Relay Therapeutics, Inc. · NASDAQ:RLAY

Relay Therapeutics — Technical Presentation (April 2023)

20 slides from Relay Therapeutics's technical presentation, April 2023

  1. Slide 1: RLY-2608 selective targeting in first-in-human ReDiscover trial of PIK3CA-mutant solid tumors

    Pan-mutant and isoform selective PI3K⍺ inhibitor, RLY-2608, demonstrates selective targeting in a first-in-human study of PIK3CA-mutant solid tumor patients: ReDiscover trial Andreas Varkaris,1 Komal Jhaveri,2 Cesar A. Perez,3 Janice S. Kim,1 Jason T. Henry,4 Vivek Subbiah,5 Alexander I. Spira,6 Luc

  2. Slide 2: Disclosure Information

    Disclosure Information Andreas Varkaris, M.D., Ph.D. I have no financial relationships to disclose.

  3. Slide 3: Mutant PI3Kα is a Validated Cancer Target with Significant Unrealized Therapeutic Potential

    Mutant PI3Kα is a Validated Cancer Target with Significant Unrealized Therapeutic Potential PI3Kα is the most frequently mutated PI3Kα regulates WT PI3Kα and off-isoform toxicity kinase in solid tumors glucose homeostasis limit the clinical benefit of alpelisib % of all solid tumors with alteration

  4. Slide 4: RLY-2608 is First Allosteric Mutant Selective PI3Kα Inhibitor

    RLY-2608 is First Allosteric Mutant Selective PI3Kα Inhibitor RLY-2608 selectively High selectivity over the kinome and within PI3K family inhibits mutant PI3Kα Biochemical IC50 Protein Kinases Atypical Mutant 50 TKL 40 TK STE Potency (nM) 30 CK1 20 Lipid 10 OTHER AGC 0 Pathogen Alpelisib Inavolisib

  5. Slide 5: RLY-2608 - Robust Efficacy with Limited Impact on Glucose Homeostasis in Preclinical Models

    RLY-2608 - Robust Efficacy with Limited Impact on Glucose Homeostasis in Preclinical Models Tumor regression in mutant PIK3CA mouse breast cancer models Minimal perturbation of insulin levels H1047R (Kinase mutant) E545K (Helical mutant) Insulin levels at steady state HCC1954 (HCC1954) MDAMB361 (MDA

  6. Slide 6: ReDiscover: First-in-Human Study of RLY-2608

    ReDiscover: First-in-Human Study of RLY-2608 Part 1: Dose Escalations (ongoing) Part 2: Dose Expansion RLY-2608 PIK3CA-mutant solid tumors PIK3CA-mutant advanced MTD/RP2D (clear-cell ovarian cancer, HNSCC, cervical cancer, solid tumors PIK3CA double-mutant, other) PIK3CA-mutant, HR+, HER2– advanced

  7. Slide 7: ReDiscover: Interim Part 1 Results

    ReDiscover: Interim Part 1 Results Part 1: Dose Escalations – Bayesian optimal interval design with cohort enrichment RLY-2608 daily via continuous oral administration RLY-2608 RLY-2608 + fulvestrant PIK3CA-mutant advanced solid tumors (N=19) PIK3CA-mutant, HR+, HER2– advanced / metastatic breast ca

  8. Slide 8: Baseline Demographics

    Baseline Demographics RLY-2608 RLY-2608 + fulvestrant Total (N=19) (N=23) (N=42) Age, median (range), years 63 (42-85) 57 (40-83) 60 (40-85) Female, n (%) 11 (58%) 23 (100%) 34 (81%) Ethnicity, % White / Asian / American Indian / Black / Unknown 95% / 0% / 0% / 0% / 5% 78% / 4% / 4% / 4% / 9% 86% /

  9. Slide 9: Favorable RLY-2608 PK Profile Optimizes Mutant-Selective Inhibition

    Favorable RLY-2608 PK Profile Optimizes Mutant-Selective Inhibition RLY-2608 RLY-2608 + fulvestrant C1D15 C1D15 Exposure associated RLY-2608 Plasma Concentration (ng/mL) RLY-2608 Plasma Concentration (ng/mL) with efficacy in mouse BID tumor models 800mg BID 600mg Mean+SD Mean+SD 400mg 400mg 300mg ~8

  10. Slide 10: Ex Vivo Target Inhibition Shows Concentration-Dependent Pathway Suppression

    Ex Vivo Target Inhibition Shows Concentration-Dependent Pathway Suppression Ex-vivo suppression of pAKT in PIK3CA-mutant cancer cells Patient Plasma Sample* (Pre-dose) 80% pAKT inhibition (human) pAKT Inhibition (%) 50% pAKT inhibition ~80%+ pAKT inhibition at trough: 400mg BID mono PIK3CA-mutant ca

  11. Slide 11: Minimal Impact on Glucose Homeostasis Confirms Mutant Selective Targeting

    Minimal Impact on Glucose Homeostasis Confirms Mutant Selective Targeting No Grade 3 hyperglycemia per CTCAE v5.0 No dose interruptions or dose reductions due to hyperglycemia RLY-2608 Alpelisib label criteria Glucose Concentration Grade 3 (250-500 mg/dL) (mg/dL) Grade 2 (160-250 mg/dL) Grade 1 (115

  12. Slide 12: Partial Response per RECIST in PIK3CA-Mutant Breast Cancer

    Partial Response per RECIST in PIK3CA-Mutant Breast Cancer* uPR* with -36% tumor reduction per RECIST Marked regression of multiple liver metastases No adverse events reported Baseline ctDNA at 4 weeks First Assessment (8 weeks) ESR1 D538G Variant allele freq. (%) -93% PIK3CA PIK3CA H1047R E453K -91

  13. Slide 13: Radiographic Tumor Regression & Response Across PIK3CA Breast Cancer Genotypes

    Radiographic Tumor Regression & Response Across PIK3CA Breast Cancer Genotypes Breast Cancer Patients (RECIST Measurable Disease) N=16 Per protocol all combo patients previously treated with endocrine therapy and CDK4/6 PD 56% of patients (9/16) exhibit radiographic tumor reductions 81% of patients

  14. Slide 14: RLY-2608 Induces Declines in Mutant PIK3CA ctDNA

    RLY-2608 Induces Declines in Mutant PIK3CA ctDNA 400mg BID Combo, 400mg BID Mono, <400mg Mono 600mg & 800mg BID Combo 100 100 PIK3CA variant allele frequency (%) PIK3CA variant allele frequency (%) 31 patients with evaluable paired C1D1-C2D1 ctDNA samples 10 10 6 patients have ≥2 PIK3CA mutations 1

  15. Slide 15: Disease Stabilization Across PIK3CA Breast Cancer Genotypes

    Disease Stabilization Across PIK3CA Breast Cancer Genotypes Breast Cancer Patients (Measurable and Non-Measurable Disease) N=27 19/27 patients (70%) ongoing Duration on treatment: • Median: 16 weeks 200 QD • Range: 4 – 44 weeks 21/24 RECIST evaluable patients (88%) had non- CR/non-PD, SD or response

  16. Slide 16: RLY-2608-101 Monotherapy – Other tumor types

    RLY-2608-101 Monotherapy – Other tumor types RLY-2608 Non-Breast Cancer Patients N=15 H&N Colon Colon Assessment Non-CR/Non-PD Ovarian SD PD Prostate Duration on treatment: Colon • Median: 8 weeks • Range: 1 – 52 weeks Liposarcoma Colon 14/14 discontinued due to Prostate progressive disease • No AEs

  17. Slide 17: Favorable Safety Profile Consistent with Mutant-Selective Inhibition

    Favorable Safety Profile Consistent with Mutant-Selective Inhibition Treatment Emergent Adverse Events (TEAEs) ≥15% Across All Doses (N=42) RLY-2608 Mono + Combo (N=42) RLY-2608 + Fulvestrant (N=23) All Gr Gr3 0% 20% 40% 60% 80% 100% 0% 20% 40% 60% 80% 100% AEs leading to alpelisib discontinuation N

  18. Slide 18: Conclusions

    Conclusions ReDiscover data validate proof of mechanism for RLY-2608 as the first allosteric, pan-mutant- and isoform-selective PI3Kα inhibitor Favorable PK-PD provides sustained target inhibition (~80%+) with minimal impact on glucose homeostasis • Dose-dependent increase in exposure with low peak-

  19. Slide 19: Acknowledgments

    Acknowledgments The authors would like to thank the study participants, their families, and the study investigators at the following institutions: Spain ▪ VHIO Vall d'Hebron Instituto de Oncología, Barcelona ▪ Instituto Valencia D’Oncología, Valencia United States ▪ The University of Arizona Cancer

  20. Slide 20: Copies of this presentation obtained through QR Code are for personal use only

    Copies of this presentation obtained through Quick Response (QR) Code are for personal use only and may not be reproduced without permission from AACR and the author of this presentation. This study was sponsored by Relay Therapeutics, Inc. Medical writing support was provided by Christine Elsner of

Relay Therapeutics — Technical Presentation (April 2023) on 6ix