Purposefully designed medicines and clinical candidates
Designing precision therapies specifically to target the underlying cause of genomically defined diseases
Avapritinib
Avapritinib is a potent and selective inhibitor of activated KIT and PDGFRA mutant kinases. In certain diseases, mutations in KIT and PDGFRA force protein kinases into an increasingly active state. Avapritinib is uniquely designed to bind and inhibit the active conformation of these proteins.
Activating mutations in KIT and PDGFRA are associated with gastrointestinal stromal tumors (GIST) and systemic mastocytosis (SM) and appear in lower frequency in a broad range of advanced malignancies.
Avapritinib in GIST
GIST is a sarcoma of the gastrointestinal tract, and is driven by the PDGFRA gene with exon 18 mutations in about 6% of patients.
Prior to tyrosine kinase inhibitor use in GIST, mutational testing in all patients is recommended by expert guidelines. People diagnosed with GIST should be tested for mutations to determine which type of therapy might be right for them.
Blueprint Medicines is developing avapritinib as a potential treatment for patients with PDGFRA exon 18 mutant GIST globally. View approved uses of avapritinib. View clinical trials of avapritinib.
Avapritinib in systemic mastocytosis
Systemic mastocytosis (SM) is a rare disease driven by the KIT D816V mutation in approximately 95 percent of cases. Uncontrolled proliferation and activation of mast cells results in chronic, severe and often unpredictable symptoms across multiple organ systems.
SM comprises a disease spectrum ranging from non-advanced SM to advanced SM.
– The vast majority of those affected have indolent SM (ISM), which frequently results in a broad range of burdensome symptoms that can lead to a profound negative impact on quality of life.
– A minority of patients have advanced SM, which is associated with organ damage due to mast cell infiltration and poor overall survival.
Blueprint Medicines is developing avapritinib as a potential treatment for a broad population of patients with SM globally, including advanced SM and ISM. View approved uses of avapritinib. View clinical trials of avapritinib.
Presentations and publications
Avapritinib in GIST
Avapritinib in systemic mastocytosis
Clinical trials
Systemic mastocytosis (SM)
Trial Phase
Target Population
Aggressive SM, SM with associated hematologic neoplasm and mast cell leukemia
Study Status
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ClinicalTrials.gov
Study Number
NCT03580655
Trial Phase
Target Population
Indolent SM
Study Status
arrow
ClinicalTrials.gov
Study Number
NCT03731260
Elenestinib (BLU-263)
Elenestinib is a next-generation KIT D816V inhibitor developed based on insights from the avapritinib program. Elenestinib was designed to potently inhibit D816V mutant KIT with minimal central nervous system penetration. These attributes may have the potential to optimize its benefit-risk profile for the treatment of broad patient populations with indolent systemic mastocytosis (SM).
Elenestinib in systemic mastocytosis
Systemic mastocytosis (SM) is a rare disease driven by the KIT D816V mutation in approximately 95 percent of cases. Uncontrolled proliferation and activation of mast cells results in chronic, severe and often unpredictable symptoms across multiple organ systems.
The vast majority of those affected have indolent SM (ISM), which frequently results in a broad range of burdensome symptoms that can lead to a profound negative impact on quality of life.
The initial focus of the elenestinib development program is ISM. View clinical trials of elenestinib.
Presentations and publications
BLU-222
BLU-222 is a potent and selective CDK2 inhibitor for the treatment of patients with CDK2-vulnerable cancers, including hormone receptor (HR)-positive, HER2-negative breast cancer and CCNE1 aberrant tumors. CDK2 and CCNE1 are central to regulating the cell cycle, which is involved in the process of cell growth and division. However, prior drug discovery efforts targeting CDK2 have been hindered by challenges in achieving selectivity over other CDK family members associated with toxicity.
CDK2 is believed to play an important role in tumor proliferation for patients with HR-positive, HER2-negative metastatic breast cancer. In subsets of patients with ovarian cancer and other tumor types, aberrant CCNE1 hyperactivates CDK2, resulting in cell cycle dysregulation and tumor growth. Preclinically, BLU-222 showed significant antitumor activity in a CCNE1-amplified ovarian cancer model, and BLU-222 in combination with standard of care agents led to sustained tumor regression even after treatment cessation.
BLU-222 in hormone receptor-positive metastatic breast cancer
Approximately 60 percent of treatment-naïve patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer receive a CDK4/6 inhibitor; however, patients ultimately become resistant to therapy over time.
There are limited treatment options for patients following disease progression on a CDK4/6 inhibitor.
Blueprint Medicines is developing BLU-222 as a monotherapy and in combination with other agents, including CDK4/6 inhibitors and ER antagonists, in HR-positive, HER2-negative breast cancer. View clinical trial of BLU-222.
BLU-222 in cyclin E aberrant cancers
Studies show that CCNE1 amplification across multiple tumor types is correlated with poor patient outcomes.
For example, approximately 10 to 20 percent of patients with high grade serous ovarian cancer, a common form of ovarian cancer, harbor CCNE1 amplifications.
Blueprint Medicines is developing BLU-222 as a monotherapy and in combination with other agents for the treatment of CCNE1 aberrant cancers. View clinical trial of BLU-222.
Presentations and publications
Fidrisertib (BLU-782, IPN60130)
Fidrisertib is an orally administered, potent and highly selective ALK2 inhibitor. It was designed specifically to target the underlying genetic driver of fibrodysplasia ossificans progressiva (FOP), a rare, severely disabling and ultimately life-shortening genetic disease. FOP is characterized by episodic soft tissue edema (flare-ups), and the progressive replacement of skeletal muscle, ligaments and connective tissue by heterotopic bone. FOP is caused by a gain-of-function mutation in ACVR1, which encodes activin-like kinase 2 (ALK2).
In October 2019, we entered into an exclusive, worldwide license agreement with Clementia Pharmaceuticals, a subsidiary of Ipsen, to develop and commercialize fidrisertib.
Fidrisertib in fibrodysplasia ossificans progressiva
FOP is a rare genetic disease, with an estimated prevalence of 1.36 per million.
In patients with FOP, mutations in the ACVR1 gene over-activate ALK2, causing disease flare-ups and heterotopic ossification (HO) or abnormal bone formation.
Disease flare-ups involve painful tumor-like swelling typically caused by physical trauma.
HO causes progressive disability and incapacitation including the locking of joints, ultimately contributing to reduced survival typically due to pulmonary insufficiency.
BLU-782 is designed to selectively target mutant ALK2, while sparing closely related anti-targets including ALK1, ALK3, and ALK6.
Presentations and publications
Systemic mastocytosis (SM) is a rare disease that can mask as other more common illnesses, making it difficult to diagnose.
Blueprint Medicines has partnered with the University of Pennsylvania to develop and publish an algorithm applying
machine learning techniques to pinpoint potential SM cases.