New Research Builds on PBI-05204's Potential for Glioblastoma Cancer Treatment

New research findings presented in November at the Italian Cancer Society's 61^st annual meeting in Naples, Italy confirm the ability of Phoenix Biotechnology's (PBI) (www.phoenixbiotechnology.com) drug PBI-05204 to act synergistically with coadministration of temozolamide and radiotherapy to kill Glioblastoma Multiforme (GBM) in mice with orthotopically implanted human GBM cells. These data are currently being prepared for publication.

The new research results are the latest in a series of evidence in support of PBI-05204, PBI's lead anticancer drug derived from Nerium oleander, as a potential treatment for GBM, according to Robert A. Newman, Ph.D., Phoenix Biotechnology's President and Chief Science Officer. The American Brain Tumor Association reports that GBM kills more than 16,000 people each year in this country. Both Senator John McCain and Senator Edward Kennedy died from complications of GBM.

The Italian research, conducted through the University of L'Aquila, shows an ability of PBI-05204 to synergistically interact with standard of care chemotherapy (temozolamide) and radiotherapy in extending the life of mice with human GBM, according to Dr. Claudio Festuccia, the lead investigator of the project.

GBM is the most common glial brain tumor and results in extremely low patient survival. A better understanding of GBM biology has recently shown some of the important reasons why current new drugs fail to produce major tumor responses, Newman said.

These include, for example, inabilities of a drug (1) to gain access to malignant tissue across the blood barrier, (2) to selectively target only malignant cells, (3) to eliminate GBM stem cells, (4) to induce the synthesis of brain derived neurotrophic factor (BDNF) recently shown to be important for a meaningful GBM response and (5) to interact in a synergistic manner with currently used standard of care therapeutic strategies, he said. In addition to these criteria, an ideal drug would also be orally bioavailable.

"Recent data from research with PBI-05204, a modified supercritical extract of Nerium oleander, has shown that it can meet each of these challenges," Newman said. "Data from Phoenix Biotechnology as well as Duke University have shown the facile ability of oleandrin, an important API within PBI-05204, to cross the blood brain barrier following oral administration to mice."^1-3

"Once in the brain, PBI-05204 induces the synthesis of brain derived neurotrophic factor (BDNF), something which very few other drugs have been able to do," he said.⁴ "PBI's lead drug also represents targeted delivery against malignant cells through their selective expression of a particular subunit of Na, K-ATPase."^5-6

"Very recent and exciting research which is also being prepared for publication has shown that PBI-05204 is very potent in elimination of human GBM stem cells, possibly eliminating the recurrence of tumor after therapy," Newman continued, noting that other scientific investigators from Istanbul, Turkey and Pozzilli, Italy have suggested that oleandrin represents a new approach to brain cancer therapy.^7-8

PBI-05204 is the only patented drug containing oleandrin that has been through Phase I and Phase II clinical cancer trials in the United States.

About Phoenix Biotechnology, Inc.

Phoenix Biotechnology, Inc., a San Antonio, Texas-based biotechnology company, was incorporated in Texas in 2003 to develop promising agents with minimal or no side effects for targeted therapy of malignant tumor growth and other life-threatening diseases.

References cited.

1. Murine pharmacokinetics and metabolism of oleandrin, a cytotoxic component of Nerium oleander. J. Exp Ther Oncol 2002 Sep-Oct; 2(5): 278-85.
2. In vitro and in vivo neuroprotective activity of the cardiac glycoside oleandrin from Nerium oleander in brain sliced-based stroke models. J. Neurochem 2011; 119(4):805-14
3. BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin. J. Neurosci 2014; 34(3): 963-8.
4. Cellular location and expression of Na, K-ATPase alpha subunits affect anti-proliferative activity of oleandrin. Mol Carcinog. 2014; 53(4):253-63.
5. Human tumor cell sensitivity to oleandrin is dependent on relative expression of Na, K-ATPase subunits. J. Exp. Ther. Oncol/ 2010; 8(4):271-86.
6. Oleandrin-mediated inhibition of human tumor cell proliferation: Importance of Na, K-ATPase alpha subunits as drug targets. Mol Cancer Ther 2009; 8(8): 2319-28.
7. Neuroprotective and tumoricidal activities of cardiac glycosides. Could oleandrin be new weapon against stroke and glioblastoma? Int. J. Neurosci. 2018; 128(9): 865-877. The glycoside oleandrin reduces glioma growth with direct and indirect effects on tumor cells. J. Neurosci 2017; 37(14): 3926-3939.
8. The glycoside oleandrin reduces glioma growth with direct and indirect effects on tumor cells. J. Neurosci 2017; 37(14): 3926-3939.