WELLESLEY, Mass., and LANGENFELD, Germany, Oct. 30 /CNW/ --
Coley Pharmaceutical Group, Inc. today announced the identification of a novel
class of its proprietary CpG oligo drug candidates, termed "C-Class" oligos.
One member of this class, CpG 10101, strongly stimulates in vitro immune
responses in cells isolated from individuals chronically infected with
Hepatitis C virus (HCV). These findings support the development of CpG 10101,
Coley's lead C class oligo candidate, as a potential treatment for HCV.
Heather Davis, Ph.D., Coley's Vice President of Pharmacology Research and
Development and a company co-founder, presented the study today at the
Therapies for Viral Hepatitis Conference in Cambridge, MA, U.S.A.
"With CpG 10101 we are taking a completely new approach to treating
chronic viral diseases," said Robert L. Bratzler, Ph.D., Coley's President and
Chief Executive Officer. "Instead of just shutting down viral replication, we
are using this drug candidate to induce potent, long-lasting immunological
anti-viral activity by both the innate and adaptive immune systems. We are
optimistic that this approach will prove effective in future clinical
studies."
Study Details
Coley had previously described two different classes of oligos: A-Class
CpG oligos which stimulate dendritic cells to make large amounts of interferon
(IFN) alpha but have a weak effect on B cells; and B-Class CpG oligos which
only weakly induce IFN-alpha production, despite inducing very strong B cell
activation and antibody production. Coley's C-Class oligos are designed to
combine the immune effects of the company's A- and B-Class oligonucleotides by
exhibiting strong B cell, type 1 IFN-alpha stimulation, and natural killer
cell activation. This study evaluated the ability of CpG 10101 to stimulate in
vitro immune activity in human white blood cells (peripheral blood mononuclear
cells, or PBMCs) collected from fifteen HCV chronic carriers and ten healthy
volunteers. B cell proliferation and secretion of key cytokines and
chemokines, including IFN-alpha, were measured. The study demonstrates that
CpG 10101 induces equally strong B cell proliferation and dendritic cell IFN-
alpha secretion in PBMCs from both healthy and HCV infected people. This is an
exciting discovery because it is known that the HCV virus may infect the PBMCs
of HCV chronic carriers, and that dendritic cells which normally produce IFN-
alpha and control infections become functionally impaired during HCV
infection.
The study also evaluated the ability of marketed HCV treatments Intron-
A(R) and Ribavarin(R) to stimulate immune responses in PBMCs from both groups.
Neither Intron-A nor Ribavarin induced IFN-alpha secretion or B cell
proliferation when administered alone or together with each other. However,
when CpG 10101 was administered together with Intron-A, a strong synergistic
stimulation of IFN-alpha secretion was observed in cells from both healthy and
HCV-infected donors.
"Dendritic cells, key cells that produce IFN-alpha and that are critical
in the initiation of an adaptive immune response, become functionally impaired
when infected with HCV. CpG 10101 appears to reverse this impairment since it
stimulates the same levels of IFN-alpha secretion as it does in cells from
healthy individuals," stated Dr. Davis. "The immune stimulation induced by CpG
10101 suggests that it may have utility in treating chronic Hepatitis C
infection by two mechanisms: first, through an innate immune antiviral effect,
and second, by stimulating the adaptive immune system to develop virus-
specific immune responses that will destroy virally infected cells,
eliminating the reservoirs for the infection. It is this second mechanism that
is so hard to attain with current therapies."
Coley intends to initiate clinical trials in the second half of 2003 to
evaluate the ability of CpG 10101 to reduce viral load in individuals
chronically infected with Hepatitis C.
About Hepatitis C Infection
Hepatitis C afflicts nearly 4 million people in the United States alone.
Of those who contract the disease, 85 percent remain chronically infected, and
the virus continues to replicate throughout their lifetimes. The best
treatments available today are based on extended treatment (6 months to 1
year) with pegylated interferon-alpha combined with Ribavirin, but this still
fails to cure over 50 percent of those infected with genotype 1, the most
common genotype in North America and is associated with significant side
effects. A major cause of chronic liver disease, HCV is responsible for a
third of all cases of cirrhosis and liver cancer, half of all liver
transplants and for 8 to 10,000 deaths annually in North America.
About Coley Pharmaceutical Group
Coley Pharmaceutical Group is developing several classes of
immunomodulatory oligonucleotide drugs with broad potential applications in
cancer, asthma, allergy and infectious diseases. The current CpG drug
candidates activate the human immune system to fight disease. Coley has
sixteen Phase I and Phase II clinical trials completed or ongoing. Its lead
product candidate, CpG 7909, a B-Class oligo, is in clinical trials as a
monotherapy for melanoma and renal cell carcinoma, and in combination with
Rituxan(R) for non-Hodgkin's B cell lymphoma and with Herceptin(R) for breast
cancer. Coley has established a novel Human Cell Screening drug discovery and
development platform for the rapid validation and optimization of new product
candidates. Coley has a product development and licensing agreement with
Aventis Pharmaceuticals, Inc., for the development of CpG products in the
treatment of asthma and allergic rhinitis as well as a license agreement with
GlaxoSmithlKline for the use of certain CpG drug candidates in specified
preventive and therapeutic infectious disease vaccines. Coley's patent
portfolio includes 65 U.S. patents and patent applications and their worldwide
counterparts, including 10 U.S. patents that have been issued. Coley is a
private company with operations in the United States, Germany and Canada. For
further information, please visit www.coleypharma.com.
Contact.
Patricia F. Dimond, Ph.D.
VP, Corporate Communications
Strategic Development
Coley Pharmaceutical Group
+1-781-431-9000 x1257
pdimondcoleypharma.com
Beth Preston or Candace Ashir
Feinstein Kean Healthcare (U.S.)
+1-617-577-8110
eprestonfkhealth.com
Michael Sinclair or Fay Weston
Burns McClellan (Europe)
+44.20.7534.1520
fwestonburnsmc.co.uk |
