The chemokine receptor CCR2 has a central role in the establishment and maintenance of chronic inflammatory processes.
CCR2 and its primary ligand, MCP-1, represent a signalling pathway for the recruitment of peripheral blood monocytes to sites of immune-mediated inflammation, where they become inflammatory macrophages.
Macrophages are found at sites of chronic inflammation, and trials show a close correlation between lower macrophage burden, reduced severity of disease, and improved outcomes in rheumatoid arthritis.
Presence of inflammatory macrophages contributes to the pathogenesis of other disorders, and blocking of the CCR2/MCP-1 axis has been shown in animal models of rheumatoid arthritis, multiple sclerosis, diabetes, atherosclerosis, neuropathic pain and inflammatory bowel disease.
Under the terms of the agreement, Incyte could receive up to $803 million (€687 million) in payments, made up of an upfront payment of $40 million with the opportunity to receive additional milestone payments of up to $743 million.
This is subject to the successful development and commercialisation of CCR2 antagonists in multiple indications, as well as royalties on worldwide sales.
Meanwhile, Pfizer gains exclusive worldwide development and commercialisation rights to Incyte's portfolio of CCR2 antagonist compounds, one of which is currently in Phase IIa studies in rheumatoid arthritis and insulin-resistant obese patients.
Pfizer's rights extend to the full scope of potential indications, with the exception of multiple sclerosis and one other undisclosed indication, where Incyte retains exclusive worldwide rights, along with certain compounds.
Incyte will not have obligations to Pfizer on pre-clinical development candidates it selects for pursuit in these indications.
Pfizer will also provide research funding to Incyte to support the continued expansion of the CCR2 compound portfolio.
"We are excited about Incyte's CCR2 antagonist program and its potential use in treating a range of chronic diseases with significant unmet medical need," said Martin Mackay, Pfizer senior vice president, Worldwide Research and Technology.
The unmet need is nowhere more clearly exhibited than in Rheumatoid arthritis (RA) - a chronic, progressive inflammatory disease of the articular (rotating) joints that results in pain, stiffness and swelling, which CCR2 antagonists have proved effective against.
According to the Arthritis Foundation, RA affects 2.1 million Americans and is about three times more common in women than men. The disease has a significant socioeconomic impact with medical costs and indirect expenses due to lost wages for RA estimated to be over $3 billion per year.
The cause of RA is not known. However, it is believed that RA is an autoimmune disease where the body's natural immune system attacks healthy joint tissue causing inflammation and subsequent joint damage.