Halozyme's PEGPH20 Increases Immune Response and Effectiveness of Immunotherapies in Preclinical Cancer Models

SAN DIEGO, April 3, 2017 /PRNewswire/ -- Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, demonstrated in preclinical models that its investigational drug PEGPH20 increases the number of cancer-fighting white blood cells accumulating in the tumor and the effectiveness of immunotherapies. The research was presented at the 108^th annual meeting of the American Association of Cancer Research (AACR) and builds upon prior preclinical findings.

"We are encouraged that these findings from our animal models continue to support the potential benefits of remodeling the tumor microenvironment in stimulating an immune response and improving the efficacy of checkpoint inhibitors and cell-based immunotherapies," said Dr. Helen Torley, president and CEO. "We are pleased that PEGPH20 continues to demonstrate significantly improved tumor growth inhibition in certain hard-to-treat hyaluronan-rich cancer models when administered in combination with additional cancer fighting agents."

PEGPH20 is a proprietary enzyme that targets and degrades hyaluronan (HA), a glycosaminoglycan or naturally occurring sugar in the body. HA accumulates in higher concentrations around many solid tumors, potentially constricting blood vessels, impeding the immune response and the access of other therapies.

Research to be presented includes data from a breast cancer mouse model treated with PEGPH20 which showed a significant increase in the accumulation of cancer-fighting CD8⁺ T cells, also called tumor infiltrating lymphocytes (TILs), compared to mice untreated with PEGPH20. Additional research shows that PEGPH20 administered in combination with an anti-PD-L1 immune checkpoint inhibitor and with Aduro's Listeria-based vaccine immunotherapy facilitated CD8⁺ T-cell accumulation and improved effectiveness over what was achieved with either the anti-PD-L1 or Listeria immunotherapy alone.

PEGPH20 increased the anti-PD-L1 effectiveness by 411 percent compared to anti-PD-L1 alone as measured by tumor growth inhibition (93% vs 18.2%, p<0.0001) and increased the accumulation of CD8⁺ T cells by 176 percent (p=0.0025) in an HA-rich mouse model. Taken together, these data suggest that tumor HA accumulation may act as a barrier to immune cell access and that PEGPH20-mediated HA reduction facilitates increased access of CD8⁺ T cells.

Halozyme and other researchers are conducting further investigations to determine the potential of combining PEGPH20 with adoptive T cell and other immunotherapies. Halozyme has ongoing clinical studies of PEGPH20 in combination with chemotherapy and immunotherapies, with plans to initiate new studies in a previously announced clinical collaboration with Genentech combining PEGPH20 with atezolizumab, an anti-PD-L1 therapy, in up to eight tumor types.

Halozyme's AACR abstracts include:

PEGylated recombinant hyaluronidase PH20 (PEGPH20) enhances tumor infiltrating CD8⁺ T-cell accumulation and improves checkpoint inhibitor efficacy in murine syngeneic breast cancer models. Abstract 641.Sunday, April 2, 1 to 5 p.m. ET

HTI-1511, a novel anti-EGFR-ADC, overcomes mutation resistance and demonstrates significant activity against multiple tumor types in preclinical studies. Abstract 50.  Sunday, April 2, 1 to 5 p.m. ET

Evaluating clinically relevant pharmacological agents in a rat ambulation model to ameliorate PEGylated recombinant hyaluronidase PH20 (PEGPH20)-mediated musculoskeletal adverse events. Abstract 1240. Monday, April 3, 8 a.m. to noon ET

A Phase 1b study of PEGPH20 plus pembrolizumab in patients with selected hyaluronan-high solid tumors. Abstract CT032. Monday, April 3, 8 a.m. to noon ET.

Global phase 3, randomized, double-blind, placebo-controlled study evaluating PEGylated recombinant human hyaluronidase PH20 (PEGPH20) plus nab-paclitaxel and gemcitabine in patients with previously untreated, hyaluronan (HA)-high, stage IV pancreatic ductal adenocarcinoma. Abstract CT066. Monday, April 3, 1 to 5 p.m. ET

Combination of PEGylated recombinant hyaluronidase PH20 (PEGPH20) with Live-attenuated, Double-Deleted (LADD) Listeria enhances tumor infiltrating
CD8⁺ T cell response and antitumor efficacy in mice. Abstract LB-198. Tuesday, April 4, 8 a.m. to noon ET

PEGylated adenosine deaminase 2 (PEG-ADA2) abrogates the cytoprotectiveeffects of adenosine against chronic lymphocytic leukemia cells. Abstract 5583.Wednesday, April 5, 8 a.m. to noon ET

About PEGPH20

PEGPH20 is an investigational PEGylated form of Halozyme's proprietary recombinant human hyaluronidase under clinical development for the potential systemic treatment of tumors that accumulate hyaluronan. PEGPH20 is an enzyme that temporarily degrades HA, a dense component of the tumor microenvironment that can accumulate in higher concentrations around certain cancer cells, potentially constricting blood vessels and impeding the access of other therapies. In January, Halozyme announced the positive topline results as of December 2016 of its randomized phase 2 HALO-202 study of PEGPH20 in combination with ABRAXANE (nab-paclitaxel) and gemcitabine chemotherapy in metastatic pancreatic cancer. In the study, PEGPH20 met key endpoints, including in the targeted HA-High patient population.

FDA granted orphan drug designation to PEGPH20 for treatment of pancreas cancer and fast track for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreas cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreas cancer.

About Halozyme
Halozyme Therapeutics is a biotechnology company focused on developing and commercializing novel oncology therapies that target the tumor microenvironment. Halozyme's lead proprietary program, investigational drug PEGPH20, applies a unique approach to targeting solid tumors, allowing increased access of co-administered cancer drug therapies to the tumor in animal models. PEGPH20 is currently in development for metastatic pancreatic cancer, non-small cell lung cancer, gastric cancer, metastatic breast cancer and has potential across additional cancers in combination with different types of cancer therapies. In addition to its proprietary product portfolio, Halozyme has established value-driving partnerships with leading pharmaceutical companies including Roche, Baxalta, Pfizer, Janssen, AbbVie and Lilly for its ENHANZE™ drug delivery platform. Halozyme is headquartered in San Diego. For more information, visit www.halozyme.com.

Safe Harbor Statement
In addition to historical information, the statements set forth above include forward-looking statements (including, without limitation, statements concerning the possible activity, benefits and attributes of PEGPH20, the possible method of action of PEGPH20, its potential application to improve cancer therapies and statements concerning future actions relating to the development of PEGPH20) that involve risk and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. The forward-looking statements are typically, but not always, identified through use of the words "believe," "enable," "may," "will," "could," "intends," "estimate," "anticipate," "plan," "predict," "probable," "potential," "possible," "should," "continue," and other words of similar meaning. Actual results could differ materially from the expectations contained in forward-looking statements as a result of several factors, including unexpected expenditures and costs, unexpected results or delays in development and regulatory review, regulatory approval requirements, unexpected adverse events and competitive conditions. These and other factors that may result in differences are discussed in greater detail in the Company's most recent Annual and Quarterly Reports filed with the Securities and Exchange Commission.

Contacts:
Jim Mazzola
858-704-8122
ir@halozyme.com

Chris Burton
858-704-8352
ir@halozyme.com

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SOURCE Halozyme Therapeutics, Inc.