Relay Therapeutics, Inc. · NASDAQ:RLAY

Relay Therapeutics — AACR-NCI-EORTC Molecular Targets Conference 2021

24 slides from Relay Therapeutics's conference presentation, October 2021

  1. Slide 1: First Results of RLY-4008, a Potent and Highly Selective FGFR2 Inhibitor in a First-in-Human Study

    First Results of RLY-4008, a Potent and Highly Selective FGFR2 Inhibitor in a First-in-Human Study in Patients with FGFR2-Altered Cholangiocarcinoma and Multiple Solid Tumors Lipika Goyal1, Mitesh J. Borad2, Vivek Subbiah3, Amit Mahipal4, Suneel Kamath5, Kabir Mody6, Robin Kate Kelley7, Richard Kim8

  2. Slide 2: Disclosures

    Disclosures Speaker Name: Dr. Lipika Goyal I have the following financial relationships to disclose: Consultant for: Alentis Therapeutics AG, Black Diamond, Basilea, Exelixis, H3Biomedicine, Incyte Corporation, QED Therapeutics, Servier, Sirtex Medical Ltd, Taiho Oncology Inc. Grant/Research support

  3. Slide 3: FGFR2 is a clinically validated therapeutic target

    FGFR2 is a clinically validated therapeutic target FGFR2 alterations drive multiple FGFR2-altered cancers remain 3 key oncogenic FGFR2 alterations solid tumors* a high medical need Current FDA Accelerated Approvals (AA) for FGFR2-Altered Cancers FGFR2 Fusion & FGFR2 Oncogenic FGFR2 Tumor Type Rearra

  4. Slide 4: RLY-4008 is the first highly selective irreversible FGFR2 inhibitor

    RLY-4008 is the first highly selective irreversible FGFR2 inhibitor RLY-4008 is highly selective for FGFR2 RLY-4008 potently and selectively inhibits over FGFR1, FGFR3, and FGFR4 FGFR2 driven cellular proliferation * * * A D A A A F M M M F F M RLY-4008 was designed to selectively bind to FGFR2 to a

  5. Slide 5: RLY-4008 has potent in vivo antitumor activity against primary FGFR2 alterations and common resistance mutations

    RLY-4008 has potent in vivo antitumor activity against primary FGFR2 alterations and common resistance mutations A.A.FGFR2-fusion+ ICC B. FGFR2-fusion+ ICC FGFR2-fusion+ ICC B. FGFR2-fusion+ ICC D. D. FGFR2-mutation+ FGFR2 activating mutation+ E. FGFR2-amplification+ E. FGFR2-amplification+ FGFRi-re

  6. Slide 6: RLY-4008 first-in-human (FIH) study design

    RLY-4008 first-in-human (FIH) study design Key Objectives: MTD/RP2D, safety, pharmacokinetics, biomarkers (ctDNA, tumor markers), preliminary anti-tumor activity Part 1: Dose Escalation - Enrolling Part 2: Dose Expansion – Not Started FGFR2-fusion+ intrahepatic cholangiocarcinoma without prior FGFRi

  7. Slide 7: FIH Study: Baseline characteristics

    RLY-4008 FIH Study: Baseline characteristics Parameter Total (N=49) Parameter Total (N=49) Sex, n (%) Tumor types, n (%) Female 29 (59%) Cholangiocarcinoma (CCA) 40 (82%) Male 20 (41%) Breast cancer 4 (8%) Age (years), median (range) 60 (23-87) Endometrial cancer 1 (2%) Race, n (%) Prostate adenocar

  8. Slide 8: FIH Study: Cholangiocarcinoma population

    RLY-4008 FIH Study: Cholangiocarcinoma population FGFR2-Fusion FGFR2 Resistance Mutations at Baseline in Fusion+ Patients N=25 evaluable by ctDNA FGFR2-Fusion; FGFR2-Fusion FGFR2-Fusion 2+ N=32 FGFRi-naïve 1 prior FGFRi* prior FGFRi* (80%) (n=6) (n=12) (n=7) N550X (molecular brake) 0 4 6 V565X (gate

  9. Slide 9: FIH Study: Pharmacokinetics and predicted receptor occupancy support QD dosing

    RLY-4008 FIH Study: Pharmacokinetics and predicted receptor occupancy support QD dosing RLY-4008 shows ≥ 85 % predicted median receptor occupancy (based on modeling) across all dose levels Half-life ~15-30h supports QD dosing Predicted receptor occupancy: projected level of engagement of oncogenic F

  10. Slide 10: FIH Study: Confirmation of FGFR1- and FGFR4-sparing in the clinic

    RLY-4008 FIH Study: Confirmation of FGFR1- and FGFR4-sparing in the clinic QD Schedule BID Schedule Normal Normal range range FGFR1 sparing: Hyperphosphatemia: n=9/49 (18%) patients, all low grade (Grade 1-2). Only 1/49 (2%) patients was prescribed phosphate binders. FGFR4 sparing: Diarrhea: n=3/49

  11. Slide 11: FIH Study: Dose-limiting toxicities (DLTs)

    RLY-4008 FIH Study: Dose-limiting toxicities (DLTs) QD Schedule (ongoing) BID Schedule (deprioritized) 70 mg 100 mg QD BID 40 mg 50 mg QD QD 50 mg 30 mg 30 mg BID BID Starting dose QD Starting dose 20 mg 20 mg QD BID Dose DLT evaluable Dose Limiting Dose DLT evaluable Dose Limiting (mg QD) patients*

  12. Slide 12: FIH Study: Treatment-emergent adverse events (TEAEs) ≥ 20%

    RLY-4008 FIH Study: Treatment-emergent adverse events (TEAEs) ≥ 20% QD Schedule QD Schedule (n=32) (n = 32) BID Schedule (n=17) Most AEs are low-grade TEAEs profile consistent with FGFR1- and FGFR4-sparing Retinopathy/Retinal Pigment Epithelial Detachment (RPED): 7 cases [BID n=4/17 (24%); QD n=3/32

  13. Slide 13: FIH Study: RLY-4008 induces radiographic tumor regression across FGFR2 alterations

    RLY-4008 FIH Study: RLY-4008 induces radiographic tumor regression across FGFR2 alterations # * * N=38 evaluable patients with FGFR2 altered solid tumors ^ 66% patients (25/38) exhibit radiographic tumor reductions of ≥ 10% * Preliminary efficacy observed across FGFR2 alterations (fusions, mutations

  14. Slide 14: RLY-4008 induces radiographic tumor regression across FGFR2 alterations, FGFR inhibitor status, tumor types and dose levels

    RLY-4008 induces radiographic tumor regression across FGFR2 alterations, FGFR inhibitor status, tumor types and dose levels A Across FGFR2 alteration B Across prior FGFR inhibitor status C Across tumor type D Across starting dose level FGFRi, fibroblast growth factor receptor inhibitor. Preliminary

  15. Slide 15: FIH Study: Time on treatment and response by FGFR2-alteration

    RLY-4008 FIH Study: Time on treatment and response by FGFR2-alteration N=48 patients 26/48 patients (54%) ongoing on treatment • Most treatment discontinuations (73%) due to Progressive Disease Duration on treatment: range 4-45 weeks FGFRi, fibroblast growth factor receptor inhibitor; NE, not evalua

  16. Slide 16: Preliminary efficacy of RLY-4008 across specific subpopulations

    Preliminary efficacy of RLY-4008 across specific subpopulations 1. FGFR2 fusion+ cholangiocarcinoma, FGFR inhibitor-naïve 2. FGFR2 fusion+ cholangiocarcinoma, FGFR inhibitor-pretreated 3. FGFR2 mutant or amplified solid tumors FGFRi, fibroblast growth factor receptor inhibitor; NE, not evaluable; PR

  17. Slide 17: RLY-4008 induces radiographic tumor regression in FGFR inhibitor-naïve FGFR2-fusion+ cholangiocarcinoma

    RLY-4008 induces radiographic tumor regression in FGFR inhibitor-naïve FGFR2-fusion+ cholangiocarcinoma Best RECIST change from baseline Relative change from baseline in tumor size * * # * Resection 3/6 patients exhibit a confirmed PR 3/6 patients ongoing on treatment, and 1 patient had resection in

  18. Slide 18: RLY-4008 results in near complete regression in a patient with FGFR2-fusion, FGFRi-naïve cholangiocarcinoma

    RLY-4008 results in near complete regression in a patient with FGFR2-fusion, FGFRi-naïve cholangiocarcinoma, leading to surgical resection 35-year-old male with FGFR2-FLIP1 fusion ICC. Prior treatment: Gemcitabine/Cisplatin 70 mg QD dosing (no dose modification). Relevant AEs: Gr 1 dry eye, Gr 1 ony

  19. Slide 19: RLY-4008 exhibits activity in pan-FGFR inhibitor resistant FGFR2-fusion cholangiocarcinoma

    RLY-4008 exhibits activity in pan-FGFR inhibitor resistant FGFR2-fusion cholangiocarcinoma regardless of FGFR2 resistance mutations 13/21 (62%) patients with tumor reduction > 10% 7/10 (70%) patients with FGFR2 resistance mutations at baseline had all identified resistance mutations rendered undetec

  20. Slide 20: RLY-4008 produces tumor regression in a patient with FGFR2-fusion+ cholangiocarcinoma pretreated with futibatinib

    RLY-4008 produces tumor regression in a patient with FGFR2-fusion+ cholangiocarcinoma pretreated with futibatinib 51-year-old female with FGFR2-CIT fusion ICC. Prior treatments: Gemcitabine/Cisplatin, Futibatinib Baseline Cycle 7 60 x 46 mm 53 x 27 mm 42 x 35 mm 23 x 22 mm Sustained tumor reduction

  21. Slide 21: RLY-4008 induces radiographic tumor regression in FGFR2 oncogenic mutations and in FGFR2 amplifications

    RLY-4008 induces radiographic tumor regression in FGFR2 oncogenic mutations and in FGFR2 amplifications FGFR2 Oncogenic Mutations FGFR2 Amplifications * ^ ^ *Confirmed PR with increased tumor reduction after data cut; ^PR pending confirmation. FC, fold change; CN, copy number. Preliminary data as of

  22. Slide 22: RLY-4008 results in confirmed PR in a patient with heavily pretreated FGFR2 N550K mutant breast cancer

    RLY-4008 results in confirmed PR in a patient with heavily pretreated FGFR2 N550K mutant breast cancer 60-year-old female with breast cancer ER+ HER2- ESR1 mut PIK3CA mut FGFR2 N550K-mut, 12 prior lines of therapy including Alpelisib (PI3Ki) + Palbociclib (CDKi) Baseline Cycle 5 C3D1 Confirmed PR at

  23. Slide 23: Conclusions

    Conclusions RLY-4008 is the first highly selective FGFR2 inhibitor in the clinic that targets driver alterations and FGFR inhibitor resistance mutations Robust FGFR2 inhibition with ≥ 85% receptor occupancy and minimal off-isoform toxicity across a wide dose range Favorable QD PK and safety profile

  24. Slide 24: Acknowledgements

    Acknowledgements We thank the participating patients, their families, and all study team members at the following institutions: • Massachusetts General Hospital, Boston, MA • Mayo Clinic, Phoenix, AZ • The University of Texas M.D. Anderson Cancer Center, Houston, TX • Mayo Clinic, Rochester, MN • Cl

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