ZM-8195

ZM-8195 is a potent, selective, and brain-penetrant small molecule inhibitor of Anaplastic Lymphoma Kinase (ALK). It is currently in the IND-enabling stage for the treatment of ALK-positive non-small cell lung cancer (NSCLC), with a specific focus on overcoming resistance mutations such as the G1202R/L1196M compound mutations that emerge after treatment with second- and third-generation inhibitors. ZM-8195 is distinguished by its high selectivity for ALK over the TRK family of kinases (TRKA, TRKB, and TRKC), a design feature intended to avoid the central nervous system adverse effects typically associated with TRK inhibition. Preclinical data demonstrate that ZM-8195 achieves complete tumor regression in EML4-ALK fusion and resistant mutant models, including robust efficacy in orthotopic brain models.