Blueprint Medicines Presents Foundational Preclinical Data Supporting the Development of BLU-782, a Highly Selective ALK2 Inhibitor, for the Treatment of Patients with Fibrodysplasia Ossificans Progressiva
"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
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
BLU-782 is an oral precision therapy specifically designed to selectively target mutant ALK2, the underlying cause of FOP.
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.
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
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Kristin Hodous, 617-714-6674, KHodous@blueprintmedicines.com; Jim Baker, 617-844-8236, JBaker@blueprintmedicines.com