Myriad Genetics' Alzheimer's Disease Drug Mechanism Of Action Detailed In Nature Article

Main Category: Alzheimer's / Dementia
Also Included In: Neurology / Neuroscience
Article Date: 12 Jun 2008 - 6:00 PDT

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Myriad Genetics, Inc. (NASDAQ: MYGN) announced that the mechanism of action of Flurizan® (tarenflurbil) -- its drug candidate for the treatment of Alzheimer's disease, is elucidated in the scientific journal Nature. The article, "Substrate-targeting Gamma-secretase Modulators," will be published in the June 12, 2008 issue of Nature.

Previous studies, in vitro, in animal models and in humans, have demonstrated that Flurizan selectively lowers toxic amyloid beta 42, and is the first member of a new class of drugs known as selective amyloid lowering agents (SALAs). Further, Flurizan has been shown to modify the processing of the amyloid precursor protein (APP) by the gamma secretase enzyme. The specific way in which Flurizan accomplishes this reduction in the toxic amyloid beta 42 had remained a mystery until now.

The Nature paper confirms the SALA properties of Flurizan and establishes the mechanism by which Flurizan modulates the APP-gamma secretase interaction. The authors demonstrate that the molecular target of Flurizan is the amyloid precursor protein itself -- the substrate of gamma secretase. Flurizan modifies the conformation of the APP molecule as it is bound to the gamma secretase complex. This change in the shape and/or position of APP in the complex results in cleavage by gamma secretase that produces shorter length, non-toxic amyloid beta fragments, such as amyloid beta 38 and amyloid beta 40. This exciting finding is novel in that most drugs target enzymes, blocking their function directly, but the substrate of an enzyme has not generally been seen as a drug target. These new findings are consistent with previous studies that show that Flurizan selectively lowers amyloid beta 42 by shifting the conformation of the APP/gamma secretase complex through allosteric binding.

"The article in Nature adds to the understanding of the mechanism of action of Flurizan, providing a molecular basis for its ability to slow the progression of Alzheimer's disease, as was demonstrated in previous human clinical studies," said Adrian Hobden, Ph.D., President of Myriad Pharmaceuticals, Inc. "The findings help explain why compounds like Flurizan can have a dramatic effect on lowering amyloid beta 42, the initiator of plaque formation in the human brain, and offer hope for the treatment of patients who suffer from Alzheimer's disease."

Flurizan U.S. Phase 3 Clinical Trial

Flurizan has recently completed a Phase 3 clinical trial in the U.S. of 1684 patients from 131 investigator sites. Topline data from the trial is scheduled for reporting in June 2008, and a full analysis of the data will be presented at the Alzheimer's Association's International Conference on Alzheimer's Disease in Chicago on July 29, 2008.

Flurizan is a registered trademark of Myriad Genetics, Inc. in the United States and other countries.

Myriad Genetics, Inc. is a biopharmaceutical company focused on the development of novel healthcare products. The Company develops and markets predictive medicine products, and is developing and intends to market therapeutic products. Myriad's news and other information are available on the Company's Web site at http://www.myriad.com.

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the publication of the article, "Substrate-targeting Gamma-secretase Modulators" in the scientific journal Nature; the ability of Flurizan to selectively lower toxic amyloid beta 42 and to modify the processing of the amyloid precursor protein (APP) by the gamma secretase enzyme; the mechanism by which Flurizan modulates the APP-gamma secretase interaction; the ability of Flurizan to have a dramatic effect on lowering amyloid beta 42, the initiator of plaque formation in the human brain, and offer hope for the treatment of patients who suffer from Alzheimer's disease; the reporting of topline data from the Phase 3 US trial in June 2008, and the presentation of a full analysis of the data at the Alzheimer's Association's International Conference on Alzheimer's Disease in Chicago on June 29, 2008. These risks and uncertainties include, but are not limited to, our inability to further identify, develop and achieve commercial success for new products and technologies; our ability to discover drugs that are safer and more efficacious than our competitors; our ability to develop molecular diagnostic products that help assess which patients are subject to greater risk of developing diseases and who would therefore benefit from new preventive therapies; the possibility of delays in the research and development necessary to select drug development candidates and delays in clinical trials; the risk that clinical trials may not result in marketable products; the risk that we may be unable to successfully finance and secure regulatory approval of and market our drug candidates, or that clinical trials will not be completed on the timelines we have estimated; uncertainties about our ability to obtain new corporate collaborations and acquire new technologies on satisfactory terms, if at all; the development of competing products and services; our ability to protect our proprietary technologies; patent-infringement claims; risks of new, changing and competitive technologies and regulations in the United States and internationally; and other factors discussed under the heading "Risk Factors" contained in Item 1A in our Annual Report on Form 10-K for the year ended June 30, 2007, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

http://www.myriad.com

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