ChemoCentryx, Inc., today announced that it has undertaken a Phase II clinical trial of CCX140, a novel, orally-available small molecule compound designed to specifically target the chemokine receptor known as CCR2. This receptor has been shown to play a role in the inflammatory response associated with metabolic diseases including type 2 diabetes, as well as other diseases including vascular restenosis following stent placement, and multiple sclerosis.
Chronic inflammation is now thought to be central to the development of insulin resistance in type 2 diabetes. Macrophages represent as much as 40% of the cell population in obese adipose tissue; the majority of these macrophages are derived from CCR2-positive monocytes recruited from the blood. CCX140 is a potent and selective antagonist of the CCR2 chemokine receptor. CCX140 works by blocking the monocyte/macrophage infiltration that occurs during inflammation and thus is designed to provide selective treatment of the disease without compromising other immune functions. Successful completion of single and multiple ascending dose Phase I studies in healthy volunteers showed that CCX140 was safe and well-tolerated. In preclinical models, CCX140 has demonstrated an efficacy profile similar to that of the glitazones, a class of drugs currently used for diabetes therapy, with CCX140 also exhibiting an improved safety profile exemplified by the absence of fluid retention and lack of drug-induced weight gain.
CCX140 is chemically distinct from all other known antagonists of CCR2. Preclinical data show that the compound selectively inhibits CCR2-mediated migration of monocytes and does not inhibit migration mediated by other chemokine receptors, even when the compound is given at high doses. This high degree of target specificity is an important safety feature designed to allow CCX140 to be effective while avoiding unwanted side effects.