BONITA SPRINGS, Fla., April 30 /PRNewswire/ -- Tigris Pharmaceuticals, Inc., a privately held drug development company, announced that preclinical data were presented on its novel molecule, AFP-464, during the recent AACR 100th Annual Meeting 2009 in Denver. “This research represents a significant advancement in the treatment of Triple Negative Breast Cancer, one of the most aggressive forms of invasive breast cancer,” stated Edmundo Muniz, M.D., Ph.D., President and Chief Executive Officer of Tigris.
Sponsored by Tigris, the research was led by Angelika Burger, Ph.D., director of the Translational Research Laboratory at the Barbara Ann Karmanos Cancer Institute and professor of Pharmacology at Wayne State University School of Medicine in Detroit. The research found that the luminal (ER-positive) and the triple negative (ER, PR, and HER-2 negative) breast cancer cell lines with the basal A gene profile subtype were very sensitive to AFP-464, while the triple negative cell lines with the basal B subtype were not. However, when the latter was pre-treated with a histone deacetylase inhibitor, such as the suberoylanilide hydroxamic acid (SAHA), also known as vorinostat (Zolinza(R), Merck & Co. Inc.), the cells became very sensitive to AFP-464. The mechanism in which this is achieved is believed to be the de-silencing of ER expression by the histone deacetylase inhibitor, followed by CYP1A1 induction and subsequent AFP metabolism into active species that covalently bind to DNA in these cancer cells and cause specific cell death.
Dr. Burger said the findings offer particular hope to those women battling triple-negative breast cancer. “We could now find a way to treat every kind of invasive, metastatic breast cancer, the ER-positive and ER-negative types with AFP-464,” said Dr. Burger. “The synergism between AFP-464 and vorinostat in the triple negative breast cancer cell lines is very impressive.”
AFP464 is nearing completion of Phase I clinical testing at Jules Bordet Institute in Belgium, Institut Gustav Roussy in Paris, Mayo Clinic in Rochester, Minnesota, Karmanos Cancer Institute in Detroit and University of Maryland Marlene and Stewart Greenebaum Cancer Center in Baltimore. Tigris Pharmaceuticals expects to soon move to Phase II clinical studies, including studies in triple-negative breast cancer patients with the drug alone or in combination with vorinostat, depending on the molecular gene profile subtypes of the patients. Triple-negative breast cancer afflicts mostly young women under the age of 40 and is more prevalent in the African-American and Hispanic community. About 182,460 women in the United States were diagnosed with invasive breast cancer in 2008, approximately 15-18% of which are triple negative, and about 40,480 will die from the disease, according to the American Cancer Society.
“Patients with triple negative breast cancer do not benefit from endocrine therapy or molecularly targeted therapy such as trastuzumab because they lack the targets for these drugs,” said Dr. Binh Nguyen, M.D., Ph.D., Chief Medical Officer of Tigris. “The potential of using molecular gene profile to target the appropriate patient population that most likely could benefit from the treatment with AFP-464 is the right direction in the clinical development of this difficult to treat disease.”
About AFP-464
AFP-464, a Lysol prodrug of aminoflavone (AF), undergoes rapid conversion to AF by nonspecific plasma esterases. It has shown a unique pattern of growth inhibitory activity in the NCI’s 60 tumor cell line screen, with breast, ovarian, lung and renal lines exhibiting particular sensitivity. The mechanism of action of AF is believed to be that treatment with AF results in translocation of the arylhydrocarbon receptor (AhR; a transcriptional regulator of CYP1A1) from the cytoplasm to the nucleus, and its subsequent interaction with the xenobiotic-response element (XRE) sequence on the CYP1A1 promoter region, causing induction of CYP1A1 transcription. This enzyme expression converts AF to metabolites that are covalently bound to DNA. This results in phosphorylation of p53 with induction of the p53 downstream target p21Waf1/Cip1 and apotosis.
About Tigris Pharmaceuticals, Inc.
Tigris Pharmaceuticals, Inc. is a privately held biopharmaceutical company that develops therapeutic technologies, using a translational research approach, for use in oncology and other areas of unmet medical need. Tigris’ mission is to efficiently move its existing and future technologies through the various stages of clinical development in order to meet patients’ needs for safe and effective treatments of human illnesses.
About the Barbara Ann Karmanos Cancer Institute
Located in mid-town Detroit, Michigan, the Barbara Ann Karmanos Cancer Institute is one of 40 National Cancer Institute-designated comprehensive cancer centers in the United States. Caring for more than 6,000 new patients annually on a budget of $216 million, conducting more than 700 cancer-specific scientific investigation programs and clinical trials, the Karmanos Cancer Institute is among the nation’s best cancer centers. Through the commitment of 1,000 staff, including nearly 300 faculty members, and supported by thousands of volunteer and financial donors, the Institute strives to prevent, detect and eradicate all forms of cancer. For more information call 1-800-KARMANOS or go to www.karmanos.org.
This news release contains forward-looking statements that involve risks and uncertainties that could cause our actual results and experiences to differ materially from anticipated results and expectations expressed in such forward-looking statement. These forward-looking statements include, without limitation, statements regarding the mechanism of action of AFP-464, its potential advantages, its potential for use in treating cancer, as well as the timing, progress and anticipated results of the clinical development and regulatory processes concerning AFP-464. These statements are based on our current beliefs and expectations as to such future outcomes, and are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. Factors that might cause such a material difference include, among others, risks that the results of clinical trials will not support our claims or beliefs concerning the effectiveness of AFP-464, our ability to finance our development of AFP-464, regulatory risks, and our reliance on third party researchers and other collaborators. We assume no obligation to update these statements, except as required by law.
CONTACT: Anne White, Chief Operating Officer, Tigris Pharmaceuticals,
Inc., +1-239-444-5400, info@tigrispharma.com,
Web site: http://www.tigrispharma.com/
