Novogen NV-128 Induces Novel Mode of Cell Death in Cancer Cells

NV-128 is a derivative of phenoxodiol, an investigationaldrug licensed byNovogen (NasdaqGM: - ) to Marshall Edwards, Inc. (NasdaqGM: - ) that is nowin Phase III clinical development for patients with latestage ovariancancer.

Whereas phenoxodiol induces caspase-mediated apoptosis,which is oftennon-functional in highly chemoresistant cancer cells dueto highlyover-expressed anti-apoptotic proteins, NV-128 has beenshown to inducecaspase-independent DNA degradation and cancer cell death.

"The identification of a compound that is able to invokecancer cell deathvia a pathway that is not compromised in highly chemoresistantovariancancer cells, and not reliant on combination therapy withcytotoxic drugshas the potential to provide a significant benefit for treatinglate stageovarian cancer patients for whom there are limited treatmentoptions," saidDr. Mor.

Importantly, these data demonstrate that the Novogen proprietarymolecularscaffold can be synthetically modified to yield new moleculesthat arebiologically active, and have the potential for diverseapplication in theclinic. Another phenoxodiol derivative, NV-196 is also beingdevelopedunder license to Marshall Edwards, Inc., as a therapy forlate stagechemoresistant pancreatic and bile duct cancers. NV-128is the next drugcandidate being developed from the Novogen technology platform.Thisportfolio of oncology drugs will become available for licensingto MarshallEdwards, Inc. when each drug enters human clinical trials,under the "firstright and last right" option agreement held by MarshallEdwards, Inc.

Multinational Trial Underway

Phenoxodiol in combination with carboplatin is currentlybeing studied in amulti-national Phase III clinical trial called the OVATURE(OVArian TUmorREsponse) Trial, following positive findings of previoustrials conductedin Australia and at Yale-New Haven Hospital. The OVATUREtrial is takingplace at up to 60 clinical sites in the United States, Europe,andAustralia. Preliminary results from the trial are expectedwithin 18months. For more information on the trial, visit .

About phenoxodiol and NV-128:

Phenoxodiol is being developed as a therapy for late-stage,chemo-resistantprostate, ovarian and cervical cancers. Phenoxodiol is aninvestigationaldrug and, as such, is not commercially available. It isa novel-actingdrug that inhibits key pro-survival signaling pathways operatingviasphingosine-1-phosphate and Akt. Inhibition of these pathwaysleads toprevention of phosphorylation of key anti-apoptotic proteinssuch as XIAP.Loss of activity of these proteins restores the abilityof chemoresistanttumor cells to undergo apoptosis in response to chemotherapy.The putativemolecular target for phenoxodiol is a tumor-specific protein,accountingfor the highly selective nature of the drug.

In contrast to phenoxodiol, NV-128 has been shown to inducecaspase-independent DNA degradation and cancer cell deathvia a pathwayinvolving pAKT down-regulation, LC3 cleavage to LC3-II,and thetranslocation of Beclin to the mitochondria resulting inBcl2 inactivationand nuclear translocation of EndoG. This offers an opportunityfor use asa monotherapy in chemoresistant cancers and enhanced efficacyagainstcancer targets less susceptible to phenoxodiol. The optionforco-administration of both drugs is also under investigationto extend thepotential therapeutic range of this unique class of oncologycompounds.

About Novogen and Marshall Edwards, Inc.

Novogen is an Australian based biotechnology company inthe business ofresearch and development of drugs derived from its phenolictechnologyplatform. The Company manages its research and developmentprograms usingthe expertise and clinical research capabilities of universitiesandhospitals in Australia, the US and Europe. Novogen's drugprogram isresearching and developing compounds for the treatment ofcancer,cardiovascular disease, inflammatory bowel disease and osteoarthritis.Todate Novogen has had 77 patents granted and a further 230patents arepending.

Novogen is the world leader in isoflavone research. Fromits originaltechnology platform of natural isoflavones (representedin OTC productssuch as Promensil) the Company has developed a discoveryprogramsurrounding novel chemical entities based on a flavonoidscaffold. One ofthese compounds, phenoxodiol, is currently in a Phase IIIclinical trialfor treatment of late stage ovarian cancer and a Phase IItrial forprostate cancer. Marshall Edwards, Inc. is majority ownedby NovogenLimited, and has licensed rights from Novogen to bring threeoncology drugs-- phenoxodiol, NV-196 and NV-143 -- to market globally.

More information on phenoxodiol and on the Novogen groupof companies canbe found at and .

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