Blueprint Medicines Publication in Cancer Discovery Highlights Preclinical and Clinical Proof-of-Concept Data for Highly Selective RET Inhibitor BLU-667

CAMBRIDGE, Mass., April 15, 2018 /PRNewswire/ -- Blueprint Medicines Corporation (NASDAQ:BPMC), a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases, today announced the online publication of preclinical and clinical proof-of-concept data for BLU-667 in Cancer Discovery, an American Association for Cancer Research (AACR) journal. Designed and developed by Blueprint Medicines, BLU-667 is a potent and highly selective inhibitor targeting oncogenic RET fusions and mutations, which are key drivers across multiple cancers, including subsets of patients with non-small cell lung cancer (NSCLC) and medullary thyroid cancer (MTC).

The manuscript reports detailed preclinical data characterizing the potency and selectivity of BLU-667 against oncogenic RET variants and resistant mutants and anti-tumor activity in multiple solid tumor models. In addition, four patient vignettes from the ongoing Phase 1 ARROW clinical trial describe clinical responses in patients with RET-KIF5B-altered NSCLC and medullary thyroid cancer (MTC) harboring multiple RET mutations, including patients who had progressed on prior multi-kinase therapy.

"The publication of our work in Cancer Discovery highlights BLU-667's compelling preclinical profile and preliminary clinical activity in patients with RET-altered cancers and further demonstrates the power of Blueprint Medicines' scientific platform," said Erica Evans, Ph.D., Senior Director of Biology at Blueprint Medicines and the senior author of the paper. "The published data show BLU-667 has the potential to deliver anti-tumor activity and meaningful clinical responses, regardless of tumor type, RET alteration or prior therapy. Coupled with the initial results from the ongoing Phase 1 ARROW clinical trial that will be presented today at the AACR Annual Meeting, these data support the rapid development of BLU-667 in patients with RET-altered cancers."

RET has long been recognized as an oncogene that drives multiple cancers. However, there are currently no approved selective RET inhibitors, and RET-targeted treatment is limited to non-selective multi-kinase therapies that can have significant off-target toxicities and limited efficacy. BLU-667 was specifically designed by Blueprint Medicines to target oncogenic RET fusions and mutations, including predicted resistance mutations, with the goal of providing durable clinical responses to patients with RET-altered cancers.

Key highlights included:

• In vitro studies show BLU-667 has 10- to 10,000-fold increased potency against oncogenic RET variants and resistant mutants over approved multi-kinase inhibitors. In addition, BLU-667 has 20-fold increased potency against RET-KIF5B fusions, the most common RET alteration in patients with NSCLC, compared to the investigational multi-kinase inhibitor RXDX-105.
• Additional in vitro studies show BLU-667 is 88-fold more selective for RET over VEGFR-2, which when inhibited can result in dose-limiting toxicities. Overall, BLU-667 is 100-fold more selective for RET over 96 percent of 371 kinases tested.
• In vivo studies show BLU-667 potently inhibits the growth of NSCLC, MTC and colorectal tumors in RET-driven disease models, including models harboring multi-kinase inhibitor-resistant mutants.
• Four patient vignettes from the ongoing Phase 1 ARROW clinical trial show that BLU-667 significantly inhibits RET signaling and induces durable clinical responses in patients with RET-altered NSCLC and MTC without notable off-target toxicity, providing clinical validation for selective RET targeting.

The paper, titled "Precision targeted therapy with BLU-667 for RET-driven cancers," was published online in Cancer Discovery on April 15, 2018.

About BLU-667

BLU-667 is an orally available, potent and highly selective inhibitor designed to target RET fusions, mutations and predicted resistance mutations. Blueprint Medicines is developing BLU-667, an investigational medicine, for the treatment of patients with RET-altered NSCLC, MTC and other solid tumors. BLU-667 was discovered by Blueprint Medicine's research team leveraging its proprietary compound library, and Blueprint Medicines retains worldwide development and commercialization rights for BLU-667.

About RET-Altered NSCLC, MTC and Other Solid Tumors

RET activating fusions and mutations are a key disease driver in multiple cancers, including NSCLC and MTC. RET fusions are implicated in approximately 1-2% of patients with NSCLC, while RET mutations are implicated in approximately 60% of patients with MTC and 10% of papillary thyroid cancer. In addition, genomic analyses published by scientists at Blueprint Medicines have identified RET fusions at low frequencies in colon and breast cancer. Currently, there are no approved therapies that selectively target RET-driven cancers, though there are several approved multi-kinase inhibitors with RET activity being evaluated in clinical trials. Thus far, clinical activity attributable to RET inhibition has been uncertain for these inhibitors, likely due to insufficient inhibition of RET and off-target toxicities.

About Blueprint Medicines

Blueprint Medicines is developing a new generation of targeted and potent kinase medicines to improve the lives of patients with genomically defined diseases. Its approach is rooted in a deep understanding of the genetic blueprint of cancer and other disease driven by the abnormal activation of kinases. Blueprint Medicines is advancing multiple programs in clinical development for subsets of patients with gastrointestinal stromal tumors, hepatocellular carcinoma, systemic mastocytosis, non-small cell lung cancer, medullary thyroid cancer and other advanced solid tumors, as well as multiple programs in research and preclinical development. For more information, please visit www.blueprintmedicines.com.

Cautionary Note Regarding Forward-Looking Statements

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 clinical development of BLU-667; expectations regarding the safety and efficacy of BLU-667 and the potential benefits of BLU-667 in treating patients with RET-altered cancers; and Blueprint Medicines' strategy, business plans and focus. The words "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 delay of any current or planned clinical trials or the development of Blueprint Medicines' drug candidates, including avapritinib, BLU-554, BLU-667 and BLU-782; Blueprint Medicines' advancement of multiple early-stage efforts; Blueprint Medicines' ability to successfully demonstrate the safety and efficacy of its drug candidates; the preclinical and clinical results for Blueprint Medicines' drug candidates, which may not support further development of such drug candidates; and 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, including companion diagnostic tests for BLU-554 for FGFR4-driven HCC, avapritinib for PDGFRα D842V-driven GIST and BLU-667 for RET-driven NSCLC; and the success of Blueprint Medicines' cancer immunotherapy collaboration with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Blueprint Medicines' Annual Report on Form 10-K for the year ended December 31, 2017, as filed with the Securities and Exchange Commission (SEC) on February 21, 2018, and 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. Blueprint Medicines explicitly disclaims any obligation to update any forward-looking statements.

SOURCE Blueprint Medicines

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