Millennium Pharmaceuticals Inc has initiated a multicenter phase II clinical trial of MLN1202 in approximately 30 patients with rheumatoid arthritis. MLN1202, a novel humanized monoclonal antibody, is specifically designed to block the MCP-1/CCR2 chemokine pathway, which is believed to play a central role in a number of inflammatory conditions, including rheumatoid arthritis. Primary objectives of this double-blind, placebo-controlled, multiple dose-escalation study are to assess the safety, tolerability, pharmacokinetic, pharmacodynamic properties and biological activity of MLN1202 via synovial biopsy in patients with rheumatoid arthritis. The study will be conducted in Europe and Australia.

A phase I single dose-escalation study was initiated in December 2002 to evaluate the tolerability, pharmacokinetic and pharmacodynamic effects of MLN1202 in healthy volunteers. MLN1202 was well tolerated and no drug-related serious adverse events were reported among the 48 volunteers in that study. In that study, MLN1202 also demonstrated predictable dose-dependent pharmacokinetics and significant blockade of the MCP-1/CCR2 pathway.

"Our confidence in the initial data we have reviewed has encouraged us to move MLN1202 rapidly into phase II trials, only nine months after the initiation of the phase I trial," said Arthur Hiller, vice president, global strategic marketing at Millennium. "Rheumatoid arthritis remains a significant area of unmet medical need and we are hopeful that MLN1202's novel mechanism of action may someday provide patients with a new treatment option."

The MCP-1/CCR2 pathway plays a central role in the pathogenic inflammatory response cycle of cell signaling, activation and amplification of inflammation. CCR2 receptors are found on the surface of monocytes, macrophages and T-cells and bind hormone-like "chemokines" known as monocyte chemoattractant proteins (MCPs). By binding to the CCR2 receptor, MCPs signal monocytes and T-cells to migrate to sites of injury as part of the inflammatory process. MLN1202 is designed to specifically block the MCP-1/CCR2 chemokine pathway and prevent infiltration of immune cells into inflammatory sites, such as arthritic joints.

A number of published preclinical studies suggest that the MCP-1/CCR2 pathway plays an important role in the inflammatory response and that antagonism of CCR2 could potentially be an effective therapeutic approach in a variety of inflammatory and autoimmune indications, including rheumatoid arthritis, multiple sclerosis, atherosclerosis, restenosis and fibrosis.