EX-99.2 3 rlay-ex99_2.htm EX-99.2

Corporate Presentation As of August 08, 2023 Exhibit 99.2

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 clinical development of the programs across our portfolio, including the expected therapeutic benefits of our programs, timing of enrollment completion, and potential efficacy and tolerability, and the timing and success of interactions with and approval of regulatory authorities; the timing of clinical data updates for RLY-2608 and RLY-4008, the initiation of expansion cohorts for RLY-2608, the completion of the pivotal cohort enrollment for RLY-4008, the clinical initiation of RLY-2139, and the nomination of a development candidate for our ERα degrader program; our expectations with respect to the potential pivotal dose for RLY-4008, including potential regulatory filings and interactions; expectations regarding our pipeline, operating plan, use of capital, expenses and other financial results; our cash runway projection; the competitive landscape and potential market opportunities for our product candidates; the expected strategic benefits under our collaborations; our ability to successfully establish or maintain collaborations or strategic relationships for our product candidates; expectations regarding current and future interactions with the U.S. Food and Drug Administration (FDA); our ability to manufacture our product candidates in conformity with the FDA’s requirements; the capabilities and development of our DynamoTM platform; our plans to develop, manufacture and commercialize our current product candidates and any future product candidates; and the implementation of our business model and strategic plans for our business, current product candidates and any future product candidates. 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Relay Tx – Patient-Driven

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-based simulations AI / ML COMPUTATION 1 2 …aims to address selectivity on validated targets 3 Selectivity Efficacy Tolerability Target Inhibition

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 ERα Degrader ~29-196K3 Undisclosed 1 program To be announced FGFR2 RLY-4008 Mutant + WT ~11-35K4 Tumor Agnostic SHP2 GDC-1971 ~37-69K5 Undisclosed 2 programs To be announced GD Genetic diseases 2 programs To be announced Relay Tx – Extensive Precision Medicine Pipeline Preclinical Early Clinical Late Clinical CCA + other Breast Cancer 1. Unless otherwise indicated, all breast cancer patient numbers refer to HR+/HER2- breast cancer tumors; 2. ~46K HR+/HER2- breast cancer patients expected to receive CDK 4/6 inhibitors in adjuvant setting, first-line setting, and second-line setting in 2023, per Decision Resources Breast Cancer Market Forecast report dated June 2022; 3. HR+/HER2- US late-line breast cancer patients compared to HR+/HER2- US incident breast cancer patients; 4. FGFR2 altered late-line solid tumors compared to comprehensive annual FGFR2 altered incident solid tumors including additional FGFR gene fusions and rearrangements resulting from truncation of the protein at exon 18 and all breast cancer patients with FGFR2 alterations; 5. SHP2 combo only includes KRAS G12C in lung and colorectal, EGFR mutations in lung, and ALK fusions in lung Note: Unless otherwise indicated, patient #’s refer to total annual number of US patients with late-line cancers compared to comprehensive annual incidence that may be amenable to treatment with our programs

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 FGFR2) Full dose escalation data in 1H 2023 (2023 ASCO) Non-CCA expansion cohorts data in 2H 2023 Pivotal cohort full enrollment in 2H 2023 GDC-1971 (SHP2) Ongoing combo trials; Genentech controls data disclosures Clinical start in early 2024 RLY-2139 (Selective CDK2) Development candidate nomination in 2023 ERα Degrader To be announced 5+ undisclosed programs in preclinical development and additional early-stage efforts across platform PI3KαPAN Initial RLY-2608 data in 1H 2023 RLY-5836 clinical start in 2Q 2023 RLY-2608 expansion cohorts initiated in 2H 2023 Additional data update in 2024 Tumor Agnostic Breast Cancer Franchise

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 Selection2 First Patient Dosed Early Clinical Validation Approval3 Pivotal Initiation3 Multiple Inhibitor Degrader Inhibitor, Degrader, Chaperone, etc. Modality Compound

Relay Tx Programs

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 Tx – Extensive Precision Medicine Pipeline Preclinical Early Clinical Late Clinical CCA + other Breast Cancer

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. Nat Rev Cancer 2017;17: 318-332; Internal analysis based on third party industry data 1. All patient #’s refer to total annual number of US patients with late-line cancers vs. comprehensive annual incidence that may be amenable to treatment with our programs including additional FGFR gene fusions and rearrangements resulting from truncation of the protein at exon 18; 2. Cholangio, cholangiocarcinoma (CCA); CUP, carcinoma unknown primary; 3. FGFR2 fusion estimates include del18 truncations; Fusions3 Amplifications Mutations FGFR2 Annual Cases(US, comprehensive) Pancreatic Breast Endometrial Lung Stomach Skin Melanoma Bladder CUP Ovarian Cholangio

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 FGFR2α at trough" FDA Approved Compound % of Patients with Hyperphosphatemia % of Patients with Diarrhea Pemigatinib 94% 47% Futibatinib 88% 39% Erdafitinib 76% 47% Limited Tolerability Limited Target Inhibition Limited Efficacy 36-42% Objective Response Rate in Fusion+ CCA FGFRi-naïve pts Limited Selectivity Approved Pan-FGFRis are non-specific across FGFR family Pemigatinib 13.5mg QD achieves 76% inhibition of FGFR2 at trough1 High rates of off-target toxicity (esp. FGFR1,4) Limited Limited Limited Limited

FGFR2 – Standard Approach to Discovery Has Had Limited Success Standard Approach FGFR1 FGFR2

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 extended outwards more frequently than the same segment in FGFR2

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 Eurofins DiscoverX FGFR1 FGFR2 FGFR3 FGFR4 Percent Control Percent Control

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 treatment (N=20) Any FGFR2-mutant/amplified CCA (N=20) FGFR2-fusion+ CCA with prior FGFRi (N=50) FGFR2-fusion+ CCA without prior FGFRi (N=100) Pivotal cohort Non-CCA advanced, solid tumors with FGFR2 alterations FGFR2-fusion+ non-CCA solid tumors (N=50) FGFR2-amplified non-CCA solid tumors (N=50) FGFR2-mutant non-CCA solid tumors (N=50)

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% / 18% ECOG PS3, % 0 53% 50% 38% 1 47% 50% 58% 2 0% 0% 3% Prior lines of systemic therapy, % 0 0% 0% 2% 1 41% 47% 20% 2 47% 32% 29% 3+ 12% 21% 49% Baseline sum of target lesions (RECIST 1.1, mm), median (range) 57 (10-157) 63 (10-216) 79 (10-274) Efficacy analysis includes patients with previously treated, FGFR2i-naïve CCA treated at the RP2D. Patients with measurable disease who had opportunity for ≥2 tumor assessments to confirm response or discontinued treatment with <2 tumor assessments Patients in safety population who received ≥1 dose of RLY-4008 at any dose level ECOG PS = Eastern Cooperative Oncology Group Performance Scale Data cut-off: August 01, 2022; efficacy analysis includes patients with measurable disease who had opportunity for ≥2 tumor assessments or discontinued treatment with <2 tumor assessments Data from 2022 ESMO Congress (September 2022)

RLY-4008 – Interim Response DataFGFRi-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% ORR (24 of 38 patients)1 SD uPR PR Stable Disease Unconfirmed Partial Response Confirmed Partial Response Progressive Disease PD BOR = Best Overall Response: 1. For 70 mg QD: Confirmed ORR = 82%: 14 confirmed PRs, 1 unconfirmed PR in an ongoing patient; For all doses: Confirmed ORR = 58%: 22 confirmed PRs, 2 unconfirmed PR; 2. Complete tumor resection: R0 resection performed in curative intent, patient remains no evidence of disease as of 31 May 2022; 3. Based on pemigatinib, erdafitinib, and futibatinib prescribing information. These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. Note: QDi = once daily dosing on an intermittent schedule (3 weeks on drug, 1 week off); BID = twice daily dosing Data cut-off: August 01, 2022; efficacy analysis includes patients with measurable disease who had opportunity for ≥2 tumor assessments or discontinued treatment with <2 tumor assessments

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 had opportunity for ≥2 tumor assessments or discontinued treatment with <2 tumor assessments SD uPR PR Stable Disease Unconfirmed Partial Response Confirmed Partial Response Progressive Disease PD BOR = Best Overall Response: 13 of 15 (87%) 70 mg QD responders remain on treatment Complete Tumor Resection1 Duration of exposure (weeks) Median duration of exposure: 5.5 months (range: <0.1 to 18.5 months) Median time to response: 1.8 months 12/38 (32%) Discontinued - 1 resection with curative intent, 8 PD, 1 AE, 2 withdrawal of consent Went on to Resection with Curative Intent1 Data from 2022 ESMO Congress (September 2022)

RLY-4008 – Treatment-Related Adverse Events (TRAEs) Interim ProfileTRAEs > 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 1-2) and Diarrhea (4%, all Gr 1-2) Allow for Optimization of FGFR2 Inhibition Doses at ≥40 mg QD result in 90%+ target inhibition Most AEs have been expected FGFR2-on target, low-grade, monitorable, manageable and largely reversible RP2D, 70 mg QD (N=89) All doses (N=195) Data from 2022 ESMO Congress (September 2022) All Grades Grade 3 * 1 hypersensitivity, 1 retinal pigment epithelial detachment, both resolved Data cut-off: August 01, 2022; efficacy analysis includes patients with measurable disease who had opportunity for ≥2 tumor assessments or discontinued treatment with <2 tumor assessments

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 Disclosure From Tumor Agnostic Cohorts Anticipated in 2H 2023 Non-CCA advanced, solid tumors with FGFR2 alterations FGFR2-fusion+ non-CCA solid tumors (N=50) FGFR2-amplified non-CCA solid tumors (N=50) FGFR2-mutant non-CCA solid tumors (N=50) Mutations (N=7) Amplifications (N=3) BC BC BC BC Breast Cancer BC Data from 2021 Triple Meeting (October 2021, N=49 patients)

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 ATP and without preincubation; 3. Toxicity rates across all doses, n=195 patients Favorable Selectivity1 ~200x selective for FGFR2 over FGFR1, ~5000x selective over FGFR42 Favorable Target Inhibition1 FGFR2 Favorable Interim Efficacy1 Doses at ≥40 mg QD result in 90%+ target inhibition Favorable Interim Tolerability1 Minimized key off-target toxicities3 Hyper-phosphatemia1 Diarrhea Discontinuation 12% 4% 1% All Gr1-2 All Gr1-2 FGFR2 driven tumor shrinkage: 88% ORR in fusion+, FGFRi-naïve CCA 15 of 17 pts at 70mg QD pivotal dose (based on interim data) Most AEs have been expected FGFR2-on target, low-grade, monitorable, manageable and largely reversible Favorable Favorable Favorable Favorable 95% RO 90% RO RLY-4008 Concentration (Mean+SD) (ng/mL) Time (hr) 63% interim ORR for fusion+, FGFRi-naïve CCA across all doses

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 tumors Advanced solid tumors with FGFR2 alterations per local assessment; Both FGFRi-naïve & FGFRi-treated allowed Focus of Disclosure Early Signals of Efficacy 4Q 2021: Triple Meeting Validated hypothesis with target inhibition and acute tolerability Provided early efficacy signals in heterogeneous populations 2023: Anticipated Milestones 2023 ASCO: Full dose escalation data 2H 2023: Pivotal cohort full enrollment 2H 2023: Non-CCA expansion cohorts data 3Q 2022: ESMO Confirmed longer term safety and tolerability Established stronger support for FGFR2 fusion+ CCA, FGFRi-naïve efficacy Interpretable Efficacy

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 +/- ET2, CDK4/6, PI3K, mTOR ~196k annual HR+/HER2- breast cancer patients in US, of whom ~50k advance to later lines of treatment Source: Internal analysis based on third party industry data 1. Standard of care for HR+/HER2- breast cancer is illustrative; 2. AI = Aromatase Inhibitor; SERD: Selective Estrogen Receptor Degrader; ET = Endocrine Therapy Efficacy Selectivity Limited Limited Tolerability Limited Target Inhibition Limited

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 Mutant PI3Kα Next-gen ET Sel. CDKs Mut. PI3Kα Relay Tx aims to transform the standard of care for HR+/HER2- breast cancer Relay Tx Breast Cancer Portfolio PI3Kα Franchise RLY-2608 (pan-mutant) RLY-5836 (pan-mutant) H1047R (mutant-specific) Selective CDK2 Inhibitor ERα Degrader Other Undisclosed Programs Relay Tx Solution 1. Aspirational future state standard of care for HR+/HER2- breast cancer is illustrative

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-free-survival Metastatic Setting – Significant unmet need "Early Setting" (Patients with tumor Stages I-III) ~25% Relay Tx BC portfolio aspirational positioning ~75% 25.3 - 28.2 ET ± CDK4/6 1.9 - 2.8 PI3K Path. + ET CDK4/6 + ET SERD 7.3 Relay Tx BC portfolio planned initial positioning PFS = Progression Free Survival CBR = Clinical Benefit Rate ORR = Objective Response Rate Significant need for improved PFS in 2L ~196,000 new HR+/HER2- breast cancer cases diagnosed each year in USA ~50,000 met HR+/HER2- BC cases/yr in US Of patients require treatment in advanced or metastatic setting Figures generated based on publicly available data for both approved and investigational products (alpelisib, ribociclib, elacastrant (investigatonal), fulvestrant (investigatonal), palbociclib, ribociclib, abemaciclib, capivasertib (investigational)). Sources: SEER, Metastatic Breast Cancer Network (MBCN), Johnston 2019 NPJ Breast Cancer 5:5, Goetz 2017 JCO 35:3638, Rugo 2019 Breast Cancer Res Treat 174:719, Ibrance Label, Finn 2016 N Engl J Med 375:1925, Hortobagyi 2018 Ann Oncol 29:1541, Kisqali label, SABCS 2021 #P1-18-03, SABCS 2022 #GS3-04, ASCO 2022 #LBA1004, Bardia 2022 Cancer Research 82, ASCO 2022 LBA3, ASCO 2022 LBA1001, Wander 2021 J NCCN 24:1, ASCO 2022 #1055, Xi J 2019 J NCCN 17:141

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 Alpelisib, the only FDA-approved PI3Kα inhibitor for solid tumors, is not mutant-selective and disrupts glucose metabolism, causing hyperglycemia AEs frequently leading to treatment discontinuation for alpelisib 65% (37%) 36% (10%) 60% (7%) All Gr (Gr3+) Hyperglycemia Diarrhea Rash AE PI3Kα is the most frequently mutated kinase in solid tumors PI3Kα 14% EGFR ERBB2 6% 6% ALK BRAF 6% 1% % of tumors with alteration ~100K breast cancer patients with PI3Kα mutation in US annually E542X E545X $5.9B $11.7B H1047X ~$7B Total 2022 Revenue: (Global) ~$9B ~$2B *Tafinlar + Mekinist Sources: Internal analysis based on third party industry data; Alpelisib data: SOLAR-1 (long-term follow up): Andre 2021 Ann Oncol 32:208 * ~$3B

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 Target Inhibition Limited Regimen Interruption Reduction Discont. Alpelisib6,7 58% 38% 15% Alpelisib + fulv1 74% 64% 25% Inavolisib + fulv8 41% 18% 2% Capivasertib+fulv18 35% 20% 13% Alpelisib: Observed coverage (based on IC80) at median dose intensity 9-13hr7 Regimen ORR CBR PFS (mo) Alpelisib Mono Ph 1a7 4% 17% 5.5 Alpelisib + fulv Ph 24 19% 46% 7.3 Inavolisib + fulv Ph 1b13 19% 48% 7.1 Capivasertib + fulv Ph 318 29% NR* 7.3 Data from RP2D of alpelisib, inavolisib, and capivasertib 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% Capivasertib14-18 21-62% 16-43% 2-20% 64-82% 22-53% Limited Tolerability Limited AKT inhibitor Limited Selectivity Limited * NR = Not Recorded Note: fulv = fulvestrant; all referenced studies are for their patient populations which are analogous to ongoing breast cancer pt populations within RLY-2608 clinical trials; Alpelisib and fulvestrant are FDA approved, inavolisib and capivasertib are in Phase 3 clinical trials Sources: Alpelisib – 1. SOLAR-1: Andre 2019 N Engl J Med 380:1929, 2. Ph 1b: SABCS 2013 P2-16-14, 3. Ph 1b: SABCS 2014 PD5-5, 4. Ph 2 ByLIEVE: Rugo 2021 Lancet Oncol 22:489, SABCS 2021 #P1-18-03, 5. Ph 1b mono: Annals of Oncol 25 2014 (suppl 4), 6. Ph 2 mono: Savas Cancer Discov 2022 Sep 12:2058, 7. Ph 1a mono: Juric 2018 J Clin Oncol 36:1291; Inavolisib – 8. ASCO 2022 #1052 (note: pooled rates across cohorts), 9. SABCS 2020 #PS11-11, 10. AACR 2020 CT109, 11. SABCS 2019 OT1-08-04; 12. SABCS 2019 P1-19-46, 13. SABCS 2021 #P5-17-05; Capivasertib – 14. Ph 1 mono: Banerji 2018 Clin Cancer Res 24:2050, ASCO 2015 #2500; 15. Ph 2 mono: SABCS 2019 P1-19-14; 16. Ph 1 combo: Smyth 2020 Clin Cancer Res 26:3947; 17. Ph 2 FAKTION: ASCO 2022 #1005; 18. Ph 3 CAPItello-291: SABCS 2022 #GS3-04 Note: These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted.

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 pocket favored in mutant protein Solved first full-length structures of PI3Kα (mutant and wild-type) Orthosteric Site Mutant PI3Kα

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 regression at tolerable doses in mouse model Favorable Target Inhibition Favorable Vehicle RLY-2608 25mg/kg BID RLY-2608 100mg/kg BID RLY-2608 50mg/kg QD Maintains approx. 80% mutant PI3Kα inhibition in mouse model Vehicle Alpelisib 50mg/kg QD Inavolisib 25mg/kg QD RLY-2608 25mg/kg BID RLY-2608 50mg/kg BID RLY-2608 100mg/kg BID Manageable key toxicities, especially hyperglycemia shown in dog study Favorable Tolerability Favorable Vehicle RLY-2608 10mg/kg BID RLY-2608 50mg/kg BID RLY-2608 20mg/kg BID

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 Efficacy Focus of Disclosure AACR 2023: Acute safety and tolerability within context of mutant target inhibition Opened expansion cohort at 600 mg BID Next disclosure in 2024: Longer-term safety and tolerability Early efficacy signals at RP2D for expansion cohorts

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 profile at therapeutically active doses Initial anti-tumor activity observed across range of doses Continuous pAKT inhibition ~80%+ achieved at ≥400mg BID Limited observed impact on glucose homeostasis No grade 3 hyperglycemia observed2 Low rates of hyperglycemia, rash and diarrhea No DLTs and no AEs leading to treatment discontinuation Safety profile at 600mg BID compelling for use in mBC combinations At 600mg BID combo dose: 86% interim CBR (6 of 7 patients with CR, PR, or SD for ≥6mo) 1 cPR out of 5 evaluable1 patients with measurable disease Overall, 4 PRs* (of 24 evaluable1 breast cancer pts) observed across mono and combo, dose levels and PI3Kα genotypes DLTs = dose limiting toxicities; CBR: Clinical Benefit defined as all patients with confirmed complete response or partial response or stable disease ≥24 weeks; evaluable patients started treatment ≥24 weeks prior to the data cutoff 1. Efficacy analysis includes patients with measurable disease who had opportunity for ≥1 tumor assessment or discontinued treatment with <1 tumor assessment; 2. per CTCAE v5.0 * Includes 3 confirmed partial responses and 1 unconfirmed partial response

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 with intolerance to PI3Kαi defined as treatment discontinuation due to treatment-related AE (e.g., hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome; 4. RLY-2608 + fulvestrant + CDK4/6 arm expected to be added in a protocol amendment Part 1: Dose Escalation Part 2: Dose Expansion RLY-2608 Arm PIK3CAmut adv solid tumors Includes mixed histologies PIK3CAmut advanced solid tumors (CCOC, HNSCC, Cervical, other1, double PIK3CA mutants2) MTD/RP2D PIK3CAmut, HR+, HER2- advanced breast cancer (with & without prior PI3Kα inhibitor3) RLY-2608 + Fulvestrant Arm PIK3CAmut, HR+/HER2- adv / met breast cancer MTD/RP2D RLY-2608 + Fulvestrant + CDK4/6 Arm4 PIK3CAmut, HR+, HER2- advanced breast cancer PIK3CAmut, HR+/HER2- adv / met BC MTD/RP2D First expansion cohort initiated at 600mg BID dose

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 cohort initiated Favorable PK Profile Across Dose Levels ~50% pAKT inhibition 400mg 200mg 100mg 800mg 600mg BID ~80% pAKT inhibition (predicted from mouse PK/PD models) ~50% pAKT inhibition No DLTs and MTD has yet to be defined Dose-dependent increase in exposure and low peak to trough fluctuations across dose levels Continuous coverage at ~IC80+ across dosing interval at 400mg BID combo and above RLY-2608 + fulvestrant Similar exposure as 400mg BID mono

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 / Asian / American Indian / Black / Unknown 67% / 3% / 3% / 3% / 23% 59% / 0% / 0% / 0% / 41% 100% / 0% / 0% / 0% / 0% ECOG, n (%) 0 21 (54%) 8 (47%) 2 (50%) 1 18 (46%) 9 (53%) 2 (50%) BMI, kg/m2, median (range) 25 (18-41) 23 (19-36) 26 (18, 44) <30, n (%) 29 (74%) 14 (82%) 3 (75%) ≥30, n (%) 10 (26%) 3 (18%) 1 (25%) Prior regimens of therapy in metastatic setting, median (range) 1 (1,6) 2 (1,6) 5 (1, 12) Pending data entry 2 (5%) 1 (6%) 0 (0%) 1 19 (49%) 6 (35%) 1 (25%) 2 10 (26%) 6 (35%) 0 (0%) 3+ 8 (21%) 4 (24%) 3 (75%) Preliminary data as of 07/24/23

RLY-2608 – 600 mg BID Dose Selected for Expansion Cohort17 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 least 6 months follow up Confirmed PR achieved in 1 of 5 efficacy evaluable1 patients with measurable disease 17 patients treated, 15 remain on treatment* mDoT: 12wk (range: 1-41wk) SD Stable Disease BOR = Best Overall Response: Partial Response PR CBR: Clinical Benefit defined as all patients with confirmed complete response or partial response or stable disease ≥24 weeks; evaluable patients started treatment ≥24 weeks prior to the data cutoff * Note: one additional pt at 600mg BID dose remains on treatment after PD assessment; 1. Efficacy analysis includes patients with measurable disease who had opportunity for ≥1 tumor assessment or discontinued treatment with <1 tumor assessment

RLY-2608 – Breast Cancer Disease Control Across Dose Levels43 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: 1-41wk) Across all doses: 43 patients treated, 28 remain on treatment* mDoT: 15wk (range: 1-64wk) CBR: Clinical Benefit defined as all patients with confirmed complete response or partial response or stable disease ≥24 weeks; evaluable patients started treatment ≥24 weeks prior to the data cutoff; N/A: not available as of data cut off, pending data entry * Note: one additional pt at 600mg BID dose remains on treatment after PD assessment N/A 2nd PIK3CA mutation in double mutation Primary PIK3CA mutation type PIK3CA Mutation Key:

RLY-2608 – Evidence of Anti-Tumor Activity Supports Selective Target Engagement24 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 to first scan and is not shown on waterfall plot At 600mg BID combo, 80% of patients (4/5) exhibited radiographic tumor reductions 1 pt experienced a partial response and remains on treatment Overall, 63% of patients (15/24) exhibited radiographic tumor reductions; 13/24 patients ongoing 4 partial responses observed across mono and combo, dose levels and PI3Kα genotypes Stable Disease Unconfirmed Partial Response Progressive Disease Partial Response 2nd PIK3CA mutation in double mutation Primary PIK3CA mutation type PIK3CA Mutation Key:

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 completely cleared PIK3CA ctDNA by C2D1 Patients with paired evaluable ctDNA Mono: n=2 Combo: n=10 Mono: n= 1 Combo: n=17 Mono: n= 0 Combo: n=8 Preliminary data as of 07/24/2023 Note: data points at zero are below limits of detection Source: Central lab analysis RLY-2608 RLY-2608 + fulvestrant

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 (160-250 mg/dL) Grade 1 (115-160 mg/dL) Alpelisib label criteria RLY-2608 + Fulvestrant Combination No Grade 3 hyperglycemia per CTCAE v5.0 Preliminary data as of 07/24/2023

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 Appetite Vomiting 0% 0% 0% 0% 0% 0% 0% Nausea Hyperglycemia2 Blood Creatinine Increased Fatigue2 Diarrhea Hypokalemia Headache Decreased Appetite Vomiting TEAEs ≥15% in Breast Cancer Patients1 All Gr Gr3 (no Gr4-5) 1. TEAEs that occurred in >=15% of the Breast Cancer Safety Set (N=43) are shown for both populations; 2. Hyperglycemia includes the MedDRA v26.0 Preferred Terms (PT): Hyperglycemia and Blood Glucose Increased, Fatigue includes the PTs: Fatigue and Asthenia.

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 term: rash and rash maculo-papular; 2. Capivasertib rash includes events related to rash including: rash, rash macular, maculopapular rash, rash papular and rash pruritic; Sources: alpelisib: SOLAR-1 (initial publication): Andre 2019 N Engl J Med 380:1929, inavolisib: ASCO 2022 #1052 (note: reported rates are for invavolisib-related AEs pooled across study cohorts including monotherapy and combinations with letrozole, fulvestrant, and palbociclib), capivasertib: CAPItello-291: SABCS 2022 #GS3-04 Note: These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted.

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 07/24/2023 RLY-2608 in BC Patients (N=43) RLY-2608 600mg BID (N=17)

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- advanced breast cancer, with no prior PI3Kα inhibitor (n=~15) PIK3CAmut advanced solid tumor (n=~15) PIK3CAmut, HR+, HER2- advanced breast cancer3 (n=~15 for each arm, ~45 total) MTD/RP2D MTD/RP2D MTD/RP2D RLY-5836 + Fulvestrant combination arm may start after one dose level higher of RLY-5836 single agent is cleared and determined tolerable RLY-5836 + CDK4/6i + ET combination arms may start after one dose level higher of RLY-5836 + Fulvestrant combination is cleared and determined tolerable. Three separate CDK4/6 arms, one for each of the following CDK4/6 agents: pablociclib, abemaciclib, ribociclib One or more of the RLY-5836 + CDK4/6i + Fulvestrant arms may open at Sponsor discretion and SRC agreement BOIN design with molecular enrichment PIK3CA mutation status per local assessment RLY-5836 PO BID or QD RLY-5836 clinical start in Apr 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 doses with less insulin than orthosteric inhibitors

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 ML to predict selectivity without bias or intervention Computational modeling enabled breakthrough speed Relay Tx’s Development Candidate observed to be highly selective Higher CDK2 activity associated with worse response to CDK4/6 inhibition in ER+ breast cancer CDK2 is important in ER+ breast cancer ~23K ~18K Patients receiving adjuvant CDK 4/6i Patients receiving 1L CDK 4/6i ~5K Patients receiving 2L CDK 4/6i Source: Internal analysis based on third party industry data RLY-2139 Benchmark Biochemical Potency CDK2/CycE IC50 (µM) 0.004 0.017 Biochemical selectivity (fold over) CDK1/CycB 100x 99x CDK6/CycD3 320x 270x CDK9/CycT1 2400x 2400x GSK3β 68000x 12000x

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 Traditional Approach Relay Tx Approach Endocrine therapies are used in every line of therapy in HR+/HER2- Breast Cancer 195k annual US patients with HR+/HER2- breast cancer Second Line + First Line Adjuvant Line of Therapy Endocrine Tx Use of Endocrine Therapies Source: Internal analysis based on third party industry data

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 Undisclosed 1 program FGFR2 RLY-4008 Mutant + WT Preclinical Early Clin. Late Clin. …aims to address selectivity on validated targets for breast cancer The Relay Tx Solution…

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, ORR) Longer-Term Tolerability Next milestone: additional RLY-2608 clinical data in 2024 RLY-2608 Evolution of Data Relay Tx Breast Cancer Portfolio First expansion cohort initiated at 600 mg BID dose PI3Kα Franchise RLY-2608 RLY-5836 H1047R-specific RLY-2139 (CDK2) ERα Degrader Other Undisclosed Programs

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 in potential additional total milestones, low-to-mid teen royalties on global net sales plus eligible to receive additional royalties upon approval of GDC-1971 and GDC-6036 in combination GDC-1971 + Atezolizumab (PD-L1 Ab) initiated August 2022 GDC-1971 + GDC-6036 (KRAS G12Ci) initiated July 2021 Unconfirmed ORR: 53% (30/57 patients) Confirmed ORR: 46% (26/57 patients) Three ongoing trials with GDC-1971: Clinical Update for GDC-6036 Monotherapy at World Lung 2022 GDC-1971 + Osimertinib/Cetuximab (EGFRi) initiated July 2023

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 Chemical Design 5+ Undisclosed Programs Inhibitors Degraders New Modalities Chaperones Platform capabilities and expertise continue to expand Enabling deep and diversified early pipeline Deep structural understanding Chemical biology insights

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 Franchise Undisclosed RLY-4008 (Selective FGFR2) Full dose escalation data in 1H 2023 (2023 ASCO) Non-CCA expansion cohorts data in 2H 2023 Pivotal cohort full enrollment in 2H 2023 GDC-1971 (SHP2) Ongoing combo trials; Genentech controls data disclosures Clinical start in early 2024 RLY-2139 (Selective CDK2) Development candidate nomination in 2023 ERα Degrader To be announced 5+ undisclosed programs in preclinical development and additional early-stage efforts across platform PI3KαPAN Initial RLY-2608 data in 1H 2023 RLY-5836 clinical start in 2Q 2023 RLY-2608 expansion cohorts initiated in 2H 2023 Additional data update in 2024

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 respondents "would recommend Relay Tx as a great place to work" Turnover below industry average rates Diversity & inclusion advisory group Training and development opportunities Equitable compensation 4 clinical programs Committed to clinical trial patient safety Committed to product safety and quality Note: Relay Tx is a development stage company Responsible energy consumption* Reducing water consumption Hazardous and lab waste management Non-hazardous waste management Average Tenure 5yrs Racial/Ethnic Diversity 38% Women 38% Independence (Separate CEO and Chair Role) 88% The Nom/Gov and Audit Committees oversee ESG efforts, with the full BOD getting ~quarterly updates 8 Directors Total* *Efforts to reduce energy consumption lend to our ambitions to limit carbon emissions