On November 4, 2015 ChemoCentryx, Inc., (Nasdaq:CCXI), a clinical-stage biopharmaceutical company focused on autoimmune diseases, inflammatory disorders and cancer, reported that two abstracts from the Company’s immuno-oncology programs have been selected for presentation at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) being held November 5-9, 2015 in Boston, Massachusetts (Press release, ChemoCentryx, NOV 4, 2015, View Source [SID:1234507942]). The abstracts highlight clinical stage results in a pancreatic cancer trial with CCX872, the Company’s second inhibitor of the chemokine receptor known as CCR2, and, separately, preclinical results in a model of triple negative breast cancer using combination therapy employing an antibody against the checkpoint inhibitor PD-L1 in conjunction with CCX9588, an inhibitor of the chemokine receptor known as CCR1.

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"Tumors have devised ways to suppress anti-tumor immune responses in part by importing immune suppressor cells into the tumor microenvironment. One goal of our chemoattractant based immuno-oncology program is to develop treatments that specifically reduce the content of immune suppressive elements in the tumor mass, thus enabling the body’s effector immune response to predominate," said Thomas J. Schall, Ph.D., President and Chief Executive Officer. "Towards this end, in our pancreatic cancer trial we are encouraged by observations to date of excellent coverage of the receptor CCR2, which guides suppressor cells to the tumor, by our drug CCX872, and we except to see greater than 90 percent receptor coverage continuously in the ongoing multi-dose portion of the study. Patient recruitment in the trial is ramping up, having reached 20 percent of the target enrollment, and we look forward to efficacy data from this trial in 2016. Also, our preclinical model work using a combination of checkpoint inhibitor antibody therapy in combination with an orally administered chemokine receptor inhibitor may pave the way for new treatment options in such important areas as triple negative breast cancer."

Part A Results of Pancreatic Cancer Clinical Trial for CCX872

Pharmacokinetic and pharmacodynamic profile of the novel, oral and selective CCR2 inhibitor CCX872-B in a Phase Ib pancreatic cancer trial, Hezel et al, (Abstract #B24, poster presentation November 7 from 12:30-3:30 p.m. ET, Session B, Hall C-D)

In the ongoing clinical trial in patients with pancreatic cancer with the Company’s CCR2 inhibitor, CCX872, all patients are receiving FOLFIRINOX and CCX872. The two-part trial includes Part A, in which patients receive a single dose of CCX872, and Part B, in which patients receive once or twice daily doses of CCX872 initially for 12 weeks with the ability to continue treatment unless disease progression or unacceptable intolerability occurs. In the trial, the Company plans to evaluate CCX872 in up to 54 patients. The primary efficacy measurement is progression-free survival when patients have completed at least 24 weeks of treatment.

From the abstract, after a single dose of CCX872, across four patients in Part A, the pharmacokinetic profile was favorable and pharmacodynamic assays demonstrated excellent receptor coverage after 12 hours. With 4 to 5-fold accumulation of plasma concentrations with twice daily dosing in Part B, the authors expect to see greater than 90 percent coverage of the receptor throughout the day.

Preclinical Data of Combination Therapy of Chemokine Receptor and Checkpoint Inhibitors

Combination therapy of chemokine receptor inhibition plus PD-L1 blockade potentiates anti-tumor effects in a murine model of breast cancer, Jung et al, (Abstract #A90, poster presentation November 6 from 12:15-3:15 p.m. ET, Session A, Hall C-D)

The Company’s immuno-oncology program is pursuing a better understanding of the body’s immune response to tumors and is therefore conducting studies with various chemokine receptor inhibitors in combination with checkpoint inhibitors that may result in beneficial anti-tumor effects. Results from a study of one of the Company’s inhibitors of the chemokine receptor known as CCR1, CCX9588, demonstrated the ability to act synergistically with a PD-L1 inhibitor to reduce tumor burden in a preclinical model of triple negative breast cancer.

From the abstract, CCX9588, when delivered in combination with an anti-PDL1 antibody, resulted in significantly reduced primary tumor growth and lung metastasis, as compared to either agent alone. In addition, an analysis of tumor-infiltrating cells revealed that the addition of CCX9588 to the anti-PD-L1 antibody significantly reduced the number of myeloid derived suppressor cells (MDSCs) in primary tumors, potentially contributing to the overall reduction of tumor burden. These preclinical results were also accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting being held from November 4-8, in National Harbor, MD.

"One of the most exciting advances in oncology in decades is the recent observation that modifiers of the activity of the body’s own immune system can profoundly enhance the response to chemotherapy," said Israel F. Charo, M.D., Ph.D., Senior Vice President, Research, ChemoCentryx. "We believe that chemokine receptor inhibitors such as CCX9588, combined with immunotherapy or traditional chemotherapy, may result in greater efficacy and fewer systemic side effects."

About the ChemoCentryx Immuno-Oncology Program

CCR1- and CCR2-bearing cells, such as myeloid derived suppressor cells (MDSCs), are thought to possess an immunosuppressive behavior. MDSCs effectively help tumors hide from the body’s natural cytotoxic immune response to tumor cells. Inhibiting CCR1 and CCR2, may lead to the liberation of the cytotoxic immune response against tumor cells, reduced tumor burden and potentially lead to improved patient survival.

The Company currently has an ongoing clinical trial of CCX872, an inhibitor of the chemokine receptor known as CCR2, in patients with non-resectable pancreatic cancer. In addition, the Company is conducting preclinical research with various chemokine receptor inhibitors in combination with checkpoint inhibitors, such as those inhibiting the PD-L1 pathway, which may result in a greater anti-tumor effect than with checkpoint inhibition alone. CCX9588 is a small molecule inhibitor of CCR1 and is currently in preclinical development for certain oncology indications targeting both solid and liquid tumors.