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CCR5 ZFP Therapeutic Expected to Enter Human Clinical Trials in 2006
RICHMOND, Calif., Dec. 17 /PRNewswire-FirstCall/ -- Sangamo BioSciences,
Inc. (Nasdaq: SGMO) today announced that data from its program to develop a
ZFP Therapeutic(TM) for HIV/AIDS were presented at the 45th Annual
Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in
Washington, DC. The study represents the first demonstration that cells can
be made resistant to HIV infection by treatment with Sangamos proprietary
zinc finger DNA-binding protein nucleases (ZFN(TM)) designed to specifically
disrupt the CCR5 gene.
In its anti-HIV preclinical research program, Sangamo has designed ZFNs
that can be used to disrupt the CCR5 gene, a receptor required for HIV entry
into immune cells. The researchers found that ZFN-modified cells were
resistant to HIV infection whereas control cells were infected when challenged
with the virus. Furthermore, when CCR5 expression was experimentally restored
in the ZFN-modified cells, HIV was once again able to infect these cells.
Sangamo has shown disruption of the CCR5 gene in a number of different cell
types including T-cells, the target cell for this therapeutic approach.
"CCR5 is an important target in the fight against HIV/AIDS," stated Edward
Lanphier, Sangamos president and CEO. "Individuals with a natural mutation
of their CCR5 gene have been shown to be resistant to HIV infection. Several
major pharmaceutical companies have initiated programs to develop small
molecule drugs to block HIV binding to CCR5, but in recent months two trials
have been halted, one due to reports of liver toxicity of the candidate drug.
We believe that using ZFNs to permanently modify the CCR5 gene specifically in
T-cells and thus directly block the expression of the protein on the surface
of these cells may have several advantages over the systemic effects of other
drugs in development."
Small molecule or antibody approaches require the constant presence of
antagonist in high enough concentrations to block therapeutically relevant
numbers of the CCR5 protein, of which there are approximately 10,000 copies on
the surface of each T-cell. In contrast, brief exposure of T-cells to
Sangamos ZFNs has been shown to result in permanent modification of the CCR5
gene and consequent alteration of the CCR5 protein.
"We believe that the data presented at ICAAC provide another important
validation of our novel approach to HIV," said Dale Ando, M.D., Sangamos vice
president of therapeutic development and chief medical officer. "By
administering ZFNs to patients, we could potentially provide HIV-infected
individuals with a reservoir of healthy and uninfectable T-cells that would be
available to fight both opportunistic infections and HIV itself. In this
program, we have been working in close collaboration with Dr. Carl June at the
University of Pennsylvania with the goal of initiating a Phase 1 clinical
trial to test our ZFP Therapeutic in 2006."
Dr. Carl June, Director of Translational Research at the Abramson Family
Cancer Research Institute at the University of Pennsylvania School of
Medicine, is a leader in the field of research testing T-cell therapies for
cancer and HIV infection. Dr. June stated, "After the recent negative news
regarding trials with pharmacologic blockade of CCR5, it is very important
that we focus on positive results involving this well-validated disease
target. I am encouraged by Sangamos findings and look forward to
collaborating with the Company further to bring this promising approach into
the clinic."
About HIV/AIDS and CCR5
HIV stands for Human Immunodeficiency Virus. HIV infection kills or
impairs cells of the immune system, progressively destroying the bodys
ability to fight infections and certain cancers resulting in AIDS (Acquired
Immune Deficiency Syndrome). Individuals diagnosed with AIDS are susceptible
to life-threatening diseases called opportunistic infections, which are caused
by microbes that usually do not cause illness in healthy people. According to
Worldaidsday.org, in 2005, over 3 million people were infected with HIV, which
means there are now over 40 million people living with HIV and AIDS.
CCR5 is the chemokine receptor that HIV uses as a coreceptor to gain entry
into immune cells. CCR5 is perhaps the most important of the known coreceptors
for HIV, since the most commonly transmitted strains of HIV are strains that
bind to CCR5 -- so-called "R5" strains. A small fraction of the population
carries a mutation in their CCR5 gene, called the delta32 mutation. This
mutated version of the gene produces malformed CCR5 proteins, which cannot be
used by HIV as a coreceptor. Individuals that have mutant delta 32 versions
of both of their CCR5 genes are resistant to infection by R5 HIV strains.
About Sangamo
Sangamo BioSciences, Inc. is focused on the research and development of
novel DNA-binding proteins for therapeutic gene regulation and modification.
The most advanced ZFP Therapeutic(TM) development programs are currently in
Phase I clinical trials for evaluation of safety in patients with diabetic
neuropathy and peripheral artery disease. Other therapeutic development
programs are focused on macular degeneration, ischemic heart disease,
congestive heart failure, neuropathic pain, and infectious and monogenic
diseases. Sangamos core competencies enable the engineering of a class of
DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). By
engineering ZFPs that recognize a specific DNA sequence Sangamo has created
ZFP transcription factors (ZFP TF(TM)) that can control gene expression and,
consequently, cell function. Sangamo is also developing sequence-specific ZFP
Nucleases (ZFN(TM)) for therapeutic gene modification as a treatment for a
variety of monogenic diseases, such as sickle cell anemia, and for infectious
diseases, such as HIV. Sangamo has established several Enabling Technology
Agreements with companies to apply its ZFP Technology to enhance the
production of protein pharmaceuticals. For more information about Sangamo,
visit the companys web site at http://www.sangamo.com.
This press release may contain forward-looking statements based on
Sangamos current expectations. These forward-looking statements include,
without limitation, references to the effectiveness of using ZFNs to treat
patients with HIV, the initiation of clinical trials, research and development
of novel ZFP TFs and ZFNs and therapeutic applications of Sangamos ZFP
technology platform. Actual results may differ materially from these forward-
looking statements due to a number of factors, including uncertainties
relating to the further study and development of our ZFN technology,
initiation of clinical trials of ZFP Therapeutics, whether such clinical
trials will validate and support tolerability and efficacy of ZFP
Therapeutics, the effectiveness of our research and development of novel ZFP
TFs and ZFNs and therapeutic applications of Sangamos ZFP technology
platform, technological challenges, Sangamos ability to develop commercially
viable products and technological developments by our competitors. See the
companys SEC filings, and in particular, the risk factors described in the
companys Annual Report on Form 10-K and its most recent 10-Q. Sangamo
BioSciences, Inc. assumes no obligation to update the forward-looking
information contained in this press release.
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