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Five Prime Therapeutics Announces New Pre-Clinical Data on FPA144 Presented at the 2016 AACR Annual Meeting

On April 18, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that new preclinical data on FPA144 were featured today in a poster presentation from 8 AM to 12 PM (CDT) during the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held April 16-20, in New Orleans (Press release, Five Prime Therapeutics, APR 18, 2016, View Source [SID:1234510972]).

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The poster titled "FPA144, a Therapeutic Monoclonal Antibody Targeting the FGFR2b Receptor, Promotes Antibody Dependent Cell-Mediated Cytotoxicity and Stimulates Sensitivity to PD-1 in the 4T1 Breast Tumor Model in Mice" will be made available on the publications page of the Five Prime website.

"The ability of FPA144 to both recruit and drive an innate response with NK cells followed by an adaptive response with T cells is new and striking biology," said Drew Pardoll, M.D., Ph.D., Seraph Professor of Oncology, Medicine, Pathology and Molecular Biology and Genetics at the Johns Hopkins University of Medicine. "Driving this immune cascade in a patient’s tumor could provide a new therapeutic mechanism for treating solid tumors."

FPA144 is an FGFR2b-specific humanized monoclonal antibody designed to treat patients with cancers that overexpress FGFR2b. FPA144 is a targeted immunotherapy that Five Prime engineered to recruit NK cells into the tumor microenvironment and kill cancer cells by antibody-dependent cell-mediated cytotoxicity (ADCC).

"We are excited by the results we’ve seen in this model. Surprisingly, they suggest that FPA144 can drive an anti-tumor response that involves multiple immune cell types. The upregulation of PD-L1 suggests that combination with an anti-PD-1 agent could yield even more activity," said Robert Sikorski, M.D., Ph.D., Senior Vice President of Global Clinical Development at Five Prime. "Based on these results and the preliminary clinical data we reported in January, we are considering opportunities to evaluate FPA144 in immuno-oncology combination therapies and in tumors types beyond gastric cancer, including those with moderate levels of FGFR2b expression."

Five Prime evaluated the immune cell recruitment and anti-tumor effects of FPA144 in the orthotopic 4T1 model of breast cancer. In this model, the FGFR2 gene is not amplified and tumor cells express only moderate levels of FGFR2b. Doses of FPA144 or FPA144 N297Q (a modified antibody lacking Fc effector function) were administered at Day 0 and Day 3 and tumor histology and FACS were conducted at Day 1 and Day 4. The following was observed with FPA144 treatment:

24 Hours Post 1st Dose 24 Hours Post 2nd Dose
NK cell infiltration within the tumor Persistence of NK cells
Increase in PD-L1-positive cells within the tumor Persistence of PD-L1-positive cells
No change in T cells Increase in T cells within the tumor

Furthermore, therapeutic treatment with FPA144 in this model resulted in a reduction in tumor burden (33%, P < 0.001), while FPA144 N297Q neither inhibited tumor growth nor led to the recruitment of NK cells. These data provide further evidence of the ability of FPA144 to increase NK and T cell numbers within a tumor and suggest that its enhanced ADCC activity may play an important mechanistic role in anti-tumor efficacy in cancers with modest FGFR2b expression.

Additionally, the 4T1 model was used to evaluate the anti-tumor effect of FPA144 alone and in combination with an anti-PD-1 antibody (RMP1-14). Following biweekly dosing, tumor volume was assessed at day 19. Although anti-PD-1 treatment alone did not inhibit tumor growth, treatment with anti-PD-1 in combination with FPA144 inhibited tumor growth by 49% (P < 0.001). Collectively, these results suggest that FPA144 alters the immune cell composition of the tumor microenvironment in a way that primes the tumor to respond to anti-PD-1 therapy, and an additive anti-tumor effect is observed when FPA144 is combined with PD-1 blockade.

Dose expansion is ongoing in the Phase 1 monotherapy trial of FPA144 in patients with gastric cancer, a disease in which FGFR2b protein overexpression and FGFR2 gene amplification have been associated with poor prognosis. Preliminary data showing anti-cancer activity during the dose escalation portion of the trial were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2016. Updated data from the trial have been accepted for oral presentation during the ASCO (Free ASCO Whitepaper) Annual Meeting in June 2016.

About FPA144

FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FPA144 is designed to block tumor growth through two distinct mechanisms. First, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. Second, it has been engineered to drive immune-based killing of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC) and the recruitment of natural killer (NK) cells. FGFR2 gene amplification (as identified by FISH) is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis.

Epizyme Presents Data from Tazemetostat Clinical Pharmacology Studies at American Association for Cancer Research Annual Meeting 2016

On April 18, 2016 Epizyme, Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapeutics for cancer patients, reported data from clinical studies that investigated the effect of food intake on the pharmacokinetics of tazemetostat, the company’s lead investigational medicine, and the effect of tazemetostat on drugs that are metabolized by the enzyme CYP3A4/5 (Press release, Epizyme, APR 18, 2016, View Source [SID:1234510971]). Epizyme reports that tazemetostat can be dosed with or without food and that the product candidate is a weak inducer of CYP3A-mediated metabolism, suggesting any potential interactions with other treatments metabolized through this pathway will be mild. The data were presented at the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

Tazemetostat is a first-in-class oral EZH2 inhibitor in phase 2 development for patients with non-Hodgkin lymphoma (NHL) and patients with certain genetically defined solid tumors.

"The favorable findings from these studies further support the development of tazemetostat both as a monotherapy and in combination with other agents," said Peter Ho, M.D., Ph.D., Chief Medical Officer, Epizyme. "People living with cancer are often treated with a number of concomitant therapies, so the reduced potential for drug-drug interactions is an important consideration in treatment decision making. Additionally, the ability to take tazemetostat with or without food greatly enhances dosing convenience for patients we are treating."

Epizyme presented results from a 13-patient study on the effect of food on the pharmacokinetics of tazemetostat in subjects with advanced solid tumors or B-cell lymphomas (abstract CT031, poster #12). Pharmacokinetic studies serve to provide information about the absorption and metabolism of medicinal compounds. The area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) are pharmacokinetic parameters of the overall exposure to a drug following administration. Study findings showed that:

AUC decreased by 7 percent and Cmax decreased by 28 percent when patients consumed a high-fat meal prior to drug administration.
There was no observed clinically relevant effect of food intake on tazemetostat’s overall exposure.
Epizyme also presented results of a single-sequence, open-label crossover study of tazemetostat administered in conjunction with midazolam, a well-understood sedative that is a preferred probe drug in pharmacokinetic studies to predict drug-drug interactions with CYP3A (abstract CT029, poster #10). In summary, data show:

Tazemetostat resulted in net induction of CYP3A-mediated midazolam metabolism
Midazolam AUC and Cmax decreased approximately 40 percent and 22 percent, respectively
Tazemetostat is shown to be a weak inducer of CYP3A-mediated metabolism
About EZH2 in Cancer

EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include non-Hodgkin lymphoma, INI1-negative cancers such as malignant rhabdoid tumors and epithelioid sarcomas, certain SMARCA4-negative solid tumors, synovial sarcoma, and a range of other solid tumors.

About Tazemetostat

Epizyme is developing tazemetostat for the treatment of patients with non-Hodgkin lymphoma and for patients with certain genetically defined solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In some human cancers, aberrant EZH2 enzyme activity results in dysregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non- Proprietary Name (INN) for compound EPZ-6438.

Additional information about tazemetostat, including clinical trial information, can be found here.

DelMar’s VAL-083 Demonstrates Promise in the Treatment of Non-Small Cell Lung Cancer and Ovarian Cancer

On April 18, 2016 DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that the Company’s collaborators from the University of Texas MD Anderson Cancer Center (MD Anderson) presented new pre-clinical data supporting the promising potential of its lead anti-cancer product candidate, VAL-083 (dianhydrogalactitol), in the treatment of non-small cell lung cancer (NSCLC) and ovarian cancer (Press release, DelMar Pharmaceuticals, APR 18, 2016, View Source [SID:1234510970]).

Abstract (#2157): "Enhanced in vitro activity of dianhydrogalactitol (VAL-083) in combination with platinum drugs: Impact of p53 and platinum-resistance," was presented at AACR (Free AACR Whitepaper) during the "New Drugs, Therapeutic Targets, and Treatment Approaches" session.

In summary, MD Anderson researchers presented new in vitro data from their studies with VAL-083 indicating that:

VAL-083 induces apoptosis independent of p53 status, and appears to have a distinct mode of action from platinum-based chemotherapies widely used in the treatment of NSCLC and ovarian cancer;

VAL-083 demonstrated ability to circumvent cisplatin-resistance in all ovarian cell lines tested;

VAL-083 was active against NSCLC tumors harboring T790M, p53 and/or KRAS mutations, known to confer resistance to currently available therapies; and

VAL-083 demonstrated super-additivity or synergy in combination with platinum-based chemotherapy.

"These results support VAL-083 as a viable treatment option for refractory NSCLC and ovarian cancer patients failing platinum-based therapy as well as the potential benefit of a VAL-083-platinum combination," said Jeffrey Bacha, DelMar’s chairman & CEO.

Dr. Dennis Brown, DelMar’s Chief Scientific Officer, added, "The activity of VAL-083 observed in tumors harboring mutations known to be correlated with resistant phenotypes and poor treatment outcomes provides clarity and direction as we advance toward planned clinical trials in NSCLC. We can use these biomarkers for patient selection in a personalized-medicine approach to establish clinical proof-of-concept in specific tumor sub-types representing significant unmet needs within the cancer treatment market."

DelMar previously announced plans to initiate clinical trials with VAL-083 in the treatment of NSCLC in cooperation with Guangxi Wuzhou Pharmaceutical (Group) Co., Ltd., who is to provide funding for the trial in accordance with the terms of a collaboration agreement.

About VAL-083

VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia (CML) and lung cancer, and has received orphan drug designation in Europe and the U.S. for the treatment of malignant gliomas. DelMar recently announced that the FDA’s Office of Orphan Products had also granted an orphan designation to VAL-083 for the treatment of medulloblastoma.

DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by the expression of MGMT, a DNA repair enzyme that is implicated in chemotherapy resistance and poor outcomes in GBM patients following standard front-line treatment with Temodar (temozolomide).

DelMar has been conducting a Phase I/II clinical trial in GBM patients whose tumors have progressed following standard treatment with temozolomide, radiotherapy, bevacizumab and a range of salvage therapies.

Data from the Phase I dose-escalation of the study suggest that VAL-083 is well tolerated using a regimen of 40mg/m2 daily x 3 every 21 days. Dose limiting toxicity (DLT) defined by thrombocytopenia (low platelet counts) was observed at doses above 40 mg/m2. Generally, DLT-related symptoms resolved rapidly and spontaneously without concomitant treatment.

Sub-group analysis of Phase I data suggests a dose-dependent and clinically meaningful survival benefit following treatment with VAL-083. Patients in a low dose (≤5mg/m2) sub-group had a median survival of approximately five (5) months versus median survival of approximately nine (9) months for patients in the therapeutic dose (30mg/m2 & 40mg/m2) sub-group following initiation of VAL-083 treatment. DelMar also reported increased survival at 6, 9 and 12 months following initiation of treatment with VAL-083 in the therapeutic dose sub-group compared to the low dose sub-group.

Based on these data, DelMar initiated a Phase II expansion cohort utilizing the 40mg/m2 dosing regimen in June 2015 at five clinical centers in the United States: Mayo Clinic (Rochester, MN); UCSF (San Francisco, CA) and three centers associated with the Sarah Cannon Cancer Research Institute (Nashville, TN, Sarasota, FL and Denver, CO). DelMar announced the completion of enrollment in a Phase II expansion cohort in September, 2015.

Updated interim data from this ongoing study will be presented on Tuesday April 19, 2016 at the AACR (Free AACR Whitepaper) Annual Meeting in the Phase II/III Clinical Trials in Progress" session (Abstract #CT074).

Further details can be found at View Source

About NSCLC

Lung cancer is a leading cause of cancer-related mortality around the world and effective treatment for lung cancer remains a significant global unmet need despite advances in therapy. In general, prognosis for lung cancer patients remains poor, with 5-year relative survival less than 14% among males and less than 18% among females in most countries. Globally, the market for lung cancer treatment may exceed $7 billion by 2019 according to a report published by Transparency Market research.

Non-small cell lung cancer ("NSCLC") is the most common type of lung cancer. There are three common forms of NSCLC: adenocarcinomas are often found in an outer area of the lung; squamous cell carcinomas are usually found in the center of the lung next to an air tube (bronchus); and large cell carcinomas, which can occur in any part of the lung and tend to grow and spread faster than adenocarcinoma. NSCLC accounts for 85% of all lung cancer cases in the United States and approximately 90% of lung cancer cases diagnosed in China.

The current standard of care for newly diagnosed NSCLC is platinum-based combination therapy or tyrosine kinase inhibitor (TKI) therapy for patients whose cancer exhibits over expression of epidermal growth factor receptor ("EGFR") mutations. Patients exhibiting an over expression of EGFR mutations have shown an initial response rate to TKIs which exceeds the response rate for conventional chemotherapy. However, resistance to TKI therapy has emerged as an important unmet medical need commonly linked to the emergence of specific mutations such as T790M.

About Ovarian Cancer

The American Cancer Society estimates for 2015 about 21,290 women will receive a new diagnosis of ovarian cancer and approximately 14,180 women will die from ovarian cancer in the United States. Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. A woman’s risk of getting ovarian cancer during her lifetime is about 1 in 75. Her lifetime chance of dying from ovarian cancer is about 1 in 100. Although initially responsive to standard-of-care chemotherapy based on platinum-taxane combinations, most tumors recur and median survival for recurrent ovarian cancer is 12 to 24 months. According to The Cancer Genome Atlas, there is a major clinical need for treatment with alternatives that can circumvent resistance to currently available chemotherapies.

Cyclacel’s Second-Generation CDK2/9 Inhibitor, CYC065, is an Effective Inducer of Cell Death in B-cell Lymphoma and Synergizes With Bcl-2 or BET Inhibitors

On April 18, 2016 Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC) (NASDAQ:CYCCP) (Cyclacel or the Company), reported the presentation of preclinical data demonstrating therapeutic potential of CYC065, the Company’s second-generation, cyclin-dependent kinase (CDK) 2/9 inhibitor, as a targeted anti-cancer agent (Press release, Cyclacel, APR 18, 2016, View Source [SID:1234510969]). The data show that CYC065 can induce cell death and combined beneficially with anti-cancer drugs from the Bcl-2 and BET inhibitor classes, in in vitro models of B-cell lymphoma, including double-hit lymphomas. The data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016, April 16 – 20, 2016, in New Orleans.

"CYC065 is currently in a Phase 1 clinical trial to evaluate its safety, pharmacokinetic and pharmacodynamic activity in patients with solid tumors and lymphomas," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "Data presented at AACR (Free AACR Whitepaper) highlights its potential as an agent to treat hematological malignancies, such as B-cell lymphoma. Data from this study are particularly important as they validate the mechanism of action of CYC065, which is reducing MYC and Mcl-1 levels, both of which can be elevated in B-cell lymphoma. The study also suggests that CYC065 may be used effectively in combination with other targeted anti-tumor agents in lymphomas. In parallel with collecting preclinical data, we continue to enroll patients in the Phase 1 trial and look forward to reporting initial results from the clinical study."

Double‐hit B-cell lymphomas, defined by concurrent MYC and BCL2 rearrangements, have poor prognosis compared to standard‐risk diffuse large B-cell lymphomas (DLBCL). There is a need for novel treatments specifically exploiting molecular features of the disease. DLBCL show frequent overexpression of Mcl‐1, 50% in ABC and 30% in GCB subtypes respectively. MYC‐driven lymphomas are highly sensitive to depletion of Mcl‐1. MYC overexpression and CDK inhibition have shown synthetic lethality.

The preclinical study evaluated both single-agent activity of CYC065 and combinations of CYC065 with the Bcl-2 inhibitor, venetoclax (ABT-199, Venclexta), and BET (Bromodomain and Extra-Terminal) inhibitors in B-cell lymphoma cell lines. Short exposure to CYC065 was sufficient to downregulate MYC, an oncogene aberrantly expressed in many cancers, and Mcl-1, an anti-apoptotic member of the Bcl-2 family, and to induce cell death. CYC065 treatment had no impact on Bcl-2 levels. Combinations of CYC065 with venetoclax or BET inhibitors were both synergistic. CYC065 targets key oncogenic and survival pathways in double-hit B-cell lymphomas suggesting a therapeutic rationale for this indication.

Abstract: 1309
Title: CYC065, a novel CDK2/9 inhibitor, is an effective inducer of cell death and synergizes with BCL2 and BET inhibitors in B-cell lymphoma, including double-hit lymphomas
Date/Time: Monday, April 18, 2016 8 a.m. – 12 p.m. CDT
Location: Section 18, Poster Board 28
Session Title: Regulation of Anticancer Drug Effects
Authors: Sheelagh M. Frame, Elizabeth Pohler, Craig MacKay, Daniella Zheleva, David Blake, Cyclacel Limited, Dundee, UK

The abstract can be accessed through the AACR (Free AACR Whitepaper) website, www.aacr.org.

About CDK Inhibition

CDK enzymes, in particular CDK2, 4, 6 and 9, play pivotal roles in cancer cell growth, survival, metastatic spread and repair of DNA damage. Pharmacological inhibition of CDK2/9 has been shown to have potent anticancer effects in certain cancer types, including some that are resistant to approved treatments. CDK2/9 inhibitors have been shown to induce apoptosis, or programmed death of cancer cells, whereas CDK4/6 inhibitors, such as palbociclib (Ibrance), induce senescence or dormancy of cancer cells. Senescence may be associated with emergence of resistance.

About CYC065 (second generation CDK inhibitor)

CYC065 is a highly-selective, orally- and intravenously-available, second generation inhibitor of CDK2 and CDK9 and causes apoptotic death of cancer cells at sub-micromolar concentrations. Antitumor efficacy has been achieved in vivo with once a day oral dosing at well tolerated doses. Evidence from published nonclinical studies show that CYC065 may benefit patients with adult and pediatric hematological malignancies, including certain Acute Myeloid Leukemias (AML), Acute Lymphocytic Leukemias (ALL), Chronic Lymphocytic Leukemias (CLL), B-cell lymphomas, multiple myelomas, and certain solid tumors, including breast and uterine cancers. Independent investigators published nonclinical evidence that CYC065 as a single-agent can induce tumor growth delay to HER2-positive breast cancer cells addicted to cyclin E, the partner protein of CDK2, and resistant to trastuzumab (Herceptin), while administration of CYC065 in combination with trastuzumab resulted in regression or sustained tumor growth inhibition.

CYC065 is mechanistically similar but has much higher dose potency, in vitro and in vivo, improved metabolic stability and longer patent protection than seliciclib, Cyclacel’s first generation CDK inhibitor. Translational biology data support development of CYC065 as a stratified medicine for solid and liquid cancers. CYC065 has been shown to reverse drug resistance associated with the addiction of cancer cells to cyclin E and may inhibit CDK9-dependent oncogenic and leukemogenic pathways, including malignancies driven by certain oncogenes and mixed lineage leukemia rearrangements (MLL-r). CYC065 causes prolonged down regulation of the Mcl-1-mediated pro-survival pathway in cancer cells.

A grant of approximately $1.9 million from the U.K. government’s Biomedical Catalyst has supported IND-directed development of CYC065.

ChemoCentryx Announces Immuno-Oncology Data Presentation at the American Association for Cancer Research (AACR) Annual Meeting

On April 18, 2016 ChemoCentryx, Inc., (Nasdaq:CCXI), a clinical-stage biopharmaceutical company developing orally-administered therapeutics to treat autoimmune diseases, inflammatory disorders, and cancer, reported the presentation of data from its immuno-oncology program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2016 Annual Meeting, being held April 16-20, 2016 in New Orleans, Louisiana (Press release, ChemoCentryx, APR 18, 2016, View Source [SID:1234510968]). The preclinical data highlight the synergistic effect of employing an antibody against the checkpoint inhibitor PD-L1 in conjunction with CCX9588, in a model of triple negative breast cancer. CCX9588 is a small molecule inhibitor of the chemokine receptor known as CCR1 and is currently in preclinical development for certain oncology indications targeting both solid and liquid tumors.

The preclinical results were presented in a poster titled, "Combination therapy of chemokine receptor inhibition plus PD-L1 blockade potentiates anti-tumor effects in a murine model of breast cancer" (Abstract #3298, April 17, 1:00 to 5:00 p.m. ET, Session: Immune Modulating Agents 1, Convention Center, Halls G-J, Poster Section 26).

The presentation from the Company’s ongoing preclinical research investigating the effects of combining CCX9588 with an anti-PD-L1 antibody includes the following results and data:

The combination of CCX9588 and the anti-PD-L1 antibody ("Combination Treatment") significantly decreased circulating and tumor infiltrating granulocytic myeloid-derived suppressor cells, or G-MDSC’s.
G-MDSCs are known to be responsible for the induction of an immunosuppressive environment around the growing tumor, as well as a metastatic phenotype in primary tumors which can lead to the early dissemination of cancer cells.
G-MDSCs were demonstrated to be attracted by chemokines produced by the breast cancer cells, and directed migration of the G-MDSCs were shown to be specifically blocked by inhibiting CCR1 with CCX9588.
Combination Treatment increased the number of effector T cells in the tumor infiltrate, which is known to have an anti-cancer effect.

Overall tumor size and progression was also significantly reduced by the Combination Treatment.
"These results suggest that an orally-administered CCR1 inhibitor, such as CCX9588, combined with an antibody against the checkpoint inhibitor PD-L1, may be of utility in treating triple negative breast cancer, which we modeled in these experiments," said Pirow Bekker, MD, PhD, Chief Medical Officer, ChemoCentryx. "These data reveal an important role for the chemokine receptor CCR1 in modulating the suppressive nature of the tumor microenvironment, and suggest that blocking CCR1 could significantly help to unleash the potential of the body’s own immune system to attack cancer."

About the ChemoCentryx Immuno-Oncology Program

Myeloid derived suppressor cells (MDSCs) are thought to possess an immunosuppressive behavior, effectively helping tumors hide from the body’s natural cytotoxic immune response to tumor cells. These cells are thought to express chemokine receptors such CCR1 and CCR2 and are guided to the tumor microenvironment by the action of these receptors. Inhibiting CCR1 and CCR2 may lead to a reduction of MDSCs in the tumor microenvironment, and the concomitant 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.