ChemoCentryx, Inc., today announced that it reported positive preclinical and Phase I study results at the European Association for the Study of Diabetes (EASD). CCX140, a novel, orally bioavailable small molecule antagonist of the chemokine receptor CCR2, improved metabolic function while significantly reducing inflammatory macrophages found in adipose tissue in an animal model, and was well tolerated in Phase I clinical trials. These data were presented today in a poster presentation entitled "CCR2 Antagonist CCX140-B in Phase 2 for Diabetes" in Stockholm, Sweden. Data from an ongoing Phase II clinical trial in patients with type 2 diabetes mellitus is expected by the end of 2010 or early 2011.
Results showed that daily treatment with CCX140 significantly improved fasting glucose and ameliorated insulin resistance (HOMA-IR) in obese, diabetic mice over a 28 day treatment period without a corresponding increase in MCP-1 (also called chemokine ligand 2 (CCL2)), the main ligand for CCR2. Circulating adiponectin levels were significantly reduced in obese, diabetic mice and this was reversed when treated with CCX140. The metabolic improvements also correlated with a significant reduction in adipose tissue inflammatory macrophage numbers. The preclinical studies were followed by Phase I clinical trials in 88 healthy human subjects. These Phase I studies comprised single and multiple ascending dose placebo-controlled administration of CCX140 at doses ranging from 0.05 mg to 10 mg per day. CCX140 was well tolerated in the Phase I trials with a favorable pharmacokinetic profile suitable for 5 to 10 mg once-daily oral treatment. A Phase II clinical trial in 140 subjects with type 2 diabetes mellitus on stable doses of metformin was initiated earlier this year based on these encouraging preclinical and Phase I clinical results. The Phase II clinical trial is ongoing.
"These very encouraging results to date support further evaluation of CCX140 in advanced clinical trials for the treatment of patients with type 2 diabetes," said Thomas J. Schall, President and Chief Executive Officer of ChemoCentryx. "In addition to a high degree of target specificity and metabolic benefits, CCX140 is clearly differentiated from other marketed products with its added potential to treat the underlying mechanisms of type 2 diabetes and associated complications such as nephropathy and retinopathy. The results of these trials continue to lead us to believe that CCX140 will be a meaningful and novel treatment option for patients who suffer from type 2 diabetes."