Black Diamond Therapeutics Presents Novel Real-World Evidence of the Evolving EGFR Mutation Landscape in NSCLC and the Opportunity for BDTX-1535 in an Oral Presentation at the 2024 American Association of Cancer Research Annual Meeting - Seite 2

Preclinical data demonstrated that BDTX-1535 potently inhibits more than 50 clinically relevant, non-classical EGFR mutations (as well as the classical L858R and exon19-del mutations) while sparing wild-type EGFR. The compound also potently inhibits the drug resistance C797S mutation, which emerges following treatment with third-generation EGFR inhibitors, including osimertinib. Real-world data indicate non-classical EGFR mutations can be co-expressed with classical mutation L858R, a setting that has been characterized by shorter duration of response to osimertinib first-line therapy. Preclinical data show that BDTX-1535 potently inhibits these co-expressed non-classical mutations.

“BDTX-1535 was designed to address a broad spectrum of more than 50 non-classical oncogenic EGFR mutations, as well as the C797S resistance mutation,” said Elizabeth Buck, Ph.D., Chief Scientific Officer and co-founder of Black Diamond Therapeutics. “We believe that the potency of BDTX-1535 against the full spectrum of classical, non-classical, and C797S mutations positions the compound as the first and best-in-class fourth-generation EGFR inhibitor potentially offering NSCLC patients a well-tolerated, brain-penetrant, oral therapy across various lines of treatment.”

Phase 1 proof-of-concept data demonstrating durable responses in recurrent NSCLC patients with both non-classical and acquired resistance C797S mutations were presented in October 2023. Black Diamond is currently advancing BDTX-1535 in a Phase 2 trial for patients with EGFRm NSCLC across multiple lines of therapy. Patients are being enrolled both in a first-line (1L) setting (for those expressing EGFR non-classical mutations) and in second- and third-line (2L/3L) settings following prior treatment with an EGFR inhibitor. Initial results from 2L/3L patients are anticipated in the third quarter of 2024.

About BDTX-1535
BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), including classical driver mutations, non-classical driver mutations, and the acquired resistance C797S mutation. BDTX-1535 is a fourth-generation tyrosine kinase inhibitor (TKI) that potently inhibits, based on preclinical data, more than 50 oncogenic EGFR mutations expressed across a diverse group of patients with NSCLC in multiple lines of therapy. Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) and avoids paradoxical activation observed with earlier generation reversible TKIs. A “window of opportunity” trial of BDTX-1535 in patients with GBM is ongoing (NCT06072586) and a Phase 2 trial is ongoing in patients with NSCLC (NCT05256290).