Nuvalent, Inc.

The company is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer. It develops innovative small molecules designed to overcome limitations of existing therapies for clinically proven kinase targets. These limitations include kinase resistance (new mutations enabling resistance), kinase selectivity (inhibition of similar targets leading to off-target adverse events), and limited brain penetrance (inability to treat disease spread to the brain). The company prioritizes target selectivity to potentially overcome resistance, avoid dose-limiting off-target adverse events, address brain metastases, and drive more durable responses. Its first lead product candidate, zidesamtinib (NVL-520), is being developed for patients with ROS proto-oncogene 1 (ROS1)-positive non-small cell lung cancer (NSCLC). Zidesamtinib is a novel ROS1-selective inhibitor designed to address emergent treatment resistance, central nervous system (CNS)-related adverse events, and brain metastases that may limit current ROS1 tyrosine kinase inhibitors (TKIs). Zidesamtinib has received FDA Breakthrough Therapy designation for patients with locally advanced or metastatic ROS1-positive NSCLC previously treated with two or more prior ROS1 TKIs, and orphan drug designation for ROS1-positive NSCLC. The ARROS-1 clinical trial is a first-in-human global Phase 1/2, multicenter, open-label, dose-escalation and expansion study evaluating zidesamtinib as an oral monotherapy in patients with advanced ROS1-positive NSCLC and other solid tumors. Dosing in the Phase 1 portion of the ARROS-1 clinical trial began in January 2022.