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12:00 AM
 | 
Jul 19, 2010
 |  BioCentury  |  Product Development

Selectively seeking SYK

Gilead picks CGI's platform of SYK inhibitors to enter rheumatoid arthritis space

CGI Pharmaceuticals Inc. has created a preclinical library of SYK inhibitors for rheumatoid arthritis and other inflammatory diseases that it believes are best in class because they are more selective than competing compounds in the clinic. Gilead Sciences Inc. seems to agree, and is paying up to $120 million to acquire the company. The takeout represents a new disease focus for Gilead, which gains molecules that could have an effect on all three phases of the pathology of RA.

In the first stage of RA, inflammatory cells are triggered by auto-antigens such as type II collagen in the peripheral lymphoid region, leading to antibody production and deposition of immune complexes in the joints.

These complexes then activate macrophages, which release cytokines, chemokines and other inflammatory mediators. This phase, called the effector phase, results in the formation of pannus tissue at the synovial membrane of joints.

Lastly, the pannus recruits multiple cell types, such as osteoclasts, which release various proteases and other molecules that irreversibly destroy cartilage and bone.

There are no marketed RA treatments that address both the inflammation components of the first two phases and the tissue damage component of the third phase without causing severe side effects. For example, NSAIDs treat symptoms by interfering with a small portion of the inflammatory cascade, but do not affect downstream inflammatory events or joint destruction. Corticosteroids suppress the inflammatory response but do not stop tissue damage and have myriad adverse effects associated with long-term use.

DMARDS, like anti-tumor necrosis factor (TNF) alpha antibodies, reduce inflammation and slow...

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