BPTH: Bio-Path Achieves Major Milestone and On Track To Advance Clinical Programs

Zacks Small Cap Research

By Grant Zent, CFA

Bio-Path’s Liposomal Delivery Technology Achieves Major Milestone

On August 9, 2013, Bio-Path Holdings, Inc. (BPTH) announced that a scientific assay has confirmed that its lead product candidate BP-100-1.01 (Liposomal Grb-2) inhibits the disease-causing target protein in patients with blood cancers. The assay was applied to patient samples taken from Bio-Path’s Phase I clinical trial which is evaluating Liposomal Grb-2 in blood cancers including acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndrome (MDS).

The data confirm that L-Grb-2 blocks the production of its target protein Grb-2 in clinical trial patient samples. L-Grb-2 was designed to block the protein production of Growth factor Receptor Bound protein-2 (Grb-2), and disrupt the activity (i.e. phosphorylation) of its downstream effector extracellular signals regulated kinases 1,2 (ERK1,2). To verify that L-Grb-2 decreases Grb-2 protein production and ERK1,2 phosphorylation, flow cytometric analysis was performed on the samples. Fluorescent-labeled antibodies for Grb-2 and phosphorylated ERK1,2 were purchased from commercial suppliers which have previously demonstrated the reactivity and specificity of these antibodies. Leukemic cell lines as well as peripheral blood samples from healthy volunteers and diseased patients were used to validate the precision and the reproducibility of the flow cytometry protocol. Peripheral blood samples were obtained from patients prior to study initiation (baseline) and during the course of therapy. The medium fluorescence of Grb-2 and the median fluorescence of phosphorylated ERK1,2 on CD33-expressing leukemic cells were compared to baseline to assess inhibition of the target proteins. The testing was performed by a third party certified Good Laboratory Practice (GLP) testing laboratory.

The specific data from this testing is planned to be reviewed at the Annual Society of Hematology (ASH) meeting in December by Jorge Cortes, M.D., Professor and Deputy Chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center (MD Anderson Cancer Center).

We think this discovery is a significant milestone in the development of Bio-Path’s liposomal delivery technology. The significance of this testing is that it confirms Bio-Path’s delivery technology value proposition. Bio-Path’s product candidates are administered to the patient by simple intravenous transfusion and are perfused throughout the body via blood flow. As evidenced to date in the Company’s clinical trial, the liposomal drug product produces no toxic side effects, and safely transports the antisense drug substance throughout the body to reach the diseased cell for insertion across the cell membrane. Success of Bio-Path’s delivery technology affirmed through testing opens several avenues to maximize growth in the value of the Company.

Inhibition of the disease-causing protein has the effect of down regulating the disease. This will allow for Liposomal Grb-2 to be used potentially in combination with current frontline treatments. This discovery also points to the potential use of a liposomal antisense treatment as a standalone treatment to transform and manage a disease, which has a disease-causing protein, as a chronic disorder.

Further, the scientific proof of principle for the drug delivery technology may lead to licensing and business development opportunities for Bio-Path.

Fifth Cohort of Phase I Liposomal Grb-2 Completed

On June 6, 2013, BPTH announced that it has completed treatment of the fifth dosage cohort in its Phase I clinical trial of its lead product candidate Liposomal Grb-2.

The drug’s safety profile continues to be favorable with no treatment-related serious adverse events reported and data continues to suggest possible anti-leukemia activity.

A total of three patients were enrolled and dosed in the fifth cohort of the study. All three patients completed the 28-day treatment cycle and were evaluable. Liposomal Grb-2 is systemically delivered by intravenous injection. Patients received a dose of 60 mg/m2 twice a week for four weeks, for a total of eight doses. Preliminary results suggest that Liposomal Grb-2 at a dose of 60 mg/m2 is well tolerated.

As was the case with the four previous cohorts, there continues to be a suggestion of possible anti-leukemia activity. All three patients in this cohort were of the more proliferative AML type compared to some of the more indolent patients that have been enrolled into the study and treated in the past. Two of the three patients had a transient decrease in the peripheral blood blast percentage with Liposomal Grb-2. The third AML patient had more than a 90 percent blast count and did not respond to treatment at this dose level to the degree that the other two patients responded.

As a result of the favorable safety profile, the Company closed Cohort 5 of the trial and opened Cohort 6 for enrollment, in which patients will be treated at a dose of 90 mg/m2.

Bio-Path Initiates Development of Liposomal Grb-2 for Triple Negative and Inflammatory Breast Cancers

On July 22, 2013, Bio-Path announced that it is initiating preclinical testing of its lead product candidate Liposomal Grb-2 into two additional indications: triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC), two cancers characterized by formation of aggressive tumors and relatively high mortality rates.

Liposomal Grb-2
(L-Grb-2) is the Company’s lead drug candidate currently in a Phase I clinical trial. L-Grb-2 is a liposomal delivered antisense cancer drug that targets an multibillion dollar annual market for Chronic Myelogenous Leukemia (CML), Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), and Myelodysplastic Syndrome (MDS).

Grb-2 (growth factor-bound protein-2) is an adaptor protein which is essential to cancer cell signaling because it is utilized by oncogenic tyrosine kinases to induce cancer progression. Suppressing the function or expression of Grb-2 should interrupt its vital signaling function and have a therapeutic application in cancer. L-Grb-2 is a neutral-charge, liposome-incorporated antisense drug substance designed to inhibit Grb-2 expression.

Bio-Path’s plan is to develop Liposomal Grb-2 as a targeted therapy against TNBC and IBC. Treatment goals are two-pronged: the first being to develop Liposomal Grb-2 as a tumor reduction agent in combination with other approved drugs in pre-operative settings, and the second is to develop Liposomal Grb-2 as a drug to treat and control or eliminate cancer metastasis in TNBC and IBC patients. Both of these treatment goals address high need situations for patients. Following successful completion of the preclinical studies, Bio-Path expects to start a Phase I clinical trial in TNBC and IBC in 2014.

We think the development of Liposomal Grb-2 for the treatment of TNBC and IBC is a major milestone for Bio-Path that has the opportunity to produce substantial value for the Company. Successful development of these applications will be of great benefit to TNBC and IBC patients. Further, the treatment goal for tumor inhibition and reduction in a pre-operative setting providvery also points to the potential use of a liposomal antisense treatment as a standalone treatment to transform and manage a disease, which has a disease-causing protein, as a chronic disorder.

Further, the scientific proof of principle for the drug delivery technology may lead to licensing and business development opportunities for Bio-Path.

Fifth Cohort of Phase I Liposomal Grb-2 Completed

On June 6, 2013, BPTH announced that it has completed treatment of the fifth dosage cohort in its Phase I clinical trial of its lead product candidate Liposomal Grb-2.

The drug’s safety profile continues to be favorable with no treatment-related serious adverse events reported and data continues to suggest possible anti-leukemia activity.

A total of three patients were enrolled and dosed in the fifth cohort of the study. All three patients completed the 28-day treatment cycle and were evaluable. Liposomal Grb-2 is systemically delivered by intravenous injection. Patients received a dose of 60 mg/m2 twice a week for four weeks, for a total of eight doses. Preliminary results suggest that Liposomal Grb-2 at a dose of 60 mg/m2 is well tolerated.

As was the case with the four previous cohorts, there continues to be a suggestion of possible anti-leukemia activity. All three patients in this cohort were of the more proliferative AML type compared to some of the more indolent patients that have been enrolled into the study and treated in the past. Two of the three patients had a transient decrease in the peripheral blood blast percentage with Liposomal Grb-2. The third AML patient had more than a 90 percent blast count and did not respond to treatment at this dose level to the degree that the other two patients responded.

As a result of the favorable safety profile, the Company closed Cohort 5 of the trial and opened Cohort 6 for enrollment, in which patients will be treated at a dose of 90 mg/m2.

Bio-Path Initiates Development of Liposomal Grb-2 for Triple Negative and Inflammatory Breast Cancers

On July 22, 2013, Bio-Path announced that it is initiating preclinical testing of its lead product candidate Liposomal Grb-2 into two additional indications: triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC), two cancers characterized by formation of aggressive tumors and relatively high mortality rates.

Liposomal Grb-2
(L-Grb-2) is the Company’s lead drug candidate currently in a Phase I clinical trial. L-Grb-2 is a liposomal delivered antisense cancer drug that targets an multibillion dollar annual market for Chronic Myelogenous Leukemia (CML), Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), and Myelodysplastic Syndrome (MDS).

Grb-2 (growth factor-bound protein-2) is an adaptor protein which is essential to cancer cell signaling because it is utilized by oncogenic tyrosine kinases to induce cancer progression. Suppressing the function or expression of Grb-2 should interrupt its vital signaling function and have a therapeutic application in cancer. L-Grb-2 is a neutral-charge, liposome-incorporated antisense drug substance designed to inhibit Grb-2 expression.

Bio-Path’s plan is to develop Liposomal Grb-2 as a targeted therapy against TNBC and IBC. Treatment goals are two-pronged: the first being to develop Liposomal Grb-2 as a tumor reduction agent in combination with other approved drugs in pre-operative settings, and the second is to develop Liposomal Grb-2 as a drug to treat and control or eliminate cancer metastasis in TNBC and IBC patients. Both of these treatment goals address high need situations for patients. Following successful completion of the preclinical studies, Bio-Path expects to start a Phase I clinical trial in TNBC and IBC in 2014.

We think the development of Liposomal Grb-2 for the treatment of TNBC and IBC is a major milestone for Bio-Path that has the opportunity to produce substantial value for the Company. Successful development of these applications will be of great benefit to TNBC and IBC patients. Further, the treatment goal for tumor inhibition and reduction in a pre-operative setting provides a potential pathway for rapid approval by the FDA of Liposomal Grb-2, while the longer term effects of controlling or eliminating metastasis will build long term use of our drug.

The new development of L-Grb-2 also expands Bio-Path’s pipeline.

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  Bio-Path Report

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