Relay Therapeutics, Inc. · NASDAQ:RLAY
Relay Therapeutics — AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2023
21 slides from Relay Therapeutics's conference presentation, October 2023
Slide 1: Clinical activity of lirafugratinib (RLY-4008), a highly selective FGFR2 inhibitor: the ReFocus study
Clinical activity of lirafugratinib (RLY-4008), a highly selective FGFR2 inhibitor, in patients with advanced FGFR2-altered solid tumors: the ReFocus study Alison M. Schram1; Vivek Subbiah2*; Chih-Yi (Andy) Liao3; Victor Moreno4; Desamparados Roda5; Mariano Ponz-Sarvisé6; Efrat Dotan7; Philippe Alex
Slide 2: Disclosure Information
Disclosure Information Molecular Targets and Cancer Therapeutics October 11-15, 2023 | Boston, MA Alison M. Schram I have the following relevant financial relationships to disclose: § Employee of: Memorial Sloan Kettering Cancer Center § Grant/Research support (to institution) from: AstraZeneca, ArQ
Slide 3: Oncogenic Activation of FGFR2 Drives Multiple Cancers, But Selective Targeting Has Not Been Achieved
Oncogenic Activation of FGFR2 Drives Multiple Cancers, But Selective Targeting of FGFR2 Has Not Been Achieved FGFR2 is a clinically validated FGFR2 alterations drive multiple solid Pan-FGFR inhibitors approved in oncogene1 tumor types2-4 only 2 solid tumor indications Breast cancer Non-small cell lu
Slide 4: Lirafugratinib: The First Highly Selective FGFR2 Inhibitor
Lirafugratinib: The First Highly Selective FGFR2 Inhibitor In contrast to pan-FGFRi, lirafugratinib is a potent Lirafugratinib has potent in vivo activity and selective FGFR2 inhibitor across FGFR2 alterations and tumor types Lirafugratinib selectively inhibits FGFR2 based on unique Tumor volume (mm
Slide 5: ReFocus Design and Milestones
ReFocus Design and Milestones Part 2: Dose Expansion – ORR/DoR per RECIST 1.1, safety per CTCAE v5 Cholangiocarcinoma (CCA) Enrollment Pivotal cohort FGFR2-fusion+ CCA without prior FGFRi (N=100) LPI 9/2023 Part 1: Dose Escalation – MTD/RP2D, safety, PK-PD, anti-tumor activity Pivotal supportive FGF
Slide 6: ReFocus: Early Clinical Validation of Lirafugratinib in Patients with Cholangiocarcinoma
ReFocus: Early Clinical Validation of Lirafugratinib in Patients with Cholangiocarcinoma Irreversible FGFR2 Inhibition Provides Robust Target Coverage Without FGFR1-Related Hyperphosphatemia 96% Receptor Occupancy at 70 mg RP2D Normal Phosphate Levels at RP2D Figure 14.4.1.1.d Phosphate (Mean ± SE)
Slide 7: ReFocus: Early Clinical Validation of Lirafugratinib in Patients with Cholangiocarcinoma
ReFocus: Early Clinical Validation of Lirafugratinib in Patients with Cholangiocarcinoma Robust Initial Efficacy in Cholangiocarcinoma with FGFR2-Fusion/Rearrangement FGFRi-naïve All Doses (N=38) FGFRi-naïve 70 mg QD (RP2D, N=17) 57.9% confirmed ORR 82.4% confirmed ORR (22 of 38 patients) (14 of 17
Slide 8: ReFocus: Solid Tumor Patient Baseline Characteristics (excluding cholangiocarcinoma)
ReFocus: Solid Tumor Patient Baseline Characteristics (excluding cholangiocarcinoma) Efficacy Safety Pop. Efficacy Population Parameter Parameter Pop. (N=84) (N=124) (N=84) Female, n (%) 51 (61) 74 (60) Tumor types, n (%) Age (years), median (range) 62 (33, 84) 62 (20, 84) Gastric cancer 26 (31) Rac
Slide 9: Solid Tumors with FGFR2-Fusion/Rearrangement: Radiographic Tumor Regression and Response
Solid Tumors with FGFR2-Fusion/Rearrangement: Radiographic Tumor Regression and Response per RECIST 1.1 ORR: 35% (9/26) DCR: 69% (18/26) DoE range: 1-56+ weeks 6 patients ongoing: • 3 responders • 3 stable disease Waterfall includes patients with post-baseline scans. Objective response rate (ORR) ca
Slide 10: Solid Tumors with FGFR2 Amplification: Radiographic Tumor Regression and Response
Solid Tumors with FGFR2 Amplification: Radiographic Tumor Regression and Response per RECIST 1.1 ORR: 24% (8/34) DCR: 62% (21/34) DoE range: 1-72+ weeks 6 patients ongoing: • 4 responders • 1 stable disease • 1 treatment beyond progression * Waterfall includes patients with post-baseline scans. Obje
Slide 11: Solid Tumors with Select FGFR2 Mutations: Radiographic Tumor Regression and Response
Solid Tumors with Select FGFR2 Mutations: Radiographic Tumor Regression and Response per RECIST 1.1 ORR: 13% (3/24) DCR: 42% (10/24) DoE range: 1-72+ weeks 4 patients ongoing: • 2 responders • 2 stable disease Waterfall includes patients with post-baseline scans. Objective response rate (ORR) calcul
Slide 12: Responses Are Durable Across Solid Tumors with FGFR2 Alterations
Responses Are Durable Across Solid Tumors with FGFR2 Alterations * DoR ≥ 6 months or response ongoing N=10/17 (58.8%), all alterations CUP: carcinoma of unknown primary; DoR: duration of response; NE: non-evaluable; NSCLC: non-small cell lung cancer; PD: progressive disease; PR: partial response; SD
Slide 13: Efficacy Across FGFR2 Alterations
Efficacy Across FGFR2 Alterations Fusion Amplification Mutation Efficacy Parameter N=26 N=34 N=24 Best Overall Response, n (%) Partial response* 9 (35) 8 (24) 3 (13) Stable disease 9 (35) 13 (38) 7 (29) Progressive disease 6 (23) 9 (26) 12 (50) Not evaluable** 2 (8) 4 (12) 2 (8) ORR n (%) 9 (35) 8 (
Slide 14: Responses Observed Across Diverse Tumor Types with FGFR2 Fusion/Rearrangement and Amplification
Responses Observed Across Diverse Tumor Types with FGFR2 Fusion/Rearrangement and Amplification Efficacy Evaluable Fusions and Amplifications (N=60) All Tumor Types (N=60) 28% 65% ORR Gastric (N=22) 18% 64% DCR Breast (N=7) 43% 71% Pancreatic (N=6) 33% 67% NSCLC (N=4) 50% 75% Ovarian (N=4) 50% 75% C
Slide 15: Marked Response in a Patient with Heavily Pretreated HR+ HER2- Breast Cancer
Marked Response in a Patient with Heavily Pretreated HR+ HER2- Breast Cancer with FGFR2 Amplification Baseline Cycle 9 Patient Profile • 66 yo female with HR+/HER2- mBC • FGFR2 amplification (copy number: 10) • 6 prior lines of therapy, including endocrine therapy, CDK4/6 inhibitor and chemotherapy
Slide 16: Promising Activity In Patients with Heavily Pretreated HR+ HER2- Breast Cancer
Promising Activity In Patients with Heavily Pretreated HR+ HER2- Breast Cancer with FGFR2 Alterations Of 14 patients with Breast Cancer, 10 with HR+ HER2- disease: • Median 7 prior lines (range 3-11) • 70% with ESR1 mutations • 70% with tumor shrinkage/DCR • 40% with partial responses ORR: 40% (4/10
Slide 17: Response and duration across HR+ HER2- Breast Cancer
Response and duration across HR+ HER2- Breast Cancer Range DoR (mo): 5.6+, 12.8+ % pt with DoR ≥6mo: 100% * Patient was treated with a single dose of concomitant fulvestrant BOR: best overall response; DoR: duration of response; LoT: lines of treatment; NE: non-evaluable; PD: progressive disease; PR
Slide 18: Lirafugratinib Safety in Patients with Solid Tumors
Lirafugratinib Safety in Patients with Solid Tumors Consistent, manageable safety profile that minimizes off-isoform toxicity Treatment-related AEs ≥15% Treatment-related Dose Modifications Solid Tumor; 70mg QD (N=124)* Solid Tumor; 70mg QD (N=124)* Nail toxicities 48% All Grades 3% Interruption, n
Slide 19: Conclusions
Conclusions ReFocus data validate lirafugratinib as the first highly selective FGFR2 inhibitor active across oncogenic driver alterations Encouraging response rates and initial durability across refractory solid tumors augment promising efficacy previously demonstrated in cholangiocarcinoma (ORR 58%
Slide 20: Acknowledgments
Acknowledgments We would like to thank the patients and their families, all study investigators, sub-investigators, and research staff at the following institutions: Australia Spain, cont’d • Jia Liu - St. Vincent's Hospital Sydney, New South Wales • Mariano Ponz-Sarvisé - Clinica Universidad Navarr
Slide 21: 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 the AACR- NCI-EORTC International Conference and the author of this poster.