-- Studies highlight CCX4503, a unique small molecule inhibitor of immune checkpoint molecules PD-1/PD-L1, demonstrates anti-tumor efficacy in vivo --
-- Company’s studies also show CCR4 inhibition enhances effectiveness of checkpoint inhibition in tumor models in vivo --
MOUNTAIN VIEW, Calif., Nov. 29, 2018 (GLOBE NEWSWIRE) -- ChemoCentryx, Inc., (CCXI), today announced upcoming presentations on two programs featuring small molecule inhibitors of important therapeutic targets in cancer. ChemoCentryx’s novel small molecules – one which profoundly inhibits the PD-1/PD-L1 immune checkpoints, and another which targets the chemokine receptor known as CCR4 – have both exhibited marked activity in cancer models in vivo. The studies will be featured during the 2018 American Association for Cancer Research (AACR) Tumor Immunology and Immunotherapy Conference, November 27-30, 2018 in Miami Beach, Florida.
Tumor Reduction by a Small Molecule Human PD-1/PD-L1 Inhibitor in a Human Melanoma / PBMC Co-implantation Model
While FDA approved antibody-based therapies targeting the Programmed cell Death-1 / Programmed Death-Ligand 1 (PD-1/PD-L1) immune checkpoint axis have gained considerable attention and success in human cancer immunotherapy, small molecule inhibition of this same pathway could provide significant advantages over antibody therapeutics.
In a poster presentation on November 29, ChemoCentryx researchers will highlight a study of potential next generation cancer therapy, novel small molecule inhibitors targeting PD-1/PD-L1. ChemoCentryx’s unique molecule, CCX4503, exhibited marked inhibition of the checkpoint interaction and downstream signaling, as well as markedly reduced tumor growth in vivo. The study findings demonstrate that the small molecule inhibitors identified and advanced by ChemoCentryx may offer the potential for effective anti-tumor therapy, and with greater ability to manage the side effects associated with current anti-checkpoint therapy.
C-C Chemokine Receptor 4 (CCR4) Antagonism Enhances the Effectiveness of Checkpoint Inhibition in Mouse Tumor Models
Chemokines and their receptors also influence many of the key processes in cancer. CCR4 and its ligands have been found to be highly expressed in multiple types of human tumors and are associated with poor prognosis. CCR4 inhibition has been demonstrated to reduce tumor growth in various mouse tumor models.
In a poster presentation on November 29, ChemoCentryx researchers will highlight a study assessing small molecule inhibition of CCR4 to potentiate the effects of checkpoint inhibitors in colon and pancreatic tumor models. Findings illustrate how the CCR4 inhibitor CCX6239 enhanced the effectiveness of anti-CTLA-4, demonstrating that targeting CCR4 may be an effective clinical approach for combinatorial treatment with checkpoint blockers in cancer therapy.
Separately, further validation of chemokine receptor inhibition in cancer therapy was provided in a poster presentation given on Friday, November 16 at the Society for Neuro-Oncology Annual Scientific Meeting. ChemoCentryx’s novel CCR2 inhibitor, CCX872, was highlighted in anti-PD-1 resistant glioma treatment models. In findings presented by CCXI collaborators at the University of Florida College of Medicine, CCX872 significantly increased median survival as a monotherapy in murine glioma models, and further increased median and durable overall survival when combined with anti-PD-1, providing a basis on which this novel combination treatment could progress toward human trials.
ChemoCentryx is a biopharmaceutical company developing new medications targeted at inflammatory and autoimmune diseases and cancer. ChemoCentryx targets the chemokine and chemoattractant systems to discover, develop and commercialize orally-administered therapies. ChemoCentryx is currently focusing on its late stage drug candidates for patients with rare diseases, avacopan (CCX168) and CCX140.
Avacopan is an orally-administered small molecule that is a selective inhibitor of the complement C5a receptor, or C5aR. Avacopan is in Phase III development for the treatment of anti-neutrophil cytoplasmic auto-antibody-associated vasculitis (ANCA-associated Vasculitis). In clinical studies to date, avacopan was shown to be safe, well tolerated and provided effective control of the disease while allowing elimination of high-dose steroids, part of the current standard of care. ChemoCentryx is also developing avacopan for the treatment of patients with C3 glomerulopathy (C3G) and hidradenitis suppurativa (HS). The U.S. Food and Drug Administration has granted avacopan orphan-drug designation for ANCA-associated Vasculitis, C3G and atypical hemolytic uremic syndrome (aHUS). The European Commission has granted orphan medicinal product designation for avacopan for the treatment of two forms of ANCA-associated Vasculitis: microscopic polyangiitis and granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis), as well as for C3G. Avacopan was also granted access to the European Medicines Agency's (EMA) PRIority MEdicines (PRIME) initiative, which supports accelerated assessment of investigational therapies addressing unmet medical need.
The Company's other late stage drug candidate is CCX140, an inhibitor of the chemokine receptor known as CCR2, which is currently being developed for patients with focal segmental glomerulosclerosis (FSGS), a debilitating kidney disease. The U.S. Food and Drug Administration has granted CCX140 orphan-drug designation for the treatment of FSGS.
ChemoCentryx's Kidney Health Alliance with Vifor Pharma provides Vifor Pharma with exclusive rights to commercialize avacopan and CCX140 in markets outside of the U.S.
ChemoCentryx also has early stage drug candidates that target chemoattractant receptors in other Inflammatory and autoimmune diseases and in cancer.
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 the achievement of anticipated goals and milestones, whether CCR4 inhibition will enhance the effectiveness of checkpoint inhibition, whether small molecule inhibitors such as CCX4503 will be an effective anti-tumor treatment and CCX872 will be effective in combination with an anti-PD-1, and whether the Company's drug candidates will be shown to be effective in ongoing or future clinical trials. 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 on March 12, 2018 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 caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
Susan M. Kanaya
Executive Vice President,
Chief Financial and Administrative Officer
William Slattery, Jr., Burns McClellan