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Halozyme Studies Target Hyaluronan Surrounding Solid Tumors, May Offer New Approach to Cancer Treatment
AACR presentations show that PEGPH20 produces anti-cancer activity in models of breast, prostate, and brain metastases that produce hyaluronan

SAN DIEGO--(BUSINESS WIRE)--Apr. 20, 2009-- Halozyme Therapeutics, Inc. (Nasdaq:HALO), a biopharmaceutical company developing and commercializing products targeting the extracellular matrix, today announced that treatment with PEGPH20 significantly delayed tumor growth in breast and prostate cancer models. Moreover, in a brain metastasis model, PEGPH20 combined with chemotherapy showed increased efficacy and PEGPH20 combined with radiation prolonged survival. PEGPH20 targets and degrades the hyaluronan (HA) coating that surrounds certain solid tumor cells. Halozyme presented its findings at the American Association for Cancer Research (AACR) meeting in Denver.

“These studies advance our understanding of the pharmacology of PEGPH20 as a novel extracellular matrix-targeted approach for the treatment of solid tumor malignancies,” stated Gregory Frost, Ph.D., Halozyme’s Chief Scientific Officer. “We are also encouraged by the findings demonstrating access to tumor hyaluronan in brain metastases, and the exploratory studies with chemotherapy and radiation.”

Halozyme has recently initiated a Phase 1 single agent clinical trial with intravenously administered PEGPH20 in treatment refractory cancer patients. Additional investigations are anticipated to explore combinations of PEGPH20 with other targeted and cytotoxic agents for potential clinical investigation.

Summary of AACR Poster Presentations

Halozyme presented the results from three preclinical studies at the 2009 AACR Annual Meeting in Denver on Sunday, April 19, 2009, 8:00 a.m. to 12:00 p.m. as part of the poster session titled “Targets in the Microenvironment.” HA is a glycosaminoglycan that frequently accumulates in the area outside the cell, also known as the extracellular matrix, of many solid tumors including prostate, breast, lung, pancreas, stomach and colon. PEGPH20, an enzyme that degrades HA, has been studied in several animal models utilizing a variety of tumor types.

Antitumor activity of PEGylated recombinant human hyaluronidase (PEGPH20) in xenograft and syngeneic rat MatLyLu prostate carcinoma models. Abstract # 260.

In this study, rat MatLyLu hormone refractory HA producing prostate cancer cells were implanted in the hind legs of nude mice and in the prostates of Copenhagen rats. Strongly positive tumor HA expression was confirmed in the animals. A single bolus dose of PEGPH20 produced a reduction in tumor interstitial fluid pressure of 46% to 68% at 60 minutes after administration. Tumor growth inhibition for the PEGPH20 treated mice was 34% along with a 1.3 fold delay in time to tumor volume of 1,500 mm3 (p=0.0008 vs. control) on day 9, the final day of the study. For the rats treated with PEGPH20, tumor growth inhibition of 46% (p=0.001) was observed at day 6 with an approximate 1.4 fold delay in the time for tumors in the treated animals to reach 3,500 mm3.

PEGylated human recombinant hyaluronidase (PEGPH20) removes peritumoral hyaluronan and increases the efficacy of chemotherapy and radiotherapy in an experimental brain metastasis model. Abstract # 262.

Hormone refractory human PC3 prostate cancer cells were injected into the brains of nude mice and disruption of the blood brain barrier was confirmed on days 11, 15, 22 and 40 of the study. Twice-weekly intravenous (IV) injections of PEGPH20 on days 12 through 38 resulted in a sustained degradation of HA from tumor cells in the brain. Mice bearing PC3 tumors were randomized into one of two groups; chemotherapy treatment to begin on day 8 or radiation commencing on day 14 of the study. The chemotherapy group received once weekly IV docetaxel for four weeks and the radiation group received four whole brain irradiation treatments every three days. IV PEGPH20 was administered prior to treatment with chemotherapy or radiation. Docetaxel alone showed minimal anti-tumor activity in this model but the combination of docetaxel and PEGPH20 prolonged median survival time by 20% (NS). Radiation plus PEGPH20 improved survival by 45% relative to control (p=0.0028) and demonstrated a favorable trend (NS) relative to radiation treatment alone. The small sample size of six may have limited the power of this study to achieve significance. Additional brain metastasis studies are underway with larger sample sizes to better characterize PEGPH20 combination treatment in this model.

PEGPH20: PEGylated recombinant human hyaluronidase antitumor activity in the 4T1 orthotopic breast carcinoma model. Abstract # 267.

This study investigated the in vitro and in vivo effects of PEGPH20 on the 4T1-GFP mouse breast carcinoma line. When grown in culture as a monolayer, 4T1-GFP cells produced large pericellular HA matrices that were absent when incubated with PEGPH20. 4T1-GFP cells co-cultured with PEGPH20 resulted in suppression of cell growth, a reduction in fibroblast/tumor hybrid spheroid diameters and volume, and a significantly reduced cell fraction survival. Nude mice inoculated with 4T1-GFP cells in mammary fat pads were randomized to receive control buffer or three different doses of PEGPH20 on days 0, 2, 4, 7, 9, and 11. Treatment with PEGPH20 resulted in dose dependent degradation or complete removal of tumor HA and statistically significant tumor growth inhibition of 43% to 61% at day 14 of the study. Time to tumor volume of 1,500 mm3 was 17 days for controls and 29 days for the PEGPH20 treated animals (p<0.05) resulting in a 1.7 fold advantage for the treatment group.

Pegylation refers to the covalent attachment of polyethylene glycol to a molecule, usually a drug or therapeutic protein. The pegylation of the rHuPH20 enzyme increases its plasma half-life to greater than 24 hours compared to less than one minute for the unpegylated enzyme, therefore resulting in a longer duration of action.

About Halozyme Therapeutics, Inc.

Halozyme is a biopharmaceutical company developing and commercializing products targeting the extracellular matrix for the endocrinology, oncology, dermatology and drug delivery markets. The company's portfolio of products and product candidates is based on intellectual property covering the family of human enzymes known as hyaluronidases and additional enzymes that affect the extracellular matrix. Halozyme’s Enhanze™ Technology is a novel drug delivery platform designed to increase the absorption and dispersion of biologics. The company has key partnerships with Roche to apply Enhanze Technology to Roche’s biological therapeutics for up to 13 targets and with Baxter BioScience to apply Enhanze Technology to Baxter’s biological therapeutic compound, GAMMAGARD LIQUID. Halozyme’s research pipeline candidates target significant areas of unmet medical need. 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 results of studies and benefits associated with 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 also 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 regulatory approval requirements and competitive conditions. These and other factors that may result in differences are discussed in greater detail in the company's reports on Forms 10-K, 10-Q, and other filings with the Securities and Exchange Commission.

Source: Halozyme Therapeutics, Inc.

Halozyme Therapeutics, Inc.
Robert H. Uhl
Senior Director, Investor Relations

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