Relay Therapeutics, Inc. · NASDAQ:RLAY

Relay Therapeutics — Technical Presentation (March 2026)

13 slides from Relay Therapeutics's technical presentation, Mar 16, 2026

  1. Slide 1: Dose Optimization of Zovegalisib, a Novel PI3Kα Inhibitor, in PIK3CA-Mutant HR+/HER2− Advanced Breast Cancer

    Dose Optimization of Zovegalisib, a Novel PI3Kα Inhibitor, in Patients with PIK3CA-Mutant HR+/HER2− Advanced Breast Cancer Results from the First-In-Human Study to Support the Recommended Phase III Dose Andreas Varkaris,1 Antoine Italiano,2 Sarah L. Sammons,3 Eudald Felip,4 Alison M. Schram,5 Barbar

  2. Slide 2: Declaration of Interests

    Declaration of Interests Institutional clinical trial contract: Alterome, BeiGene, Boehringer Ingelheim, BridgeBio, OnKure Therapeutics, Relay Therapeutics, Synovation Therapeutics, Totus Medicines Institutional sponsor research agreement: OnKure Therapeutics, Relay Therapeutics Travel: Roche Dr. An

  3. Slide 3: Zovegalisib (RLY-2608) – 1st Mutant-Selective PI3Kα Inhibitor for HR+/HER2- Breast Cancer

    Zovegalisib (RLY-2608) – 1st Mutant-Selective PI3K⍺ Inhibitor for HR+/HER2- Breast Cancer Mutant PI3K⍺ Drives ~40% of HR+/HER2- BC1-3 Zovegalisib’s Novel MOA Selectively Targets Mutant PI3K⍺4 The PI3K pathway5 Zovegalisib Non–mutant-selective Zovegalisib, a pan-mutant– PI3Kα inhibitors selective PI3

  4. Slide 4: ReDiscover First-in-Human Study – PIK3CAm HR+/HER2- Advanced Breast Cancer

    ReDiscover First-in-Human Study – PIK3CAm HR+/HER2- Advanced Breast Cancer Zovegalisib + Fulvestrant Enrollment – CDK4/6i + ET Experienced Patients Study Arm Part 1 – Dose Escalation Part 2 – Dose Expansion 1000 mg BID – N=1 800 mg BID – N=16 N=64 at Zovegalisib + RP2D 600 mg BID 600 mg BID – N=17 6

  5. Slide 5: Zovegalisib Exposures Comparable Between 400 mg BID Fed and 600 mg BID Fasted Doses

    Zovegalisib Exposures Comparable Between 400 mg BID Fed and 600 mg BID Fasted Doses Mean Concentration vs Time Pharmacokinetic Parameter (Cycle 1 Day 15) (Cycle 1 Day 15) Following 400 mg BID fed dosing, mean zovegalisib concentrations remain above IC80 throughout the dosing interval Ful: Fulvestran

  6. Slide 6: Baseline Demographics Reflect Previously Treated FIH Population

    Baseline Demographics Reflect Previously Treated FIH Population Zovegalisib + Fulvestrant RP2D 600 mg BID (RP2D, N=64) 400 mg BID fed (RP2D, N=60) Median age (range), years 59.0 (34, 80) 60.0 (32, 78) ECOG 0/1, n (%) 38 (59.4) / 26 (40.6) 33 (55.0) / 27 (45.0) Local PIK3CA baseline results Kinase mu

  7. Slide 7: Zovegalisib + Fulvestrant – Rapid Decline in PIK3CA and ESR1 ctDNA Across Mutations

    Zovegalisib + Fulvestrant – Rapid Decline in PIK3CA and ESR1 ctDNA Across Mutations Circulating Tumor DNA Clearance – Zovega 400 mg BID Fed + Fulvestrant • 46 patients had detectable PIK3CA mutations at PIK3CA ctDNA: baseline and a paired result Percent Change • 6 patients had ≥1 from Baseline mutat

  8. Slide 8: Zovegalisib + Fulvestrant Demonstrates Clinically Meaningful Anti-Tumor Activity

    Zovegalisib + Fulvestrant Demonstrates Clinically Meaningful Anti-Tumor Activity Zovegalisib 400 mg BID Fed (RP2D) + fulvestrant – Radiographic Tumor Reduction and Response per RECIST v1.1 (N=35)1 ORR: 15/351,2 (42.9%) (95% CI: 26.3, 60.6) ORR in 2L only: 52.4% (N=21) 1 Excludes patients with PTEN o

  9. Slide 9: Zovegalisib + Fulvestrant Achieves Progression-free Survival of 11.1 months

    Zovegalisib + Fulvestrant Achieves Progression-free Survival of 11.1 months Zovegalisib + Fulvestrant – 400 mg BID Fed Progression-free Survival1 Overall mPFS: 11.1 months (95% CI: 7.3-13.0; N=57) • Median follow-up: 12.0 months • Kinase mPFS: 11.2 months (N=33) • Non-kinase mPFS: 11.0 months (N=24)

  10. Slide 10: Zovegalisib – Treatment-related Adverse Events Largely Low-grade and Reversible

    Zovegalisib – Treatment-related Adverse Events Largely Low-grade and Reversible ReDiscover – Zovega 400 mg BID Fed + Fulvestrant (n=60): 33.4 weeks mDOE (Range: 2.9 – 80.1) N=60 Diarrhea 32% 22% 3% 57% Fatigue1 20% 27% 5% 52% Nausea 28% 22% 2% 52% Creatinine Increased 2 25% 20% 2% 47% Hyperglycemia3

  11. Slide 11: ReDiscover-2 – Phase III Registrational Trial for Post-CDK4/6 inhibitor HR+/HER2- ABC

    ReDiscover-2 – Phase III Registrational Trial for Post-CDK4/6 inhibitor HR+/HER2- Advanced Breast Cancer with a PIK3CA Mutation1,2 Key Eligibility Criteria: Zovegalisib (400 mg BIDb) Inclusion criteria + fulvestrant • PIK3CA-mutated HR+/HER2- ABC • No concomitant PTEN or AKT tumor alterations R N=54

  12. Slide 12: Conclusions

    Conclusions Zovegalisib is the first oral, pan-mutant-selective PI3Kα inhibitor for patients with HR+/HER2– advanced breast cancer harboring PIK3CA mutations1 Prior data with zovegalisib 600 mg BID + fulvestrant in fasted patients demonstrated clinically meaningful activity and tolerability, establi

  13. Slide 13: European Society for Medical Oncology (ESMO)

    European Society for Medical Oncology (ESMO) Via Ginevra 4, CH-6900 Lugano T. +41 (0)91 973 19 00 esmo@esmo.org esmo.org

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