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Pharmacyclics Novel Btk Inhibitor Shows Efficacy in Preclinical Models of Rheumatoid Arthritis and Lymphoma
Date:6/9/2008

SUNNYVALE, Calif., June 9 /PRNewswire-FirstCall/ -- Pharmacyclics, Inc. (Nasdaq: PCYC) today announced results from a preclinical study evaluating PCI-32765, an orally available, selective inhibitor of Bruton's tyrosine kinase, or Btk, in collagen induced arthritis, an established animal model for rheumatoid arthritis (RA). The data were presented during the Federation of Clinical Immunology Societies (FOCIS) meeting being held this week in Boston, MA.

Researchers examined the impact of treatment with PCI-32765 on mouse models of rheumatoid arthritis at disease onset, and with established active disease. Treatment prevented further joint swelling when animals were dosed at early stages of disease. In animals with advanced disease, treatment with PCI-32765 reduced inflammation and induced regression of disease with approximately 50% reduction in histopathologic score after only five days of dosing. Treatment with PCI-32765 was found to inhibit mast cell function and to prevent allergic reaction, with passive cutaneous analphylaxis inhibited by more than 95%. In other studies, human B-cell activation was shown to be selectively inhibited by drug treatment in vitro. PCI-32765 also inhibited the proliferation of, and induced apoptosis in, multiple B-cell lymphoma cell lines in vitro, suggesting that Btk inhibition could be a novel drug target in lymphoma.

"This study suggests that treatment with PCI-32765 causes a potent combined blockade of both B-cell and mast cell activation," said Joseph J. Buggy, Ph.D., vice president of research for Pharmacyclics. "This dual blockade may account for the preclinical efficacy seen in established arthritis models and holds promise for potential use in humans with advanced RA and other immune
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SOURCE Pharmacyclics, Inc.
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