Relay Therapeutics, Inc. · NASDAQ:RLAY

Relay Therapeutics — Technical Presentation (March 2026)

31 slides from Relay Therapeutics's technical presentation, March 2026

1. Slide 1: Webinar: Vascular Anomalies

   Webinar: Vascular Anomalies March 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 the progress and timing of the clinical development of the programs across

3. Slide 3: Vascular Anomalies Overview

   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 PI3Kα inhibitor Initial clinical da

4. Slide 4: Vascular Anomalies – Driven By Vascular Overgrowth

   Vascular Anomalies – Driven By Vascular Overgrowth Normal Blood and Lymphatic System Vascular Malformation Artery Vein Capillary Lymphatic vessels Lymphatic malformation The type and location of vasculature that overgrows drives clinical presentation © 2026 Relay Therapeutics 4

5. Slide 5: Vascular Anomalies – Disparate Disorders Classified by Phenotype

   Vascular Anomalies – Disparate Disorders Classified by Phenotype Long history of Vascular Anomaly disorders being described and named by highly heterogenous clinical presentations LMs MCAP CLOVE FAVA 1828 1997 S 2014 2007 KTS CLAPO PROS GLA 1900 2008 2013 2014 2010s Genetic testing of these diseases

6. Slide 6: Vascular Anomalies – Disparate Disorders Driven by Common Somatic Mutations

   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 Unlike cancer, these are often singl

7. Slide 7: Timing & Location of Somatic Mutation Determines Phenotype

   Vascular Anomalies – Timing & Location of Somatic Mutation Determines Phenotype Timing and Location of Somatic Mutation During Embryogenesis Mut Earlier Widespread Phenotype Observed Symptoms mutation with a Range of Severity Key factors include • Location of lesion Mut Internal vs. cutaneous Later

8. Slide 8: Vascular Anomalies – Phenotype & Symptoms

   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 Lymphatic Malformations (LM) O2 PIK3

9. Slide 9: Deep Dive – PIK3CA-Related Overgrowth Spectrum (PROS)

   Deep Dive – PIK3CA-Related Overgrowth Spectrum (PROS) PIK3CA-Related Overgrowth Spectrum (PROS) Includes many Multifocal, syndromic disease presentation: conditions: • Malformation of multiple types of vasculature (LM and/or VeM) CLOVES • May also include many different tissues: fat, muscle, bone, n

10. Slide 10: Deep Dive – PIK3CA-Driven Lymphatic Malformations (LM)

    Deep Dive – PIK3CA-Driven Lymphatic Malformations (LM) Lymphatic Malformations (LM) Disease presents with malformed lymphatic vessels/channels: Simple/Isolated • Often occur in lymph-rich regions like head and neck, though may (Cystic) infiltrate other soft tissues anywhere on the body Micro • Cysti

11. Slide 11: Deep Dive – PIK3CA-Driven Venous Malformations

    Deep Dive – PIK3CA-Driven Venous Malformations Venous Malformations (VeM) Disease presents with abnormal, dilated veins containing blood • Soft, compressible lesions with blueish color, often sub-cutaneous • Veins consist of enlarged or distorted endothelial cells surrounded by disorganized extracel

12. Slide 12: Deep Dive – PIK3CA-Driven Cerebral Cavernous Malformation

    Deep Dive – PIK3CA-Driven Cerebral Cavernous Malformation Cerebral Cavernous Malformation (CCM) ` Defined by enlarged capillary cavities in the brain: • Often asymptomatic for years, avg age of symptom onset is ~45 years • “Popcorn” like presentation on MRI ` Symptoms include: • Lesions can cause he

13. Slide 13: Vascular Anomalies – Patient Numbers

    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 Malformations Venous Malformations (PROS)

14. Slide 14: Patient Referral Pathway

    Patient Referral Pathway Referral may Local Providers take years: Vascular Anomaly Centers • range of symptoms Details Generalized set of healthcare • rarity of conditions Coordinated care from vascular anomaly providers: • misdiagnosis experts: • Primary care • Genetic testing, multidisciplinary ca

15. Slide 15: Current Treatment Paradigm

    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 garments • Surgery • Non-selective targeting: Options • Ant

16. Slide 16: Potential Future Treatment Paradigm

    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 • Compression garments Available Tx Options • Anticoagulants Mut

17. Slide 17: Example Case Study #1 – PROS

    Example Case Study #1 – PROS 8-Year-Old Patient With PROS (CLOVES)1 H1047R (11% of variant 3 months old: First of three ~7 years old: started alpelisib Misdiagnosed allele frequency) identified scleroembolization (50 mg) and has had partial at birth by whole exome procedures regression sequencing 12

18. Slide 18: Example Case Study #2 – LM

    Example Case Study #2 – LM 8-Year-Old Patient with LM At birth: Presented with Patient had substantially LM of the tongue reduced QoL, experiencing ~3 years old: and mouth repeated periods of Underwent a surgical hospitalization; impaired intervention including a speech development, and partial tong

19. Slide 19: Vascular Anomalies – Systemic Therapy Options

    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 Serabelisib Alpelisib Zovegalisib (mTORi) (KP-001) 1st Patent 19941 2007 2008 2019 Filing 2010s:

20. Slide 20: Alpelisib – Development & Regulatory Timeline

    Alpelisib – Development & Regulatory Timeline 2020 2025 2030 Breast Cancer: 1st Confirmatory Retrospective 2nd Confirmatory (failed) SOLAR-1 readout + FDA EPIK-P1 EPIK-P2 EPIK-P43 approval in outcome outcome 2019 outcome Conditional Failed to meet primary Pending, at 250mg QD Approval for endpoint2

21. Slide 21: EPIK-P2 Results – Radiological Response Rate

    EPIK-P2 Results – Radiological Response Rate EPIK-P2 Efficacy Results (Adults started at 125mg QD, n=54)1 Volumetric response rate by MRI (>20% reduction) Failed on primary endpoint (lower bound CI >15%, thru wk48) 17% 17% EPIK-P2 Waterfall (presented at ASPHO 20252) 15% 11% • Median depth of reduct

22. Slide 22: EPIK-P2 Safety Data in Adults

    EPIK-P2 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 starting dose Gr3+ after Week 28 33% Gr1-2 2nd confirmatory

23. Slide 23: All Current Treatments Leave Large Unmet Medical Need

    All Current Treatments Leave Large Unmet Medical Need Volumetric Response Rates for Systemic Therapies in VAs 100% 24wk or later Initial zovega data will 75% predominantly focus on Earlier than 24wk 12-week response rate 50% 33% 27% 26% 25% 17% 16% 11% Wk 26 Wk 16 Wk 12 0% EPIK-P11 EPIK-P22 Serabeli

24. Slide 24: Zovega – Inhibits The Core Driver of The Disease

    Zovega – Inhibits The Core Driver of The Disease Favorable Selectivity Favorable Tolerability Favorable Efficacy Selective for mutant PI3Kα Fewer key common PI3K class AEs Reduction of lesions in vivo3 Zovegalisib1 Alpelisib2 150 Lesion Area change (%) 3% Vehicle Hyper- 49% 52% 40% 33% 73% glycemia

25. Slide 25: Zovega – Preclinical Data

    Zovega – Preclinical Data Zovegalisib’s greater target coverage pre-clinically leads to greater lesion size reduction Efficacy vs. Insulin induction PIK3CA-Driven VM PDX (H1047R)1 40 Alpelisib dose response 150 30 Lesion area change (%) Insulin (ng/mL) Vehicle ~Vijoice label 100 dose 250mg 20 Alpeli

26. Slide 26: ReInspire – Zovegalisib Study Design

    ReInspire – Zovegalisib Study Design Part 1: Dose Selection Part 2: Dose Expansion All PIK3CA-driven Vascular Anomalies Expansion patient population (primary focus: PROS and LMs) to be confirmed Initial clinical data Randomized dose finding: Adults & Adolescents RP2D(s) Expansion cohort(s) 400mg, 30

27. Slide 27: Endpoints

    Endpoints Regulatory Endpoint: Radiographic Response (MRI) Reported Outcome Endpoints Caregiver/patient reported outcomes have been Response defined as ≥20% volumetric reduction explored by other groups, but not yet validated Used in EPIK-P1, -P2, -P3, -P4, and -L1 trials of Relay Tx in process of v

28. Slide 28: Blockbuster Potential Across Concentrated Centers

    Blockbuster Potential Across Concentrated Centers Vascular Anomaly Centers (VACs) identified by ISSVA United States Europe Primary treatment for VAs patients is concentrated in <100 multidisciplinary VACs across US and Europe © 2026 Relay Therapeutics Source: ISSVA https://www.issva.org/resources/mu

29. Slide 29: ReInspire – Potential Regulatory Approach

    ReInspire – Potential Regulatory Approach Part 1: Dose Selection Part 2: Dose Expansion All PIK3CA-driven Vascular Anomalies Expansion patient population (primary focus: PROS and LMs) to be confirmed Adults & Adolescents Randomized dose finding: RP2D(s) Expansion cohort(s) (≥12 years old) 3 Doses: N

30. Slide 30: Vascular Anomalies Overview

    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 PI3Kα inhibitor Initial clinical da

31. Slide 31: © 2026 Relay Therapeutics

    © 2026 Relay Therapeutics 31

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