα RLY-2608 (pan-mutant selective)
Slide 33: PI3Kα – Proprietary Insights Unlock Additional Approaches
PI3Kα – Proprietary Insights Unlock Additional Approaches A differentiated understanding of the structure of PI3Kα and its relationship to function equips Relay Tx to design optimal mutant-selective inhibitors of PI3Kα Designed pan-mutant selective PI3Kα inhibitor (PI3KαPAN) Discovered novel alloste
Slide 34: PI3Kα – RLY-2608 Has Shown Mutant and Isoform Biochemical Selectivity
PI3Kα – RLY-2608 Has Shown Mutant and Isoform Biochemical Selectivity Potency (nM) H1047R E542K E545K WT Alpelisib Inavolisib RLY-2608 RLY-2608 has shown biochemical selectivity for mutant over wild type PI3Kα α-mut Potency (nM) β δ Alpelisib RLY-2608 Inavolisib RLY-2608 was inactive on other isofor
Slide 35: PI3Kα – RLY-2608 Is Selective Across the Kinome
PI3Kα – RLY-2608 Is Selective Across the Kinome RLY-2608 inhibited only PI3Kα, with preferential inhibition of mutant Source: RLY-2608 data as presented in 2021 AACR-NCI-EORTC Molecular Targets Conference poster presentation
Slide 36: PI3Kα – In Vivo Tumor Regressions Across Both Mutation Hotspots
PI3Kα – In Vivo Tumor Regressions Across Both Mutation Hotspots (Mouse Study) H1047R mutant (HCC1954) (mouse) Source: RLY-2608 data as presented in 2021 AACR-NCI-EORTC Molecular Targets Conference poster presentation 1. This model also carries a second mutation at K567R; 2. HSC2 model; 3. Similar re
Slide 37: PI3Kα – RLY-2608 Combines with Standard of Care Therapies
PI3Kα – RLY-2608 Combines with Standard of Care Therapies to Drive Regressions in ER+/HER2- Breast Cancer Models ST1056 (ER+/HER2-; H1047R) ST986 (ER+/HER2-; E542K) Combination arms with similar tolerability to monotherapy arms RLY-2608 RLY-2608 Fulvestrant and combo Fulvestrant and combo Abemacicli
Slide 38: PI3Kα – RLY-2608 Trial Design
PI3Kα – RLY-2608 Trial Design Part 1: Dose Escalation a. Excludes PIK3CAmut clear cell OvCA, HNSCC, and Cervical cancer patients; b. Double mutation defined as one major PIK3CA mutation (E542X, E545X, H1047X) + ≥1 additional PI3KCA mutation per local assessment; c. Intolerance to PI3K alpha inhibito
Slide 39: Challengers – Supporting the Build of Our Dynamo Platform
Challengers – Supporting the Build of Our Dynamo™ Platform Increasing Technical Difficulty Increasing Competition Innovators Challengers Challengers Have Lower Technical Risk Challengers Solve Problems with “Known” Answers Enable higher volume of programs Serve as a data factory and increase experie
Slide 40: SHP2 – RLY-1971 Is Potent and Selective with Potential for Multiple Therapeutic Uses
SHP2 – RLY-1971 Is Potent and Selective with Potential for Multiple Therapeutic Uses Potential Patient Populations Key Differentiating Features of RLY-1971 RLY-1971 and GDC-6036 (KRAS G12C) combination trial initiated in July 2021 Projected to be continuous once daily dosing Dosing potential Demonst
Slide 41: Challengers – Creating a Data Factory
Challengers – Creating a Data Factory The acquisition of our ML-DEL capabilities unlocks our ability to be a data factory Chemical biology insights Deep structural understanding Physics-based simulations AI / ML Dynamo™️ Platform EXPERIMENTATION COMPUTATION ML-DEL 00100000100100100101011100100100100
Slide 42: Relay Tx – What to Expect
Relay Tx – What to Expect Execution focus underpins value creation RLY-2608 (PI3KαPAN) RLY-4008 (FGFR2) To be disclosed in 1H 2022 Next target in pipeline RLY-1971 (SHP2) $617M Cash, cash equivalents and investments as of the end of Q3 2021 $381M Net proceeds from follow-on offering in October 2021
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