Blueprint Medicines Announces Publication of BLU-285 Translational Data
"The publication of our work in Science Translational Medicine highlights the power of our proprietary drug discovery platform to successfully target specific drivers of disease with potent and highly selective kinase medicines," said
The paper highlighted the in-depth mechanistic evaluation conducted by
Key insights included:
- Currently available therapies for advanced GIST and advanced SM have limited activity against KIT and PDGFRα activation loop mutations, including KIT D816V, PDGFRα D842V, and additional resistance mutations located on exons 17 and 18. These mutations induce the KIT and PDGFRα proteins to adopt an active conformation, resulting in structural changes in the kinases that decrease the binding affinity of current therapeutic agents. BLU-285 was specifically designed to inhibit KIT and PDGFRα activation loop mutations.
- In vitro studies demonstrated potent activity of BLU-285 against activation loop mutations, as well as a broad spectrum of additional clinically relevant mutations, with a selectivity profile minimizing inhibition of other kinases. In vivo studies in multiple disease models showed BLU-285 induced potent anti-tumor effects.
- BLU-285 has demonstrated clinical proof-of concept in ongoing Phase 1 clinical trials in patients with advanced GIST and advanced SM.
The paper, titled "A precision therapy against cancers driven by KIT/PDGFRA mutations" was published online in Science Translational Medicine on
BLU-285, an investigational medicine, is an orally available, potent and highly selective inhibitor of KIT and PDGFRα. Blueprint Medicines is initially developing BLU-285 for the treatment of patients with advanced GIST and advanced SM.
In June 2017, BLU-285 received breakthrough therapy designation from the U.S. Food and Drug Administration (
BLU-285 was discovered by Blueprint Medicines' research team, which leveraged its proprietary compound library. The Company retains worldwide development and commercialization rights for BLU-285.
GIST is the most common sarcoma, or tumor of bone or connective tissue, of the gastrointestinal (GI) tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50-80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction. Approximately 80 percent of GIST patients have KIT-driven GIST, and
There are several forms of SM, including indolent SM and more advanced forms of SM, which include aggressive SM, SM with an associated hematologic neoplasm (SM-AHN) and mast cell leukemia (MCL). SM is characterized by the buildup of mast cells, which are immune cells that produce histamine and other mediators of the body's inflammatory and allergic responses. In patients with SM, mast cell mediator release leads to mild to life-threatening symptoms, including pain, nausea, rash, fever, fatigue and anaphylaxis. In patients with advanced SM, including aggressive SM, SM-AHN and MCL, mast cell infiltration in bone marrow, liver and other vital organs can eventually lead to organ dysfunction and lower life expectancy, with a median overall survival of approximately four years or less. Patients with indolent SM have a normal life expectancy, but symptoms can have a significant impact on their quality of life. The KIT D816V mutation is the primary driver of disease in approximately 90 to 95 percent of SM patients, and there is a clear need for more effective therapies for patients with advanced SM and for patients with indolent SM who have a heavy symptom burden.
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 diseases driven by the abnormal activation of kinases. Blueprint Medicines is advancing four 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 the potential for BLU-285 to address unmet patient needs in GIST and SM; plans and timelines for the clinical development of BLU-285; the timing of updated clinical data for
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Media and Investor Relations Contacts - Kristin Hodous, 617-714-6674, KHodous@blueprintmedicines.com; Jim Baker, 617-844-8236, JBaker@blueprintmedicines.com