Black Diamond Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for its MasterKey inhibitor BDTX-1535, an irreversible, mutant selective, brain-penetrant inhibitor of oncogenic mutations of epidermal growth factor receptor (EGFR) expressed in glioblastoma multiforme (GBM) and intrinsic and acquired resistance EGFR mutations in non-small cell lung cancer (NSCLC). The Company expects to initiate the Phase 1 study of BDTX-1535 in the first quarter of 2022 and expects to provide a clinical update in the second half of 2023. In pre-clinical studies, Black Diamond has demonstrated that oncogenic alterations of EGFR, particularly those associated with GBM, result in distinct conformations which impart unique pharmacology and drug resistance.

In cell-based assays, BDTX-1535 achieved potent and selective inhibition of a range of EGFR mutations expressed in GBM and NSCLC, including canonical, non-canonical, and drug-resistance mutations, such as EGFR-C797S that can arise following treatment with third generation EGFR inhibitor. BDTX-1535 demonstrated a favorable brain-penetrant pharmacokinetic (PK) profile in animal models. In a range of tumor models, including intracranial GBM models and lung cancer drug resistance models expressing the targeted EGFR mutations, BDTX-1535 showed dose-dependent tumor growth inhibition and achieved complete regression without impact on body weight.