Purposefully designed medicines and clinical candidates
Designing medicines to target root causes of disease
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 systemic mastocytosis (SM) and gastrointestinal stromal tumors (GIST), and appear in lower frequency in a broad range of advanced malignancies.
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, including indolent SM (ISM) and advanced SM.
– The vast majority of those affected have 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 advancing avapritinib as a treatment for a broad population of patients with advanced SM and ISM globally. View approved uses of avapritinib. View clinical trials of avapritinib.
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 advancing avapritinib as a treatment for patients with exon 18 mutant GIST, including PDGFRA D842V mutation, globally. 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)
A clinical trial for people with indolent systemic mastocytosis
Trial Phase
Target Population
Indolent SM
Study Status
arrow
ClinicalTrials.gov
Study Number
NCT03731260
A clinical trial for people with advanced systemic mastocytosis
Trial Phase
Target Population
Aggressive SM, SM with associated hematologic neoplasm and mast cell leukemia
Study Status
arrow
ClinicalTrials.gov
Study Number
NCT03580655
Elenestinib
Elenestinib is an investigational next-generation KIT D816V inhibitor designed to potently inhibit the KIT D816V mutation with low off-target activity. Elenestinib is in clinical development for the treatment of indolent systemic mastocytosis and other mast cell disorders.
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-808
BLU-808 is an investigational oral, highly potent and selective wild-type KIT inhibitor that was developed leveraging our expertise in mast cell biology. Wild-type KIT plays a central role in mast cell activation, which is implicated in a broad range of inflammatory diseases including chronic urticaria.
BLU-808 in chronic urticaria
Chronic urticaria is a debilitating inflammatory skin disorder characterized by wheals (hives).
Sleep disruption, stress and anxiety due to severe itching are major contributors to disease burden, with a significant impact on patients’ quality of life.
Blueprint Medicines is developing BLU-808 as a potential treatment for patients with mast cell disorders, including chronic urticaria.
Presentations and publications
BLU-222
BLU-222 is an investigational potent and selective inhibitor for the treatment of patients with cancers vulnerable to CDK2 inhibition. CDK2 is a cell cycle regulator and an important therapeutic target across multiple cancers, including hormone-receptor-positive, HER2-negative breast cancer; advanced gynecological cancers, such as subsets of ovarian and endometrial cancer; and other cyclin E1 (CCNE1) aberrant tumors.
Across multiple tumor types, CDK2 activation results in cell cycle dysregulation and tumor proliferation. CDK2 activation is a mechanism of resistance to CDK4/6 inhibitors and other therapies, as well as a primary driver of disease in CCNE1 aberrant cancers.
BLU-222 in hormone-receptor-positive, HER2-negative breast cancer
CDK2 is believed to play an important role in tumor proliferation for patients with hormone-receptor (HR)-positive, HER2-negative metastatic breast cancer.
Approximately 60 percent of treatment-naïve patients with 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 metastatic breast cancer. View clinical trial of BLU-222.
BLU-222 in CCNE1-amplified ovarian cancer
In subsets of patients with ovarian cancer and other tumor types, amplification of the CCNE1 gene and subsequent elevation of cyclin E protein levels result in cell cycle dysregulation and tumor growth.
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
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.