Actual-world information show non-classical mutations are current in 20-30% of all sufferers with EGFRm NSCLC
Rising information present non-classical EGFR mutations will be co-expressed with the classical L858R mutation, a setting characterised by shorter length of response to osimertinib
BDTX-1535 profile differentiated as essentially the most superior fourth-generation oral TKI in medical improvement addressing the total spectrum of classical, non-classical, and C797S resistance EGFR mutations
CAMBRIDGE, Mass., April 07, 2024 (GLOBE NEWSWIRE) — Black Diamond Therapeutics (NASDAQ:), Inc. (Nasdaq: BDTX), a clinical-stage oncology firm creating MasterKey therapies that concentrate on households of oncogenic mutations in sufferers with most cancers, offered real-world proof of the evolving epidermal progress issue receptor (EGFR) mutation panorama in non-small cell lung most cancers (NSCLC), and the potential of BDTX-1535 to handle a broader vary of mutations in comparison with current therapies. The outcomes had been disclosed in an oral presentation on April 7, 2024, on the 2024 American Affiliation of Most cancers Analysis (AACR) Annual Assembly held in San Diego, California.
The oral presentation, titled BDTX-1535 “ A MasterKey EGFR Inhibitor Focusing on Classical, Non-Classical and the C797S Resistance Mutation to Tackle the Developed Panorama of EGFR Mutant NSCLC, evaluated greater than 235,000 sequenced circumstances of NSCLC sourced from Guardant Well being (NASDAQ:) (GuardantINFORM™) and Basis Medication (FoundationInsights™). The analyses reveal a broad spectrum of non-classical mutations, in addition to an elevated prevalence of the acquired resistance mutation, C797S. Over 100 distinctive non-classical EGFR oncogenic driver mutations had been recognized in newly identified sufferers with NSCLC, and these non-classical EGFR mutations had been current in 20-30% of sufferers throughout all strains of therapy.
The panorama of EGFR mutations in NSCLC continues to evolve, revealing classical and non-classical driver mutations, stated John Heymach, M.D., Ph.D., Chair of Thoracic/Head and Neck Medical Oncology at MD Anderson Most cancers Heart. Non-classical mutations fall into classes together with kinase area PACC mutations and ectodomain mutations; due to this fact, subsequent era EGFR focused therapies should successfully cowl a number of subgroups of mutations.
Novel focused therapies are nonetheless wanted to proceed to enhance medical outcomes for sufferers with EGFR-mutant lung cancers, added Xiuning Le, M.D., Ph.D., Affiliate Professor, Thoracic/Head and Neck Medical Oncology at MD Anderson Most cancers Heart. To increase survival for our sufferers, newer medicine must have good mutational protection, good tolerability, and good mind penetrance.
Preclinical information demonstrated that BDTX-1535 potently inhibits greater than 50 clinically related, non-classical EGFR mutations (in addition to the classical L858R and exon19-del mutations) whereas sparing wild-type EGFR. The compound additionally potently inhibits the drug resistance C797S mutation, which emerges following therapy with third-generation EGFR inhibitors, together with osimertinib. Actual-world information point out non-classical EGFR mutations will be co-expressed with classical mutation L858R, a setting that has been characterised by shorter length of response to osimertinib first-line remedy. Preclinical information present that BDTX-1535 potently inhibits these co-expressed non-classical mutations.
BDTX-1535 was designed to handle a broad spectrum of greater than 50 non-classical oncogenic EGFR mutations, in addition to the C797S resistance mutation, stated Elizabeth Buck, Ph.D., Chief Scientific Officer and co-founder of Black Diamond Therapeutics. We consider that the efficiency of BDTX-1535 towards the total spectrum of classical, non-classical, and C797S mutations positions the compound as the primary and best-in-class fourth-generation EGFR inhibitor doubtlessly providing NSCLC sufferers a well-tolerated, brain-penetrant, oral remedy throughout varied strains of therapy.
Part 1 proof-of-concept information demonstrating sturdy responses in recurrent NSCLC sufferers with each non-classical and purchased resistance C797S mutations had been offered in October 2023. Black Diamond is at present advancing BDTX-1535 in a Part 2 trial for sufferers with EGFRm NSCLC throughout a number of strains of remedy. Sufferers are being enrolled each in a first-line (1L) setting (for these expressing EGFR non-classical mutations) and in second- and third-line (2L/3L) settings following prior therapy with an EGFR inhibitor. Preliminary outcomes from 2L/3L sufferers are anticipated within the third quarter of 2024.
About BDTX-1535
BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic epidermal progress issue receptor (EGFR) mutations in non-small cell lung most cancers (NSCLC), together with 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 mostly on preclinical information, greater than 50 oncogenic EGFR mutations expressed throughout a various group of sufferers with NSCLC in a number of strains of remedy. Primarily based on preclinical information, BDTX-1535 additionally inhibits EGFR extracellular area mutations and alterations generally expressed in glioblastoma (GBM) and avoids paradoxical activation noticed with earlier era reversible TKIs. A window of alternative trial of BDTX-1535 in sufferers with GBM is ongoing (NCT06072586) and a Part 2 trial is ongoing in sufferers with NSCLC (NCT05256290).
About Black Diamond Therapeutics
Black Diamond Therapeutics is a clinical-stage oncology firm targeted on the event of MasterKey therapies that deal with households of oncogenic mutations in clinically validated targets. The Firm’s MasterKey therapies are designed to handle broad genetically outlined affected person populations, overcome resistance, decrease wild-type mediated toxicities, and be mind penetrant to deal with CNS illness. The Firm is advancing two clinical-stage packages: BDTX-1535, a brain-penetrant fourth-generation EGFR MasterKey inhibitor concentrating on EGFR mutant NSCLC and GBM, and BDTX-4933, a brain-penetrant RAF MasterKey inhibitor concentrating on KRAS, NRAS and BRAF alterations in stable tumors. For extra data, please go to www.blackdiamondtherapeutics.com.
Ahead-Trying Statements
Statements contained on this press launch concerning issues that aren’t historic info are forward-looking statements inside the that means of the Non-public Securities Litigation Reform Act of 1995. As a result of such statements are topic to dangers and uncertainties, precise outcomes might differ materially from these expressed or implied by such forward-looking statements. Such statements embody, however aren’t restricted to, statements concerning: the potential of BDTX-1535 to handle a broader vary of mutations in comparison with current therapies, the place of BDTX-1535 as in comparison with different fourth-generation EGFR inhibitors, the timing of medical updates for BDTX-1535 in sufferers with NSCLC and in sufferers with recurrent GBM, and the potential of BDTX-1535 to learn sufferers with NSCLC. Any forward-looking statements on this assertion are based mostly on administration’s present expectations of future occasions and are topic to numerous dangers and uncertainties that might trigger precise outcomes to vary materially and adversely from these set forth in or implied by such forward-looking statements. Dangers that contribute to the unsure nature of the forward-looking statements embody these dangers and uncertainties set forth in its Annual Report on Kind 10-Okay for the 12 months ended December 31, 2023, filed with america Securities and Alternate Fee and in its subsequent filings filed with america Securities and Alternate Fee. All forward-looking statements contained on this press launch converse solely as of the date on which they had been made. The Firm undertakes no obligation to replace such statements to replicate occasions that happen or circumstances that exist after the date on which they had been made.
Contacts
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