- New Approach to Targeting the Tumor Microenvironment -
SAN DIEGO, April 15 /PRNewswire-FirstCall/ -- Halozyme Therapeutics, Inc. (Nasdaq: HALO), a biopharmaceutical company developing and commercializing products targeting the extracellular matrix, today announced new pre-clinical findings on the treatment of prostate cancer models at the American Association for Cancer Research (AACR) conference. Halozyme is investigating its Pegylated-rHuPH20 enzyme (PEGrHuPH20) as a candidate for the systemic treatment of tumors rich in hyaluronan (HA) in combination with chemotherapy.
The studies explored the physiologic responses to enzymatic removal of HA-based matrices surrounding tumor cells in the tumor microenvironment of prostate tumors following systemic administration of its PEGrHuPH20 pre-clinical candidate. In animal pharmacokinetic models, PEGrHuPH20 demonstrated a more than 2,000-fold increase in plasma half-life compared to the unmodified enzyme. Prostate tumors were grown around the bone as a model of elevated interstitial fluid pressure (IFP). Treatment commenced when tumors had reached approximately 500 mm3 in size and pressure within the tumor had reached 30-40 mm Hg.
The objectives of these studies were to determine whether HA-dependent
pericellular matrices produced in vitro and in vivo by hormone refractory
prostate cancer cell line could be enzymatically depleted in prostate
carcinoma xenografts following intravenous (IV) administration of the
PEGrHuPH20 enzyme. The dose dependent effects of systemic enzyme treatment
were evaluated by a combination of direct micropressure measurements,
magnetic resonance imaging (MRI), ultrasound, immunohistochemistry, and
determination of tumor water content. A summary of findings is as follows:
-- Prostate carcinoma cells assembled large pericellular coats in vitro
that collapsed in the presence of the hyaluronidase enzyme, rHuPH20.
Similar pericellular matrices containing HA were also assembled in vivo
following inoculation of tumors around the bone in mice.
-- PEGrHuPH20 significantly reduced tumor IFP in a dose dependent fashion,
achieving more than 85% reduction in IFP following IV administration.
Peritumoral HA remained depleted over 3 days after a single dose of
-- Consistent with the histologic collapse of pericellular HA surrounding
the tumor cells, tumor water content significantly decreased over 3
days, consistent with changes detected in the tumor by MRI and IFP
-- Furthermore, a 3.5-fold selective increase in tumor vascular volume was
achieved within 8 hours post-dosing as a result of vascular
decompression of blood vessels within the tumor, which was confirmed by
histology and ultrasound.
"These findings represent significant advancements towards our goal of understanding the role of HA in the tumor microenvironment and mechanism of action of PEGrHuPH20" said Gregory Frost, PhD, Halozyme's Vice President and Chief Scientific Officer. "By selectively decompressing tumor vessels, we may significantly improve tumor exposure and responses to chemotherapy regimens. These findings have facilitated our efficacy studies in combination with selected chemotherapy agents, which will be presented later this year as part of our overall development strategy for this new compound."
About Halozyme Therapeutics, Inc.
Halozyme is a biopharmaceutical company developing and commercializing products targeting the extracellular matrix for the drug delivery, oncology and dermatology markets. The company's portfolio of products and product candidates is based on intellectual property covering the family of human enzymes known as hyaluronidases. The company's Enhanze(TM) Technology is a novel drug delivery platform designed to increase the absorption and dispersion of biologics. Its key partnerships are with Roche to apply Enhanze Technology to Roche's biological therapeutic compounds for up to 13 targets and with Baxter to apply Enhanze Technology to Baxter's biological therapeutic compound, GAMMAGARD LIQUID 10%. In addition, the company has received FDA approval for two products: Cumulase(R), for use in in-vitro fertilization, and HYLENEX, for use as an adjuvant to increase the absorption and dispersion of other injected drugs and fluids. HYLENEX is partnered with Baxter International Inc. The Company also has a number of different enzymes in its portfolio that are targeting significant areas of unmet need.
Safe Harbor Statement
In addition to historical information, the statements set forth above
include forward-looking statements (including, without limitation,
statements concerning the pre-clinical results of the company's pegylated
rHuPH20 enzyme) 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
Halozyme Contact Media Contacts
David A. Ramsay Karen Sparks / Joleen Schultz
Chief Financial Officer Mentus
(858) 704-8260 (858) 455-5500, x275/x215
|SOURCE Halozyme Therapeutics, Inc.|
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