In Vivo Data Also Show Synergistic Effect of Combination Therapy With CCX507 and Approved Anti-Integrin Antibody in Colitis Model
Data Featured at the 79th Annual Scientific Meeting of the American College of Gastroenterology (ACG)
MOUNTAIN VIEW, Calif., Oct. 21, 2014 (GLOBE NEWSWIRE) -- ChemoCentryx, Inc., (Nasdaq:CCXI), a clinical-stage biopharmaceutical company focused on autoimmune diseases, inflammatory disorders and cancer, today announced Phase I data with CCX507, a next-generation potent and specific inhibitor of the chemokine receptor known as CCR9. Data showed that CCX507 is safe and well tolerated in healthy volunteers at all doses tested, and effectively blocked CCR9 on circulating leukocytes. Preclinical data were also presented showing that CCX507, in combination with an anti-alpha4beta7 (α4β7) blocking antibody markedly reduced the severity of colitis more effectively in vivo than monotherapy treatment with either CCX507 or an anti-α4β7 blocking antibody alone.
CCX507 is being evaluated for treatment of patients with inflammatory bowel diseases (IBD) including ulcerative colitis, and primary sclerosing cholangitis (PSC). Data were presented at the ACG meeting being held October 17-22 in Philadelphia.
"This Phase I study provided data allowing us to identify an oral dose regimen of CCX507 that is safe and well tolerated, and blocked 99% of CCR9 on circulating leukocytes. Results support our plans to move the compound forward in Phase II clinical trials, potentially in conjunction with a strategic partner," said Thomas J. Schall, Ph.D., President and Chief Executive Officer, ChemoCentryx. "The preclinical data are equally compelling, and suggest that combination therapy with CCX507 and an anti-α4β7 blocking antibody may offer significant benefit to colitis sufferers."
Phase I Study Design and Results
Thirty healthy adult volunteers were enrolled in the randomized, double-blind, placebo-controlled trial. Subjects received single doses of one of three doses of CCX507 (30, 60, or 90 mg) administered, followed by once daily or twice daily doses of CCX507 for seven days in either a fasted or fed state.
There were no serious adverse events or dropouts from the study. There were no changes of concern in safety laboratory parameters, vital signs, or electrocardiography (ECG) measurements. Results of a functional ex vivo assay of ligand-induced CCR9 internalization by blood leukocytes showed that a dose regimen of 60 mg of CCX507 twice daily blocked 99 percent of CCR9 on circulating leukocytes around the clock.
Preclinical Study Design and Results
In a scientifically-accepted preclinical model of spontaneous colitis (piroxicam-accelerated), a measure of colitis severity was assessed by the ratio of colon weight vs. length (the higher the ratio, the more severe the colitis). Treatment with CCX507 alone showed significant benefit, but treatment with the combination of CCX507 and the anti-α4β7 blocking antibody demonstrated marked additional benefit.
ACG Poster # P1660 October 21, 2014 from 10:30 am to 4:00 pm ET
"Orally Administered CCR9 Inhibitor CCX507 Effectively Blocks CCR9 in Circulating Human Leukocytes"
ACG Poster # P1674 October 21, 2014 from 10:30 am to 4:00 pm ET
"Small Molecule Inhibition of Chemokine Receptor 'CCR9' Combined with Anti-α4β7 Blocking Antibody Confers Synergistic Protection Against Piroxicam-Accelerated Colitis in Mice"
About Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) involves chronic inflammation of all or part of the digestive tract. IBD primarily includes ulcerative colitis and Crohn's disease. Both usually involve severe diarrhea, pain, fatigue and weight loss. IBD can be debilitating and sometimes leads to life-threatening complications.
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. CCX140, a CCR2 inhibitor, has been shown to be safe and well tolerated while demonstrating clinical activity on glycemic indices in a Phase II clinical trial in type 2 diabetics, and is now in Phase II clinical development for the treatment of diabetic nephropathy. CCX168, a C5aR inhibitor, is in Phase II development for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). CCX168 appeared to be safe, well tolerated and successful in allowing both reduction and elimination of high-dose corticosteroids, part of standard of care for AAV patients, without compromising efficacy or safety during a 12-week treatment period. Vercirnon (also known as Traficet-EN or CCX282) is a specific CCR9 inhibitor for the treatment of inflammatory bowel disease. Other clinical programs include CCX872, a next generation CCR2 inhibitor, currently in Phase I clinical development, CCX507, a next generation CCR9 inhibitor, which has successfully completed Phase I development 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. Additional information is available at www.chemocentryx.com
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" or "continue" 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 the ability of combination therapy with CCX507 and an anti-a4b7 blocking antibody to offer significant benefit to colitis sufferers. 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 Quarterly Report on Form 10-Q filed with the SEC August 8, 2014 and its other reports which are available from the SEC's website (www.sec.gov) and on ChemoCentryx's website (www.chemocentryx.com) under the heading "Investors." All forward-looking statements are qualified in their entirety by this cautionary statement. This cautionary statement is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
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