Next Generation of Investigational Anti-Cancer Agents Unveiled at ASCO by AstraZeneca

Next Generation of Investigational Anti-Cancer Agents Unveiled at ASCO by AstraZeneca

June 04, 2007

    ALDERLEY PARK, England, June 4 /Xinhua-PRNewswire/ --
AstraZeneca (LSN: AZN; NYSE: AZN) 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 tumour cells are unable to
repair, resulting in tumour cell death.

    AZD2281 has been studied in a range of tumour types in
Phase I studies.  The study presented 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. We have seen promising
early results in patients with hereditary ovarian cancer,
which 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
progression 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 at
ASCO, Jose Baselga MD, Chairman and Professor of Medicine,
Vall d'Hebron University Hospital, Barcelona, Spain
commented: "Through inhibiting Src in preclinical
studies, AZD0530 has shown promise to target a wide range
of tumors and has the potential to be used in patients with
either early or advanced cancers.

    AZD0530 offers a `multi-mechanistic' approach to
fighting cancer, meaning it not only delays tumour spread
but has additional potential to treat tumours that have
spread to patients' bones, enhance the efficacy of many
standard cancer therapies and to treat leukemia. "

    Highlighting the advantage of this study for patients,
he added, "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."

    Notes to Editors:

    -- Both of these studies were presented at oral
sessions at
       ASCO 2007.

    -- An ASCO merit award was given for the AZD2281
presentation
       (First in human phase I pharmacokinetic (PK) and
       pharmacodynamic (PD) study of KU-0059436 (Ku), a
small
       molecule inhibitor of Poly ADP-Ribose Polymerase
       (PARP) in cancer patients (p), including BRCA1/2
mutation
       carriers).

    -- AstraZeneca 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
US$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 FTSE4
Good Index.

    -- For more information about AstraZeneca, please
visit:
       http://www.astrazeneca.com 

    - KuDOS Pharmaceuticals Ltd is a wholly-owned
subsidiary of
      AstraZeneca.  AstraZeneca acquired KuDOS
Pharmaceuticals in
      Feb 2006. KuDOS research is focused on the discovery
of
      molecules to treat cancer in the area of DNA repair
inhibition.

    (1) Phase I study of AZD0530, an oral potent inhibitor
of Src kinase: first demonstration of inhibition of Src
activity in human cancers


    For more information, please contact:

     Carrie Deverell, AstraZeneca
     Tel:   [phone]
     Email: [e-mail]