CAMBRIDGE, Mass., Oct. 1, 2018 /PRNewswire/ -- Blueprint Medicines
Corporation (NASDAQ: BPMC), a leader in discovering and developing
targeted kinase medicines for patients with genomically defined
diseases, today announced preclinical proof-of-concept data for
BLU-782, an investigational oral precision therapy specifically
designed to target mutant activin-like kinase 2 (ALK2), the
underlying cause of fibrodysplasia ossificans progressiva (FOP).
Preclinical studies in a well-characterized, genetically accurate
FOP model showed BLU-782 prevented injury- and surgery-induced
heterotopic ossification (HO), reduced edema and restored healthy
tissue response to muscle injury. The data were presented on
September 30 in a plenary oral
session at the 2018 American Society for Bone and Mineral Research
(ASBMR) Annual Meeting in Quebec,
Canada.
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"We are excited to report preclinical proof-of-concept data for
BLU-782, a highly selective oral inhibitor of mutant ALK2, the
underlying cause of FOP," said Marion
Dorsch, Ph.D., Chief Scientific Officer of Blueprint
Medicines. "Despite the discovery of the FOP gene more than a
decade ago, prior efforts to develop a selective ALK2 inhibitor
faltered due to persistent technical challenges. By leveraging our
proprietary compound library and expertise in structure-guided
medicinal chemistry, we overcame these challenges and successfully
designed BLU-782 to selectively target mutant ALK2. The new
preclinical data reported at the ASBMR Annual Meeting showed
BLU-782 prevented abnormal bone growth in a well-characterized FOP
model, validating selective ALK2 inhibition as an important
potential therapeutic strategy."
FOP is a rare genetic disorder characterized by the abnormal
transformation of skeletal muscle, ligaments and tendons into bone,
either spontaneously or as the result of physical trauma. FOP is
caused by a mutation in the gene for ALK2, which is known as ACVR1,
that causes hypersensitivity to certain bone morphogenetic proteins
(BMP) and a neomorphic response to activins.
In the preclinical data presented at the ASBMR meeting, BLU-782
demonstrated exquisite selectivity for R206H mutant ALK2 in
cellular assays, while sparing closely related anti-targets
including ALK1, ALK3, and ALK6. Additionally, BLU-782 potently
inhibited mutant ALK2 in vitro, regardless of the activating
ligand, including Activin A, Activin B and BMP6. In vivo
studies in a conditional knock-in ALK2R206H transgenic
mouse model showed BLU-782 prevented the formation of
injury-induced HO and edema, as measured by micro computed
tomography and magnetic resonance imaging. Immunohistochemistry
analyses also showed restoration of a healthy response to tissue
injury in ALK2R206H mice, including skeletal myofiber
regeneration. In addition, BLU-782 prevented the formation of
surgery-induced HO following fibular osteotomy surgery in
ALK2R206H mice.
"Given the disabling and destructive nature of this disease,
people living with FOP have a desperate need for a safe and
effective treatment," said Adam
Sherman, Research Development and Partnerships Director at
the International Fibrodysplasia Ossificans Progressiva
Association. "We are immensely grateful to have companies like
Blueprint Medicines developing new treatments for those living with
FOP. We look forward to seeing BLU-782 advance through the
development pathway and hope a therapeutic option will one day
change the course of this disease."
Blueprint Medicines expects to submit an investigational new
drug (IND) application for BLU-782 by the end of 2018, and subject
to approval of the IND application by the U.S. Food and Drug
Administration, plans to initiate a Phase 1 clinical trial in
healthy volunteers in the first quarter of 2019. In addition,
Blueprint Medicines plans to continue working with clinical experts
and the patient community to design a potential Phase 2 clinical
trial of BLU-782 in patients with FOP.
About BLU-782
BLU-782 is an oral precision therapy specifically designed to
selectively target mutant ALK2, the underlying cause of FOP.
Blueprint Medicines is developing BLU-782, an investigational
medicine, for the treatment of patients with FOP. BLU-782 was
derived from Blueprint Medicines' proprietary compound library and
optimized via structure-guided medicinal chemistry for potent and
selective targeting of mutant ALK2. Blueprint Medicines owns
worldwide development and commercialization rights for BLU-782.
About Fibrodysplasia Ossificans Progressiva
FOP is a rare, severely disabling genetic disorder characterized
by progressive HO, or the abnormal transformation of muscle,
ligaments and tendons into bone. HO may be spontaneous or
associated with painful episodic disease flare-ups that are usually
precipitated by soft tissue injury. As the disease progresses,
extra-skeletal bone increasingly restricts joints, resulting in
severe disability and loss of mobility, compromised respiratory
function and increased risk of early death. FOP is caused by a
mutation in the gene for ALK2, which is known as ACVR1, leading to
inappropriate activation of the bone morphogenetic pathway.
Currently, there are no approved therapies for FOP.
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 preclinical and clinical
development of BLU-782, including a Phase 1 clinical trial in
healthy volunteers and a Phase 2 clinical trial in patients with
FOP; the potential benefits of BLU-782 in treating patients with
FOP; plans and timelines for submitting an IND application for
BLU-782; 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; 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
hepatocellular carcinoma, avapritinib for PDGFRα D842V-driven
gastrointestinal stromal tumors and BLU-667 for RET-driven
non-small cell lung cancer; and the success of Blueprint Medicines'
cancer immunotherapy collaboration with F. Hoffmann-La Roche Ltd
and Hoffmann-La Roche Inc and Blueprint Medicines' collaboration
with CStone Pharmaceuticals. These and other risks and
uncertainties are described in greater detail in the section
entitled "Risk Factors" in Blueprint Medicines' Quarterly Report on
Form 10-Q for the quarter ended June 30,
2018, as filed with the Securities and Exchange Commission
(SEC) on August 1, 2018, 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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