Nuvalent reports new preclinical data on neurological candidate NVL-655

Nuvalent announced the presentation of new preclinical data supporting the intracranial activity NVL-655. NVL-655 is a brain-penetrant, ALK-selective tyrosine kinase inhibitor – TKI – designed to maintain activity against ALK and ALK mutations that confer resistance to currently approved therapies, and to avoid neurological adverse events and dose-limiting toxicities associated with TRK inhibition. The data result will be presented at the American Association for Cancer Research Annual Meeting 2023, April 14-19 in Orlando. Cell viability and ALK signaling assays confirmed potent in vitro activity of NVL-655 and limited sensitivity to first- and second-generation ALK TKIs. Upon treatment with NVL-655, intracranial efficacy was confirmed via MRI. NVL-655 has previously demonstrated preclinical efficacy in a cell line model of intracranial disease, as well as preclinical activity across diverse ALK resistance mutations and tumor types while maintaining strong selectivity for ALK over TRKB. NVL-655 is currently being investigated in a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive NSCLC and other solid tumors.