Contact Information: CONTACT: Prof. Alan Husband +61 2 9878 0088 David Sheon 202 547 2880
Triphendiol Safety Data Clears the Way for Compound to Be Studied Further in the Treatment of Pancreatic Cancer
AACR Abstract # 5101; Poster Presentation, 4/22, 8 am - Noon
| Source: Marshall Edwards, Inc.
NEW CANAAN, CT--(Marketwire - March 18, 2009) - Marshall Edwards, Inc. (NASDAQ : MSHL ). An
abstract titled "Pre-clinical Toxicology of Triphendiol (NV-196)" will be
presented at the Annual Meeting of the American Association for Cancer
Research, April 18-22 in Denver, showing that triphendiol has an acceptable
toxicity profile in animals. To view the abstract online, click here.
Triphendiol was granted orphan drug status by the U.S. Food and Drug
Administration for pancreatic cancer and cholangiocarcinoma in January
2008, and for treatment of stage IIb-IV malignant melanoma in February
2008. In January of 2009, triphendiol was granted an Investigative New
Drug (IND) approval by the United States Food and Drug Administration to
undertake clinical studies with triphendiol as a chemosensitizing agent in
combination with gemcitabine.
The abstract, to be presented by Dr. Wasif Saif, Associate Professor and
Co-Director, Yale Cancer Center Gastrointestinal Cancers Program, Yale
University School of Medicine, summarizes data from a number of preclinical
studies performed in order to obtain data to support the IND filing. In in
vitro studies, triphendiol was non-mutagenic in the bacterial reverse
mutation assay (Ames test) and non-clastogenic in the mouse erythrocyte
micronucleus assay. Studies in animals indicated not only acceptable
pharmacokinetics, but also no accumulation of triphendiol when administered
to animals in repeated doses. Also there were no toxicologically important
changes in clinical signs, body weights, hematology, coagulation time,
serum chemistry, urinalysis, gross observations, organ weights or
histologic findings for any study animal. There were no significant
changes to heart rate and the Q-T segment interval indicating a lack of
cardiovascular toxicity.
There is an urgent need for new pancreatic cancer treatments because fewer
than 20 percent of patients are candidates for surgery (pancreatectomy).
Current treatment is limited to chemotherapy with gemcitabine, to which
most patients are resistant or acquire resistance. A study presented at
AACR's 2008 Annual Meeting assessed the potential of triphendiol as a
treatment for pancreatic adenocarcinoma, using three representative cell
lines. Triphendiol induced apoptosis (cell death) in all cell lines and
pre-treatment with triphendiol increased gemcitabine-dependent apoptosis.
Animal model studies showed that triphendiol in combination with
gemcitabine inhibits tumor growth more effectively than each drug alone.
Both triphendiol and gemcitabine induce apoptosis via a mitochondrial
pathway.
Laboratory testing in vitro and in animals bearing human pancreatic and
bile duct tumors has demonstrated selective activity of triphendiol against
cancer cells. In mice bearing a human pancreatic cancer tumor, triphendiol
administration resulted in a mean reduction in tumor volume by 62 percent
compared with untreated control animals. In the two Phase I clinical
studies completed thus far, the investigational drug has demonstrated
acceptable pharmacokinetic profiles in human volunteers with no reported
side effects.
Professor Alan Husband, Group Director of Research for Marshall Edwards,
said, "This study is further evidence that triphendiol has an acceptable
toxicity profile. This creates a strong foundation for our clinical
development program for triphendiol as a safer multipotent anti-cancer
agent than current treatments for pancreatic and bile duct cancers."
"We are hopeful that triphendiol will continue to show benefit in unusually
aggressive and difficult-to-treat diseases such as pancreatic cancer,"
Professor Husband said.
Pancreatic cancer is considered an "orphan" cancer, because of its
relatively low incidence and high mortality. It is slightly more common in
men than in women. In the U.S., it is the fourth leading cause of
cancer-related death in men and the fifth leading cause of cancer-related
deaths in women with a death rate estimated by the National Cancer
Institute of approximately 96 percent of patients with the disease. The
estimated number of new cases of pancreatic cancer in the U.S. in 2008 is
37,680, with 34,290 deaths caused by the disease according to the National
Cancer Institute. Pancreatic cancer has a poor prognosis. The disease is
difficult to diagnose in its early stage, and patients usually present with
incurable disease. It has a high mortality rate, and no therapy has been
shown to significantly impact survival.
About Triphendiol
Triphendiol (NV-196) is another investigational drug in the Marshall
Edwards, Inc., oncology drug pipeline, currently being developed as an
orally-delivered chemosensitizing agent, intended for use in conjunction
with standard chemotoxic anti-cancer drugs for the treatment of late stage
pancreatic cancer, cholangiocarcinoma, and melanoma. Triphendiol is broadly
cytostatic and cytotoxic against most forms of human cancer cells in vitro,
and has been shown to cause cell cycle arrest (or stop cells increasing in
number) and to induce apoptosis (or initiate programmed cell death) in
various cancer cell lines.
Biological studies suggest a mechanism of cytotoxicity that involves
mitochondrial depolarization and down-regulation of XIAP. It exhibits high
selectivity, little effect on non-tumor cells and no observable toxicity in
animals at therapeutically effective doses. In human studies conducted so
far, no adverse events or side effects have been reported when administered
to volunteers.
About Marshall Edwards, Inc. and Novogen Limited
Marshall Edwards, Inc. is a specialist oncology company focused on the
clinical development of novel anti-cancer therapeutics. These derive from a
flavonoid technology platform that has generated a number of novel
compounds characterized by broad ranging activity in laboratory testing
against a range of cancer targets with few side effects. The ability of
these compounds to target an enzyme present on the surface of cancer cells,
and inhibit the production of pro-survival proteins within the cancer cell
suggests that they may possess a unique combination of efficacy and safety.
Marshall Edwards, Inc. has licensed rights from Novogen Limited (ASX : NRT )
(NASDAQ : NVGN ) to bring three oncology drugs -- phenoxodiol, triphendiol
(NV-196) and NV-143 -- to market globally. Marshall Edwards, Inc. is
majority owned by Novogen, an Australian biotechnology company that is
specializing in the development of therapeutics based on a flavonoid
technology platform. Novogen, based in Sydney, Australia, is developing a
range of oncology therapeutics from its proprietary flavonoid synthetic
chemistry technology platform. More information on phenoxodiol, triphendiol
and on the Novogen group of companies can be found at
www.marshalledwardsinc.com and www.novogen.com.
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