Procyon Reports Further Positive Clinical Results with PCK3145
Therapeutic for Metastatic Hormone-Refractory Prostate Cancer
Monday February 16, 7:30 am ET
Concomitant animal model studies show significant reduction in bone metastasis with PCK3145
MONTREAL, Feb. 16 /CNW Telbec/ - Procyon Biopharma Inc. (TSX: PBP - News) reported today additional
positive results from the Phase IIa clinical trial currently ongoing in the UK with PCK3145, its therapeutic peptide
indicated for metastatic hormone-refractory prostate cancer. The new data from the third cohort confirms
PCK3145's safety profile as well as potential therapeutic effect on the reduction of metastasis as suggested by
the results of the first two cohorts released last September. The results from the total of twelve patients so far
confirm PSA (Prostate Specific Antigen) reduction or stabilization in nine patients and reduction or normalization
of plasma MMP-9 (Matrix metalloproteinase 9, an enzyme involved in tumor invasion) in all of the patients.
The Company also reported that studies conducted in the laboratory of its collaborator Dr. Shafaat Rabbani of
the McGill University Health Centre have shown that PCK3145 significantly reduced skeletal metastasis as well
as hypercalcaemia in an experimental rat prostate cancer model. These studies validate PCK3145's potential to
reduce and/or prevent tumor metastasis.
"We are greatly encouraged with the outcomes of these studies and are pleased to observe consistency in the
results of the Phase IIa trial. This confirms our belief that PCK3145 affects the metastatic process by modulating
the production of MMP-9, an enzyme involved in tumor invasion," said Hans J. Mader, President and CEO of
Procyon Biopharma Inc. "The exciting results from the animal studies of Dr. Rabbani's group further confirm the
inhibitory effect of PCK3145 on bone metastasis, an event which eventually results in a fatal outcome in patients
with prostate cancer," he added.
Update on the human clinical Phase IIa trial
The study design includes 4 cohorts of 4 patients, each to receive respectively 5, 20, 40 and 80 mg/m2,
intravenously, 3 times a week for 4 weeks followed by a 7-day observation period. The primary objective of this
study is to evaluate the safety and the tolerability of PCK3145 administered intravenously for the therapeutic
doses. The secondary objectives are to determine the pharmacokinetic profile of PCK3145 administered
intravenously and to evaluate efficacy data, tumor response and hormone levels.
The new data observed in the third cohort (40 mg/m2) confirms the results obtained with the two first cohorts (5
and 20 mg/m2). All patients from the third cohort have received two treatment cycles and one patient has
received four cycles (almost 5 months of treatment). No drug-related adverse effects were observed and the
drug was well-tolerated in all 12 patients.
The most dramatic results presented last September and confirmed with the new data show a reduction in the
levels of MMP-9 - Matrix Metalloproteinase-9 - a Gelatinase B enzyme involved in extracellular matrix
degradation and tumor invasion (metastasis). All five patients who had plasma MMP-9 levels over 100 ug/L
before treatment had reductions ranging from 34% to 90% after two cycles of treatment. In the patient that
received 5 cycles (approximately 6 months treatment), the MMP-9 level went down sequentially from 156 ug/L
to 39 ug/L. One patient was unevaluable and in the remaining six patients who had low levels of MMP-9 prior to
treatment (22 to 58 ug/L), they remained low and increased in only two cases when cancer relapse was deemed
to have occurred after two and three cycles.
Also, as observed with some patients of the two first cohorts, an additional patient in the third cohort showed an
initial response in PSA reduction following treatment. The time to PSA progression in these late-stage
hormone-refractory patients ranged from 14 days to over 160 days. The Karnofsky Performance Status,
indicating the general health of the patients, remained high (80-100). CT scans showed disease stabilization during
the treatment period.
The treatment phase for the fourth cohort is now completed and the Company expects to disclose the final results
of the study during Q2 2004.
New Proof-of-Concept for reduction of metastatic tumors in an animal
model
In related animal studies led by Dr. Rabbani, rat prostate cancer cells Mat Ly Lu overexpressing parathyroid
hormone related protein (PTHrP) were either inoculated subcutaneously, S.C., (for tumor inhibition studies) or
injected intracardially, I.C., (for studying metastasis resulting in hind limb paralysis) in syngeneic male
Copenhagen rats, and treated with three different doses of PCK3145. Treatment with the drug resulted in a dose
dependent decrease in tumor volume of about 30-40%, while bone histomorphometry showed that following I.C.
inoculation of tumor cells, treatment with the drug at 100 ug/kg/day resulted in a marked decrease in tumor/bone
volume ratio. In addition, histologic analysis of vertebra showed a marked absence of spinal cord compression
which was consistently/or significantly present in untreated control animals.
The animal studies also showed the effect of PCK3145 in significantly reducing PTHrP expression in the tumor
cells, hypercalcaemia and hind limb paralysis. Tumor cells were found to be undergoing apoptosis (programmed
cell death) when treated with the drug. Detailed results will be presented at a major conference during the first
half of this year.
"The effect of PCK3145 in our experimental skeletal metastasis rat model in reducing bone metastasis of the
prostate cancer as well as tumor growth inhibition is very convincing and encouraging", said Dr. Rabbani,
Professor, Department of Medicine, Physiology and Oncology, McGill University. "Our studies clearly show the
potential of the peptide drug for the inhibition and control of metastatic spread of prostate cancer in humans", he
added.
"We are very pleased with the new results from the clinical trial as well as the animal studies and are currently
working on elucidating the complete mechanism of action of PCK3145 in tumor growth reduction as well as
metastasis and MMP-9 reduction," said Dr. Chandra Panchal, Senior Executive Vice- President, New
Technologies and Preclinical Research, Procyon Biopharma Inc. "As the utility of plasma levels of MMP-9 as a
prognostic marker has been suggested in other types of cancers such as for breast, colon, lung and ovarian
cancers, we hope that the mechanism of action will demonstrate if PCK3145 is specific to prostate cancer. In
light of these results and with the help of our collaborators and medical consultants we are in the process of
establishing the protocol for the clinical Phase IIb study anticipated to commence later this year," he added.
About Procyon Biopharma
Procyon Biopharma Inc. is a publicly traded, Montreal-based, Canadian biotechnology company actively engaged
in the discovery and development of innovative therapeutics and diagnostics in the fields of oncology and
infectious diseases. Procyon brings its products and technologies from the laboratory to the clinical trials and
licenses them to larger pharmaceutical partners for further development and commercialization. Procyon's
pipeline comprises a healthy combination of early-stage anti-cancer platforms, PSP94 and ANsA, as well as
anti-HIV/AIDS compounds, PL-100, a protease inhibitor, and PL-2500, a lead candidate integrase inhibitor. The
Company also has two late-stage products: Fibrostat(R), licensed to Biovail Corporation, and
Colopath(R)/ColorectAlert(TM), licensed to IMI International Medical Innovations Inc. Procyon shares are listed
on the Toronto Stock Exchange (TSX) under the ticker symbol PBP. (www.procyonbiopharma.com)
This release contains forward-looking statements that reflect the
company's current expectation regarding future events. The forward-
looking statements involve risks and uncertainties. Actual events could
differ materially from those projected herein and depend on a number of
factors including, but not limited to, changing market conditions,
successful and timely completion of clinical studies, uncertainties
related to the regulatory approval process, establishment of corporate
alliances and other risks detailed from time to time in the company's
filings.
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