Plexxikon Initiates Phase 1 Clinical Trial for Oral Rheumatoid Arthritis Agent PLX5622

Plexxikon Inc. announced that dosing began in the first of two Phase 1 clinical trials with PLX5622, a novel, oral and highly selective Fms inhibitor, targeted for the treatment of rheumatoid arthritis (RA). PLX5622 has been shown in preclinical arthritis models to reduce inflammation, reduce cartilage damage and prevent bone resorption. Fms-related inflammatory mediators and cells, including macrophages, osteoclasts and T-cells, have been validated as key players in RA, other autoimmune diseases and osteoarthritis. The initial Phase 1 trial is a single-ascending dose study in 32 healthy volunteers. The second trial is a multiple-ascending dose study in 32 RA patients that will begin once the first cohort of healthy volunteers has been cleared for safety, with continued enrollment in a staggered fashion relative to the single-ascending dose study.

“PLX5622 is an important and differentiated candidate among Plexxikon’s portfolio of Fms inhibitors that are being developed for multiple indications, and yet another first-in-class compound from Plexxikon,” said K. Peter Hirth, CEO of Plexxikon. “By targeting key drivers of the inflammatory process, we are hopeful that PLX5622 may provide relief to patients with rheumatoid arthritis and other autoimmune disorders, with the convenience of a pill.”

PLX5622 is expected to provide therapeutic benefit by modulating macrophage proliferation, inhibiting production of pro-inflammatory cytokines, and preventing the formation of osteoclasts. Osteoclasts’ bone resorptive activity is responsible for excessive bone destruction in several diseases.

In preclinical models of arthritis, PLX5622 demonstrated substantial disease suppression, including in advanced models of collagen-induced arthritis. PLX5622 significantly improved grip strength and clinical scores, as well as improved knee joint range-of-motion scores.

Plexxikon is completing a Phase 1 trial with PLX3397, another Plexxikon Fms inhibitor that selectively targets Fms, Kit and the Flt-3-ITD mutation. This study has provided validation of Fms-specific biomarkers, which will be directly applicable to the development of PLX5622 in defining a dose response. The company plans to initiate several proof-of-concept clinical trials with PLX3397, including in Hodgkin lymphoma, glioblastoma, acute myelogenous leukemia (AML) and metastatic breast cancer in 2011.

About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic disease that causes pain, stiffness, and swelling primarily in the joints, and affects more than 1.3 million Americans.

RA occurs when the body’s immune system malfunctions and attacks healthy tissue. This malfunction causes inflammation which leads to pain, swelling in the joints and may eventually cause permanent joint damage, bone erosion and deformation, and painful disability.

About Plexxikon

Plexxikon is a leader in the structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease. The company’s lead compound, PLX4032, recently met overall survival and progression-free survival endpoints in a Phase 3 trial of melanoma patients. The company is developing a portfolio of clinical and preclinical stage compounds to address significant unmet medical needs in cardio-renal disease, CNS disorders, autoimmune and neuro-inflammatory diseases, and oncology. Plexxikon’s proprietary Scaffold-Based Drug Discovery™ platform integrates multiple state-of-the-art technologies, including structural screening as a key component that provides a significant competitive advantage over other drug discovery approaches. For more information, please visit