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.
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SOURCE Blueprint Medicines