24
OCTOBER, 2007
NOVOGEN
NV-128 INDUCES NOVEL MODE OF CELL DEATH IN CANCER CELLS
(San
Francisco – 24 October) - Laboratory studies presented late yesterday at the
annual AACR/EORTC/NCI Molecular Targets and Cancer Therapeutics conference,
demonstrate that the Novogen drug candidate NV-128 induces autophagy, a novel
mode of cell death in multi-drug resistant ovarian cancer cells. The data
were
presented by Gil Mor, MD, Associate Professor, Department of Obstetrics and
Gynecology, Yale University School of Medicine.
NV-128
is
a derivative of phenoxodiol, an investigational drug licensed by Novogen
Limited
(ASX: NRT NASDAQ: NVGN) to Marshall Edwards, Inc. (NASDAQ: MSHL) that
is now in Phase III clinical development for patients with late stage ovarian
cancer.
Whereas
phenoxodiol induces caspase-mediated apoptosis, which is often non-functional
in
highly chemoresistant cancer cells due to highly over-expressed anti-apoptotic
proteins, NV-128 has been shown to induce caspase-independent DNA degradation
and cancer cell death.
“The
identification of a compound that is able to invoke cancer cell death via
a
pathway that is not compromised in highly chemoresistant ovarian cancer cells,
and not reliant on combination therapy with cytotoxic drugs has the potential
to
provide a significant benefit for treating late stage ovarian cancer patients
for whom there are limited treatment options,” said Dr. Mor.
Importantly,
these data demonstrate that the Novogen proprietary molecular scaffold can
be
synthetically modified to yield new molecules that are biologically active,
and
have the potential for diverse application in the clinic. Another
phenoxodiol derivative, NV-196 is also being developed under license to Marshall
Edwards, Inc., as a therapy for late stage chemoresistant pancreatic and
bile
duct cancers. NV -128 is the next drug candidate being developed from
the Novogen technology platform. This portfolio of oncology drugs
will become available for licensing to Marshall Edwards, Inc. when each drug
enters human clinical trials, under the “first right and last right” option
agreement held by Marshall Edwards, Inc.
Multinational
Trial Underway
Phenoxodiol
in combination with carboplatin is currently being studied
in
a multi-national Phase III clinical trial called the
OVATURE (
OVA
rian
TU
mor
RE
sponse) Trial, following positive findings of previous trials
conducted in Australia and at Yale-New Haven Hospital. The OVATURE
trial is taking place at up to 60 clinical sites in the United States, Europe,
and Australia. Preliminary results from the trial are expected within
18 months. For more information on the trial, visit
www.OVATUREtrial.com
.
About
phenoxodiol and NV-128:
Phenoxodiol
is being developed as a therapy for late-stage, chemo-resistant prostate,
ovarian and cervical cancers. Phenoxodiol is an investigational drug
and, as such, is not commercially available. It is a novel-acting
drug that inhibits key pro-survival signalling pathways operating via
sphingosine-1-phosphate and Akt. Inhibition of these pathways leads
to prevention of phosphorylation of key anti-apoptotic proteins such as
XIAP. Loss of activity of these proteins restores the ability of
chemoresistant tumour cells to undergo apoptosis in response to
chemotherapy. The putative molecular target for phenoxodiol is a
tumour-specific protein, accounting for the highly selective nature of the
drug.
In
contrast to phenoxodiol, NV-128 has been shown to induce caspase-independent
DNA
degradation and cancer cell death via a pathway involving pAKT down-regulation,
LC3 cleavage to LC3-II, and the translocation of Beclin to the mitochondria
resulting in Bcl2 inactivation and nuclear translocation of
EndoG. This offers an opportunity for use as a monotherapy in
chemoresistant cancers and enhanced efficacy against cancer targets less
susceptible to phenoxodiol. The option for co-administration of both
drugs is also under investigation to extend the potential therapeutic range
of
this unique class of oncology compounds.
About
Novogen and Marshall Edwards, Inc.
Novogen
is an Australian based biotechnology company in the business of research
and
development of drugs derived from its phenolic technology platform. The Company
manages its research and development programs using the expertise and clinical
research capabilities of universities and hospitals in Australia, the US
and
Europe. Novogen's drug program is researching and developing compounds for
the
treatment of cancer, cardiovascular disease, inflammatory bowel disease and
osteoarthritis. To date Novogen has had 77 patents granted and a further
230
patents are pending.
Novogen
is the world leader in isoflavone research. From its original technology
platform of natural isoflavones (represented in OTC products such as Promensil)
the Company has developed a discovery program surrounding novel chemical
entities based on a flavonoid scaffold. One of these compounds, phenoxodiol,
is
currently in a Phase III clinical trial for treatment of late stage ovarian
cancer and a Phase II trial for prostate cancer. Marshall Edwards, Inc. is
majority owned by Novogen Limited, and has licensed rights from Novogen to
bring
three oncology drugs – phenoxodiol, NV-196 and NV-143 – to market
globally.
More
information on phenoxodiol and on the Novogen group of companies can be found
at
www.marshalledwardsinc.com
and
www.novogen.com
.
Under
U.S. law, a new drug cannot be marketed until it has been investigated in
clinical trials and approved by the FDA as being safe and effective for the
intended use. Statements included in this press release that are not historical
in nature are "forward-looking statements" within the meaning of the "safe
harbor" provisions of the Private Securities Litigation Reform Act of 1995.
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should be aware that our actual results could differ materially from those
contained in the forward-looking statements, which are based on management's
current expectations and are subject to a number of risks and uncertainties,
including, but not limited to, our failure to successfully commercialize
our
product candidates; costs and delays in the development and/or FDA approval,
or
the failure to obtain such approval, of our product candidates; uncertainties
in
clinical trial results; our inability to maintain or enter into, and the
risks
resulting from our dependence upon, collaboration or contractual arrangements
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to
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market
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