Relay Therapeutics, Inc. · NASDAQ:RLAY
Relay Therapeutics — J.P. Morgan Healthcare Conference 2023
51 slides from Relay Therapeutics's conference presentation, Jan 9, 2023
Slide 1: JPM Presentation January 2023
JPM Presentation January 2023
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
Relay Tx — Patient-Driven revay Validated Approach Clinical EXPERIMENTATION +) COMPUTATION Pre-clinical piakarn) selective) ERa Q RLY-5836 cDK2 Degrader New Breed of Biotech Clear Focus Execution-Focused Targets & L =| Validated Genetic Therapeutic Ta colt ‘Oncology Areas . diseases - oo r= = Small
Slide 4: Relay Tx – Dynamo Platform
Relay Tx – Dynamo™ Platform Dynamo™ Platform… …is focused on making medicines …aims to address selectivity on validated targets Modulation Hypothesis Hit Identification Lead Optimization Target Identification Develop-ment Commercial-ization Focus of platform PEOPLE Chemical biology insights Deep str
Slide 5: Relay Tx – Execution Focused
Relay Tx – Execution Focused Public, clinical org Cash runway into 2025 5 disclosed programs 5+ unnamed programs Platform: + ML-DEL and Automation Presented clinical data at ESMO & Triple Meeting 3 assets in clinic Company Programs Jan 2020 Jan 2023 Private Preclinical Purely research 2 disclosed ta
Slide 6: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Annual US Patient # Breast Cancer1 PI3Kα franchise PI3KαPAN RLY-26082 ~8-51K ~50-156K all solid tumors RLY-58362 PI3KαSPECIFIC H1047R-specific ~4-25K ~15-48K all solid tumors Challengers CDK2 Selective CDK2 ~46K3 (Patients receiving CDK4/6i) Challengers Degrader ERα Degrader ~29-196K4
Slide 7: Relay Tx – Capital, Team & Execution Focus to Deliver
Relay Tx – Capital, Team & Execution Focus to Deliver $1.1B Cash, cash equivalents and investments as of the end of 3Q 2022 Current cash, cash equivalents and investments are expected to be sufficient to fund current operating plan into 2025 Tumor Agnostic Breast Cancer Franchise GDC-1971 (SHP2) RLY
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 Selective CDK2 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
Slide 10: FGFR2 – Validated Target Present in Several Tumor Types
FGFR2 – Validated Target Present in Several Tumor Types Fusions3 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 ~4.5K-7.5K FGFR2 alterations ar
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 – Is A 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 Data cut-off: August 01, 2022; efficacy analysis includes patients with measurable disease who had o
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
Approved Pan-FGFR Inhibitors Demonstrate 23-36% ORR in This Population3 RLY-4008 – Interim Response Data FGFRi-Naïve Fusion+ CCA Patients at Pivotal Dose (70 mg QD) Best RECIST Change (%) from Baseline Based on Investigator Evaluated Response for Fusion+ CCA FGFRi-Naïve Patients at 70 mg QD (N=17) 1
Slide 18: RLY-4008 – Interim Response Data Across All Doses
RLY-4008 – Interim Response Data FGFRi-Naïve Fusion+ CCA Patients Across All Doses 92% of Patients With Tumor Reduction Across All Dose Levels, Majority of Patients With Partial Response per RECIST 1.1 Best RECIST Change (%) from Baseline Based on Investigator Evaluated Response for Fusion+ CCA FGFR
Slide 19: RLY-4008 – Time on Treatment for Fusion+ CCA FGFRi-Naïve Patients
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 20: RLY-4008 – Treatment-Related Adverse Events Interim Profile
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 21: RLY-4008 Poised for Tumor Agnostic Validation Across FGFR2 Alterations
RLY-4008 Poised for Tumor Agnostic Validation Across FGFR2 Alterations Non-CCA advanced, solid tumors with FGFR2 alterations Non-CCA patients with FGFR2-fusion Non-CCA patients with FGFR2-amplification Non-CCA patients with FGFR2-mutation Tumor regression observed across FGFR2 mutations and amplific
Slide 22: 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 23: 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 24: Relay Tx – Emerging Breast Cancer Franchise
Target Program Breast Cancer PI3Kα franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 Selective CDK2 Challengers Degrader ERα Degrader Undisclosed 1 program FGFR2 RLY-4008 – Mutant + WT Tumor Agnostic SHP2 GDC-1971 Undisclosed 2 programs GD Genetic diseases 2 program
Slide 25: 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 26: 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 27: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 Selective CDK2 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
Slide 28: PI3Kα – Large Precision Oncology Opportunity
PI3Kα – Large Precision Oncology Opportunity (excl. H1047R) HR+/HER2- breast cancer is the largest single indication with PI3Kα mutated patients Pan-mutant selective drug is a significant clinical opportunity for solid tumors… …with HR+/HER2- breast cancer as the single largest indication with PI3Kα
Slide 29: PI3Kα – Existing Inhibitors Have Limited Therapeutic Window
based PI3Kα – Existing Inhibitors Have Limited Therapeutic Window Limited Target Inhibition Limited Tolerability Compound All Gr3+ Tox Hyperglycemia GI Tox (all Gr) Rash (all Gr) All Gr Gr3+ Alpelisib1-7 44-78% 33-65% 13-37% 33-60% 20-36% Inavolisib8-12 33-54% 55-70% 5-22% 27-50% 7-27% Note: fulv =
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 – Mutant and Isoform Selectivity
RLY-2608 – Mutant and Isoform 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 isoforms γ α-mut β δ γ α-mut β δ γ
Slide 32: RLY-2608 – Selective Across the Kinome
RLY-2608 – 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 Selectivity
Slide 33: RLY-2608 – Reduced Impact on Glucose Homeostasis
In higher species, dosing of RLY-2608 for 28 days showed no histopathological or ophthalmic findings associated with hyperglycemia RLY-2608 – Reduced Impact on Glucose Homeostasis Tolerability Hyperglycemia Definitions (CTCAE v5.0) Grade CTCAE Definition (v5.0) Gr 1 Abnormal glucose above baseline,
Slide 34: RLY-2608 – In Vivo Tumor Regressions
RLY-2608 – In Vivo Tumor Regressions Target Inhibition and Efficacy
Slide 35: 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 Favorable Target Inhibition Manageable key toxicities, especially
Slide 36: RLY-2608 – Trial Design
RLY-2608 – Trial Design Part 1: Dose Escalation 1. Excludes PIK3CAmut clear cell OvCA, HNSCC, and Cervical cancer patients; 2. Double mutation defined as one major PIK3CA mutation (E542X, E545X, H1047X) + ≥1 additional PI3KCA mutation per local assessment; 3. Intolerance to PI3Kα inhibitors is defin
Slide 37: RLY-2608 – Data Disclosure
RLY-2608 – Data Disclosure 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 Effica
Slide 38: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 Selective CDK2 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
Slide 39: RLY-5836 – Similar Pre-clinical Profile, Different Chemical Properties
Clinical start anticipated in 2Q 2023 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 do
Slide 40: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 Selective CDK2 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
Slide 41: CDK2 – Highly Selective Inhibitors Identified
CDK2 – Highly Selective Inhibitors Identified Clinical start expected in early 2024 First compound synthesized to identification of lead compounds in <1 year RTX-1 RTX-2 Biochemical Potency CDK2/CycE IC50 (mM) 0.002 0.004 Biochemical Selectivity (fold over) CDK1/CycB 260x 100x CDK4/CycD1 685x 273x C
Slide 42: ERα Degrader – Rapidly Obtained Potent Compounds
ERα Degrader – Rapidly Obtained Potent Compounds Development Candidate nomination expected in 2023 …to obtain potent ERα degraders Cellular proliferation Pathway suppression Relay Tx is leveraging rational design… Multiple experimental tools deployed to develop conformational models that enable effe
Slide 43: Relay Tx Solution – Highly Selective Breast Cancer Franchise
Relay Tx Solution – Highly Selective Breast Cancer Franchise Efficacy Target Inhibition Tolerability Selectivity Relay Tx Solution Target Program Breast Cancer PI3Kα franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 Selective CDK2 Challengers Degrader ERα Degrader U
Slide 44: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 Selective CDK2 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
Slide 45: 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 December 31, 2022: $105 million in upfront & milestone payments received, plus an opt-in option for 50/50 profit share and up to $
Slide 46: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Breast Cancer PI3Kα franchise PI3KαPAN RLY-2608 RLY-5836 PI3KαSPECIFIC H1047R-specific Challengers CDK2 Selective CDK2 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
Slide 47: Relay Tx – The Dynamo Platform
Relay Tx – The Dynamo™ Platform 5+ Undisclosed Programs Inhibitors Degraders New Modalities Chaperones Platform capabilities and expertise continue to expand Enabling deep and diversified early pipeline
Slide 48: Relay Tx – Extensive Precision Medicine Pipeline
Target Program Annual US Patient # Breast Cancer1 PI3Kα franchise PI3KαPAN RLY-26082 ~8-51K ~50-156K all solid tumors RLY-58362 PI3KαSPECIFIC H1047R-specific ~4-25K ~15-48K all solid tumors Challengers CDK2 Selective CDK2 ~46K3 (Patients receiving CDK4/6i) Challengers Degrader ERα Degrader ~29-196K4
Slide 49: Relay Tx – Capital, Team & Execution Focus to Deliver
Relay Tx – Capital, Team & Execution Focus to Deliver $1.1B Cash, cash equivalents and investments as of the end of 3Q 2022 Current cash, cash equivalents and investments are expected to be sufficient to fund current operating plan into 2025 Tumor Agnostic Breast Cancer Franchise GDC-1971 (SHP2) RLY
Slide 50: Relay Tx 2021 ESG Report – Continuing Our ESG Journey
Relay Tx 2021 ESG Report – Continuing Our ESG Journey Relay Tx’s First Full 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 2021 People 98% employee res
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