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BST-236 (aspacytarabine)

Acute myeloid leukemia (AML) is associated with poor outcome in older patients and in patients unfit for standard induction therapy. Cytarabine serves as the backbone of treatment for AML for decades, however, standard cytarabine therapy is associated with severe side effects, such as cerebellar toxicity, bone marrow suppression, and infections, leading to high treatment-related mortality rates.

Hence, while the incidence of AML increases with age, advanced age and comorbidities may preclude the administration of intensive induction therapy altogether due to its potential toxicities. The outcome in older patients who are unable to receive intensive chemotherapy remains poor, in spite of recent approvals of new therapeutics.

BST-236 (INN aspacytarabine) is a novel proprietary anti-metabolite. It is composed of cytarabine covalently bound to asparagine, acting as a pro-drug of cytarabine, enabling delivery of high cytarabine doses to leukemia patients with lower systemic exposure to the free drug.

BST-236 Mechanism of Action

  • Intact BST-236 is inactive and non-toxic, allowing high-dose administration

  • BST-236 gradually releases cytarabine via non-enzymatic hydrolysis

  • Cellular availability of BST-236-released cytarabine has different kinetics compared to free cytarabine

  • Therefore, peak toxic systemic exposure to cytarabine is avoided

  • Until its release, cytarabine is protected from inactivation by deamination or activation by phosphorylation

  • Released cytarabine is activated by phosphorylation, incorporated into the DNA and induces apoptosis, mainly in mitotic malignant cells

>> For more information regarding BST-236 mechanism of action

Results from a recently completed Phase 1/2a study, presented by Dr. Zuckerman at the 59th Annual American Society of Hematology meeting in Atlanta, GA, USA, demonstrate that BST-236 treatment of acute leukemia patients is safe and well tolerated, enabling delivery of high doses of cytarabine to older and unfit patients, leading to high response rates and prolonged survival.

>> Phase 1/2 publication: Zuckerman et al., BST-236 Phase 1/2a article, Blood Advances 2019

A multi-center Phase 2b trial in the US and Israel was recently launched and is currently enrolling newly-diagnosed AML patients who are unfit for standard chemotherapy.  

Additional clinical studies in various hematological indications are planned to be initiated in the coming months.

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