Addressing unmet needs for fragile populations

Bio-Path is developing RNAi nanoparticle drugs for some of the most lethal blood cancers and solid tumors. The company’s anticancer drug candidates target the expression of proteins that have been implicated in cancer progression and resistance to chemotherapy. Inhibition of these proteins may prove to be a low-toxicity approach to treating patients who would not historically be eligible for anticancer therapies because of their age or other comorbidities or whose cancers are unresponsive to standard therapeutic approaches.


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 www.clinicaltrials.gov.

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.

BP1002 (Liposomal Bcl-2) for Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia

Lymphoma can start anywhere in the body where lymph tissue is found. The major sites of lymph tissue are: lymph nodes, bone marrow, spleen, thymus, adenoids & tonsils, digestive tract. Non-Hodgkin’s lymphoma (NHL) is a term used for many different types of lymphoma that share some common characteristics. In the U.S., approximately 77,240 new cases and 19,940 deaths from NHL were expected in 2020. Approximately 40% of NHLs are indolent lymphomas and approximately 60% are the more aggressive lymphomas. Indolent lymphomas grow and spread slowly. Some indolent lymphomas might not need to be treated right away but can be watched closely instead. On the other hand, aggressive lymphomas usually need to be treated right away as they grow and can spread quickly to other parts of the lymph system or to other parts of the body, such as the liver, brain, or bone marrow.

BP1002 (Liposomal Bcl-2) is a neutral-charge, liposome-incorporated antisense drug designed to inhibit protein synthesis of Bcl-2, a protein involved in blocking programmed cell death. Bcl-2 is overexpressed in a wide variety of tumors, including NHL and chronic lymphocytic leukemia. Overexpression of Bcl-2 stops affected cells from being killed by chemotherapy. We believe that BP1002 will inhibit Bcl-2 protein expression without inherent toxicity. The introduction of a new, non-toxic, and specific Bcl-2 inhibitor could be a major advance in cancer therapeutics.

A Phase 1 clinical trial for BP1002 in patients with relapsed or refractory NHL or chronic lymphocytic leukemia is currently underway. More details for this study may be found www.clinicaltrials.gov.

BP1002 (Liposomal Bcl-2) for AML patients relapsed from Bcl-2 inhibitor treatment

The Bcl-2 inhibitor venetoclax is used in frontline combination therapies for elderly patients with acute myeloid leukemia (AML); however, venetoclax resistance had been observed. A recent study found that AML patients who had relapsed from frontline venetoclax-based treatment had a very poor prognosis, with a median survival of less than 3 months. Since venetoclax and BP1002 utilize different mechanisms of action, we believe BP1002 may be a potential treatment for venetoclax-relapsed AML patients. Preclinical studies suggest that the combination of BP1002 with decitabine is efficacious in venetoclax-resistant cells. A Phase 1/1b study of BP1002 in combination with decitabine in AML patients who have relapsed from venetoclax-based treatment is being planned.

BP1003 (Liposomal Stat3) for Pancreatic Cancer

Pancreatic adenocarcinoma (PDAC) is a cancer of the exocrine cells of the pancreas. In the U.S. in 2020, approximately 57,600 people were diagnosed with PDAC, and approximately 47,050 died from the disease. It is estimated that by 2030, PDAC will become the second most lethal cancer behind lung cancer.

Because most people are diagnosed with PDAC late in the disease’s progression, survival rates are very low. Typical survival for a metastatic patient is only 3-6 months from diagnosis. Treatment of this disease is hampered by the location of the pancreas, which is difficult to reach with conventional therapies and the fibrotic nature of the tumors, which protects them from penetration by chemotherapeutics. A novel and unconventional therapeutic is needed to overcome these barriers to treatment.

BP1003 is an RNAi nanoparticle containing antisense DNA targeting STAT3, a protein associated with increased PDAC severity and poorer survival in patients with PDAC. Preclinical studies show that BP1003 enhances the efficacy of gemcitabine in mouse models of pancreatic cancer. Bio-Path has initiated IND-enabling studies of BP1003.

In addition, expression of STAT3 has been associated with higher disease severity in numerous other cancers including non-small cell lung (NSCLC) and AML. A drug that inhibits STAT3 will have significant clinical impact for all solid cancers that have high STAT3 expression or activity.

Delivering a Better Path for Cancer Patients.