Early Study Provides Evidence That Investigational Drug Phenoxodiol Targets Prostate Cancer Protein

A new study demonstrates that the investigational drug, phenoxodiol, may be effective in the treatment of prostate cancer through its ability to target a protein that appears to be selective for prostate cancer cells. Prostate cancer is one of the most serious and common types of cancer found in American men, killing more than 30,000 men in the U.S. every year.

In a new study, a research group headed by James Morre, Ph.D., professor of medicinal chemistry at Purdue University, obtained results supporting that phenoxodiol specifically targets a protein on prostate cancer cells known as tNOX 75 alpha.

The Purdue team has identified the protein, tumor-associated NADH oxidase (or tNOX), as a pan-cancer marker. The protein is critical to the ability of the tumor cell to grow and to survive. They also have shown that there are different forms of this protein, known as isoforms, and that different tNOX isoforms are associated with different forms of cancer.

The team has demonstrated previously that tNOX is the primary molecular target for phenoxodiol. The 75 alpha protein appears to be the particular tNOX isoform found in prostate cancer patients, and that is one of the isoforms targeted by phenoxodiol.

Prostate specific antigen (PSA) is another protein found exclusively on prostate cancer cells, and is used widely to diagnose prostate cancer and to determine response to therapy. However, no anti-cancer drug specifically targets PSA because the protein is not essential to tumor cell survival, so it is not a universally reliable marker of the efficacy of a particular drug. tNOX is essential for tumor cell survival, making it an excellent target for anti-cancer drug activity.

When phenoxodiol binds to tNOX, the protein is inhibited, blocking the cell from dividing, and switching off a variety of pro-survival signaling mechanisms within the cell. Where this inhibition reaches a certain level, the cell dies; where it is below a lethal level, the cell is blocked from dividing.

Results of the study, which involved 19 patients with late-stage, hormone- refractory prostate cancer, were presented today at the International Conference on Molecular Diagnostics in Cancer Therapeutics, held September 12th to the 15th by the American Association of Cancer Research.

In the clinical study, phenoxodiol was administered orally three times daily until patients showed disease progression. Blood samples were obtained prior to treatment, after two months of treatment, and at the completion of the schedule. All 19 patients had tNOX 75 alpha in their bloodstream; it has not been found in patients without evidence of cancer.

Blood analysis revealed that tNOX 75 alpha levels responded to administration of phenoxodiol in 11 of the 19 patients.

"The study demonstrates a clear association between tNOX 75 alpha levels, prostate cancer, and response to phenoxodiol therapy," says Graham Kelly Ph.D., Chairman of Marshall Edwards Inc., the company developing phenoxodiol. "In the study, tNOX 75alpha levels fell as the dosage of phenoxodiol increased, and patients responded by slowing down the rate of tumor growth. This supports that tNOX is the target for phenoxodiol, and that inhibition of this protein is an exciting new approach to the treatment of cancer."

About Prostate Cancer

According to data provided by the American Cancer Society (ACS), prostate cancer is one of the most common types of cancer found in American men, second only to skin cancer. ACS estimates that there will be more than 232,000 new cases of prostate cancer in the United States in 2005 and about 30,350 men will die of this disease. One man in six will get prostate cancer during his lifetime, and one in 34 will die of the disease.

Most cases of prostate cancer are sensitive to male sex hormones (androgen), and blocking the effect of these hormones is a common therapeutic process. Ultimately, however, most prostate cancers become insensitive to androgens, at which time the tumor is referred to as being hormone-refractory. The approved anti-tumor therapy for these patients is docetaxel (Taxotere(R)), which has been shown to provide a modest extension of survival in some patients, before the tumors become docetaxel-refractory. Hormone-refractory, docetaxel refractory patients represent the end-stage of this disease.

About Phenoxodiol

Phenoxodiol is being developed as a therapy for late-stage, chemo- resistant prostate, ovarian and cervical cancers.

Phenoxodiol targets the tNOX protein, which regulates a number of vital cell functions, including a hydrogen excretion pump. Inhibition of tNOX leads to inhibition of this pump and loss of the cell's redox potential, producing a generalized biochemical disruption including inhibition of phosphorylation of the key pro-survival sphingosine-1-phosphate and Akt signaling pathways. Inhibition of production of anti-apoptotic proteins including XIAP is a key biochemical outcome.

The mechanism of action of phenoxodiol suggests a potential to be used both as a single-agent therapy and in combination with standard anti-cancer drugs where it acts to enhance the efficacy of those drugs in chemo-sensitive patients and to restore sensitivity to those drugs in chemo-resistant patients. Phenoxodiol currently is undergoing clinical studies in the US and Australia.

Phenoxodiol is an investigational drug and, as such, is not marketed in the US.

More information about phenoxodiol can be found at http://www.phenoxodiol.com.

About Marshall Edwards, Inc.

Marshall Edwards, Inc., (Nasdaq: MSHL) has licensed rights to bring phenoxodiol to market globally from its parent company, Novogen Limited. (ASX: NRT)(Nasdaq: NVGN). Novogen is developing a range of therapeutics across the fields of oncology, cardiovascular disease and inflammatory diseases based on its phenolic drug technology platform. More information on the Novogen group of companies can be found at http://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. 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 arty 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.

Marshall Edwards, Inc.
http://www.novogen.com
http://www.phenoxodiol.com