NEW CANAAN, CT and SYDNEY, AUSTRALIA--(Marketwire - October 30, 2008) - Pre-clinical studies presented at the 9th International Conference on Membrane Redox Systems in Wellington New Zealand this week demonstrate that Novogen's NV-128 (a novel mTOR inhibitor), when used in combination with the Marshall Edwards, Inc.'s Phase III anti-ovarian cancer drug, phenoxodiol, produces potent synergistic anti-cancer activity against non-small cell lung carcinoma cell lines (NSCLC). Importantly, the synergistic cytotoxicity observed between NV-128 and phenoxodiol was superior to the synergy observed between NV-128 and paclitaxel against NSCLC. These data were presented by Dr. David Brown, Program Manager (Cancer Biology), Novogen.
"In NSCLC targets, these two drugs in combination produced an anti-cancer effect superior to that achieved with either drug alone or in combination with current approved anti-cancer cytotoxic drugs. The potential for improved efficacy, coupled with the safety profile of these novel drugs, suggests the potential for clinical benefits in lung cancer patients which cannot be achieved with current standard of care drugs," Dr. Brown said.
Phenoxodiol is being developed as a therapy for late-stage, chemoresistant prostate and ovarian cancers. It is a novel-acting drug that inhibits key pro-survival signaling 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 and FLIPs. Loss of activity of these proteins restores the ability of chemoresistant tumor cells to undergo caspase-mediated apoptosis in response to chemotherapy. The putative molecular target for phenoxodiol is a surface oxidase which is preferentially expressed on cancer cells and is linked to the expression of pro-survival pathways in these cells. The ability of the drug to bind preferentially to cancer cells rather than normal cells is reflected in its high safety profile in clinical use.
In contrast to phenoxodiol, NV-128 does not induce caspase-mediated apoptosis, a death mechanism which is often non-functional in chemoresistant cancer cells due to accumulated mutations in tumor suppressor/promoter genes and over-expression of anti-apoptotic proteins. Rather, NV-128 uncouples the akt-mTOR-P70S6K signal transduction cascade which has a key role in driving protein translation and uncontrolled cancer cell proliferation. Further, NV-128 induces mitochondrial depolarization via a novel pathway involving the autophagy protein Beclin-1 and Bcl-2, thereby resulting in endonuclease G translocation to the nucleus and cell death. Importantly, when NV-128 is used in combination with phenoxodiol, XIAP is degraded in these cells allowing the caspase-mediated apoptosis cascade to be engaged in addition to NV-128-endonuclease G mediated apoptosis resulting in two pathways to cell death.
"These data provide direct evidence that while invoking discrete modes of cell death, NV-128 and phenoxodiol can be used synergistically to force the convergence of caspase-mediated and caspase-independent cell death pathways to drive overall cell death," said Dr. Brown.
About Novogen Limited:
Novogen Limited (
About Marshall Edwards, Inc:
Marshall Edwards, Inc. (
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. You 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 necessary for the development, manufacture, commercialization, marketing, sales and distribution of any products; competitive factors; our inability to protect our patents or proprietary rights and obtain necessary rights to third party patents and intellectual property to operate our business; our inability to operate our business without infringing the patents and proprietary rights of others; general economic conditions; the failure of any products to gain market acceptance; our inability to obtain any additional required financing; technological changes; government regulation; changes in industry practice; and one-time events. We do not intend to update any of these factors or to publicly announce the results of any revisions to these forward-looking statements.
Contact Information: Contacts: David Sheon 202 422-6999 Christopher Naughton 011 61 2 9878 0088