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Astrazeneca's Investigational Cancer Therapies Revealed at ASCO

CHICAGO, AstraZeneca today announced details of two new investigational cancer therapies at the American Society of Clinical Oncology (ASCO) meeting. AZD2281 (KU-0059436) is a small molecule inhibitor of Poly-ADP Ribose Polymerase (PARP).

PARP is an enzyme involved in Base Excision Repair which is a key pathway in the repair of DNA single-stranded breaks. Inhibiting this DNA repair mechanism, in tandem with a defective DNA repair gene like BRCA1 or BRCA2, is thought to lead to double-stranded DNA breaks that tumor cells are unable to repair, resulting in tumor cell death.

AZD2281 has been studied in a range of tumor types in Phase I studies. The study presented today at ASCO showed that treatment with AZD2281 led to inhibition of PARP functional activity in both surrogate and tumor tissue, and reported that strong signals were detected in hereditary ovarian cancer. Between 5% and 10% of all breast and ovarian cancers are believed to be associated with mutations in the BRCA1 or BRCA2 mutations.

Women with BRCA mutations are reported to have up to an 87% risk of developing breast cancer, and up to a 44% risk of developing ovarian cancer by the age of 70.Professor James Carmichael of AstraZeneca said, "We are delighted to be working with The Royal Marsden Hospital and Netherlands Cancer Institute (NKI) on this study, which is at the forefront of research into new targeted treatments for cancer.

The early results we have seen in patients with hereditary ovarian cancer have encouraged us to move rapidly into the next phase of development for this compound."AZD0530, another investigational compound in Phase II clinical development is an inhibitor of Src in tumours. Src was the first cancer-causing gene to be discovered in the 1970s. Src kinases are a family of molecules that play an important role in cancer growth, spread, apoptosis and cell proliferation.

By inhibiting Src it is hoped that cancer prog ression may be delayed.Preclinical studies have identified AZD0530 as a selective inhibitor of Src activity. In the study data presented today, biomarkers confirmed inhibition of Src in human cancers for the first time.Principal Investigator for the study(1) presented today at ASCO, Jose Baselga MD, Chairman and Professor of Medicine, Vall d'Hebron University Hospital, Barcelona, Spain commented, "The AZD0530 clinical trial program was exceptionally well-designed allowing full evaluation of the optimal methodology for measuring Src activation prior measuring its inhibition by AZD0530.

By collecting as much information early on in our clinical trials we give ourselves the best chance of identifying those patients who could benefit most from treatment with AZD0530 in the future."About AstraZenecaAstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services.

It is one of the world's leading pharmaceutical companies with healthcare sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.In the United States, AstraZeneca is a $12.44 billion healthcare business with more than 12,000 employees.

For nearly three decades, AstraZeneca has offered drug assistance programs side by side with its medicines, and over the past five years, has provided over $3 billion in savings to more than 1 million patients throughout the US and Puerto Rico. AstraZeneca has been named one of the "100 Best Companies for Working Mothers" by Working Mother magazine and is the only large pharmaceutical company named to FORTUNE magazine's 2007 list of "100 Best Companies to Work For." In 2006, for the fifth consecutive year, Science magazine named AstraZeneca a "Top Employer" on its ranking of the world's most respected biopharmaceutical employers.


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