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

Acute myeloid leukemia (AML) is characterized by the rapid accumulation of immature myeloid cells in the blood, resulting in a drop of the other cell types, such as red blood cells and platelets. AML incidence increases with age, with a majority of patients aged 60 or older. AML is the most common acute leukemia in adults. The National Cancer Institute estimates that approximately 20,000 new cases occur each year. There is a critically unmet need for non-toxic therapies for older, fragile AML patients who are unfit or ineligible for high-dose chemotherapy or a stem cell transplant. The cure rate is between 5 to 15% in older adults, and those who cannot receive the standard course of chemotherapy have an average survival rate of five to ten months.

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 progression via the RAS activation pathway. Grb2 is an adapter protein that bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of downstream 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 propagation and enhance cell killing by chemotherapeutic agents without added toxicity.

Bio-Path has completed a Phase 1 clinical trial on prexigebersen as a monotherapy in relapsed and refractory AML, CML, and MDS patients and a Phase 2 safety segment for AML in combination with the frontline treatment, low dose Ara C (LDAC). Prexigebersen demonstrates excellent safety profiles with no serious treatment-related adverse events reported, and with data suggesting potential anti-leukemic activity. In the Phase 2 combination trial safety segment, out of a total of six evaluable patients, three patients achieved complete remission, and two achieved stable disease.

Prexigebersen has received orphan drug designation from the FDA and from the European Medicines Agency for AML.

Bio-Path is currently conducting a Phase 2 program, in which prexigebersen is combined with chemotherapy. The program will evaluate the efficacy of prexigebersen in combination with venetoclax and decitabine in untreated AML patients who are elderly and induction therapy ineligible as well as in relapsed or refractory AML patients. The program will also evaluate the efficacy of prexigebersen in combination with decitabine in relapsed or refractory AML patients who are resistant or intolerant of venetoclax. More details for this program may be found on

Prexigebersen-A (Liposomal Grb2 Antisense) for Solid Tumors

Analyses of solid tumors with activated or mutated tyrosine kinases indicate that prexigebersen-A has high potential for success in treatment of diseases beyond blood cancers. Published studies demonstrate the efficacy of prexigebersen-A against ovarian or endometrial tumors in animal models. A Phase I/Ib study will evaluate the safety and anti-tumor effects of prexigebersen-A in combination with paclitaxel in patients with recurrent ovarian or endometrial cancer.


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