Avapritinib is an orally available, potent and highly selective inhibitor of KIT and PDGFRA. In certain diseases, a spectrum of clinically relevant mutations forces the KIT or PDGFRA protein kinases into an increasingly active state. Avapritinib is uniquely designed to bind and inhibit the active conformation of these proteins, including PDGFRα D842V and KIT D816V at sub-nanomolar potency. Blueprint Medicines is initially developing avapritinib, an investigational medicine, for the treatment of patients with advanced GIST and systemic mastocytosis. In June 2017, avapritinib received Breakthrough Therapy Designation from the FDA for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation. Previously, the FDA granted orphan drug designation to avapritinib for GIST and mastocytosis and fast track designation to avapritinib for GIST. In addition, the European Commission has granted orphan drug designation to avapritinib for GIST. In May 2018, Blueprint Medicines announced plans to submit a New Drug Application to the FDA for avapritinib for the treatment of PDGFRα D842V-driven GIST in the first half of 2019. In June 2018, Blueprint Medicines announced an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan.
Blueprint Medicines is rapidly advancing a deep pipeline of potent and selective kinase inhibitors for genomically defined subsets of patients with cancer and other debilitating diseases driven by the abnormal activation of kinases. By identifying patients most likely to respond to our therapies, we believe that we can increase the efficiency of drug development and the likelihood of success, delivering transformative medicines for patients who currently lack effective treatments.
Since starting operations in 2011, we have advanced our two lead drug candidates , avapritinib and BLU-554, into three Phase 1 clinical trials and have multiple discovery-stage programs in our pipeline.
BLUEPRINT MEDICINES PIPELINE
Avapritinib is a potent and selective inhibitor of PDGFRα D842V and KIT Exon 17 mutants and is being developed as a highly targeted therapy for SM, a disorder of the mast cells in which a KIT Exon 17 mutation is the primary driver of disease. Advanced forms of SM have significant morbidity related to symptoms from mast cell degranulation and shortened life expectancy due to multi-organ dysfunction/failure from mast cell infiltration and tissue destruction. More than 94 percent of SM patients display the KIT Exon 17 D816V mutation in their mast cells; there is no effective approved targeted therapy for these patients. In preclinical studies, avapritinib has demonstrated proof-of-concept and resulted in significant disease control in a mouse mast cell tumor model. We have initiated a Phase 1 clinical trial for avapritinib for treatment of patients with advanced SM, including aggressive SM (ASM), SM with associated clonal hematological non-mast cell lineage diseases (SM-AHN), and mast cell leukemia (MCL), and we are currently enrolling patients. To learn more about this clinical trial, please click here.
BLU-554 is an exquisitely selective and potent kinase inhibitor that we will initially develop for a genomically defined subset of HCC patients. HCC is the most prevalent form of liver cancer and is the second-leading cause of cancer-related deaths worldwide. BLU-554 targets the fibroblast growth factor receptor 4 (FGFR4), while sparing other members of the FGFR family and showing little to no inhibition of all other kinases. Aberrant signaling of FGFR4 is a key driver in up to 30 percent of HCC, and BLU-554 has shown significant anti-tumor activity, including complete and sustained tumor regression, in preclinical models of HCC. We have initiated a Phase 1 clinical trial for BLU-554 for the treatment of patients with advanced HCC, and we are currently enrolling patients. To learn more about this clinical trial, please click here.
Our drug candidate BLU-667 is a potent and selective inhibitor of RET mutations, fusions, and predicted resistant mutants. RET fusions are key drivers of multiple cancers, including lung and thyroid cancer, and our research suggests that RET also plays a key role in some colon and breast cancers. By simultaneously targeting the primary driver and predicted resistant mutants that render cancer cells insensitive to treatment with currently approved drugs, our goal is to provide more lasting clinical responses and prevent or delay recurrences of the disease. In preclinical studies, our compounds demonstrated tumor regression in disease models driven by the primary RET fusion and predicted resistance mutants.
We previously entered into a collaboration with Alexion to research, develop and commercialize drug candidates targeting the ALK2 kinase for the treatment of fibrodysplasia ossificans progressiva (FOP). FOP is a rare genetic disease caused by mutations in the ALK2 gene, ACVR1.
Under our collaboration with Roche, we are seeking to discover, develop and commercialize up to 5 small molecule therapeutics targeting immunokinases believed to be important in cancer immunotherapy, as single products or possibly in combination with other therapeutics. The stage of development and targets for this collaboration are undisclosed. Under the Roche collaboration, Blueprint Medicines retains U.S. commercialization rights for up to 2 collaboration programs, and Roche retains worldwide commercialization rights for up to 3 collaboration programs and commercialization right outside the U.S. for up to 2 collaboration programs.