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Publication of Shire plc's Annual Report 2008

dministered, small molecule pharmacological chaperone being developed for the treatment of Pompe disease. In June 2008 Amicus initiated Phase 2 clinical trials of HGT-3510, an orally administered, small molecule pharmacological chaperone being jointly developed for the treatment of Pompe disease by Shire and Amicus. This trial was placed on clinical hold in February 2009 in response to reports of two serious adverse events probably related to treatment with HGT-3510. Shire has rights to HGT-3510 in markets outside the US.

Early Research Products

A number of additional projects are underway in the early stages of development for the HGT business area.

Business Development

As a result of the issues associated with the loss or expiry of patent protection or market exclusivity, Shire seeks to focus its business development activity on the acquisition and in-licensing of products and projects which have the benefit of long-term patent protection and market exclusivity.

The Group remains active in seeking out opportunities to acquire new products or companies that fit its business strategy, its existing therapeutic areas or are in complementary therapeutic areas. During 2008 Shire:

    - acquired more than 98% of Jerini, adding Jerini's HAE product, FIRAZYR,
      to the portfolio; and

    - acquired the global rights to METAZYM, a clinical candidate
      arylsulfatase-A, from Zymenex.

In 2007, the Group acquired New River, allowing Shire to capture the full economic value of VYVANSE and gain control of the development and commercialization of this product. In 2007 Shire also in-licensed the rights to AMIGAL, PLICERA and AT-2220, three pharmacological chaperone compounds for lysosomal storage disorders in markets outside the US; SPD550 for Celiac disease in markets outside of the US and Japan; and worldwide rights (excluding EU member states) to

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