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

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RLY-2608 Data September 9, 2024 Exhibit 99.2


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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 Relay Therapeutics' strategy, business plans and focus;  the progress and timing of the clinical development of the programs across Relay Therapeutics' portfolio; the expected therapeutic benefits and potential efficacy and tolerability of RLY-2608, both as a monotherapy and in combination with other agents, and its other programs, including lirafugratinib as well as the clinical data for RLY-2608; the interactions with and approval of regulatory authorities and any related approvals; the potential market opportunity for RLY-2608; and the expected strategic benefits under Relay Therapeutics' clinical trial collaboration with Pfizer; the cash runway projection and the expectations regarding Relay Therapeutics' use of capital and expenses. The words “may,” “might,” “will,” “could,” “would,” “should,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions, or the negative thereof, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.  Any forward-looking statements in this presentation are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this presentation, including, without limitation, risks associated with: the impact of global economic uncertainty, geopolitical instability and conflicts, or public health epidemics or outbreaks of an infectious disease on countries or regions in which we have operations or do business, as well as on the timing and anticipated results of our clinical trials, strategy, future operations and profitability; the delay or pause of any current or planned clinical trials or the development of our drug candidates; the risk that the preliminary or interim results of our preclinical or clinical trials may not be predictive of future or final results in connection with future clinical trials of our product candidates and that interim and early clinical data may change as more patient data become available and are subject to audit and verification procedures; our ability to successfully demonstrate the safety and efficacy of our drug candidates; the timing and outcome of our planned interactions with regulatory authorities; and obtaining, maintaining and protecting our intellectual property. These and other risks, uncertainties and important factors are described in the section entitled "Risk Factors" in our most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, as well as any subsequent filings with the Securities and Exchange Commission. Any forward-looking statements represent our views only as of the date of this presentation and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, the occurrence of certain events or otherwise. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research. This presentation contains trademarks, trade names and service marks of other companies, which are the property of their respective owners


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Today’s Update RLY-2608 abstract submitted to San Antonio Breast Cancer Symposium RLY-2608 – Next steps 2 ReDiscover Trial Update – RLY-2608 + Fulvestrant Doublet Data 1


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RLY-2608 – Interim Clinical Data Show Clinically Meaningful PFS 1. CAPItello-291: Turner N Engl J Med 2023; 388:2058-2070; 2. ORR includes 2 ongoing unconfirmed partial response as of the data cut-off. After the data cut-off, one uPR patient has confirmed and the other uPR patient remains on treatment; Additionally, one stable disease patient has converted to an unconfirmed partial response, remains on treatment and is not included in the ORR; 3. In CAPItello-291, CBR and ORR not reported for CDK4/6-experienced patient population; ORR = objective response rate, mPFS = median progression free survival, LoT = line of therapy (metastatic setting), SoC = Standard of Care, TRAE = treatment related adverse effects, RP2D = recommended Phase 2 dose, CBR = clinical benefit rate, SERD = selective estrogen receptor degrader; Note: data shown are not from head-to-head studies, and no head-to-head studies have been conducted. ReDiscover preliminary data as of 08/12/2024 Favorable Efficacy PIK3CAmut, HR+/HER2- Advanced / Metastatic Breast Cancer (post CDK4/6) Favorable Tolerability More Heavily Pre-Treated Patients 42% Gr3 TRAE Capivasertib + Fulv1 (4 days on, 3 off) 5.5mo mPFS CBR & ORR Not reported3 25% Gr3 TRAE RLY-2608 + Fulv (600 mg BID, RP2D) 23% ≥2 prior LoT 0% Prior SERD 45% ≥2 prior LoT 52% Prior SERD 33% ORR2 57% CBR 9.2mo mPFS 9.2mo mPFS Interim RLY-2608 safety and efficacy data supportive of pivotal trial in 2L Breast Cancer against capivasertib


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PI3Kα Mutations Represent a Large Commercial Opportunity PI3Kα mutations represent a large commercial opportunity Non-selective PI3Kα targeting has significant limitations Relay Tx’s Dynamo®️ Platform created mutant selective molecule Breast Cancer Vascular Malformations Non-Breast Cancer Solid Tumors ~150k pts (prevalence¹) ~170k pts (prevalence²) ~160k pts (incidence³) Challenging Tolerability Limited Efficacy RLY-2608 Limited Combinability 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. Prevalent US patient population of vascular malformation patients with a PIK3CA mutation (multiple sources); 3. Incident US patient population solid tumors annually with a PIK3CA mutation (SEER; 3rd party source for alteration rate, May 2024)


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RLY-2608 – Interim Clinical Data Show Clinically Meaningful PFS Interim RLY-2608 safety and efficacy data supportive of pivotal trial in 2L Breast Cancer against capivasertib ReDiscover preliminary data as of 08/12/2024 Favorable Tolerability More Heavily Pre-Treated Patients 42% Gr3 TRAE Capivasertib + Fulv1 (4 days on, 3 off) 5.5mo mPFS CBR & ORR Not reported3 25% Gr3 TRAE RLY-2608 + Fulv (600 mg BID, RP2D) 23% ≥2 prior LoT 0% Prior SERD 45% ≥2 prior LoT 52% Prior SERD 33% ORR2 57% CBR 9.2mo mPFS 9.2mo mPFS Favorable Efficacy PIK3CAmut, HR+/HER2- Advanced / Metastatic Breast Cancer (post CDK4/6) 1. CAPItello-291: Turner N Engl J Med 2023; 388:2058-2070; 2. ORR includes 2 ongoing unconfirmed partial response as of the data cut-off. After the data cut-off, one uPR patient has confirmed and the other uPR patient remains on treatment; Additionally, one stable disease patient has converted to an unconfirmed partial response, remains on treatment and is not included in the ORR; 3. In CAPItello-291, CBR and ORR not reported for CDK4/6-experienced patient population; ORR = objective response rate, mPFS = median progression free survival, LoT = line of therapy (metastatic setting), SoC = Standard of Care, TRAE = treatment related adverse effects, RP2D = recommended Phase 2 dose, CBR = clinical benefit rate, SERD = selective estrogen receptor degrader; Note: data shown are not from head-to-head studies, and no head-to-head studies have been conducted.


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RLY-2608 – Initial Pivotal Trial Planned for 2L Doublet in 2025* Eligibility Criteria: PIK3CAmut HR+, HER2- advanced / met BC 1 prior line CDK4/6 inhibitor Broad metabolic inclusion criteria No known PTEN or AKT mutation RLY-2608 (600 mg BID, RP2D) + fulvestrant Capivasertib (400 mg BID 4 days on, 3 days off) + fulvestrant R Primary Endpoint: PFS Secondary Endpoints: OS, ORR, DoR, QoL 2L Doublet 2L doublet pivotal start expected in 2025 *Subject to discussions with regulators; eligibility criteria, endpoints, RP2D, and other aspects of trial design have not yet been finalized; OS = overall survival, DoR = duration of response, QoL = quality of life, met BC = metastatic Breast Cancer; 2L = 2nd line


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PI3Kα Franchise - Opportunity for Multiple Value-Creating Datasets Over Next 2 Yrs Team and Capital to Execute Ribociclib triplet ongoing; CDK4 triplet start Monotherapy dose expansions start Clinical start 2L doublet pivotal start Vascular Malformations Solid Tumors Meaningful Efficacy Data Expected to Come Over Next 2 Years 1L + 2L Metastatic Breast Cancer $6B+ total addressable market in PIK3CAmut HR+/HER2- mBC


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Relay Tx – Broad Precision Medicine Pipeline Target Program Preclinical Early Clinical Late Clinical BREAST CANCER PI3Kα RLY-2608 (PI3KαPAN) Endocrine Tx (ET) doublet Ribociclib + ET triplet CDK4i + ET triplet Other Novel Combinations CDK2 RLY-2139 ERα RLY-1013 (Degrader) GENETIC DISEASE Fabry Disease αGal Chaperone Vascular Malformations RLY-2608 (PI3KαPAN) Other PI3KαPAN SOLID TUMORS NRAS NRAS-selective Inhibitor PI3Kα RLY-2608 Monotherapy FGFR2 Lirafugratinib (RLY-4008) Paused; IND ready Advance to IND-ready Seeking global commercialization partner ~$688M cash as of end 2Q 2024 Expected to fund current operating plan into 2H 2026 Dynamo®️ Platform 5+ unnamed research programs Note: IND = Investigational New Drug Application (FDA)


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RLY-2608 – ReDiscover Trial Overview 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; CCOC = clear cell ovarian cancer Part 2 – Dose Expansion Study Arm Part 1 – Dose Escalation MTD/RP2D PIK3CAmut, HR+/HER2- Advanced / Metastatic Breast Cancer (post-CDK4/6) PIK3CAmut, HR+/HER2- Advanced / Metastatic Breast Cancer Focus of Following Data Doublet MTD/RP2D PIK3CAmut Advanced Solid Tumors (CCOC, HNSCC, cervical, other1, double PIK3CA mutants2) PIK3CAmut Advanced Solid Tumors (mixed histologies) Mono MTD/RP2D PIK3CAmut, HR+/HER2- Advanced / Metastatic Breast Cancer (post-CDK4/6) PIK3CAmut, HR+/HER2- Advanced / Metastatic Breast Cancer Ribociclib (CDK4/6) Atirmociclib (CDK4) MTD/RP2D Triplet RLY-2608 + Fulvestrant RLY-2608 RLY-2608 + Fulvestrant + CDK4/6 & CDK4i


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RLY-2608 – ReDiscover Trial Enrollment Part 2 – Dose Expansion RLY-2608 + Fulvestrant Doublet 200 mg BID – N=3 100 mg BID – N=3 800 mg BID – N=16 1000 mg BID – N=1 600 mg BID – N=17 600 mg BID – N=47 Study Arm Part 1 – Dose Escalation 64 patients total across dose escalation and expansion at 600 mg BID 400 mg BID – N=10 400 mg BID1 – N=21 Safety Database – 118 patients across all doses Efficacy Database at 600mg BID – 52 patients (excludes 12 PTEN / AKT co-mutation patients2) ReDiscover preliminary data as of 08/12/2024 1. 400mg cohort is not yet mature for efficacy analysis. Full Phase I results, including 400mg cohort, will be disclosed at a later date; 2. As defined by central ctDNA RP2D


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RLY-2608 – ReDiscover Trial Baseline Demographics ReDiscover preliminary data as of 08/12/2024 RLY-2608 + Fulvestrant All Patients (N=118) 600 mg BID (RP2D, N=64) Age, Median (Range), Years 59.0 (34, 85) 59.0 (34, 80) ECOG, 0 / 1, n (%) 69 (58.5) / 49 (41.5) 38 (59.4) / 26 (40.6) Local PIK3CA Baseline Results Kinase Mutation, n (%) 56 (47.5) 31 (48.4) Non-Kinase Mutations, n (%) 62 (52.5) 33 (51.6) BMI >30 and/or HbA1c >5.7%, n (%) 44 (37.3) 22 (34.4) Measurable Disease, n (%) 83 (70.3) 42 (65.6) Patients with Visceral Metastases, n (%)1 75 (63.6) 38 (59.4) Prior Lines of Therapy in Advanced Setting 1, n (%) 59 (50.0) 35 (54.7) 2+, n (%) 59 (50.0) 29 (45.3) Prior Therapies in Advanced Setting CDK4/6, n (%)2 118 (100.0) 64 (100.0) Fulvestrant or Novel SERD, n (%) 66 (55.9) 33 (51.6) Chemo / ADC, n (%) 30 (25.4) 16 (25.0) ESR1 Mutation (Central Read)3, n (%) 40 (36.0) 18 (29.5) 1. Visceral metastatic sites include lung, liver, brain, pleural, peritoneal involvement; 2. Two patients received prior CDK4/6 in the adjuvant setting which is allowed per protocol; 3. Percentage was based on pts with evaluable ctDNA data at baseline; ECOG = Eastern Cooperative Oncology Group performance status


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RLY-2608 – Efficacy: Median PFS 9.2 Months ReDiscover preliminary data as of 08/12/2024 Note: Follow-up estimated based on reversed KM. PFS estimates based on KM methods. Progression-Free Survival (%) Time Since First Dose (months) 6-month PFS: 64.1% 9-month PFS: 60.1% CBR: 57.1% (20/35 pt) Median follow-up: 7.5 months Number of Patients at Risk: 9.2mo mPFS (95% CI: 5.6, 18.4) RLY-2608 600 mg BID (RP2D) + Fulvestrant Excluding PTEN / AKT Co-Mutations (N=52)


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ReDiscover preliminary data as of 08/12/2024 RLY-2608 600 mg BID (RP2D) + Fulvestrant Excluding PTEN / AKT Co-Mutations – Measurable Disease (N=30) ORR: 33.3% (10/30)1 Tumor Reduction: 73.3% (22/30) 1. ORR includes 2 ongoing unconfirmed partial response as of the data cut-off. After the data cut-off, one uPR patient has confirmed and the other uPR patient remains on treatment; Additionally, one stable disease patient has converted to an unconfirmed partial response, remains on treatment and is not included in the ORR; 2. Patient confirmed post data cut off and is not included in the ORR; 3. PIK3CA mutation: “K” = Kinase domain mutation, “NK” = Non-Kinase domain mutation; uCR = unconfirmed complete response Not shown: uCR in pt with non-measurable disease2 3 RLY-2608 – Efficacy: ORR 33%


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RLY-2608 (All Doses) + Fulvestrant (N=69) RLY-2608 – Efficacy: ctDNA Clearance PIK3CA ctDNA Variant Allele Frequency (%) Kinase Non-Kinase RLY-2608 (600 mg BID) + Fulvestrant (N=35) At 600 mg BID1 (RP2D): 34 (97.1%) patients had decline in PIK3CA ctDNA 19 (54.3%) patients completely cleared PIK3CA ctDNA by C2D1 1. N=35 patients without PTEN/AKT co-alterations who have detectable PIK3CA at baseline and a paired C1D1-C2D1 ctDNA result are presented ReDiscover preliminary data as of 08/12/2024


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RLY-2608 – Efficacy: Kinase Mutations mPFS 10.3 Months, ORR 53% ReDiscover preliminary data as of 08/12/2024 RLY-2608 600 mg BID (RP2D) + Fulvestrant PIK3CA Kinase mutations, excluding PTEN / AKT co-mutations (N=29) 10.3mo mPFS (95% CI: 5.8, NR) Progression-Free Survival (%) Time Since First Dose (months) Number of Patients at Risk: RLY-2608 600 mg BID (RP2D) + Fulvestrant PIK3CA Kinase mutations, excluding PTEN / AKT co-mutations (N=15) 53.3% ORR (8/15 pt)1 1. ORR includes 1 ongoing unconfirmed partial response as of the data cut-off. After the data cut-off, this 1 uPR patient has confirmed and remains on treatment; Additionally, one stable disease patient has converted to an unconfirmed partial response, remains on treatment and is not included in the ORR


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RLY-2608 – Tolerability: Limited Observed Impact on Glucose Homeostasis ReDiscover preliminary data as of 08/12/2024 Alpelisib Label Criteria* 100 mg BID (N=3) 200 mg BID (N=3) 400 mg BID (N=31) 600 mg BID (N=64) 800 mg BID (N=16) 1000 mg BID (N=1) Glucose (mg/dL) RLY-2608 + Fulvestrant Grade 3 (250-500 mg/dL) Grade 2  (160-250 mg/dL) Grade 1 (115-160 mg/dL) Note: *Based on CTCAE version 4 criteria; Data represent mean per cohort +/- standard deviation; Source: Central lab analysis


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RLY-2608 – Tolerability: TRAEs ReDiscover preliminary data as of 08/12/2024 No Gr4-5 TRAEs 1: Hyperglycemia includes the MedDRA v26.0 Preferred Terms (PTs): Hyperglycemia, Blood Glucose Increased, Glucose Tolerance Impaired; Fatigue includes the PTs: Fatigue and Asthenia; Hypokalemia includes the PTs: Hypokalemia and blood potassium decreased; Rash includes the PTs: Rash, Rash Macular, Rash Maculo-Papular; 2. No acute kidney injury reported All Patients (N=118) 600mg BID (RP2D, N=64) All Gr Gr3 All Gr Gr3 Any TRAE 91.5%  20.3%  93.8%  25.0%  TRAEs ≥15% of 600 mg BID Hyperglycemia1 42.4% 1.7% 46.9% 1.6% Nausea 39.8% 0.8% 48.4%  1.6% Creatinine Increased2 33.9% 0% 32.8% 0% Fatigue1 38.1% 7.6% 32.8% 7.8% Diarrhea 29.7% 1.7% 34.4% 3.1% Decreased Appetite 16.1% 0% 18.8% 0% Hypokalemia1 15.3% 1.7% 17.2% 1.6% Other select TRAEs Rash1 11.9% 0.8% 10.9% 1.6% Stomatitis 3.4% 0.8% 4.7% 0% 30% Gr1 hyperglycemia (no intervention required)


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Note: * Fatigue includes the Preferred Terms: Fatigue and Asthenia; TRAEs leading to Dose Reduction in more than 2 patients within 600 mg BID are presented.  RLY-2608 – Tolerability: Dose Intensity and Modifications Maintained 95% dose intensity with very low TRAE discontinuations at 600mg BID All Patients (N=118) 600mg BID (RP2D, N=64) Dose Intensity Relative Dose Intensity (%), Median 97.54 95.16 Dose Modifications Due to TRAE Dose Reduction, n (%) 36 (30.5) 23 (35.9) Dose Interruption, n (%) 49 (41.5) 27 (42.2) Dose Discontinuation, n (%) 7 (5.9) 2 (3.1) TRAEs Leading to Dose Reduction Fatigue* 11 (9.3) 5 (7.8) Blood Creatinine Increased 8 (6.8) 3 (4.7) Diarrhea 6 (5.1) 3 (4.7) Grade 1 pruritis; Grade 1 nausea and loss of appetite ReDiscover preliminary data as of 08/12/2024


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RLY-2608 – Initial Pivotal Trial Planned for 2L Doublet in 2025* Eligibility Criteria: PIK3CAmut HR+, HER2- advanced / met BC 1 prior line CDK4/6 inhibitor Broad metabolic inclusion criteria No known PTEN or AKT mutation RLY-2608 (600 mg BID, RP2D) + fulvestrant Capivasertib (400 mg BID 4 days on, 3 days off) + fulvestrant R Primary Endpoint: PFS Secondary Endpoints: OS, ORR, DoR, QoL 2L Doublet 2L doublet pivotal start expected in 2025 *Subject to discussions with regulators; eligibility criteria, endpoints, RP2D, and other aspects of trial design have not yet been finalized; OS = overall survival, DoR = duration of response, QoL = quality of life, met BC = metastatic Breast Cancer; 2L = 2nd line


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RLY-2608 – On Track to Realize 1L Potential with Triplet Combinations Phase 1 Aim for Triplets: Demonstrate safety, tolerability and preliminary efficacy with both current generation CDK4/6 and next-gen CDK4 to enable pivotal development potential in both Dose Escalation On track for end of year initiation Currently dosing at biologically active doses of RLY-2608 Plan to Identify Dose and Move into Expansion Cohorts On track to identify dose in 2025 On track to identify dose by late 2024/early 2025 Triplets RLY-2608 Fulvestrant + Ribociclib (CDK4/6, commercial SoC) Atirmociclib (CDK4, Pfizer) + + RLY-2608 Fulvestrant +


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Breast Cancer – Large Market in Current and Emerging Standards of Care Endocrine Sensitive CDK4 + next gen oral ET Oral SERD monoTx Inavolisib + palbo + fulv Inavolisib + fulvestrant ADCs 11,000 pts Endocrine Resistant Capivasertib + fulvestrant or Alpelisib + fulvestrant or Everolimus + AI Elacestrant (ESR1m) Chemotherapy CDK4/6 + fulvestrant Chemotherapy CDK4/6 + AI (abema / ribo / palbo) PIK3CA mutated HR+/HER2- BC Treatment Paradigm1 7,000 pts 14,000 pts Fulvestrant (ESR1WT) Current Standard of Care Emerging TX RLY-2608 combinations Current PI3Kα Pathway  Total Addressable Market2 (Metastatic HR+/HER2- Breast Cancer) $6B+ 1L 2L 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. Relay Tx PIK3CA internal market forecast (patient-based – US, EU5, Japan). Forecast includes estimates for genetic testing, class share, market access, compliance, duration of therapy and assumes current PIK3CA therapy net price (primary sources: SEER; GloboCan; Global Data; Evaluate Pharma; DRG Market Forecast; PIK3CAi PIs)


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1. SABCS 2021 #P5-17-05; 2. Rugo 2021 Lancet Oncol 22:489; 3. FDA Prescribing Information Document; 4. CAPItello-291: Turner N Engl J Med 2023; 388:2058-2070; Note: These data are derived from different clinical trials at different points in time, with differences in molecule composition, trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. Grade 3+ Hyperglycemia All Grade 3+ TRAEs Alpelisib + fulvestrant Capivasertib + fulvestrant Inavolisib + fulvestrant RLY-2608 + fulvestrant (600mg BID, RP2D) Doublet Combination Regimens PI3Kα Inhibitors – Tolerability Profiles Data below are not from head-to-head studies. Cross-trial data interpretation should be considered with caution as it is limited by differences in study population, design and many other factors. Dose Discontinuation due TRAEs not approved approved 2019 approved 2023 ReDiscover preliminary data as of 08/12/2024 Discontinuous dosing: 4 days on, 3 days off Ph1b Arm D1 (n=60) BYLieve2 (n=127) FDA Label3 (n=355) Data Benchmark ReDiscover (n=64) 0% 42%4 34% of pt BMI ≥30 and/or HbA1c ≥5.7%


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1. SABCS 2021 #P5-17-05; 2. Rugo 2021 Lancet Oncol 22:489; 3. FDA Prescribing Information Document; 4. per CAPItello-291 enrollment criteria; 5. Rash for capivasertib references Cutaneous Adverse Reactions grouped term includes a number of preferred terms listed in FDA prescribing information Note: These data are derived from different clinical trials at different points in time, with differences in molecule composition, trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. Diarrhea Rash5 Hyperglycemia Ph1b Arm D1 (n=60) BYLieve2 (n=127) FDA Label3 (n=355) Data Benchmark ReDiscover (n=64) <7% ≤6.4% <8%4 HbA1c Enrollment Criteria <7% Gr1-2 Gr3+ Gr1 Gr2 Stomatitis PI3Kα Inhibitors – Tolerability Profiles Data below are not from head-to-head studies. Cross-trial data interpretation should be considered with caution as it is limited by differences in study population, design and many other factors. 34% of pt BMI ≥30 and/or HbA1c ≥5.7% ReDiscover preliminary data as of 08/12/2024 Doublet Combination Regimens Alpelisib + fulvestrant Capivasertib + fulvestrant Inavolisib + fulvestrant RLY-2608 + fulvestrant (600mg BID, RP2D) not approved approved 2019 approved 2023 62% 6% 10% 3% 59% 60% 29% 31% 2% 12% 15% 2% 19% 77% 56% 25% 2% 3% 2% 47% 34% 11%


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PI3Kα Inhibitors – Efficacy Profiles Data below are not from head-to-head studies. Cross-trial data interpretation should be considered with caution as it is limited by differences in study population, design and many other factors. 1. SABCS 2021 #P5-17-05 (n=60); 2. SABCS 2021 #PD-13-05; 3. Turner N Engl J Med 2023; 388:2058-2070 (n=355); 4. 5.5mo mPFS reported in CDK4/6-experienced patient sub-population of CAPItello-291; 5. Prior SERD includes fulvestrant and next-generation SERDs; 6. ORR as reported in FDA Label (from CAPItello-291); 7. ORR includes 2 ongoing unconfirmed partial response as of the data cut-off. After the data cut-off, one uPR patient has confirmed and the other uPR patient remains on treatment; Additionally, one stable disease patient has converted to an unconfirmed partial response, remains on treatment and is not included in the ORR; Note: These data are derived from different clinical trials at different points in time, with differences in molecule composition, trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. 24% 37% ORR CBR 26%6 56% 19% 48% Capi ORR & CBR include 30% of pts who are CDK4/6-naïve 7.1mo 5.6mo 5.5mo 5.5mo4 mPFS 33%7 57% 9.2mo 33% 0% 47% 52% 63% 23% 57% 44% % prior SERD5 % pt with >=2 prior LoT Data Benchmark BYLieve Cohort C2 (N=126) CAPItello-2913,6 (N=355) Ph1b Arm D1 (N=60) ReDiscover (N=52) ReDiscover preliminary data as of 08/12/2024 Doublet Combination Regimens Alpelisib + fulvestrant Capivasertib + fulvestrant Inavolisib + fulvestrant RLY-2608 + fulvestrant (600mg BID, RP2D) not approved approved 2019 approved 2023


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Relay Tx’s PI3Kα Franchise – Large Opportunities Across 3 Pillars PIK3CA mutant HR+/HER2- Breast Cancer PIK3CA mutant Vascular Malformations PIK3CA mutant Other Solid Tumors 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. Prevalent US patient population of vascular malformation patients with a PIK3CA mutation (multiple sources); 3. Incident US patient population solid tumors annually with a PIK3CA mutation (SEER; 3rd party source for alteration rate, May 2024); POC = proof of concept; PROS = PIK3CA Related Overgrowth Spectrum, NSCLC = non-small cell lung cancer, HNSCC = hand and neck squamous cell carcinoma ~150k Patients (US prevalence)1 ~170k Patients (US prevalence)2 ~160k Patients (US incidence)3 RLY-2608 RLY-2608 Potential for initial POC with RLY-2608, then distinct molecule for pivotal Clinical start – Q1 2025 CDK4/6 triplet data – 2024 CDK4 triplet clinical start – 2024 CDK4/6 triplet expansion start – 1H25 2L doublet pivotal start – 2025 Open monotherapy dose expansion – YE 2024 Anticipated Next Steps Cerebral Cavernous Lymphatic Venous PROS 65k pt ~65k pt 25k pt 15k pt Colorectal Endometrial Bladder Prostate NSCLC HNSCC 28k pt 20k pt 17k pt 16k pt 14k pt 9k pt Adjuvant 1st Line 2nd Line 120k pt 18k pt 14k pt ReDiscover preliminary data as of 08/12/2024


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2024 Dynamo® Platform Relay Tx’s Dynamo® – Productive Computationally Enabled Platform Free energy calculations Digitally encoded libraries Long time-scale MD Differential dynamics Automated Chemical Design Generative design Active learning ADME/PK models ML-DEL + AI models for DEL Giga-scale virtual screening Computational fragment merging COMPUTATION NMR X-ray fragment screening HDX-MS Mechanistic enzymology Cryo-EM REL-DEL Integrated pharmacology Protein design and engineering Ambient temp. X-Ray crystallography Automated Ligand ID System (ALIS) Structure ensembles EXPERIMENTATION Exp. Comp. 2016 PEOPLE High throughput automated chemistry


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Relay Tx – Additional Near-Term Clinical Programs 1. Prevalence of Fabry patients (National Fabry Disease Foundation, Jan 2024); 2. Newly diagnosed (incident) solid tumors with an NRAS mutation, excluding melanoma stages 0-II (SEER, 3rd party source for alteration rate, Jan 2024); 3. Fabry disease forecasted 2024 market size per EvaluatePharma, includes Galafold® and ERTs (May 2024) Solid Tumors NRAS-Driven Solid tumors Clinical start in 2H 2025 ~28,000 pts2 1st NRAS-selective inhibitor Fabry Disease Clinical start in 2H 2025 ~8,000 pts1 (chronic treatment) 1st non-inhibitory αGal chaperone GENETIC DISEASE $2B current market3 Anticipated Milestones Large US Opportunity Program Updates


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Lirafugratinib (RLY-4008) – Updated Data and Next Steps Next Step: Seek global commercialization partner for lirafugratinib Updated Tumor Agnostic data ORR 37% mDoR 7.3mo Data to be presented at ENA 2024 Tumor Agnostic FGFR2 Fusions (non-CCA) N=47; preliminary data as of 06/26/24 Regulatory Feedback Suggest to file NDA in CCA Suggest to generate additional data for subsequent sNDA in Tumor Agnostic Per recent meeting with FDA: 1 2 Scope of Commercial Opportunity1 All Solid Tumors: FGFR2 Fusions CCA: FGFR2 Fusions ~4,000 US pts/yr ~13,000 Global pts/yr ~650 US pts/yr ~1,400 Global pts/yr 1. Based on annual number of patient deaths due to expected later-line use. Global figure includes U.S., EU5, Japan.; Sources: SEER 2023, Global Cancer Observatory 2022


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Relay Tx – Broad Precision Medicine Pipeline Target Program Preclinical Early Clinical Late Clinical BREAST CANCER PI3Kα RLY-2608 (PI3KαPAN) Endocrine Tx (ET) doublet Ribociclib + ET triplet CDK4i + ET triplet Other Novel Combinations CDK2 RLY-2139 ERα RLY-1013 (Degrader) GENETIC DISEASE Fabry Disease αGal Chaperone Vascular Malformations RLY-2608 (PI3KαPAN) Other PI3KαPAN SOLID TUMORS NRAS NRAS-selective Inhibitor PI3Kα RLY-2608 Monotherapy FGFR2 Lirafugratinib (RLY-4008) Paused; IND ready Advance to IND-ready Seeking global commercialization partner Dynamo®️ Platform 5+ unnamed research programs


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Relay Tx – Anticipated Milestones 2024-25 Breast Cancer Portfolio Milestones PI3Kα RLY-2608 Genetic Disease Portfolio milestones Solid Tumors portfolio milestones Clinical start – 2H 2025 ~$688M cash as of end 2Q 2024 Expected to fund current operating plan into 2H 2026 Dynamo®️ Platform 5+ unnamed research programs Open monotherapy dose expansion – YE24 PI3Kα RLY-2608 NRAS Pre-clinical Clinical start – 1Q 2025 Clinical start – 2H 2025 Vascular Malformations RLY-2608 Fabry Disease Pre-clinical Doublet 2L pivotal trial start – 2025 Ribociclib triplet data – 2024 Ribociclib triplet expansion start – 1H25 CDK4i triplet clinical start – 2024


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PI3Kα Franchise - Opportunity for Multiple Value-Creating Datasets Over Next 2 Yrs Team and Capital to Execute Ribociclib triplet ongoing; CDK4 triplet start Monotherapy dose expansions start Clinical start 2L doublet pivotal start Vascular Malformations Solid Tumors Meaningful Efficacy Data Expected to Come Over Next 2 Years 1L + 2L Metastatic Breast Cancer $6B+ total addressable market in PIK3CAmut HR+/HER2- mBC


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RLY-2608 – Efficacy: 57.1% CBR RLY-2608 600 mg BID (RP2D) + Fulvestrant Excluding PTEN / AKT Co-Mutations (N=52) CBR: 20/35 (57.1%) ReDiscover preliminary data as of 08/12/2024 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