ChemoCentryx, Inc (Mountain View, California) is a privately-held clinical-stage biopharmaceutical company focused on orally-administered therapeutics that target chemokine and chemoattractant systems in order to treat autoimmune diseases, inflammatory disorders, and cancer. The company announced the initiation of a phase I clinical trial of CCX354, an orally-available, novel small molecule compound designed to specifically target the CCR1 chemokine receptor associated with inflammatory diseases such as rheumatoid arthritis (RA). With the dosing of the first trial patient, ChemoCentryx will be entitled to receive a $10 million milestone payment from alliance partner GlaxoSmithKline.

The trial will assess the safety, tolerability, and pharmacokinetics of CCX354 in healthy volunteers in single- and multiple-ascending dose cohorts. Following favorable safety and pharmacokinetic trials of the compound in healthy volunteers, ChemoCentryx plans to initiate safety and efficacy trials of the compound in patients with RA.

Preclinical studies showed that CCX354 is a potent and selective antagonist of the CCR1 receptor without binding to other receptors, which might minimize off-target effects and global immunosuppressive effects. The high potency and selectivity of the molecule is designed to provide a wider therapeutic window allowing continuous receptor coverage throughout the dosing regimen thought to be critical for efficacy.

The chemokine receptor CCR1 drives the recruitment of immune cells, such as monocytes and macrophages, associated with the inflammation underlying certain autoimmune diseases like RA, as well as other inflammatory diseases. Significant levels of CCR1 ligands, including a set of so-called "C6 super-activated ligands" (a result of enzymatic cleavage in the inflamed joints) have been shown to be present in synovial fluid from the joints of RA patients. By blocking the CCR1 ligands including the super-activated forms from interacting with the CCR1 receptor, CCX354 is designed to reduce the migration of inflammatory cells leading to RA and subsequently joint destruction.

ChemoCentryx and GSK's Center of Excellence for External Drug Discovery (CEEDD) entered into a multiproduct strategic alliance in August 2006 for the discovery, development, and commercialization of novel medicines targeting four defined chemokine and chemoattractant receptors for the treatment of a variety of inflammatory disorders. Under the terms of the agreement, ChemoCentryx is responsible for the discovery and development of up to six small molecule drug candidates across four targets through clinical proof-of-concept, at which point GSK will have exclusive options to license each product for further development and commercialization on a worldwide basis.

CCX354 is the second compound under the GSK alliance to enter the clinic. ChemoCentryx's lead compound, Traficet-EN^® (a specific CCR9 antagonist), is in a phase II/III clinical trial in patients with moderate-to-severe Crohn's disease.