Pharmacyclics’ Bruton’s Tyrosine Kinase (Btk) Program

When immune cells called B-lymphocytes are overactive, the immune system produces inflammatory cells and antibodies that begin to attack the body's own tissue, leading to autoimmune diseases such as rheumatoid arthritis. Pharmacyclics has developed drugs that can inhibit an enzyme required for early B-cells to mature into fully functioning cells. In published studies, these compounds have shown success in treatment of arthritis in animal models. Recent studies have shown that these drugs destroy lymphoma cells, or malignancies involving B-cells, indicating their potential for treatment of certain hematologic malignancies.

Pharmacyclics plans to initiate a Phase 1 trial with its oral Btk inhibitor, PCI-32765, in patients with recurrent B-cell lymphoma in the fourth quarter of 2008. This study is designed to evaluate safety and efficacy using a novel pharmacodynamic biomarker.

In preclinical studies evaluating PCI-32765 in collagen-induced arthritis, an established animal model for rheumatoid arthritis (RA), PCI-32765 appeared to reduce inflammation and induce regression of established disease.