Nuvalent reveals preclinical data on cancer drug zidesamtinib
CAMBRIDGE, Mass. - Nuvalent, Inc., a clinical-stage biopharmaceutical company valued at $5.4 billion, has announced the publication of a manuscript in Molecular Cancer Therapeutics detailing the molecular design and preclinical activity of its novel ROS1 inhibitor, zidesamtinib (NVL-520). This drug is currently under evaluation in the ARROS-1 Phase 1/2 trial for advanced ROS1-positive non-small cell lung cancer (NSCLC) and other solid tumors. According to InvestingPro data, the company maintains a strong financial health score, with liquid assets significantly exceeding short-term obligations.
The publication sheds light on the selective targeting of ROS1 drug-resistant mutations by zidesamtinib, particularly the common G2032R mutation. Preclinical studies have shown zidesamtinib to suppress on-target resistance and inhibit brain tumors more effectively than other ROS1 tyrosine kinase inhibitors (TKIs) at clinically relevant concentrations. The manuscript also presents the first crystal structure of ROS1 G2032R in complex with zidesamtinib, providing insights into its selective molecular design and activity against resistance mutations while sparing the tropomyosin receptor kinase (TRK) family, potentially reducing neurological adverse events.
Zidesamtinib has been granted breakthrough therapy designation for treating ROS1-positive metastatic NSCLC previously treated with multiple ROS1 TKIs and orphan drug designation for ROS1-positive NSCLC. Nuvalent expects to report pivotal clinical data from the ARROS-1 trial for TKI pre-treated patients with advanced ROS1-positive NSCLC in the first half of 2025, supporting a planned New Drug Application submission by mid-year 2025. Analyst consensus remains highly bullish on the stock, with price targets ranging from $100 to $137 per share, reflecting confidence in the company’s pipeline potential.
Nuvalent, known for its targeted therapies for cancer, aims to address the limitations of existing therapies by developing small molecules that can overcome resistance, minimize adverse events, and provide more durable responses. The company is advancing a robust pipeline with investigational candidates for various cancer types, including ROS1-positive, ALK-positive, and HER2-altered NSCLC, and multiple discovery-stage research programs.
