Oral, Brain-Penetrant Inhibitor of Oncogenic EGFR MasterKey Mutations
BDTX-1535 is designed to be a potent, selective, brain penetrant and irreversible MasterKey inhibitor of EGFR mutations that expressed in glioblastoma multiforme (GBM) and intrinsic and acquired resistance EGFR mutations in non-small cell lung cancer (NSCLC).
GBM is a difficult-to-treat, aggressive type of cancer that can occur in the brain or spinal cord. Current therapy consists primarily of surgical resection of the tumor, followed by radiation and chemotherapy. Almost 50% of GBM tumors express one or more co-occurring oncogenic EGFR mutations that affects the extracellular region of the receptor tyrosine kinase, and consequently promote oncogenic activation. Although the disease appears to be genetically defined, there are no precision oncology medicines approved to treat these patients. We believe that current targeted therapies have been unsuccessful in treating GBM due to (i) insufficient drug potency for EGFR GBM mutations versus WT-EGFR, (ii) the concurrent expression of oncogenic EGFR mutations within individual patients, and (iii) low levels of brain penetration.
NSCLC accounts for approximately 85% of lung cancer cases worldwide. About 10-20% of all lung cancer patients in North American and Europe, and up to 50% of those in Asia harbor mutations in EGFR. Intrinsic resistance EGFR mutations, of which G719X, S768I, L861Q are among the most frequent, account for 10-20% of EGFR mutations in NSCLC. The common Exon19del and L858R mutations, which account for 80-90% of EGFR mutations in NSCLC, are well treated but resistance invariably emerges to current generation EGFR inhibitors. Current generation EGFR inhibitors with efficacy against uncommon mutations have poor brain penetrance or do not have broad spectrum selective activity.
BDTX-1535 is designed as a brain-penetrant and potent MasterKey inhibitor of oncogenic mutations of EGFR, including the mutations that co-occur in GBM, as well as those that commonly occur in NSCLC and those that emerge as resistance mechanisms to current-generation EGFR inhibitors.