ChemoCentryx’s CCR2 Inhibitor CCX872 Shown to Reduce Liver Fibrosis in NASH Models

-- CCX872 reduced hepatic inflammation, steatosis, and scarring in models of non-alcoholic steatohepatitis (NASH) --

-- Findings reported at the American College of Gastroenterology (ACG) 2016 Annual Meeting --

MOUNTAIN VIEW, Calif., Oct. 18, 2016 (GLOBE NEWSWIRE) -- ChemoCentryx, Inc., (Nasdaq:CCXI) today announced the presentation of data from in vivo models of non-alcoholic steatohepatitis (NASH) with CCX872, a selective orally administered inhibitor of the chemokine receptor known as CCR2, at the American College of Gastroenterology (ACG) 2016 Annual Meeting, being held October 14-19, 2016.

The Company’s CCR2 inhibitor CCX872 demonstrated significant reductions in liver fibrosis when compared to either placebo or a separate compound which is a dual inhibitor of the chemokine receptors CCR2 and CCR5 currently in clinical development by another party. The data suggest a potential application of CCX872 for the treatment of patients with NASH, a severe type of non-alcoholic fatty liver disease caused by chronic inflammation that can lead to fibrosis (scarring) of the liver. NASH affects three to five percent of the U.S. population.

“Liver fibrosis is a critical and particularly difficult to treat feature of NASH, with considerable impact on long-term mortality and liver transplantation. We are therefore very pleased to see the therapeutic effect of our CCR2 inhibitor CCX872 improving liver fibrosis in NASH disease models,” said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. “NASH is the fastest growing cause of liver cancer and liver transplant in the U.S. and other parts of the world; one for which there are no currently approved treatments. We look forward to sharing additional data from our efforts in this disease.”

Researchers believe that inhibiting CCR2 has several therapeutic benefits, including decreasing inflammatory macrophage infiltration into the liver, thus reducing hepatic inflammation and fibrosis. The data are being presented today in a poster titled “Reduction of Liver Fibrosis by CCR2 Antagonist CCX872 in Murine Models of NASH” (Abstract P2017, October 18, 10:30 a.m. to 4:00 p.m. PT) and are summarized as follows:

  • CCX872 is a potent and highly selective inhibitor of CCR2, with a marked capacity to reduce the migration of the cells responsible for liver inflammation central to fibrosis in NASH.
  • Two murine models of NASH were used to determine the efficacy of CCX872 in reducing fibrosis. One model used a high-fat diet (HFD) and the other model used a methionine-choline deficient diet (MCD), both of which are known to induce NASH.
  • In both models, treatment with CCX872 achieved a statistically significant reduction in liver fibrosis as compared to placebo control.
    • In the HFD model, there were statistically significant reductions in serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), two key measures of liver injury, as well as reductions in the accumulation of inflammatory macrophages (which are derived from CCR2 precursor cells), and triglyceride and collagen content in the liver. Insulin sensitivity and glucose tolerance were also improved in the CCX872 treated group.
    • In the MCD model, CCX872 achieved statistically significant reductions in serum ALT concentrations and liver and collagen content as compared to placebo control.
  • In a side-by-side comparison in the murine MCD model, CCX872 was more efficacious than the CCR2/CCR5 dual inhibitor, which is elsewhere in clinical development, in reducing liver fibrosis.
  • Overall treatment with selective CCR2 inhibitor CCX872 improved liver fibrosis in NASH pre-clinical models.

About Non-Alcoholic Steatohepatitis (NASH) and CCR2 Inhibition
NASH is a severe type of non-alcoholic fatty liver disease (NAFLD) characterized by the accumulation of fat in the liver with no other apparent causes. NASH occurs when the accumulation of liver fat is accompanied by inflammation and cellular damage. The inflammation can lead to fibrosis (scarring) of the liver and eventually progress to cirrhosis, portal hypertension, liver cancer, and eventual liver failure. Affecting three to five percent of the U.S. population, NASH is the fastest growing cause of liver cancer and liver transplant in the U.S. There are currently no approved treatments for NASH.

Liver fibrosis in NASH is caused by chronic inflammation with macrophage infiltration and cytokine production. Inflammatory macrophages express the chemokine receptor known as CCR2, which they use to migrate to the liver. CCX872 is the Company’s second-generation CCR2 inhibitor and has successfully completed Phase I studies in healthy volunteers with no serious adverse events. CCX872 is currently being evaluated in an on-going Phase Ib study for the treatment of non-resectable pancreatic cancer. In addition, a third-generation CCR2 inhibitor, CCX598, is poised to enter Investigational New Drug- (IND) enabling studies in 2017.

About ChemoCentryx

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 biological network that regulates inflammation via a collection of secreted chemokine molecules, or ligands, and their specific cell surface receptors. Based on its proprietary drug discovery and drug development platform, ChemoCentryx has generated multiple clinical and preclinical-stage programs, each targeting distinct chemokine and chemoattractant receptors with different small molecule compounds. CCX168 (avacopan), a C5aR inhibitor, is in Phase II development for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). CCX168 appears to be safe, well tolerated and successful in allowing reduction and elimination of high-dose steroids, part of standard of care for AAV patients, without compromising efficacy or safety during a 12-week treatment period. CCX168 is also in Phase II studies for the treatment of atypical hemolytic uremic syndrome (aHUS) and immunoglobulin A nephropathy, or IgA nephropathy (IgAN). ChemoCentryx has licensed exclusive rights to Vifor Pharma to commercialize CCX168 in Europe and certain other markets outside of the U.S. and most of Asia. CCX872, a CCR2 inhibitor, successfully completed Phase I development and is conducting a Phase Ib study for the treatment of non-resectable pancreatic cancer. CCX140, a distinct CCR2 inhibitor, successfully completed a Phase II clinical trial where it was shown to be safe and well tolerated while demonstrating statistically significant improvement in albuminuria in patients with diabetic nephropathy. Other clinical programs include CCX507, a next generation CCR9 inhibitor, which has successfully completed Phase I development, vercirnon (also known as Traficet-EN or CCX282) a specific CCR9 inhibitor for the treatment of inflammatory bowel disease, and CCX354, a CCR1 inhibitor which successfully completed a Phase II clinical trial for the treatment of rheumatoid arthritis. ChemoCentryx also has several programs in advanced preclinical development.

Forward-Looking Statements

ChemoCentryx cautions that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as "may," "could," "will," "would," "should," "expect," "plan," "anticipate," "believe," "estimate," "intend," "predict," "seek," "contemplate," "potential," "continue" or "project" or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. These statements include the Company's statements regarding whether CCX872 will be shown to be safe and effective in the treatment of NASH and when potential future clinical trials will be conducted. The inclusion of forward-looking statements should not be regarded as a representation by ChemoCentryx that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risks and uncertainties inherent in the ChemoCentryx business and other risks described in the Company's filings with the Securities and Exchange Commission ("SEC"). Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and ChemoCentryx undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included under the heading "Risk Factors" in ChemoCentryx's periodic reports filed with the SEC, including ChemoCentryx's Annual Report on Form 10-K filed with the SEC March 13, 2015 and its other reports which are available from the SEC's website ( and on ChemoCentryx's website ( under the heading "Investors." All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.


Contacts: Susan M. Kanaya Senior Vice President, Finance and Chief Financial Officer Media: Denise Powell 510.703.9491 Investors: Steven Klass Burns McClellan 212.213.0006

Source:ChemoCentryx Inc