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more on Scutellaria barbata derived new drug for Stage IV
BZL101
BZL101 is a compound that induces apoptosis through mitochondrial transmembrane potentiation. Specifically it translocates the AIF1 protein into the nucleus of the cell, causes chromatin condensation and DNA degradation and leads to the cell's death. BZL101 is an oral drug designed for the treatment of breast and ovarian cancer that targets only diseased cells but leaves the normal cells intact and functioning.
There are currently no effective therapeutic cures for advanced breast cancer and treatment is primarily aimed at palliation of symptoms as well as improving overall survival. Breast cancer is the second leading cause of cancer death with over 200,000 new cases per year. Although survival after breast cancer treatments is improving, there are still over 40,000 deaths per year due to breast cancer.
The annual market for drugs targeted at this disease is estimated at $2 billion and growing.
Bionovo has two anti-cancer drugs in development, one for metastatic breast cancer and one for ovarian cancer. Both are being developed to initiate apoptosis, cell death, of the cancerous cells while leaving normal cells unaffected.
The company's lead cancer candidate, BZL101, received an IND and entered Phase 1 clinical testing rapidly due to its presumed favorable safety profile. Early data from a Phase 1 clinical trial of BZL101 conducted at the University of California, San Francisco indicate the drug is well tolerated and safe for use.
Antiproliferative Activity
BZL101 was evaluated for antiproliferative activity on five breast cancer cell lines (SK-BR-3, MCF7, MDA-MB-231, BT-474, and MCNeuA). BZL101 showed >50% growth inhibition on a panel of lung, prostate and pancreatic cancer cell lines. BZL101 at the same dose did not cause >25% of growth inhibition on normal human mammary cells (HuMEC), demonstrating selectivity to cancer cells (Table 1). BZL101 was also orally active in preventing tumor formation in a mouse xenograph model.
note:Table 1 did not seem to copy but of the two her2+ cell lines looked at
BT-474 was + and SKBR3 was ++
Table 1. In vitro growth inhibitory effect of BZL101. 1:10 dilution- < 50% inhibition, + 51-75% inhibition, ++ >75% inhibition. BZL is active on all cancer cell lines but is not active on human mammary epithelial cells.
Phase 1 Program
In a Phase 1 clinical trial in women with advanced breast cancer, BZL101 was taken with high compliance and showed no serious adverse effects. The trial was conducted at the University of California, San Francisco and the Cancer Research Network in Miami, Florida.
Phase 2 Program
A multi-center, Phase 1/2, open-label, non-randomized, dose escalation trial to assess safety, feasibility, optimal dosing and preliminary efficacy of BZL101 for the treatment of metastatic breast cancer will be conducted under the directorship of Dr. Debu Tripathy at the University of Texas, Southwestern. Participants will be approximately 60 women with histologically confirmed breast cancer and measurable stage IV disease. The primary outcome measure will be response to therapy evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST). Secondary measures of efficacy will include: duration of overall objective response, progression free survival, overall survival, and patient reported quality of life measures. Recruitment for the clinical trial will take place at 10 clinical sites throughout the United States.
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