Bezielle^® for the Treatment of Pancreatic Cancer

Background

Pancreatic cancer is the fourth leading cause of cancer death in the United States and every year, over 30,000 people will be diagnosed with the disease. Men and women diagnosed with pancreatic cancer typically have a poor prognosis since the cancer usually causes no symptoms in its earliest phase leading to metastatic disease at the time of diagnosis. As a result, the five year survival rate for persons diagnosed with pancreatic cancer is 4% and the median survival period from diagnosis is approximately 3 to 6 months. Currently, there are only two FDA-approved pharmacological agents for the treatment of pancreatic cancer. Bionovo recognizes that more effective therapies, with fewer toxicities, are urgently needed to treat pancreatic cancer.

Mechanism of Action

Bezielle is an oral drug designed for the treatment of advanced breast cancer with a novel mechanism of action. Bezielle targets diseased cells while leaving normal cells healthy and intact. Normal cells depend primarily on the citric acid cycle (>85%) and very little on glycolysis (<7%) for energy production. In contrast, cancer cells depend largely on glycolysis (>85%) for energy production. Bezielle induces strong oxidative stress in cancer cells leading to severe DNA damage, but in normal cells the effect is blunted due to their different metabolic profile.  Cancer cells attempt but ultimately fail to repair DNA damage that results in the inhibition of glycolysis  and cancer cell death while normal cells remain unharmed.

Selective Cytotoxic Activity

Bezielle is selectively cytotoxic to most of twelve breast cancer cell lines examined, as well as to a number of cancer cell lines of different tissue origins such as prostate, lung, colon and pancreatic cancers. At the same dose, Bezielle does not induce appreciable cell death in normal cells such as fibroblasts and normal mammary epithelial cells and lines. Bezielle was also orally active in preventing tumor formation in a mouse xenograph model.

Next Steps: Phase 1/2 Clinical Trial

Bionovo intends to submit an Investigational New Drug (IND) application to the FDA for Bezielle to initiate a Phase 1/2, open-label, non-randomized, dose escalation trial to assess the safety and preliminary efficacy of Bezielle for the treatment of pancreatic cancer.