CCR1 Program

CCR1 is an important chemokine receptor target for a number of inflammatory diseases including rheumatoid arthritis (RA). Our lead CCR1 development candidate, CCX354, is currently in Phase II clinical development in patients with RA. Targeting the CCR1 chemokine receptor represents a new approach for the treatment of RA. Synovial fluid from the joints of RA patients contains high levels of CCR1 ligands. Blocking CCR1 is intended to suppress the infiltration of inflammatory cells into the arthritic joint space by reducing the inflammatory process and preventing subsequent joint destruction. The high potency and bioavailability of the molecule are expected to provide continuous receptor coverage throughout the dosing period which is thought to be critical for efficacy.

Based on our understanding of the biology of CCR1, we do not expect CCX354 to have the global immunosuppressive effects that have been observed with many other RA drugs, and we believe that CCX354 will have significant advantages over existing injectable biologics and other broad-spectrum immunosuppressive agents currently used to treat RA.

Preclinical data indicate that CCX354 selectively inhibits CCR1-mediated migration of monocytes and does not inhibit migration of immune cells mediated by other chemokine receptors, even when the compound is given at high concentrations. We believe that this high degree of target specificity is an important safety feature that may allow CCX354 to be effective while avoiding unwanted side effects.

Phase I clinical trials have been completed in order to assess the safety, tolerability and pharmacokinetics of CCX354 in healthy volunteers in single ascending dose and multiple ascending dose cohorts. CCX354 was found to be safe and well tolerated in the Phase I studies. We were able to generate data in the Phase I studies to assess the doses of CCX354 required to achieve adequate/maximal inhibition of the CCR1 receptor in patients. Based on available preclinical/clinical data, we believe that a high level of receptor inhibition is required for effective therapeutic effect. A Phase II study in patients with rheumatoid arthritis has been initiated in December 2009.

^ Return to Top