Klaus Hoeflich, Ph.D. Senior Vice President, Biology at Blueprint Medicines Blueprint Medicines Presents Foundational Preclinical Data for BLU-945 Showing Robust Anti-Tumor Activity in Treatment-Resistant EGFR-Mutated Lung Cancer at ESMO Virtual Congress 2020.
Link to Poster -
CAMBRIDGE, Mass., Sept. 17, 2020,/PRNewswire/ — Blueprint Medicines Corporation ( NASDAQ: BPMC), a genomically identified cancer, rare diseases, and cancer immunotherapy precision therapy business, today announced preclinical proof-of-concept data for BLU-945, an investigational precision therapy for non-small cell lung cancer patients with epidermal growth factor receptor-mutated (EGFRm) New preclinical data showed that BLU-945 inhibited triple-mutant EGFR strongly and selectively, harboring the most common on-target resistance mutations to standard EGFRm NSCLC therapies, resulting in robust anti-tumor activity in multiple models of lung cancer. The data was made available today in a poster presentation at the 2020 Virtual Congress of the European Society of Medical Oncology (ESMO).
Patients with osimertinib-resistant EGFRm NSCLC do not currently have approved therapies, and there is an urgent need for new therapies to overcome tumor resistance. In combination with the acquired T790 M and C797S mutations, BLU-945 was engineered to powerfully inhibit triple-mutant EGFR harboring either the activating L858R or exon 19 deletion mutations, the most common on-target resistance to standard EGFR inhibitors. Furthermore, BLU-945 was designed to be wild-type selective EGFR and kinome with the potential for enhanced tolerability and hybrid strategies.
BLU-945 inhibited triple mutant EGFR with sub-nanomolar potency in preclinical data presented at the ESMO congress and displayed greater than 900-fold selectivity over wild-type EGFR along with excellent overall selectivity of the kinome. BLU-945 potently inhibited the EGFR pathway in a triple mutant EGFR cell line, while osimertinib demonstrated minimal activity. In multiple cell line-derived and patient-derived xenograft (PDX) models of triple mutant EGFR NSCLC, BLU-945 monotherapy resulted in robust anti-tumor activity. In addition, BLU-945 treatment in conjunction with osimertinib or gefitinib resulted in tumor regression in a triple mutant EGFR NSCLC PDX model derived after five lines of previous therapy from a patient with progressive disease. Even, in an intracranial disease model, BLU-945 was highly active.
Blueprint Medicines plans to develop BLU-945 as a monotherapy and in combination with other agents for the treatment of patients with osimertinib-resistant EGFR NSCLC based on this preclinical proof-of-concept results. In the first half of 2021, the company plans to initiate an international Phase 1 dose-escalation trial of BLU-945.
Furthermore, in the fourth quarter of 2020, Blueprint Medicines expects to nominate a brain-penetrant development candidate targeting double mutant EGFR harboring the activating L858R or exon 19 deletion mutations and the acquired C797S mutation, the most common first-line osimertinib on-target resistance profile. As both a monotherapy and in conjunction with BLU-945, the company plans to grow this candidate.