Relay Therapeutics, Inc. · NASDAQ:RLAY
Relay Therapeutics — Investor Presentation (August 2023)
60 slides from Relay Therapeutics's investor presentation, Aug 8, 2023
Slide 1: Corporate Presentation
Corporate Presentation As of August 08, 2023 Exhibit 99.2
Slide 2: Disclaimer
Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding our strategy, business plans and focus; the progress and timing of the clin
Slide 3: Relay Tx — Patient-Driven
Relay Tx — Patient-Driven New Breed of Biotech EXPERIMENTATION oo --| Clear Focus Targets & = z jaliday netic BI rarcetsonly OMCOICEY diseases Areas =H Small WEST molecules Deeraders Chaperones © 2023 Relay Therapeutics Validated Approach Clinical » Pre-clinical ra QD cDK2 Q senda QD Degrader as) is
Slide 4: Relay Tx – Dynamo Platform
Relay Tx – Dynamo™ Platform Dynamo™ Platform… …is focused on making medicines Modulation Hypothesis Hit Identification Lead Optimization Target Identification Develop-ment Commercial-ization Focus of platform PEOPLE Chemical biology insights Deep structural understanding EXPERIMENTATION Physics-base
Slide 5: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Annual US Patient # Breast Cancer1 PI3Kα franchise PI3KαPAN RLY-2608 ~10-68K breast cancer ~76-238K all solid tumors RLY-5836 PI3KαSPECIFIC H1047R-specific ~4-25K breast cancer ~15-48K all solid tumors Challengers CDK2 RLY-2139 ~46K2 (Patients receiving CDK4/6i) Challengers Degrader E
Slide 6: Capital, Team & Execution Focus to Deliver on Key Milestones
Relay Tx – Capital, Team & Execution Focus to Deliver on Key Milestones ~$872M Cash, cash equivalents and investments as of the end of 2Q 2023 Current cash, cash equivalents and investments are expected to be sufficient to fund current operating plan into 2H 2025 Undisclosed RLY-4008 (Selective FGFR
Slide 7: Relay Tx – Continued Dynamo Platform Validation
GDC-1971 (SHP2) Relay Tx – Continued Dynamo™ Platform Validation 1. POC - proof-of-concept. 2. DC - development candidate. 3. Subject to alignment with regulatory authorities RLY-4008 (Selective FGFR2) RLY-2608 (PI3KαPAN) RLY-5836 (PI3KαPAN) RLY-2139 (CDK2) ERα Degrader Pre-Clinical POC1 DC Selectio
Slide 8: Relay Tx Programs
Relay Tx Programs
Slide 9: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα Franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 RLY-2139 Challengers Degrader ERα Degrader Undisclosed 1 program FGFR2 RLY-4008 Mutant + WT Tumor Agnostic SHP2 GDC-1971 Undisclosed 2 programs GD Genetic diseases 2 programs Relay
Slide 10: FGFR2 – Validated Target Present in Several Tumor Types
FGFR2 – Validated Target Present in Several Tumor Types ~6.5K-21K ~4.5K-14K FGFR2 alterations are observed across multiple tumor types2 Three classes of driver alterations in FGFR2 Annual US Patient Count1 Total FGFR2 alterations1: ~11-35K patients Sources: Image adapted from Babina IS, Turner NC. N
Slide 11: FGFR2 – Limitations of Current FGFR Inhibitor Landscape
FGFR2 – Limitations of Current FGFR Inhibitor Landscape Sources: Pemigatinib – prescribing information; futibatinib – prescribing Information; erdafitinib – prescribing information 1. From pemigatinib NDA review documents: "Pemigatinib 13.5 mg daily provided 76% inhibition of ex vivo phosphorylated
Slide 12: FGFR2 – Standard Approach to Discovery Has Had Limited Success
FGFR2 – Standard Approach to Discovery Has Had Limited Success Standard Approach FGFR1 FGFR2
Slide 13: FGFR2 – Increasing Resolution Reveals New Opportunities
FGFR2 – Increasing 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 be fully ext
Slide 14: RLY-4008 – Highly Selective and Irreversible Inhibitor
RLY-4008 – Is A Highly Selective and Irreversible 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 preincubation Source: KINOMEscanTM by Eurofi
Slide 15: RLY-4008 – ReFocus Trial Design
RLY-4008 – ReFocus Trial Design Part 1: Dose Escalation Unresectable or metastatic solid tumors FGFR2 alterations per local assessment Both FGFRi-naïve & FGFRi-treated allowed RLY-4008 RP2D: 70 mg QD Part 2: Dose Expansion Cholangiocarcinoma (CCA) Pivotal supportive FGFR2-fusion+ CCA with no prior t
Slide 16: RLY-4008 – Patient Characteristics
RLY-4008 – Patient Characteristics Fusion+ CCA FGFRi-Naïve1 Total (N=195)2 Parameter 70 mg QD (N=17) All doses (N=38) Age (years), median (range) 57 (36-81) 58 (33-81) 59 (23-87) Female, % 59% 58% 62% Race, % White / Asian / Black / Unknown 41% / 24% / 0% / 35% 58% / 21% / 3% / 18% 63% / 15% / 4% /
Slide 17: RLY-4008 – Interim Response Data
RLY-4008 – Interim Response Data FGFRi-Naïve Fusion+ CCA Patients Approved Pan-FGFR Inhibitors Demonstrate 36-42% ORR in This Population3 70 mg QD (RP2D, N=17) 88% ORR (15 of 17 patients)1 Went on to Resection with Curative Intent2 Data from 2022 ESMO Congress (September 2022) All Doses (N=38) 63% O
Slide 18: RLY-4008 – Time on Treatment for Fusion+ CCA
RLY-4008 – Time on Treatment for Fusion+ CCA FGFRi-Naïve Patients (All Doses) Complete tumor resection: R0 resection performed in curative intent, patient remains no evidence of disease as of 31 May 2022 Data cut-off: August 01, 2022; efficacy analysis includes patients with measurable disease who h
Slide 19: RLY-4008 – Treatment-Related Adverse Events
RLY-4008 – Treatment-Related Adverse Events (TRAEs) Interim Profile TRAEs > 15% TRAE Dose Modification RP2D, 70 mg QD (N=89) All Doses (N=195) Dose interruption (%) 42% 47% Dose reduction (%) 27% 33% Dose discontinuation (%) 1% 1%* Clinically Insignificant Off-Target Hyperphosphatemia (12%, all Gr 1
Slide 20: RLY-4008 Poised for Tumor Agnostic Validation
RLY-4008 Poised for Tumor Agnostic Validation Across FGFR2 Alterations Tumor regression observed across FGFR2 mutations and amplifications in ReFocus Part 1 Dose Escalation Data Continue to actively enroll tumor agnostic cohorts Data presented at 2021 ENA Meeting (data as of 09 September 2021) Data
Slide 21: Relay Tx Solution – Addressing Unmet Need Through Greater Selectivity
Relay Tx Solution – Addressing Unmet Need Through Greater Selectivity Sources: KINOMEscanTM by Eurofins DiscoverX; RLY-4008 data as presented at ESMO Congress 2022 1. Interim data as of 01 August 2022; 2. Single experiment that tested each compound run at 500nM against 468 targets in the absence of
Slide 22: RLY-4008 – ReFocus Trial
Part 1: Dose Escalation Demonstrate clinical proof of mechanism RLY-4008 – ReFocus Trial RP2D Target Inhibition Tolerability Selectivity Part 2: Dose Expansion and Pivotal Cohort Confirm dose and establish efficacy Other FGFR2-altered CCA Pivotal: Fusion+ CCA, FGFRi-naïve FGFR2-altered, non-CCA tumo
Slide 23: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα Franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 RLY-2139 Challengers Degrader ERα Degrader Undisclosed 1 program FGFR2 RLY-4008 Mutant + WT Tumor Agnostic SHP2 GDC-1971 Undisclosed 2 programs GD Genetic diseases 2 programs Relay
Slide 24: Breast Cancer – Limitations of Current Standard of Care
Breast Cancer – Limitations of Current Standard of Care …is limited by efficacy of available treatments HR+/HER2- breast cancer standard of care1… Adjuvant 1L 2L+ Chemo Chemo Chemo / Enhertu® Targeted Tx Targeted Tx Targeted Tx Endocrine Tx (AI, SERD2) CDK4/6 +/- Endocrine Tx (AI, SERD2) CDK4/6 +/-
Slide 25: Relay Tx Solution – Highly Selective Breast Cancer Franchise
Relay Tx Solution – Highly Selective Breast Cancer Franchise Aspirational future state standard of care (HR+/HER2- BC)1 Targeted Tx Chemo / Enhertu® Chemo Chemo Adjuvant 1L 2L+ Targeted Tx Targeted Tx Next Gen Endocrine Tx Selective CDKs Others Mutant PI3Kα Next Gen Endocrine Tx Selective CDKs Mutan
Slide 26: Breast Cancer – Significant Unmet Need
First Line Therapy Second Line Therapy (post CDK4/6) Adjuvant Tx Neo-adjuvant Surgery Endocrine Therapy (ET) ± CDK4/6 Chemo PFS (mo) CBR ORR PFS (mo) 4-23% 53-59% 14-46% 78-85% 1.9-7.3 25-28 Breast Cancer – Significant Unmet Need Of patients treated for early-stage disease attain long-term disease-f
Slide 27: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα Franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 RLY-2139 Challengers Degrader ERα Degrader Undisclosed 1 program FGFR2 RLY-4008 Mutant + WT Tumor Agnostic SHP2 GDC-1971 Undisclosed 2 programs GD Genetic diseases 2 programs Relay
Slide 28: PI3Kα – Validated Target with Significant Unrealized Potential
PI3Kα – A Validated Target with Significant Unrealized Therapeutic Potential PI3Kα mutants Other Kinase Helical PI3Kα regulates glucose homeostasis WT PI3Kα and off-isoform toxicity limit the clinical benefit of alpelisib PI3Ki PI3Kα InsR Insulin Glycogen Glucose Less uptake increases blood glucose
Slide 29: PI3Kα – Existing Inhibitors Have Limited Therapeutic Window
PI3Kα – Existing Inhibitors Have Limited Therapeutic Window Potency (nM) H1047R E542K E545K WT Alpelisib H1047R E542K E545K WT Alpelisib and inavolisib are equipotent for WT and mutant PIK3α Both also retain nM potency against other PI3K isoforms Inavolisib Limited Efficacy Limited based Limited Tar
Slide 30: PI3Kα – Proprietary Insights Unlock Novel Approaches
PI3Kα – Proprietary Insights Unlock Novel 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 allosteric p
Slide 31: RLY-2608 – First Mutant Selective Inhibitor to Enter the Clinic
Limited potency against WT PI3Kα and other PI3K isoforms RLY-2608 – First Mutant Selective Inhibitor to Enter the Clinic Potency (nM) Alpelisib Inavolisib RLY-2608 WT Mutant WT Mutant WT Mutant Favorable Selectivity Favorable Efficacy All Data Shown is Preclinical Favorable Favorable Robust tumor re
Slide 32: RLY-2608 – Data Disclosure Goals
RLY-2608 – Data Disclosure Goals Part 1: Dose Escalation Demonstrate clinical proof of mechanism Part 2: Dose Expansion Establish early efficacy & confirm dose Part 3: Pivotal Trial Establish definitive efficacy RP2D Target Inhibition Tolerability Selectivity Early Signals of Efficacy Interpretable
Slide 33: RLY-2608 – Initial Data Support Selective Targeting of Mutant PI3Kα
RLY-2608 – Initial Data Support Selective Targeting of Mutant PI3Kα Initial Clinical Proof of Mechanism Goal for Expansion Cohorts Interpretable Efficacy (CBR, ORR) Longer-Term Tolerability First expansion cohort initiated at 600 mg BID dose Selective target inhibition over IC80 Favorable safety pro
Slide 34: RLY-2608 – Trial Design
RLY-2608 – Trial Design 1. Excludes PIK3CAmut clear cell OvCA, HNSCC, Cervical cancer, and colorectal patients; 2. Double mutation defined as one major PIK3CA mutation (E542X, E545X, H1047X) + ≥1 additional PIK3CA mutation per local assessment; 3. Patients with previous PI3Kα inhibitor include those
Slide 35: RLY-2608 – ReDiscover Trial Interim Part 1 Results
RLY-2608 – ReDiscover Trial Interim Part 1 Results Dose Escalation: PIK3CA-mutant, HR+, HER2– advanced / metastatic breast cancer (N=39) Start: April 2022 Current doses open to enrollment 400mg BID 200mg BID 100mg BID 800mg BID 600mg BID 1000mg BID N=17 N=10 N=3 N=3 N=5 N=1 First expansion dose coho
Slide 36: RLY-2608 – Baseline Demographics and Genotype
RLY-2608 – ReDiscover Trial Breast Cancer Baseline Demographics and Genotype RLY-2608 + fulvestrant (N=39) RLY-2608 + fulvestrant 600 mg BID (N=17) RLY-2608 Monotherapy (N=4) Age, median (range), years 59 (40-82) 60 (49-80) 64 (58, 85) Female, n (%) 39 (100%) 17 (100%) 4 (100%) Ethnicity, % White /
Slide 37: RLY-2608 – 600 mg BID Dose Selected for Expansion Cohort
RLY-2608 – 600 mg BID Dose Selected for Expansion Cohort 17 Breast Cancer Patients Treated with RLY-2608 600 mg BID Dose + Fulvestrant Preliminary data as of 07/24/2023 Breast Cancer Patients 600 mg BID RLY-2608 + Fulvestrant (N=17) RLY 2608 + Fulvestrant 600mg BID: 86% (6/7) CBR in patients with at
Slide 38: RLY-2608 – Breast Cancer Disease Control Across Dose Levels
RLY-2608 – Breast Cancer Disease Control Across Dose Levels 43 Breast Cancer Patients – Measurable and Non-Measurable Disease Preliminary data as of 07/24/2023 600mg BID: 86% (6/7) interim CBR in patients with at least 6 months follow up 17 patients treated, 15 remain on treatment* mDoT: 12wk (range
Slide 39: RLY-2608 – Evidence of Anti-Tumor Activity
RLY-2608 – Evidence of Anti-Tumor Activity Supports Selective Target Engagement 24 Breast Cancer Patients* – Measurable Disease Only SD uPR PD BOR = Best Overall Response: Preliminary data as of 07/24/2023 PR Breast Cancer Patients (RECIST Measurable Disease) N=24* * one patient discontinued prior t
Slide 40: RLY-2608 – Mutant PIK3CA Decline Supports Target Inhibition
RLY-2608 – Mutant PIK3CA Decline Supports Dose Dependent Target Inhibition PIK3CA ctDNA variant allele frequency (%) 30 Breast cancer patients with evaluable paired C1D1-C2D1 ctDNA Sample Mono: 3 pt; combo: 27 pt 6 patients have ≥2 PIK3CA mutation 26 patients had decline in PIK3CA ctDNA 13 patients
Slide 41: RLY-2608 – Limited Observed Impact on Glucose Homeostasis
Note: one 1000mg BID combo pt not shown; pt had Gr2 glucose elevation per alpelisib label criteria; Data represent mean per cohort +/- standard deviation Source: Central lab analysis RLY-2608 – Limited Observed Impact on Glucose Homeostasis Supports Selectivity Grade 3 (250-500 mg/dL) Grade 2 (160-2
Slide 42: RLY-2608 – TEAEs Consistent with Mutant-Selective Inhibition
RLY-2608 – TEAEs Generally Consistent with Mutant-Selective Inhibition RLY-2608 600mg BID + Fulvestrant (N=17) All Breast Cancer Patients (N=43) 0% 0% 0% 0% 0% 0% Preliminary data as of 07/24/2023 Nausea Hyperglycemia2 Blood Creatinine Increased Fatigue2 Diarrhea Hypokalemia Headache Decreased Appet
Slide 43: Relevant Off-Target Toxicities for Non-Selective Inhibitors
Relevant Off-Target Toxicities for Non-Selective Inhibitors Hyperglycemia Rash1 Diarrhea 3 Most Common AEs Leading to Alpelisib Discontinuation Alpelisib (PI3K inhibitor) Inavolisib (PI3K inhibitor) 2% Capivasertib (AKT inhibitor) 65% 62% 16% 60% 42% 72% 36% 12% 38%2 Grade 3+ Grade 1-2 1. Grouped te
Slide 44: RLY-2608 – Low Rates of Hyperglycemia, Rash and Diarrhea
RLY-2608 – Low Rates of Hyperglycemia, Rash and Diarrhea Hyperglycemia Rash1 Diarrhea RLY-2608 RLY-2608 in BC Patients (N=43) (N=17) 37% 35% 23% 24% 2% 14% 12% Grade 1-2 Grade 3 (no Gr4-5) 1. Rash includes the MedDRA v26.0 Preferred Terms (PT): Rash maculo-papular, Rash Preliminary data as of 07/24/
Slide 45: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα Franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 RLY-2139 Challengers Degrader ERα Degrader Undisclosed 1 program FGFR2 RLY-4008 Mutant + WT Tumor Agnostic SHP2 GDC-1971 Undisclosed 2 programs GD Genetic diseases 2 programs Relay
Slide 46: RLY-5836 – Trial Design
RLY-5836 – Trial Design Part 1: Dose Escalation Part 2: Dose Expansion RLY-5836 + Fulvestrant Arm1 PIK3CAmut, HR+/HER2- advanced breast cancer PIK3CAmut advanced solid tumors RLY-5836 Arm RLY-5836 + Fulvestrant + CDK4/6 Arms2 PIK3CAmut, HR+/HER2- advanced BC, 1 prior CDK4/6 PIK3CAmut, HR+, HER2- adv
Slide 47: RLY-5836 – Similar Pre-clinical Profile, Different Chemical Properties
RLY-5836 – Similar Pre-clinical Profile, Different Chemical Properties from RLY-2608 Source: Internal RLY-5836 data 1. This model also carries a second mutation at K567R E545K mutant (MDAMB361) (mouse)1 H1047R mutant (HCC1954) (mouse) RLY-5836 achieved active doses with less insulin than orthosteric
Slide 48: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα Franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 RLY-2139 Challengers Degrader ERα Degrader Undisclosed 1 program FGFR2 RLY-4008 Mutant + WT Tumor Agnostic SHP2 GDC-1971 Undisclosed 2 programs GD Genetic diseases 2 programs Relay
Slide 49: CDK2 – Highly Selective Development Candidate Identified
CDK2 – Highly Selective Development Candidate Identified Clinical start expected in early 2024 First compound synthesized to identification of lead compounds in <1 year Collect MD frames Extract features Cluster frames & assign cluster populations Predict selectivity Novel workflow leverages MD and
Slide 50: ERα Degrader – Rapidly Obtained Potent Compounds
ERα Degrader – Rapidly Obtained Potent Compounds Development Candidate nomination expected in 2023 …to obtain potent ERα degraders Relay Tx is leveraging rational design… Multiple experimental tools deployed to develop conformational models that enable effective triage of degrader design ideas Tradi
Slide 51: Relay Tx Solution – Highly Selective Breast Cancer Franchise
Relay Tx Solution – Highly Selective Breast Cancer Franchise Efficacy Tolerability Target Inhibition Selectivity Relay Tx Solution Target Program Breast Cancer PI3Kα franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 RLY-2139 Challengers Degrader ERα Degrader Undiscl
Slide 52: Breast Cancer Franchise Continues to Progress
Breast Cancer Franchise Continues to Progress Goal for Expansion Cohorts Initial Data Supporting Selective Targeting of Mutant PI3Kα Initial Clinical Proof of Mechanism Selective target inhibition Favorable safety profile Clinical benefit observed across doses & mutations Interpretable Efficacy (CBR
Slide 53: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα Franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 RLY-2139 Challengers Degrader ERα Degrader Undisclosed 1 program FGFR2 RLY-4008 Mutant + WT Tumor Agnostic SHP2 GDC-1971 Undisclosed 2 programs GD Genetic diseases 2 programs Relay
Slide 54: SHP2 – Genentech Global Collaboration for GDC-1971
SHP2 – Genentech Global Collaboration for GDC-1971 (Formerly RLY-1971) Collaboration provides meaningful economics to Relay Tx1 Source: World Lung 2022 #OA03.04 1. As of June 30, 2023: $110 million in upfront & milestone payments received, plus an opt-in option for 50/50 profit share and up to $685M
Slide 55: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα Franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 RLY-2139 Challengers Degrader ERα Degrader Undisclosed 1 program FGFR2 RLY-4008 Mutant + WT Tumor Agnostic SHP2 GDC-1971 Undisclosed 2 programs GD Genetic diseases 2 programs Relay
Slide 56: Relay Tx – The Dynamo Platform
Relay Tx – The Dynamo™ Platform Physics-based simulations AI / ML PEOPLE EXPERIMENTATION COMPUTATION Growing Platform E.g., ML-DEL ML Predictions Experimental validation Data ML-DEL Growing Automation E.g., Automated Chemical Design (ACD) Decisions Ideas Automation Multiple Iterations Automated Chem
Slide 57: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Annual US Patient # Breast Cancer1 PI3Kα franchise PI3KαPAN RLY-2608 ~10-68K breast cancer ~76-238K all solid tumors RLY-5836 PI3KαSPECIFIC H1047R-specific ~4-25K breast cancer ~15-48K all solid tumors Challengers CDK2 RLY-2139 ~46K2 (Patients receiving CDK4/6i) Challengers Degrader E
Slide 58: Capital, Team & Execution Focus to Deliver on Key Milestones
Relay Tx – Capital, Team & Execution Focus to Deliver on Key Milestones ~$872M Cash, cash equivalents and investments as of the end of 2Q 2023 Current cash, cash equivalents and investments are expected to be sufficient to fund current operating plan into 2H 2025 Tumor Agnostic Breast Cancer Franchi
Slide 59: Relay Tx 2022 ESG Report – Continuing Our ESG Journey
Relay Tx 2022 ESG Report – Continuing Our ESG Journey Relay Tx’s 2nd ESG Annual Report Patients Community Environment Governance Our patients / future patients Our community in Cambridge and the broader Boston area The next generation of scientists *As of December 2022 People 93% of employee respond
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