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Protox Reports Completion of Pre-Clinical Studies for Lead Drug to Support
Phase 1 Human Clinical Trials
Wednesday, September 21, 2005 - Vancouver, British Columbia - Protox Therapeutics Inc. announced today that it has successfully completed pre-clinical studies of PRX302 (formerly PSA-PAH1), to support the Company’s planned Phase I human clinical trials in patients with locally recurrent prostate cancer.
The Company will provide the results of its pre-clinical testing program to the U.S. Food and Drug Administration (FDA) in support of an Investigational New Drug Application (IND). Subject to FDA agreement, the Company intends to proceed with Phase I clinical trials of PRX302 in male subjects with localized prostate cancer.
“We are very pleased to report the successful completion of our preclinical
program. This is a major accomplishment for the company as these studies,
conducted in four different species, demonstrate that local injection of PRX302
is capable of shrinking tumours and reducing PSA levels with little or no
evidence of toxicity beyond the prostate”, said Dr. Fahar Merchant, President
and CEO of Protox. He added, “these results illustrate the strength of
our PORxin™ platform, especially when taken together with the results
of our in vitro and in vivo efficacy studies?
The comprehensive pre-clinical testing program was designed to investigate
the safety and efficacy of PRX302 in the treatment of localized, recurrent
prostate cancer. Protox engaged the services of Charles River Laboratories,
a well-known international contract research organization, to conduct the
pre-clinical safety studies in a series of rodent and non-rodent models and
in conformance with good laboratory practices (GLPs) that are required by
the regulatory authorities. The dose levels were selected according to the
potential human exposure in planned human clinical trials. The intra-prostatic
injection route was selected since this is the intended route of administration
in humans for the first indication, locally recurrent prostate cancer.
PRX302 is a genetically engineered form of the naturally occurring bacterial
toxin, Proaerolysin and is injected into the prostate in an inactive
prodrug form. Once the molecules of PRX302 attach to receptors on the surface
of prostate cancer cells the inactive prodrug is activated by prostate specific
antigen (PSA). PSA is a protease overproduced in patients with prostate cancer
and benign prostatic hyperplasia (BPH or prostate enlargement). The activated
PRX302 molecules aggregate on the cell surface and produce a pore or channel
through the cell membrane causing the contents of the cell to escape resulting
in cell death.
Key findings from the pre-clinical studies are as follows:
- In rodents, a single-dose safety study revealed that PRX302 was well tolerated
and exhibited potent anti-tumour activity in mice implanted with PSA-expressing
human prostate cancer tumours.
- PRX302 exhibited a half-life of approximately 12 hours following intravenous
administration in rodents, but only very limited systemic exposure following
direct intraprostatic administration.
- In a non-rodent species that does not produce PSA, doses of PRX302 as
high as 60µg/g prostate were extremely well tolerated and as expected,
did not result in any injury of prostatic tissue.
- In a non-rodent species that does produce PSA, determined by Protox to
be most similar to humans in prostate response, injection of PRX302 into
the prostate at doses as low as 5 µg/g of prostate demonstrated potent
PSA- dependent cell killing activity following just a single intraprostatic
administration. PRX302 did not produce any evidence of toxicity beyond the
prostate and was also extremely well tolerated even at the highest dose
(25 µg/g of prostate).
The company has previously reported in a press release the efficacy of our PSA-activated PORxin™ in destroying prostate cancer cells in vitro and in vivo. These efficacy data were presented at the 2005 Annual Meeting of the American Association of Cancer Research. The pre-clinical safety studies reveal that PRX302 is toxic to prostate cancer cells but produces little evidence of toxicity beyond the prostate. These studies help to establish the margin of safety of the Company's lead product, PRX302 and provide pre-clinical support for its use in the treatment of not only localized prostate cancer but also BPH.
About Prostate Cancer:
Prostate cancer is one of the most common malignancies in American men. It
is estimated that nearly 232,090 men in the United States will be diagnosed
with prostate cancer in 2005. In most men with prostate cancer, the disease
grows very slowly and is initially found to be localized and confined to the
gland. Nearly 30,250 men will die of prostate cancer in 2005. PRX302 is being
developed for the treatment of localized recurrent prostate cancer in men
with locally progressing disease without evidence of metastases.
About Charles River Laboratories
Charles River Laboratories, based in Wilmington, Massachusetts, is a global
provider of solutions that advance the drug discovery and development process.
Their leading-edge products and services are designed to enable its clients
to bring drugs to market faster and more efficiently. Backed by rigorous,
best-in-class procedures and proven data collection, analysis and reporting
capabilities, its products and services are organized into three categories
spanning every step of the drug development pipeline: Research Models and
Services, Pre-clinical Services, and Clinical Services. Charles River's customer
base includes all of the major pharmaceutical companies and many biotechnology
companies, government agencies and leading hospitals and academic institutions.
Charles River’s 8,000 employees serve clients in more than 50 countries.
For more information on Charles River, visit their website at www.criver.com.
About Protox Therapeutics
Protox Therapeutics Inc. is developing novel therapeutics for the treatment
of cancer and other indications by engineering the naturally occurring bacterial
toxin Proaerolysin, which kills cells by puncturing their cell membrane
(PORxin™) after activation by tumour associated proteases. The Company
believes that its engineering approach will produce targeted cancer therapeutics
that may have greater efficacy and fewer side effects than existing treatments.
For more information, contact:
Terry Vanderkruyk
Director, Investor Relations, Protox Therapeutics Inc.
Tel: 604-688-4376
Cell: 604-789-0844
Fax: 604-688-0173
tvanderkruyk@protoxtherapeutics.com
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