Relay Therapeutics, Inc. · NASDAQ:RLAY

Relay Therapeutics — Investor Presentation (August 2026)

83 slides from Relay Therapeutics's investor presentation, August 2026

  1. Slide 1: Corporate Presentation

    Corporate Presentation August 2026 © 2026 Relay Therapeutics 1

  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 our strategy, business plans and focus; the progress, timing and results of

  3. Slide 3: Zovegalisib – Potential To Address Large Commercial Opportunities

    Zovegalisib – Potential To Address 3 Large Commercial Opportunities 2L Breast Cancer 1L Breast Cancer Vascular Anomalies Estimated US TAM $2-3B $7-8B $6-8B © 2026 Relay Therapeutics Note: TAM calculated based on market benchmarks and internal analysis 3

  4. Slide 4: 2L Breast Cancer – Ph1/2 Data at Ph3 Dose Showed Clinically Meaningful PFS

    2L Breast Cancer – Ph1/2 Data at Ph3 Dose Showed Clinically Meaningful PFS Ph3 regimens Zovegalisib shows favorable efficacy in 2L+ patients 2L Zovegalisib + Fulv 400mg BID 11.1mo mPFS ORR: 2L & 3L+ Breast Cancer (Phase 3 Dose) 11.2mo in Kinase | 11.0mo in Non-Kinase 43% $2-3B Capivasertib + Fulv (4

  5. Slide 5: 1L Breast Cancer – Establishing Zovega + Atirmo + AI Combinability for 1L Use

    1L Breast Cancer – Establishing Zovega + Atirmo + AI Combinability for 1L Use Doublet Triplet Standard of Care CDK4/6 + ET Zovega + Atirmo + ET Study 1L Median 3L vs. Population Patients Patients 1L Breast Cancer Efficacy 53-55% vs. 44% ORR ORR $7-8B 50-90% 40% Estimated US TAM Tolerability Gr3+ AE

  6. Slide 6: Vascular Anomalies – Zovega's Promising Initial Efficacy Data & Tolerability Profile

    Vascular Anomalies – Zovega’s Promising Initial Efficacy Data & Tolerability Profile Initial Efficacy Data Initial Tolerability Data Volumetric Response Rate (VRR) Gr3+ AEs 60% Greater 71% VRR2 Vascular volumetric Lower Gr3+ Closest response TRAEs Anomalies 400mg: 57% 300mg: 100% rates approx. of sa

  7. Slide 7: Relay Tx – Clear Path to Addressing Large Commercial Opportunities

    Relay Tx – Clear Path to Addressing Large Commercial Opportunities Zovegalisib Program Clinical Benchmark Anticipated Zovegalisib Anticipated 2026 disclosures Hurdle1 Next Steps granted BTD → key value drivers 2L Breast Phase 3 enrollment update 11.1mo mPFS at pivotal dose Capi+fulv in 2L: Cancer →

  8. Slide 8: Relay Tx – Broad Precision Medicine Pipeline

    Relay Tx – Broad Precision Medicine Pipeline Target Indication Preclinical Early Clinical Late Clinical 2L Breast Cancer ReDiscover-2 Pivotal Trial ongoing Zovegalisib Zovegalisib PI3Kα 1L Breast Cancer Phase 3 planned to start 1H27 granted BTD pan-mutant selective inhibitor Vascular Anomalies ReIns

  9. Slide 9: Zovegalisib – Potential To Address Large Commercial Opportunities

    Zovegalisib – Potential To Address 3 Large Commercial Opportunities 2L Breast Cancer 1L Breast Cancer Vascular Anomalies Estimated US TAM $2-3B $7-8B $6-8B © 2026 Relay Therapeutics Note: TAM calculated based on market benchmarks and internal analysis 9

  10. Slide 10: 2L Breast Cancer – Ph1/2 Data at Ph3 Dose Showed Clinically Meaningful PFS

    2L Breast Cancer – Ph1/2 Data at Ph3 Dose Showed Clinically Meaningful PFS Ph3 regimens Zovegalisib shows favorable efficacy in 2L+ patients 2L Zovegalisib + Fulv 400mg BID 11.1mo mPFS ORR: 2L & 3L+ Breast Cancer (Phase 3 Dose) 11.2mo in Kinase | 11.0mo in Non-Kinase 43% $2-3B Capivasertib + Fulv (4

  11. Slide 11: Zovegalisib – ReDiscover Trial Baseline Demographics

    2L Breast Cancer Zovegalisib – ReDiscover Trial Baseline Demographics ReDiscover Clinical Trial 400mg BID Fed Data Zovegalisib + Fulvestrant 600 mg BID Fasted (N=64) 400mg BID Fed (N=60) Phase 3 dose Age, Median (Range), Years 59.0 (34, 80) 60.0 (32, 78) ECOG, 0 / 1, n (%) 38 (59.4) / 26 (40.6) 33 (

  12. Slide 12: Zovegalisib – Efficacy: Median PFS 11.1 Months

    2L Breast Cancer Zovegalisib – Efficacy: Median PFS 11.1 Months ReDiscover Clinical Trial 400mg BID Fed Data Zovegalisib 400mg BID Fed + Fulvestrant (N=57) 11.1mo mPFS (95% CI: 7.3, 13.0) Progression-Free Survival (%) • 6-month PFS: 71% • 9-month PFS: 59% • CBR: 38/57 (67%) • Median follow-up: 12.0m

  13. Slide 13: Zovegalisib – Efficacy: Confirmed ORR 43%

    2L Breast Cancer Zovegalisib – Efficacy: Confirmed ORR 43% ReDiscover Clinical Trial 400mg BID Fed Data Zovegalisib 400mg BID Fed + Fulvestrant Measurable Disease (N=35)1 43% ORR Tumor Reduction: 23/35 (66%) (15/35 pt; 95% CI: 26.3%, 60.6%) 52% ORR in 2L (11/21) Prior Serd Y Y Y Y Y Y Y Y Y Y Y Y Y

  14. Slide 14: Zovegalisib – Efficacy: ctDNA Clearance

    2L Breast Cancer Zovegalisib – Efficacy: ctDNA Clearance ReDiscover Clinical Trial 400mg BID Fed Data Zovegalisib 400mg BID Fed + Fulvestrant PIK3CA (N=46) PIK3CA Kinase 46 patients without PTEN/AKT1 E17K co-alterations had detectable PIK3CA mutations at baseline and a paired result at C2D1. Notably

  15. Slide 15: PI3Kα Inhibitors – Efficacy Profiles

    2L Breast Cancer PI3Kα Inhibitors – Efficacy Profiles ReDiscover Clinical Trial 400mg BID Fed Data Doublet Combination Regimens Alpelisib + fulv Capivasertib + fulv Zovegalisib + fulv Approved 2019 Phase 3 comparator (Phase 3 Dose: 400mg BID Fed) EPIK-B51 CAPItello-2912 ReDiscover Data source (N=188

  16. Slide 16: Limited Duration of Benefit Following CDK4/6 Inhibitor Regardless of MoA

    2L Breast Cancer Limited Duration of Benefit Following CDK4/6 Inhibitor Regardless of MoA mPFS in CDK4/6-Experienced, PIK3CAmut Patient Population1 11.1 7.4 7.2 7.5 7.2 6.0 5.5 5.5 5.0 mPFS (mo) 2.6 Capivasertib Alpelisib Inavolisib Ribociclib Abemaciclib+ Abemaciclib + elacestrant8 vepdegestrant9 K

  17. Slide 17: PI3Kα Inhibitors – Tolerability Profiles

    2L Breast Cancer PI3Kα Inhibitors – Tolerability Profiles ReDiscover Clinical Trial 400mg BID Fed Data Doublet Combination Regimens Alpelisib + fulv Capivasertib + fulv Zovegalisib + fulv Approved 2019 Phase 3 comparator (Phase 3 Dose: 400mg BID Fed) EPIK-B51 CAPItello-2912 ReDiscover Data benchmark

  18. Slide 18: Zovegalisib – Consistent Activity Between 400mg & 600mg Doses

    2L Breast Cancer Zovegalisib – Consistent Activity Between 400mg & 600mg Doses 43% ORR 11.1mo 43% ORR mPFS 400mg BID Median Fed follow-up: + Fulv2 12.0mo 39% ORR 10.3mo 600mg BID mPFS Median Fasted follow-up: + Fulv1 12.5mo © 2026 Relay Therapeutics 1. ReDiscover preliminary data as of 03/26/2025; 2

  19. Slide 19: Zovegalisib – TRAEs

    2L Breast Cancer Zovegalisib – TRAEs 400mg BID Fed (N=60) All Gr Gr1 Gr2 Gr3 Diarrhea 57% 32% 22% 3% Diarrhea occurred intermittently & readily managed with oral antidiarrheal Fatigue 52% 20% 27% 5% Nausea 52% 28% 22% 2% Blood creatinine increase 47% 25% 20% 2% Hyperglycemia 43% 25% 10% 8% Most hype

  20. Slide 20: Zovegalisib – PK Profile for 400mg BID Fed Dose

    2L Breast Cancer Zovegalisib – PK Profile for 400mg BID Fed Dose Mean Concentration vs Time at Cycle 1 Day 15 Steady State Pharmacokinetics Measures at Cycle 1 Day 15 400mg BID Fed 600mg BID Fasted Area Under Curve Max Concentration Trough Concentration (AUC) (Cmax) (Ctrough) 10000 Plasma Concentrat

  21. Slide 21: Zovegalisib – Phase 3 ReDiscover-2 Trial

    2L Breast Cancer Zovegalisib – Phase 3 ReDiscover-2 Trial Initiated mid-2025, enrolling globally Zovegalisib granted BTD in 2L breast cancer setting Key eligibility criteria: • HR+/HER2- advanced Breast Cancer Primary endpoints (hierarchical): Zovegalisib (400 mg BID Fed) • Any PIK3CA mutation with

  22. Slide 22: Zovegalisib – Potential To Address Large Commercial Opportunities

    Zovegalisib – Potential To Address 3 Large Commercial Opportunities 2L Breast Cancer 1L Breast Cancer Vascular Anomalies Estimated US TAM $2-3B $7-8B $6-8B © 2026 Relay Therapeutics Note: TAM calculated based on market benchmarks and internal analysis 22

  23. Slide 23: 1L Breast Cancer – Large Commercial Market

    1L Breast Cancer 1L Breast Cancer – Large Commercial Market ~35,000 Patients Large Existing CDK4/6 Market in 1L+ 1L Breast Cancer (PIK3CA mutated) ~$3B ~$3B ~$4B Patients in G7 markets1 Estimated global sales in metastatic setting2 © 2026 Relay Therapeutics 1. Decision Resources Group market forecas

  24. Slide 24: PIK3CA Mutant Inhibition Provides Clear Benefit in 1L Breast Cancer

    1L Breast Cancer PIK3CA Mutant Inhibition Provides Clear Benefit in 1L Breast Cancer However, toxicity is limiting; Non-selective PI3Kα inhibitor has shown PFS & OS benefit in 1L inavolisib not broadly used in 1L INAVO1201: 1L Endocrine Resistant 91% Gr3+ AE rate1 “Dear Dr.” letter for ketoacidosis2

  25. Slide 25: Zovegalisib – Establishing 1L Triplet Combinability in Median 3L Patients

    1L Breast Cancer Zovegalisib – Establishing 1L Triplet Combinability in Median 3L Patients Ideal 1L Profile of Zovegalisib Triplet Supportive data from median 3L patients: Zovega + CDKi + ET Triplet similar ORR in median 3L Superior efficacy vs. CDK4/6+ET doublet ORR in 1L Triplet toxicity profile C

  26. Slide 26: 1L Breast Cancer – Demonstrating Zovega + Atirmo + AI Combinability

    1L Breast Cancer 1L Breast Cancer – Demonstrating Zovega + Atirmo + AI Combinability Doublet Triplet Standard of Care CDK4/6 + ET Zovega + Atirmo + ET Study 1L Median 3L vs. Population Patients Patients Efficacy 53-55% vs. 44% ORR ORR Tolerability 50-90% vs. 40% Gr3+ AE Gr3+ AE Zovega + Atirmo + ET

  27. Slide 27: Zovegalisib – Laying the Foundation for Potential Next-Gen 1L Combos

    1L Breast Cancer Zovegalisib – Laying the Foundation for Potential Next-Gen 1L Combos Ph1 arms for triplet combinations (in 2L+ patients) Atirmociclib Zovega + Atirmo + ET Zovegalisib + + fulvestrant Selected as preferred go-forward (CDK4-selective) regimen for 1L Phase 3 trial Zovegalisib Ribocicli

  28. Slide 28: Zovegalisib Triplet – Dose Escalation

    1L Breast Cancer Zovegalisib Triplet – Dose Escalation Positive Drug Interaction Observed Dose Escalation Zovega exposures ~2.5x higher in atirmo triplet Phase 3 dose, pending combo than in fulvestrant doublet at same dose regulatory feedback 200mg BID Zovega 150mg BID Zovega Zovega 100mg BID ~2.5x

  29. Slide 29: Zovegalisib + Atirmociclib Triplet – Demographics

    1L Breast Cancer Zovegalisib + Atirmociclib Triplet – Demographics Zovegalisib + Atirmociclib + Fulvestrant (n=62) Age, Median (Range), Years 61.5 (33, 79) ECOG, 0 / 1, n (%) 45 (72.6) / 17 (27.4) Local PIK3CA Baseline Results Kinase Mutation, n (%) 33 (53.2) Non-Kinase Mutations, n (%) 29 (46.8) Pr

  30. Slide 30: Zovegalisib PK Profiles with Atirmociclib + Fulvestrant

    1L Breast Cancer Zovegalisib PK Profiles with Atirmociclib + Fulvestrant Drug interaction observed Dose proportional exposures of zovegalisib above IC80 Zovega + atirmo Zovega ~2.5x higher exposures + fulv Exposure of zovega with atirmo 200mg zovega (atirmo triplet) Zovega 150mg zovega + fulv (atirm

  31. Slide 31: Zovegalisib + Atirmociclib Triplet – Efficacy in Median 3L Patients

    1L Breast Cancer Zovegalisib + Atirmociclib Triplet – Efficacy in Median 3L Patients 44% ORR SoC doublet: in median 3L vs. 53-55% ORR (15/34) in 1L at or below possible Ph3 doses Responses across mutation types: Kinase: 44% (8/18) Non-Kinase: 44% (7/16) Median 3L patients 21% of patients saw prior P

  32. Slide 32: Zovega Triplet Efficacy Compared Favorably to CDK Regimens in 1L and 2L+

    1L Breast Cancer Zovega Triplet Efficacy Compared Favorably to CDK Regimens in 1L and 2L+ Triplet in 2L+ Approved Regimens in 1L Median 3L: 2L+: 1L Endocrine Sensitive: 1L Endocrine Resistant: Zovega + Atirmo + Fulv Inavo + CDK4/6 + Fulv/AI CDK4/6 + AI Doublet Inavo + Palbo + Fulv 44% ORR 58% ORR 53

  33. Slide 33: Triplet Efficacy – Zovegalisib + Atirmo vs. Tersolisib + Ribo/Palbo

    1L Breast Cancer Triplet Efficacy – Zovegalisib + Atirmo vs. Tersolisib + Ribo/Palbo Zovega + Atirmo + Fulv Triplet1 Tersolisib + Ribo/Palbo Triplet (SABCS 20252) 44% 24% ORR ORR Median follow-up: 7.4mo Median follow-up: ~3mo 100-200mg Zovega + 100-300mg atirmo + 20-100mg tersolisib + fulv Full-dose

  34. Slide 34: Zovegalisib – TRAEs ≥15%

    1L Breast Cancer Zovegalisib – TRAEs ≥15% Median 3L Zovegalisib + Atirmociclib + fulvestrant (N=62) 40% Gr3+ TRAEs All Gr Gr1 Gr2 Gr3+ Diarrhea 58% 34% 18% 7% Diarrhea occurred intermittently & was readily managed with oral antidiarrheal Neutropenia1,2 48% 5% 18% 26% Fatigue2 42% 26% 13% 3% Rash2 34

  35. Slide 35: Zovega Triplet Safety Compared Favorably to CDK Regimens in 1L and 2L+

    1L Breast Cancer Zovega Triplet Safety Compared Favorably to CDK Regimens in 1L and 2L+ Triplet in 2L+ Approved Regimens in 1L Median 3L: 2L+: 1L Endocrine Sensitive: 1L Endocrine Resistant: Zovega + Atirmo + Fulv Inavo + CDK4/6 + Fulv/AI CDK4/6 + AI Doublet Inavo + Palbo + Fulv 92% 81% 88% Gr3+ AE

  36. Slide 36: Zovegalisib + Atirmociclib Triplet – Swimlane

    1L Breast Cancer Zovegalisib + Atirmociclib Triplet – Swimlane Cycle • Median follow-up: 7.4mo • 48/62 (77%) patients ongoing • Median PFS not reached © 2026 Relay Therapeutics ReDiscover preliminary data as of 04/13/2026 36

  37. Slide 37: Preliminary 1L Metastatic HR+/HER2- Breast Cancer Trial Schema

    1L Breast Cancer Preliminary 1L Metastatic HR+/HER2- Breast Cancer Trial Schema Preliminary Trial Design (subject to regulatory feedback) Zovegalisib + Atirmociclib Key eligibility criteria: + AI Key endpoints: • HR+, HER2- advanced / met BC R • PIK3CA mutation 1:1 • mPFS (primary) • No prior line o

  38. Slide 38: Zovegalisib – Multiple Future Potential Development Options

    1L Breast Cancer Zovegalisib – Multiple Future Potential Development Options PIK3CA-mutated Breast Cancer Adjuvant 1L 2L+ Opportunity Size: Zovega + ET 1L PIK3CAm Zovega + CDK + ET (+/- CDK) Zovega + fulv HR+/HER2- ~35k patients Zovega + ET1 (select populations) Zovega + Oral SERD ~10k HER2+ patient

  39. Slide 39: Clinical Trial Supply Agreement with Pfizer and Next Steps

    1L Breast Cancer Clinical Trial Supply Agreement with Pfizer and Next Steps • Relay to sponsor, fully operationalize, and fund 1L Phase 3 trial • Relay retains full global rights for zovegalisib • Pfizer supplies atirmociclib for experimental arm & palbociclib for control arm Plan for regulatory int

  40. Slide 40: Zovegalisib – Potential To Address Large Commercial Opportunities

    Zovegalisib – Potential To Address 3 Large Commercial Opportunities 2L Breast Cancer 1L Breast Cancer Vascular Anomalies Estimated US TAM $2-3B $7-8B $6-8B © 2026 Relay Therapeutics Note: TAM calculated based on market benchmarks and internal analysis 40

  41. Slide 41: Vascular Anomalies – Zovega's Promising Initial Efficacy Data & Tolerability Profile

    Vascular Anomalies – Zovega’s Promising Initial Efficacy Data & Tolerability Profile Initial Efficacy Data Initial Tolerability Data Volumetric Response Rate (VRR) Gr3+ AEs 60% Greater 71% VRR2 Vascular volumetric Lower Gr3+ Closest response TRAEs Anomalies 400mg: 57% 300mg: 100% rates approx. of sa

  42. Slide 42: Vascular Anomalies Overview

    PIK3CA-Driven Vascular Anomalies Vascular Anomalies Overview ~170k US patients with PIK3CA-driven Vascular Anomalies Somatic PIK3CA drives malformed leading to vascular Zovegalisib is mutation vasculature anomalies uniquely positioned to mut address driver of disease PIK3CA First mutant-selective PI

  43. Slide 43: Vascular Anomalies – Disparate Disorders Driven by Common Somatic Mutations

    PIK3CA-Driven Vascular Anomalies Vascular Anomalies – Disparate Disorders Driven by Common Somatic Mutations PIK3CA mutations are among the Somatic mutations to the PI3K pathway drive most common driver of Vascular Anomalies1 abnormal development in Vascular Anomalies Mutation Frequency by Gene2 Unl

  44. Slide 44: Vascular Anomalies – Patient Referral Pathway

    PIK3CA-Driven Vascular Anomalies Vascular Anomalies – Patient Referral Pathway Referral may Local Providers take years: Vascular Anomaly Centers of Excellence • range of symptoms DETAILS Generalized set of healthcare • rarity of conditions Coordinated care from vascular anomaly providers: • misdiagn

  45. Slide 45: Vascular Anomalies – Current Treatment Paradigm

    PIK3CA-Driven Vascular Anomalies Vascular Anomalies – Current Treatment Paradigm Disease severity Mild Moderate Severe Current Treatment Watch & wait; Local intervention when Attempt systemic therapy Paradigm Supportive treatment necessary/possible (limited duration) Available Tx • Compression garme

  46. Slide 46: Vascular Anomalies – Potential Future Treatment Paradigm

    PIK3CA-Driven Vascular Anomalies Vascular Anomalies – Potential Future Treatment Paradigm Disease severity Mild Moderate Severe Future Treatment Watch & wait; Evaluate chronic systemic therapy Paradigm Supportive treatment +/- complementary interventions when feasible/beneficial Potential • Compress

  47. Slide 47: Vascular Anomalies – Patient Numbers

    PIK3CA-Driven Vascular Anomalies Vascular Anomalies – Patient Numbers PIK3CA-driven Vascular Anomalies (VAs) ~170K US patients Vascular Anomaly Subtypes Initial clinical focus: ~25k US patients seeking systemic therapy PIK3CA-Related PIK3CA-driven PIK3CA-driven Overgrowth Spectrum Lymphatic Malforma

  48. Slide 48: Vascular Anomalies – Phenotype & Symptoms

    PIK3CA-Driven Vascular Anomalies Vascular Anomalies – Phenotype & Symptoms Variety of Observed Symptoms are Part of Subtypes of the Same Disease Symptoms PIK3CA-driven Vascular Anomalies PROS (PIK3CA-Related Overgrowth Spectrum) Cosmetic Pain Reduced Bleeding abnormalities mobility PIK3CA-driven Lym

  49. Slide 49: Vascular Anomalies – Systemic Therapy Options

    PIK3CA-Driven Vascular Anomalies Vascular Anomalies – Systemic Therapy Options 1st Generation 2nd Generation 3rd Generation Non-selective Non-selective Mutant-selective PI3K pathway inhibition PI3Kα inhibition PI3Kα inhibition Sirolimus Serebelisib Alpelisib Zovegalisib (mTORi) (KP-001) 1st Patent 1

  50. Slide 50: Zovegalisib – Study Design: ReInspire

    PIK3CA-Driven Vascular Anomalies Zovegalisib – Study Design: ReInspire Part 1: Dose Selection Part 2: Dose Expansion Data shown in following slides Randomized dose finding: RP2D(s) Expansion cohorts opened at: Adults & Adolescents 400mg, 300mg, 100mg BID • 300mg BID (≥12 years old) (Completed; N=~10

  51. Slide 51: Zovegalisib – ReInspire Trial Demographics

    PIK3CA-Driven Vascular Anomalies Zovegalisib – ReInspire Trial Demographics Total 100mg BID 300mg BID 400mg BID (N=32) (N=11) (N=11) (N=10) Age (years), median (range) 24.5 (12, 63) 31 (13, 50) 24 (13, 54) 19.5 (12, 63) 12-17 / ≥18, n (%) 10 (31) / 22 (69) 4 (36) / 7 (64) 2 (18) / 9 (82) 4 (40) / 6

  52. Slide 52: Zovegalisib – All Initial Doses Resulted in Exposures Projected to be Active

    PIK3CA-Driven Vascular Anomalies Zovegalisib – All Initial Doses Resulted in Exposures Projected to be Active C1D15 Mean Concentration-Time Profiles By Dose 100mg BID (N=6) 300mg BID (N=6) 400mg BID (N=7) © 2026 Relay Therapeutics ReInspire preliminary data as of 04/15/2026 52

  53. Slide 53: Zovegalisib – 60% Volumetric Response Rate by BICR Across All Doses

    PIK3CA-Driven Vascular Anomalies Zovegalisib – 60% Volumetric Response Rate by BICR Across All Doses Three 100mg pts with lesion reduction between 18.2-19.8% Volumetric Response: ≥20% reduction Best % Change Patient converted to from Baseline of unconfirmed response Target lesion(s) volume 60% after

  54. Slide 54: Zovegalisib – Volumetric Response Over Time (BICR)

    PIK3CA-Driven Vascular Anomalies Zovegalisib – Volumetric Response Over Time (BICR) 100mg VRR: 300mg VRR: 400mg VRR: 29% (2/7)1 100% (6/6) 57% (4/7) * 60% Overall VRR Three 100mg pts with lesion reduction (12/20)1 between 18.2-19.8% (all ongoing) *Patient converted to unconfirmed response after data

  55. Slide 55: Zovegalisib – Initial Efficacy Data Supports Clear Symptomatic Benefit

    PIK3CA-Driven Vascular Anomalies Zovegalisib – Initial Efficacy Data Supports Clear Symptomatic Benefit Investigator-Reported (IGIC) Patient-Reported (PGIC) Pain (IADRSS) 89% 79% 71% of patients improved by week 12 of patients improve by week 12 of pain symptoms improved by week 12 Very much improve

  56. Slide 56: Zovegalisib – Initial Efficacy Data Summary

    PIK3CA-Driven Vascular Anomalies Zovegalisib – Initial Efficacy Data Summary Meaningful Efficacy Data Consistent Across Subgroups Broad Symptomatic Benefit Volumetric Response Rate (VRR) Subgroup VRR1 % of Patients with Improvement at Week 12 100% Alpelisib3 17-27% 89% 60% Zovega Overall 60%1 79% Ov

  57. Slide 57: Zovegalisib – Treatment-Related Adverse Events ≥15% of Patients

    PIK3CA-Driven Vascular Anomalies Zovegalisib – Treatment-Related Adverse Events ≥15% of Patients No discontinuations due to adverse events 100mg BID (N=11) 300mg BID (N=11) 100mg+300mg BID (N=22) 400mg BID (N=10) All Gr Gr1 Gr2 Gr3+ All Gr Gr1 Gr2 Gr3+ All Gr Gr1 Gr2 Gr3+ All Gr Gr1 Gr2 Gr3+ Any TRA

  58. Slide 58: PI3Kα Inhibitors – Tolerability Profile Across Known Key Pathway AEs

    PIK3CA-Driven Vascular Anomalies PI3Kα Inhibitors – Tolerability Profile Across Known Key Pathway AEs EPIK-P1 (250mg) was not a prospective study and Alpelisib Zovegalisib EPIK-P2 was conducted at half the label dose5 ~220mg QD1 100mg + 300mg BID Data benchmark EPIK-B51 ReInspire At 100mg and 300mg

  59. Slide 59: Alpelisib EPIK-P2 Results – Safety Data in Adults

    PIK3CA-Driven Vascular Anomalies Alpelisib EPIK-P2 Results – Safety Data in Adults 17% ORR EPIK-P21 EPIK-P41 EPIK-B52 Up to Week 48 initiated 2025 (breast cancer) ~180mg 250mg ~220mg 71% 30% SAEs avg dose3 starting dose avg dose4 Gr3+ AEs 66% of pts escalated 73% 300mg was dose up from 125mg startin

  60. Slide 60: Patient Vignette – Adult Patient with PROS Achieved Meaningful Improvement

    PIK3CA-Driven Vascular Anomalies Patient Vignette – Adult Patient with PROS Achieved Meaningful Clinical and Radiographical Improvement with Zovega 100mg BID Baseline Week 24 • PIK3CA mutation: Q546K 44-year-old male • Prior sclerotherapy x3, no prior systemic tx with KTS (PROS) • Minimal mobility a

  61. Slide 61: Patient Vignette – Previously Systemically Treated Pediatric Patient with PROS

    PIK3CA-Driven Vascular Anomalies Patient Vignette – Previously Systemically Treated Pediatric Patient with PROS Achieved Meaningful Radiographic & Clinical Improvement with Zovega 300mg BID Baseline • PIK3CA mutation: E542K • Prior surgery x6, laser therapy x12, 12-year-old male sirolimus (no respon

  62. Slide 62: Patient Vignette – Adult patient with Facial LM

    PIK3CA-Driven Vascular Anomalies Patient Vignette – Adult patient with Facial LM Experienced Meaningful Improvement in Pain and Radiographic Response with Zovega 300 mg BID Baseline Week 24 • PIK3CA mutation: E545K • Prior sclerotherapy x3, embolization x2, 42-year-old female surgery x4, sirolimus (

  63. Slide 63: Zovegalisib - Clear Path to Finding Dose to Evaluate Potential for Differentiated Profile

    PIK3CA-Driven Vascular Anomalies Zovegalisib - Clear Path to Finding Dose to Evaluate Potential for Differentiated Profile Alpelisib Zovegalisib 100% One 100mg pt converted from SD to uVR after data cut-off7 57% Efficacy Data: Expansion Expansion Volumetric 27% 29%7 dose (I)5 dose (II) response rate

  64. Slide 64: Potential for Accelerated Approval Pathway

    PIK3CA-Driven Vascular Anomalies Potential for Accelerated Approval Pathway* Dose Selection Dose Expansion Confirmatory Dose Randomization: Adults & Adolescents 400mg BID (≥12 years old) 300mg BID 300mg BID Add’l pt at RP3D Basket of: Potential 100mg BID 400mg QD Accelerated • PROS Approval • LMs da

  65. Slide 65: Vascular Anomalies – Mutant-Selective Approach Has Potential to Unlock Significant Market

    Vascular Anomalies – Mutant-Selective Approach Has Potential to Unlock Significant Market Target Profile of Zovegalisib Potential Commercial Implications Superior Greater Efficacy Penetration Significant market opportunity Superior Greater Tolerability Superior Chronicity Greater $6-8B Estimated US

  66. Slide 66: NRAS – Large Validated Market With Significant Unmet Need

    NRAS – Large Validated Market With Significant Unmet Need Solid Tumors NRAS-Driven Solid Tumors Novel Approach RLY-8161 (1st NRAS-selective inhibitor) Genetically Defined NRAS mutations Initiated Phase 1/2 trial in NRAS-mutant melanoma Clinically Validated Non-selective RAF/MEK/Pan-RAS & other solid

  67. Slide 67: NRAS – Large Validated Market With Significant Unmet Need

    NRAS – Large Validated Market With Significant Unmet Need NRAS mutations are a key driver of solid tumors, NRAS mutations observed in broad range though no NRAS-selective agent exists of tumor types Annual US Patients1 mut Pan-RAS NRAS HRAS KRAS c ~0.6k Head and Neck ~6.0k Thyroid Cancer RAF ~2.1k N

  68. Slide 68: Limited Therapeutic Window of Current Agents – Pan-RAF/RAS & MEK Inhibitors

    Limited Therapeutic Window of Current Agents – Pan-RAF/RAS & MEK Inhibitors Non-Selective Agents in Development mut Pan-RAS NRAS HRAS KRAS RAF Downstream RAS pathway MEK (pan-RAF, MEK, ERK) ERK Scholl et al. 2007; Drosten et al. 2014; Cell growth and proliferation Esteban et al. 2001 Limited Tolerab

  69. Slide 69: NRAS – Dynamo Platform Discovered a Novel Allosteric Pocket

    NRAS – Dynamo® Platform Discovered a Novel Allosteric Pocket Exploited differences in protein motion… …to design first NRAS-selective inhibitor NRAS HRAS KRAS NRAS HRAS KRAS © 2026 Relay Therapeutics 69

  70. Slide 70: NRAS Inhibitors Are Potent, Selective & Active Across NRAS Mutations

    NRAS Inhibitors Are Potent, Selective & Active Across NRAS Mutations Relay Tx compounds bind to the …inhibit pathway signaling only in …inhibiting proliferation of only ON-state with selectivity for NRAS1 NRAS mutant cells2 NRAS mutant cells3 125 RLY-8161 Binding Affinity (nM) -5 RLY-8161 Proliferat

  71. Slide 71: Deep Regressions in PDXs Across Histologies & NRAS Genotypes

    Deep Regressions in PDXs Across Histologies & NRAS Genotypes ME12175 Melanoma (NRASQ61R/R) LU5153 NSCLC (NRASQ61K/K TP53R273L) 1500 1000 1000 800 (Mean  SEM, mm3) 600 Tumor Volume 500 (Mean  SEM, mm3) Tumor Volume 300 200 150 200 Vehicle 100 50 100 0 RLY-8161 20 mg/kg QD 0 5 10 15 0 Days of Treatm

  72. Slide 72: Fabry Disease – Large Validated Market With Significant Unmet Need

    Fabry Disease – Large Validated Market With Significant Unmet Need Genetic Disease Fabry Disease 1st non-inhibitory, allosteric αGal Novel Approach chaperone Genetically Defined GLA mutations Advance to IND-ready Galafold® (migalastat) Clinically Validated approved in Fabry Disease Limited αGal acti

  73. Slide 73: Fabry Disease – Large Validated Market With Significant Unmet Need

    Fabry Disease – Large Validated Market With Significant Unmet Need Fabry disease is a lysosomal storage Current therapies have established a market but have key limitations disorder affecting ~10,000 patients in US1 Approved Therapies Limitations of Approved Therapies Over 1,000 different GLA gene m

  74. Slide 74: Fabry Disease – Dynamo Discovered a Novel Allosteric Pocket

    Fabry Disease – Dynamo® Discovered a Novel Allosteric Pocket αGal Inhibitory vs Non-Inhibitory Chaperone Normal Mutant © 2026 Relay Therapeutics 74

  75. Slide 75: Relay Tx Compounds are Non-Inhibitory and More Potently Activate αGal in Cells

    Relay Tx Compounds are Non-Inhibitory and More Potently Activate αGal in Cells Migalastat inhibits αGal function while RTX-1 can activate αGal in cells RTX-1 still shows superior activation vs Relay compounds do not without a compound washout migalastat post-washout 20 800 800 RTX-1 RTX-1 0 600 Miga

  76. Slide 76: Fabry Disease – Potential Benefits of Non-Inhibitory Chaperone Approach

    Fabry Disease – Potential Benefits of Non-Inhibitory Chaperone Approach 20 0 (Norm to DMSO) % αGal activity -20 -40 RTX-1 Relay Tx Solution: -60 -80 Migalastat Non-Inhibitory Chaperone to -100 -120 Stabilize Protein and Increase Activity -10 -8 -6 -4 -2 log10 Compound (M) 1 2 3 Superior αGal activat

  77. Slide 77: Superior αGal Activation – RTX-1 Leads to Higher In Vivo Activity

    1 Superior αGal Activation RTX-1 Leads to Higher Levels of in Vivo αGal Activity and Substrate Clearance R301Q Mutant Mouse Model (Amenable Mutation) Kidney αGal activity Kidney Gb3 Plasma lyso-Gb3 150 2000 150 125 1500 125 (Norm to Vehicle) (Norm to Vehicle) % Plasma lyso-Gb3 (Norm to Vehicle) % αG

  78. Slide 78: Relay Tx Chaperone Outperforms Migalastat Across a Panel of ~100 Mutations

    2 αGal Activity (% WT) 0 25 50 75 100 125 M187I I317T R301P Y216C L300P L32P © 2026 Relay Therapeutics P205T K240N P259R Broad Mutational Coverage M284T R301G G325R I253S N228D S238N R220P G260A P205S R356W I242N R301Q G328A G258R D244H A143T R118C D244N Q279E G373S G85D L36W G271S N215S M51K A156T

  79. Slide 79: Relay Tx Non-Inhibitory Chaperones Combinable with ERT

    3 Combinable with ERT Relay Tx Non-Inhibitory Chaperones Combinable with ERT In vivo αGal activity In vivo lyso-Gb3 reduction Activity in kidney following single dose of ERT and Plasma lyso-Gb3 levels following single dose of ERT and 14-day treatment with RTX-1 (GLA KO mouse model) 14-day treatment

  80. Slide 80: Zovegalisib (RLY-2608) – Potential To Address Large Commercial Opportunities

    Zovegalisib (RLY-2608) – Potential To Address 3 Large Commercial Opportunities 2L Breast Cancer 1L Breast Cancer Vascular Anomalies Estimated US TAM $2-3B $7-8B $6-8B Note: TAM calculated based on market benchmarks and internal analysis © 2026 Relay Therapeutics 80

  81. Slide 81: Relay Tx – Broad Precision Medicine Pipeline

    Relay Tx – Broad Precision Medicine Pipeline Target Indication Preclinical Early Clinical Late Clinical 2L Breast Cancer ReDiscover-2 Pivotal Trial ongoing Zovegalisib Zovegalisib PI3Kα 1L Breast Cancer Phase 3 planned to start 1H27 granted BTD pan-mutant selective inhibitor Vascular Anomalies ReIns

  82. Slide 82: Relay Tx – Clear Path to Addressing Large Commercial Opportunities

    Relay Tx – Clear Path to Addressing Large Commercial Opportunities Zovegalisib Program Clinical Benchmark Anticipated Zovegalisib Anticipated 2026 disclosures Hurdle1 Next Steps granted BTD → key value drivers 2L Breast Phase 3 enrollment update 11.1mo mPFS at pivotal dose Capi+fulv in 2L: Cancer →

  83. Slide 83: © 2026 Relay Therapeutics

    © 2026 Relay Therapeutics 83

Relay Therapeutics — Investor Presentation (August 2026) on 6ix