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

CAMBRIDGE, Mass., Sept. 17, 2020 /PRNewswire/ -- Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, today announced preclinical proof-of-concept data for BLU-945, an investigational precision therapy for patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). The new preclinical data showed BLU-945 potently and selectively inhibited triple-mutant EGFR harboring the most common on-target resistance mutations to standard treatments for EGFRm NSCLC, resulting in robust anti-tumor activity in multiple lung cancer models. The data were made available today in a poster presentation at the European Society of Medical Oncology (ESMO) Virtual Congress 2020.

Currently, there are no approved therapies for patients with osimertinib-resistant EGFRm NSCLC, and there is an urgent need for new therapies to address tumor resistance. BLU-945 was designed to potently inhibit triple-mutant EGFR harboring either the activating L858R or exon 19 deletion mutations combined with the acquired T790M and C797S mutations, the most common on-target resistance to standard EGFR inhibitors. In addition, BLU-945 was designed to be wild-type EGFR and kinome selective with the potential for improved tolerability and combination strategies.

"Our scientists at Blueprint Medicines specifically engineered BLU-945 to tackle treatment resistance in patients with EGFR-mutated lung cancer, and the preclinical proof-of-concept data we're reporting today highlight the potential of BLU-945 to offer clinical benefit to patients along with a safety profile that enables combinations with other EGFR-targeted therapies across multiple treatment lines," said Marion Dorsch, Ph.D., Chief Scientific Officer of Blueprint Medicines. "The recent FDA approval of GAVRETO™ (pralsetinib) combined with our rapidly advancing EGFR research program highlight our broad commitment to patients with lung cancer, as well as the potential of our research platform to address the evolution of cancer and enable durable patient outcomes."

In preclinical data presented at the ESMO congress, BLU-945 inhibited triple mutant EGFR with sub-nanomolar potency and demonstrated greater than 900-fold selectivity over wild-type EGFR along with excellent overall kinome selectivity. In a triple mutant EGFR cell-line, BLU-945 potently inhibited the EGFR pathway, while osimertinib demonstrated limited activity. BLU-945 monotherapy resulted in robust anti-tumor activity in multiple cell line-derived and patient-derived xenograft (PDX) models of triple mutant EGFR NSCLC. In addition, BLU-945 treatment in combination with osimertinib or gefitinib resulted in tumor regression in a triple mutant EGFR NSCLC PDX model derived from a patient with progressive disease following five lines of prior therapy. BLU-945 was also highly active in an intracranial disease model.

Based on these preclinical proof-of-concept data, 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. The company plans to initiate an international Phase 1 dose-escalation trial of BLU-945 in the first half of 2021.

In addition, 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 on-target resistance profile following first-line osimertinib, in the fourth quarter of 2020. The company plans to develop this candidate as both a monotherapy and in combination with BLU-945.

About EGFRm NSCLC

Lung cancer is the leading cause of cancer death worldwide. Among the 80 to 85 percent of lung cancers classified as NSCLC, about 10 to 15 percent of cases in the US and Europe and about 40 to 50 percent of cases in Asia are caused by activating EGFR mutations. In recent years, the introduction of EGFR targeted therapies including osimertinib has dramatically improved outcomes in patients with EGFRm NSCLC. However, the emergence of tumor resistance represents an urgent medical need and there are no approved therapies for osimertinib-resistant EGFRm NSCLC.

About BLU-945

Derived from Blueprint Medicines' proprietary research platform, BLU-945 is designed to treat patients with osimertinib-resistant EGFRm NSCLC. In preclinical studies, BLU-945 potently inhibited triple-mutant EGFR harboring either the activating L858R or exon 19 deletion mutations combined with the acquired T790M and C797S mutations, the most common on-target resistance to first-generation EGFR inhibitors and the third-generation EGFR inhibitor osimertinib, respectively. In addition, BLU-945 demonstrated excellent selectivity for triple-mutant EGFR over wild-type EGFR and other clinically relevant kinases, potentially enabling well-tolerated combinations with other EGFR inhibitors. Blueprint Medicines owns worldwide development and commercialization rights for BLU-945.

About Blueprint Medicines

Blueprint Medicines is a precision therapy company striving to improve human health. With a focus on genomically defined cancers, rare diseases and cancer immunotherapy, we are developing transformational medicines rooted in our leading expertise in protein kinases, which are proven drivers of disease. Our uniquely targeted, scalable approach empowers the rapid design and development of new treatments and increases the likelihood of clinical success. We have two FDA-approved precision therapies and are currently advancing multiple investigational medicines in clinical development, along with a number of research programs. For more information, visit www.BlueprintMedicines.com and follow us on Twitter (@BlueprintMeds) and LinkedIn.

Cautionary Note Regarding Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans and timelines for the development of BLU-945 and an additional EGFR development candidate; the potential benefits of Blueprint Medicines' current and future approved drugs or drug candidates in treating patients; expectations regarding the tolerability of BLU-945; expectations regarding the use of BLU-945 or an additional EGFR development candidate as a monotherapy or combination therapy; and Blueprint Medicines' strategy, goals and anticipated milestones, business plans and focus. The words "aim," "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to the impact of the COVID-19 pandemic to Blueprint Medicines' business, operations, strategy, goals and anticipated milestones, including Blueprint Medicines' ongoing and planned research and discovery activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Blueprint Medicines' ability and plans in establishing a commercial infrastructure, and successfully launching, marketing and selling current or future approved products, including AYVAKIT™ (avapritinib) and GAVRETO; Blueprint Medicines' ability to successfully expand the approved indications for AYVAKIT and GAVRETO or obtain marketing approval for AYVAKIT and GAVRETO in additional geographies in the future; the delay of any current or planned clinical trials or the development of Blueprint Medicines' current or future drug candidates; Blueprint Medicines' advancement of multiple early-stage efforts; Blueprint Medicines' ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; the preclinical and clinical results for Blueprint Medicines' drug candidates, which may not support further development of such drug candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; Blueprint Medicines' ability to develop and commercialize companion diagnostic tests for its current and future drug candidates; and the success of Blueprint Medicines' current and future collaborations, partnerships or licensing arrangements, including Blueprint Medicines' global collaboration with Roche for the development and commercialization of pralsetinib. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Blueprint Medicines' filings with the Securities and Exchange Commission (SEC), including Blueprint Medicines' most recent Annual Report on Form 10-K, as supplemented by its most recent Quarterly Report on Form 10-Q and any other filings that Blueprint Medicines has made or may make with the SEC in the future. Any forward-looking statements contained in this press release represent Blueprint Medicines' views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Blueprint Medicines explicitly disclaims any obligation to update any forward-looking statements.

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