Nuvalent Highlights Presentation of Clinical Data at ESMO 2024 for Parallel Lead Programs for ROS1 and ALK-positive NSCLC and Accelerated Development Timelines

Core Insights - Updated Phase 1 dose-escalation data from ARROS-1 and ALKOVE-1 clinical trials support potential best-in-class profiles for zidesamtinib and NVL-655 [1][2] - Rapid enrollment in Phase 2 portions of the ARROS-1 and ALKOVE-1 clinical trials; pivotal data from both ROS1 and ALK programs anticipated in 2025 [1][2] - Initiation of ALKAZAR Phase 3 randomized, controlled trial of NVL-655 for treatment-naïve patients with advanced ALK-positive NSCLC expected in the first half of 2025 [1][2] Company Updates - Nuvalent, Inc. is a clinical-stage biopharmaceutical company focused on creating targeted therapies for kinase targets in cancer [31] - The company has achieved all supporting milestones for 2024 and is on track to share pivotal datasets from both parallel-lead programs in 2025 [4] - The company plans to host a conference call to discuss these updates [24] Clinical Trial Progress - The Phase 2 portion of the ARROS-1 trial has enrolled 227 patients from September 2023 to September 1, 2024, with pivotal data expected in 2025 [2] - The Phase 2 portion of the ALKOVE-1 trial has enrolled 229 patients from February 2024 to September 1, 2024, also with pivotal data expected in 2025 [2] - The ALKAZAR trial is designed to enroll approximately 450 patients with TKI-naïve ALK-positive NSCLC, with primary and secondary endpoints defined [4] Drug Profiles - Zidesamtinib is a novel ROS1-selective inhibitor designed to overcome limitations of existing therapies and has received FDA breakthrough therapy designation [8][26] - NVL-655 is a novel ALK-selective inhibitor with similar design goals and has also received FDA breakthrough therapy designation [18][29] - Both drugs are designed for CNS penetrance and aim to avoid TRK-related adverse events [26][29] Safety and Efficacy Data - Zidesamtinib demonstrated an overall response rate (ORR) of 44% in response-evaluable patients with ROS1-positive NSCLC [9] - NVL-655 showed an ORR of 38% in response-evaluable patients with ALK-positive NSCLC [17] - Both drugs exhibited favorable safety profiles, with no discontinuations due to treatment-related adverse events [11][20]