Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — ASCO 2024
15 slides from Scholar Rock's conference presentation, June 2024
Slide 1: Phase 1 DRAGON study of SRK-181 with pembrolizumab: updated expansion results
Phase 1 study (DRAGON) of SRK-181 (linavonkibart), a latent TGFβ1 inhibitor, combined with pembrolizumab in anti-PD1 resistant patients with advanced solid tumors: Updated results of expansion phase Ulka Vaishampayan1, Randy F. Sweis2, Deepak Kilari3, Ahmad Tarhini4, Justin F. Gainor5, Minal Barve6,
Slide 2: Mechanism of Action
2 Mechanism of Action SRK-181, a Selective Anti-TGFβ1 Antibody, Overcomes CPIs Resistance 1.Batlle E, et al. Immunity. 2019; 50(4):924-940. CPI, checkpoint inhibitor; GLP, good laboratory practice; MDSC, myeloid derived suppressor cells; TGFβ1, transforming growth factor beta-1. PRESENTED BY: Ulka V
Slide 3: Phase 1 Clinical Trial Overview
Phase 1 Clinical Trial Overview Dose Escalation (3+3) Dose Expansion Part A1: SRK-181 Single Agent Part B: SRK-181 (1500mg q3w) + Pembrolizumab (80-3000 mg q3w/2000 mg q2w) n=up to 40/cohort All advanced solid tumor Key Eligibility Criteria Study Endpoints n=19 Cohort ccRCC • ≥18-year-old and ECOG 0
Slide 4: Preliminary Safety and Efficacy
4 Preliminary Safety and Efficacy Phase 1 Dose Escalation Phase Safety • SRK-181 was well tolerated: No DLTs observed; no Grade 4 or 5 treatment- related AEs Part A1 (n=19) MAD/MTD • MAD: 3000mg q3w and 2000mg q2w for single SRK-181 and 2400mg q3w for SRK-181 in combination with anti-PD-1 • MTD not
Slide 5: Patient Demographics and Disposition
5 Patient Demographics and Disposition Phase 1 Dose Expansion Phase Category All# Category All N 78 Enrolled 78 Age, median (range) 65y (32-81y) On Study, n (%) 10 (12.8) Gender, M, n (%) 56 (71.8) Stopped Treatment, n (%) 68 (87.2) Prior Lines of Therapy, median (range) 3 (1-9) Number of Lines of P
Slide 6: Manageable Safety Profile
6 Manageable Safety Profile Phase 1 Dose Expansion Phase Treatment-Emergent AEs Related to SRK-181 or Anti-PD(L)1 All Grades (>5%) ≥Grade 3 Adverse Event • There was 1 treatment-related Grade 4 AE N=78 N= 78 Rash# 25 (32.1%)* 10 (12.8%)* (Dermatitis exfoliative generalised) Pruritus 20 (25.6%)* 1 (1
Slide 7: Efficacy in Cohort MEL
7 Efficacy in Cohort MEL Clinical Responses in Anti-PD-1 Non-responders Pt#1: Screening Axillary lymph node 17.5 mm Pt#1 Pt#1 Pt#1: C3 Axillary lymph node 10.1 mm Efficacy Intent To Treat N=11 ORR 3 (27.3%) • Median lines of prior cancer therapy: 3 (range 1 – 7) ➢ All have SD or PD as BOR to the las
Slide 8: Efficacy in Cohort UC
8 Efficacy in Cohort UC Clinical Responses in Anti-PD-1 Non-responders Pt#1 Pt#1: Screening Lung nodule 59 mm Pt#1 Pt#1: C26 Lung nodule 41.1 mm Efficacy Intent To Treat N=11 ORR 1 (9.1%) • Median lines of prior cancer therapy: 4 (range 2 – 5) Confirmed PR 1 (9.1%) ➢ All have SD or PD as BOR to the
Slide 9: Efficacy in Cohort HNSCC
9 Efficacy in Cohort HNSCC Clinical Responses in Heavily Pre-treated and Anti-PD-1 Resistant Patients Pt#1: Screening Lung nodule 16 mm Pt#1 Pt#1 Pt#1: C3 Lung nodule 0 mm Efficacy Intent To Treat N=11 • Median lines of prior cancer therapy: 3 (range 1 – 7) ORR 2 (18.2%) ➢ 10 (91%) have SD or PD as
Slide 10: Efficacy in Cohort ccRCC
Efficacy in Cohort ccRCC Clinical Responses in Heavily Pre-treated and Anti-PD-1 Resistant Patients Pt#1 Pt#1: Screening Lymph node 21.5 mm Pt#1 Pt#1: C8 Lymph node 5 mm • IMDC score: intermediate 67%; poor 30% • Median lines of prior cancer therapy: 2 (range 1 – 9) Efficacy Intent To Treat N=30 ➢ 2
Slide 11: Proof of Mechanism
11 Proof of Mechanism SRK-181 and Pembrolizumab Treatment Creates a Proinflammatory Microenvironment • SRK-181 and pembrolizumab increase CD8+ T-cells infiltration into tumors across multiple tumor types • CD8+ T-cell were activated (CD8+GrmB+) in responding patients across multiple cohorts • The nu
Slide 12: Biomarker Data May Inform Patient Selection Strategy
12 Biomarker Data May Inform Patient Selection Strategy Baseline CD8+ T-cell Infiltration Status and Baseline Treg Levels Suggest a Higher Chance of Clinical Response Baseline CD8+ Infiltration Status Suggest a Higher Chance of Elevated Baseline Treg (CD4+Foxp3+) Levels within Tumor Compartment Resp
Slide 13: Summary
13 Summary Objective evidence of anti-tumor activity across multiple cancer types with duration of response up to 20+ months • ORR 23.3% in ccRCC, 18.2% in HNSCC, 27.3% in MEL, including 1 CR, and 9.1% in UC • mDoR were 7.7+m in ccRCC, 2.2+m in HNSCC, 4.9m in MEL and 12.9m in UC Biomarker findings e
Slide 14: Conclusion
14 Conclusion • Anti-tumor activity in anti-PD1 resistant patients across multiple cancer types establishes proof-of-concept for SRK-181, a selective latent TGFβ1 inhibitor • Biomarker results establish proof of mechanism and inform potential patient selection strategy in ccRCC • These data warrant
Slide 15: Thank You For Your Attention
15 THANK YOU FOR YOUR ATTENTION The authors thank the participating patients, their families, the study centers, and investigators for their contributions to the study. This study was sponsored by Scholar Rock. PRESENTED BY: Ulka Vaishampayan, MD