Nuvalent (NUVL) 44th Annual J.P. Morgan Healthcare Conference summary

Strategic vision and approach

• Focus on precisely targeted therapies for cancer, leveraging chemistry and structure-based drug design expertise.

• Emphasis on validated kinase targets to accelerate discovery and development, learning from physician experience with earlier kinase inhibitors.

• Key innovation themes: overcoming kinase resistance and improving selectivity to reduce off-target toxicities and enhance durability.

• Portfolio includes parallel lead programs in non-small cell lung cancer (NSCLC): zidesamtinib (ROS1) and NVL-655 (ALK), both with FDA Breakthrough Therapy Designation.

• Building commercial infrastructure and aiming for sustainable growth, with a well-capitalized runway into 2029.

Clinical program highlights

• Zidesamtinib NDA accepted by FDA for ROS1 NSCLC, with PDUFA date in September; TKI-naive cohort progressing for broader indication.

• NVL-655 pivotal data presented; NDA submission planned for first half of the year for previously treated ALK patients.

• Ongoing phase 3 trial for NVL-655 versus alectinib in TKI-naive ALK-positive NSCLC patients, targeting progression-free survival.

• NVL-330 (HER2 program) in early clinical development, designed for selectivity and brain penetration, with potential beyond lung cancer.

• High enrollment in pivotal studies reflects strong patient and investigator demand for differentiated therapies.

Key clinical results and differentiation

• Zidesamtinib demonstrated activity in heavily pretreated ROS1 NSCLC patients, including those with CNS disease and resistance mutations.

• Achieved 44% response rate in highly refractory ROS1 patients, 54% in those with G2032R mutation, and 48% intracranial response.

• In less pretreated ROS1 patients, 85% intracranial response and 93% durability at 18 months; 89% response in TKI-naive cohort.

• NVL-655 showed 26% response in post-lorlatinib ALK patients with 17.6 months median duration, doubling prior benchmarks.

• In lorlatinib-naive ALK patients, 46% response and 60% durability at 18 months; 86% response in TKI-naive exploratory cohort.