ChemoCentryx Reports Positive Phase I Results For CCX168, A Novel C5aR Antagonist, At The Annual American College Of Rheumatology Meeting (ACR)

ChemoCentryx, Inc., announced favorable Phase I results for CCX168 at the Annual American College of Rheumatology Meeting (ACR). CCX168, the Company's orally-active small molecule antagonist, is designed to target the receptor for the pro-inflammatory protein known as 'complement 5a' (C5a), a so-called anaphylatoxin that drives inflammatory responses associated with autoimmune diseases such as vasculitis, aged-related macular degeneration, rheumatoid arthritis and related pathologies. Data from Phase I clinical trials showed that CCX168 exhibited an excellent safety profile, while producing greater than 90% receptor blockade of inflammatory cells in the blood throughout the day. Additionally, data from preclinical studies using transgenic mice (which express human C5aR) demonstrated robust efficacy of CCX168 in a vasculitis model. CCX168 is poised to enter Phase II clinical development for the treatment of patients with renal vasculitis.


These data were highlighted in poster presentations entitled:



-- "Phase 1 Clinical Safety, Pharmacokinetic and Pharmacodynamic Evaluation of the Novel C5aR antagonist CCX168, a Potential Therapeutic for ANCA-Vasculitis"



-- "The Human C5a Receptor (hC5aR) Antagonist CCX168 Effectively Ameliorates Symptoms in a Model of ANCA Glomerulonephritis (GN) in hC5aR Knock-in Mice"


"We are very pleased to report that CCX168 appears to be the first true orally-active small molecule C5aR antagonist drug ever advanced into the clinic," stated Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "CCX168 has the ability to safely achieve far greater than 90% receptor coverage throughout the day. While other approaches have attempted, without success, to accomplish such an attractive pharmacokinetic behavior and safety profile, CCX168 may well be in a class by itself. We think that this new agent has extraordinary potential in treating previously intractable conditions such as the devastating vasculitis seen in autoimmune diseases."


CCX168 Study Results and ANCA-Associated Vasculitis


In Phase I clinical trials CCX168 was safe and well tolerated, with excellent oral bioavailability and dose-proportional exposure increases in human subjects. Pharmacokinetic and pharmacodynamic data indicated that 30 to 50 mg of CCX168 given orally twice daily in humans results in greater than 90% C5aR coverage in blood at all times, and this is considered optimal for CCX168 evaluation in Phase II trials in vasculitis.


Supporting the Phase I data are results from a mouse model of anti-neutrophil cytoplasmic autoantibody (ANCA) associated glomerulonephritis (GN). In this study, human C5aR transgenic mice were employed, and ANCA kidney disease was profoundly inhibited by doses of CCX168 that are very similar to those achieved safely in the human Phase I studies.















CCX168 is a highly potent and very selective compound that specifically targets the receptor for the anaphylotoxin designated C5a, a component of the body's complement system and a potent driver of the inflammatory response associated with ANCA-associated vasculitis and other autoimmune disease. In ANCA disease, auto-antibodies lead to the activation and increased adhesiveness of neutrophils to endothelial cells that line the interior surfaces of blood vessels in the kidney and other organs. These adhering neutrophils accumulate inside the blood vessels and initiate an inflammatory cascade. Activation of the complement pathway occurs as a consequence, with production of C5a, one of the most potent pro-inflammatory mediators of the complement system. C5a, through binding to its receptor C5aR, induces expression of additional adhesion molecules and chemotactic factors, thus perpetually amplifying the destructive inflammatory cascade. C5aR also mediates smooth muscle contraction, increasing vascular permeability and altering blood flow. If left untreated, ANCA-associated vasculitis may lead to renal and pulmonary failure and is often fatal. Current therapies include toxic treatments such as cyclophosphamide and high dose corticosteroids. Under an alliance between ChemoCentryx and GlaxoSmithKline's (GSK's) Center of Excellence for External Drug Discovery (ceedd), GSK has the right to exercise an option to license CCX168 after Phase II clinical trials.


Certain statements in this press release may constitute "forward-looking statements". These statements are made on the basis of current expectations, forecasts and assumptions that involve risks and uncertainties, including, but not limited to, economic, competitive, governmental and technological factors outside of our control, that may cause our business, strategy or actual results to differ materially from those expressed or implied. We do not intend, and undertake no obligation, to update any forward-looking statements, whether as a result of new information, future events or otherwise.


Source: ChemoCentryx, Inc