Relay Therapeutics, Inc. · NASDAQ:RLAY
Relay Therapeutics — 2024 San Antonio Breast Cancer Symposium (SABCS)
39 slides from Relay Therapeutics's conference presentation, Dec 11, 2024
Slide 1: 2024 SABCS – RLY-2608 Data Update
2024 SABCS – RLY-2608 Data Update December 2024 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 Relay Therapeutics' strategy, business plans and focus; the progress and ti
Slide 3: Agenda
Agenda RLY-2608 data presented at 2024 San Antonio Breast Cancer Symposium RLY-2608 – Other Updates 2 ReDiscover Trial Update – RLY-2608 + Fulvestrant Doublet Data Dr. Sammons – overview of evolving treatment landscape Data summary 1 Next steps 3
Slide 4: PI3Kα Mutations Represent a Large Commercial Opportunity
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 Tumo
Slide 5: Breast Cancer – Large Market for Mutant-Selective PI3Kα Targeted Therapies
Breast Cancer – Large Market for Mutant-Selective PI3Kα Targeted Therapies CDK4/6 + AI (abema / ribo / palbo) 1L Endocrine Sensitive 10,000 pt CDK4/6 + fulvestrant Inavolisib + palbo + fulv Capivasertib + fulvestrant or Alpelisib + fulvestrant or Everolimus + AI Current PI3Kα Pathway Total Addressab
Slide 6: Interim Clinical Data Continue to Show Clinically Meaningful PFS
RLY-2608 – Interim Clinical Data Continue to Show Clinically Meaningful PFS 1. CAPItello-291: Turner N Engl J Med 2023; 388:2058-2070; 2. In CAPItello-291, CBR and ORR not reported for CDK4/6-experienced patient population; ORR = objective response rate, mPFS = median progression free survival, LoT
Slide 7: Initial Pivotal Trial Planned for 2L Doublet in 2025
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
Slide 8: Multiple Mutant-Selective PI3Kα Opportunities
RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities Clinical start expected in 1Q 2025 2L doublet pivotal start expected in 2025 Metastatic Breast Cancer 2nd Line Ribociclib triplet and CDK4 triplet ongoing Metastatic Breast Cancer 1st Line Vascular Malformations PI3Kα Franchise Team and Capita
Slide 9: RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities
Clinical start expected in 1Q 2025 2L doublet pivotal start expected in 2025 Ribociclib triplet and CDK4 triplet ongoing RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities Metastatic Breast Cancer 2nd Line Metastatic Breast Cancer 1st Line Vascular Malformations PI3Kα Franchise Team and Capita
Slide 10: Large Unmet Need in Metastatic Breast Cancer
Large Unmet Need in Metastatic Breast Cancer Large unmet need in 2L presents opportunity for well-differentiated targeted agent Ribociclib + AI2 Ribociclib + fulv3 Median PFS of Current Standard of Care 13,000 patients 2L Post-CDK4/6 PIK3CAmut, HR+/HER2- mBC1 6,000 patients 1L Endocrine Resistant 10
Slide 11: Mutant-Selective PI3Kα Additive to Many Potential Combinations
RLY-2608 – Mutant-Selective PI3Kα Additive to Many Potential Combinations PI3Kα Backbone Current Standard of Care Non-Mutant Selective Inhibitors (capivasertib, alpelisib, inavolisib) Emerging Options for Future Standard of Care RLY-2608 PIK3CAmut HR+/HER2- Breast Cancer Treatment Paradigm + Cell Cy
Slide 12: ReDiscover Trial Overview
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 –
Slide 13: ReDiscover Trial Enrollment
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
Slide 14: ReDiscover Trial Baseline Demographics
RLY-2608 – ReDiscover Trial Baseline Demographics ReDiscover preliminary data as of 11/04/2024 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 Baseli
Slide 15: Efficacy: Median PFS 9.2 Months in All Patients & 11.4 Months in 2L
RLY-2608 – Efficacy: Median PFS 9.2 Months in All Patients & 11.4 Months in 2L ReDiscover preliminary data as of 11/04/2024 Note: Follow-up estimated based on reversed KM. PFS estimates based on KM methods. Time Since First Dose (months) RLY-2608 600 mg BID (RP2D) + Fulvestrant Excluding PTEN / AKT
Slide 16: RLY-2608 – Efficacy: Confirmed ORR 39%
PR RLY-2608 – Efficacy: Confirmed ORR 39% ReDiscover preliminary data as of 11/04/2024 RLY-2608 600 mg BID (RP2D) + Fulvestrant Excluding PTEN / AKT Co-Mutations – Measurable Disease (N=31) ORR: 12/31 (38.7%) (95% CI: 21.8%, 57.8%) Tumor Reduction: 23/31 (74.2%) PIK3CA mutation: “K” = Kinase domain
Slide 17: Efficacy: ctDNA Clearance
RLY-2608 – Efficacy: ctDNA Clearance PIK3CA ctDNA Variant Allele Frequency (%) Kinase Non-Kinase 1. N=36 patients without PTEN/AKT co-alterations who have detectable PIK3CA at baseline and a paired C1D1-C2D1 ctDNA result are presented RLY-2608 (600 mg BID) + Fulvestrant (N=36) RLY-2608 (All Doses) +
Slide 18: RLY-2608 – Efficacy: Kinase Mutations mPFS 11.4 Months & Confirmed ORR 67%
RLY-2608 600 mg BID (RP2D) + Fulvestrant Excluding PTEN / AKT co-mutations (N=29) 11.4 mo mPFS (95% CI: 9.2, NR) RLY-2608 600 mg BID (RP2D) + Fulvestrant Excluding PTEN / AKT – Measurable Disease (N=15) 66.7% ORR (10/15 pt, 95% CI: 38.4%, 88.2%) Not shown: CR in pt with non-measurable disease RLY-26
Slide 19: Tolerability: Limited Observed Impact on Glucose Homeostasis
RLY-2608 – Tolerability: Limited Observed Impact on Glucose Homeostasis ReDiscover preliminary data as of 11/04/2024 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
Slide 20: RLY-2608 – Tolerability: TRAEs
All Patients (N=118) 600mg BID (RP2D, N=64) All Gr Gr3 All Gr Gr3 Any TRAE 92.4% 25.4% 93.8% 31.3% TRAEs ≥15% of 600 mg BID Hyperglycemia1 42.4% 2.5% 46.9% 3.1% Nausea 41.5% 0.8% 50.0% 1.6% Fatigue1 40.7% 8.5% 35.9% 9.4% Creatinine Increased 34.7% 0.8% 34.4% 1.6% Diarrhea 30.5% 1.7% 35.9% 3.1% Decre
Slide 21: RLY-2608 – Tolerability: Dose Intensity and Modifications
Note: 1. Fatigue includes the PTs: 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 94% dose intensity with very low TRAE discontinuations at 600mg BID All Patients (N=1
Slide 22: Doublet Combination Regimens Efficacy Benchmark
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. FDA Prescribing Information. Note: These
Slide 23: Monotherapy Activity in Breast Cancer
RLY-2608 – Monotherapy Activity in Breast Cancer ORR: 1/3 (33%) DCR: 2/3 (67%) RLY-2608 Active as Monotherapy All HR+/HER2- Breast Cancer Patients Across All Doses (N=3)* No endometrial patients dosed* Relay Tx Focus on Significant Commercial Opportunities 2L Breast Cancer 13,000 pt Vascular Malform
Slide 24: Initial Pivotal Trial Planned for 2L Doublet in 2025
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
Slide 25: RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities
Clinical start expected in 1Q 2025 2L doublet pivotal start expected in 2025 RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities Metastatic Breast Cancer 2nd Line Metastatic Breast Cancer 1st Line Vascular Malformations PI3Kα Franchise Team and Capital to Execute Ribociclib triplet and CDK4 tri
Slide 26: On Track to Realize 1L Potential with Triplet Combinations
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 Atirmociclib triplet has initiated Currently
Slide 27: RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities
2L doublet pivotal start expected in 2025 Ribociclib triplet and CDK4 triplet ongoing RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities Metastatic Breast Cancer 2nd Line Metastatic Breast Cancer 1st Line Vascular Malformations PI3Kα Franchise Team and Capital to Execute Clinical start expecte
Slide 28: Vascular Malformations – Over 170,000 US Patients
Vascular Malformations – Over 170,000 US Patients US Patients % PIK3CAmut Approved Therapies Lymphatic Malformation (LM) Venous Malformation (VM) Cerebral Cavernous Malformation (CCM) PIK3CA-Related Overgrowth Spectrum (PROS) ~80k 80% ~65k pt ~100k ~20-25% ~20-25k pt ~120k 40-55% ~50-65k pt ~5-15k 1
Slide 29: Vascular Malformations – Proposed Study Design
Vascular Malformations – Proposed Study Design PIK3CAmut Vascular Malformation (VM) Patients (PROS & Other PIK3CA VMs) Adults & Adolescents (≥12 years old) Pediatrics (6-12 years old) Pediatrics (2-6 years old) Part 1: Dose Selection RP2D(s) Part 2: Dose Expansion Expansion Cohort(s) Expansion Cohor
Slide 30: Multiple Mutant-Selective PI3Kα Opportunities
RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities Clinical start expected in 1Q 2025 2L doublet pivotal start expected in 2025 Metastatic Breast Cancer 2nd Line Ribociclib triplet and CDK4 triplet ongoing Metastatic Breast Cancer 1st Line Vascular Malformations PI3Kα Franchise Team and Capita
Slide 31: PI3Kα Inhibitors – Tolerability Profiles
PI3Kα Inhibitors – Tolerability Profiles 1. SABCS 2021 #P5-17-05; 2. Rugo 2021 Lancet Oncol 22:489; 3. FDA Prescribing Information; 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
Slide 32: PI3Kα Inhibitors – Tolerability Profiles by Adverse Event
1. SABCS 2021 #P5-17-05; 2. Rugo 2021 Lancet Oncol 22:489; 3. FDA Prescribing Information; 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 da
Slide 33: PI3Kα Inhibitors – Efficacy Profiles
PI3Kα Inhibitors – Efficacy Profiles 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. FDA
Slide 34: Large Unmet Need in Metastatic Breast Cancer
Large Unmet Need in Metastatic Breast Cancer 13,000 patients 2L Post-CDK4/6 PIK3CAmut, HR+/HER2- mBC1 6,000 patients 1L Endocrine Resistant 10,000 patients 1L Endocrine Sensitive Notes: 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy, excluding PTEN co-mutations (Gl
Slide 35: Relay Tx – Additional Near-Term Clinical Programs
Relay Tx – Additional Near-Term Clinical Programs 1. Prevalence of Fabry patients, 2025 (National Fabry Disease Foundation, Nov 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 dis
Slide 36: Relay Tx – Broad Precision Medicine Pipeline
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 Disea
Slide 37: Relay Tx – Capital, Team & Execution
Significant Capital to Achieve Goals Relay Tx – Capital, Team & Execution Focus to Deliver on Milestones Cash as of the end of 3Q 2024 ~$840M Expected to fund current operating plan into 2H 2027 Anticipated 2025 Corporate Objectives 2L pivotal trial start – 2025 Full Ph1-2 data – 2025 Breast Cancer
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Slide 39: Efficacy: CBR 67%
RLY-2608 – Efficacy: CBR 67% ReDiscover preliminary data as of 11/04/2024 RLY-2608 600 mg BID + Fulvestrant Excluding PTEN / AKT Co-Mutations (N=52) CBR: 32/48 (66.7%)
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