Prexigebersen

Prexigebersen (Liposomal Grb2 Antisense) for Acute Myeloid Leukemia (AML)

Prexigebersen (Liposomal Grb2 Antisense), formerly BP1001, is Bio-Path’s lead product candidate and is currently being studied as a treatment for patients with AML, CML and various solid tumors such as breast and ovarian cancers. Prexigebersen has received orphan drug designation from the FDA for both CML and AML, and from the European Medicines Agency for AML.

Current Development Status

- Based on successful results of a Phase 1 clinical trial, Bio-Path has initiated a Phase 2 program in AML, comprised of two clinical trials of BP1001 in combination with the first-line standard-of-care chemotherapy, low dose Ara C (LDAC):

  • The first has been initiated in 54 newly diagnosed AML patients who are not eligible for or who have decided to forego intensive induction therapy because of their age or fragile health.
  • A second study in relapsed and refractory AML patients is expected to be initiated in 2017.

- Prexigebersen has also completed a Phase 1 clinical trial in patients with CML and expects to initiate enrollment before the end of 2016 for the dose-determining segment of a Phase 2 trial of prexigebersen in combination with first-line standard-of-care for CML, dasatinib.

- Preclinical testing of prexigebersen is also ongoing in solid tumors such as those caused by triple negative breast cancer (TNBC), inflammatory breast cancer (IBC), and ovarian cancer, and in the autoimmune indication, systemic lupus erythematosus.

Bio-Path is currently conducting a Phase 2 program, which will include two clinical trials of prexigebersen in combination with frontline chemotherapy. The first trial will evaluate the efficacy of prexigebersen in combination with LDAC in de novo AML patients who are elderly and induction therapy ineligible. The second trial will evaluate the efficacy of prexigebersen in combination with LDAC in relapsed and refractory AML patients. More details for these studies may be found on www.clinicaltrials.gov.

Prexigebersen (Liposomal Grb2 Antisense) for Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia (CML) is characterized by expansion in the blood and bone marrow of mature myeloid cells and their precursors. The average age of diagnosis is 64 years old. Untreated or relapsed/refractory CML will progress to an accelerated phase and eventually blast crisis, at which point it becomes an acute leukemia. For the 1.5 percent of patients who go into blast crisis, few treatment options currently exist. Response rate to treatment for blast crisis CML is less than 30% and patients in blast crisis have an average survival of between 7 to 11 months. New therapies for this critical population are essential.

The safety segment of the Phase 2 clinical trial for prexigebersen in combination with the CML frontline therapy, dasatinib, is preparing to enroll patients for treatment.

Prexigebersen (Liposomal Grb2 antisense), Bio-Path’s lead product candidate is a neutral-charge, liposome-incorporated antisense drug designed to inhibit protein synthesis of Grb2 (growth factor receptor bound protein 2) expression, which is critical in bridging tyrosine kinases to Ras activation in cancer cells. A hallmark of CML disease is the Philadelphia chromosome abnormality, a translocation that fuses part of the BCR gene with the ABL gene, resulting in a continuously activated tyrosine kinase leading to cell proliferation. Inhibition of Grb2 by prexigebersen represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with small molecule inhibitors. Inhibition of Grb2 has been demonstrated to halt cell proliferation and enhance cell killing by chemotherapeutic agents without added toxicity.

The dose determining segment of the Phase 2 clinical trial for prexigebersen in combination with the CML frontline therapy, dasatinib, is preparing to enroll patients for treatment. More details may be found on www.clinicaltrials.gov.

Prexigebersen (Liposomal Grb2 Antisense) for Solid Tumors

Analyses of solid tumors with activated or mutated tyrosine kinases indicate that prexigebersen has high potential for success in treatment of diseases beyond blood cancers. Prexigebersen’s indications include triple negative breast cancer (TNBC), inflammatory breast cancer (IBC), and ovarian cancers. Preclinical investigation is ongoing to assess the efficacy of Prexigebersen in treating solid tumors.

Prexigebersen (Liposomal Grb2 antisense) is Bio-Path’s lead product candidate, a neutral-charge, liposome-incorporated antisense drug designed to inhibit protein synthesis of Grb2 (growth factor receptor bound protein 2). Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 is an adapter protein that bridges signals between activated and mutated tyrosine kinases, such as EGFR, HER2/Neu, and VEGFR and the Ras pathway, leading to activation of the ERK and AKT proteins. Inhibition of Grb2 by Prexigebersen represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with small molecule inhibitors. Inhibition of Grb2 has been demonstrated to halt cell proliferation and enhance cell killing by chemotherapeutic agents without added toxicity.

BP1002 (Liposomal Bcl2 Antisense)

Bio-Path is planning to initiate a Phase 1 clinical trial of BP1002 in patients with follicular lymphoma, the most common form of non-Hodgkin’s lymphoma (NHL) in 2017.

For more information on BP1002 and its mechanism of action, please click here