C5aR-targeting autoimmune diseases drug shows promise: ChemoCentryx

CCX168, an orally-administered small molecule designed to treat autoimmune diseases, is currently in clinical studies, ChemoCentryx, Inc announced.

CCX168 is a highly potent and very selective compound that specifically targets the C5a receptor (C5aR), a component of the body’s complement system and a potent driver of the inflammatory response associated with autoimmune diseases such as systemic lupus erythematosus, certain types of vasculitis, age-related macular degeneration and rheumatoid arthritis.

ChemoCentryx, Inc has started Phase I clinical trial of CCX168.

The initiation of Phase I clinical trial of CCX168 will win ChemoCentryx a $10 million milestone payment from GSK.

“CCX168 marks the fifth product candidate that we have generated from our drug discovery platform and successfully taken into clinical development,” stated Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx.

ChemoCentryx has established as the leaders in developing oral drugs targeting the chemokine and chemoattractant systems. ChemoCentryx has also demonstrated the ability to develop a compound targeting C5aR, which has up to now proved to be an enormous challenge for the pharmaceutical industry, he added.

The complement system consists of a set of proteins that regulate certain types of inflammatory responses. Fragments of complement proteins, such as the chemoattractant complement fragment known as C5a, work to recruit immune system cells, including neutrophils, to sites of inflammation by means of its receptor (C5aR).

This system is active in many diseases, thus making C5aR an attractive target for small molecule therapeutics. Given molecular structure similarities between the C5aR and chemokine receptors, ChemoCentryx researchers applied its proprietary drug discovery technologies to the design of small molecule C5aR antagonists and selected CCX168 based on its potency, selectivity and favorable pharmacokinetics.

C5aR is one of four defined chemokine and chemoattractant receptor projects covered under an alliance between ChemoCentryx and GlaxoSmithKline’s Center of Excellence for External Drug Discovery (CEEDD).

ChemoCentryx, Inc., is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing orally-administered therapeutics that target the chemokine and chemoattractant systems in order to treat autoimmune diseases, inflammatory disorders and cancer.

The chemokine system is a network of secreted chemokine molecules, or ligands, and cell surface receptors that regulates inflammation.

Based on its proprietary drug discovery and drug development platform, ChemoCentryx has internally generated multiple clinical and preclinical-stage programs, each targeting distinct chemokine and chemoattractant receptors with different small molecule compounds.

ChemoCentryx’s lead compound, Traficet-EN, a specific CCR9 antagonist, completed a Phase II multi-national clinical trial, called PROTECT-1, in patients with moderate-to-severe Crohn’s disease, where it demonstrated the ability to induce a clinical response and to maintain clinical remission over the course of the trial.

CCX025, also a CCR9 antagonist, has to date successfully completed a Phase I clinical program.

The company’s other clinical programs include CCX140, which targets the CCR2 receptor, expected to enter Phase II clinical development in the first quarter of 2010 for the treatment of type 2 diabetes mellitus, CCX354, a CCR1 antagonist in a Phase II clinical trial for the treatment of rheumatoid arthritis and CCX168, a C5aR antagonist, in Phase I clinical development.

ChemoCentryx also has several programs in preclinical development.