Sangamo Biosciences Announces Presentation Of Data Demonstrating A
Disruptive And Broadly Leverageable Platform For Protein
Replacement Therapies At American Society Of Hematology Meeting
RICHMOND, Calif., Dec. 10, 2012 /PRNewswire/ -- Sangamo
BioSciences, Inc. (Nasdaq: SGMO) announced the presentation of new
pre-clinical data demonstrating the successful application of its
In Vivo Protein Replacement Platform. Based on Sangamo's zinc
finger DNA-binding protein (ZFP) genome-editing technology, the
platform enables the permanent production of therapeutic proteins
from the liver with a single systemic treatment, potentially
providing curative treatments for a range of monogenic diseases
including hemophilia and lysosomal storage diseases (LSD) such as
Gaucher, and Fabry disease. Such diseases are currently treated by
regular infusions of protein or enzyme replacement therapy (ERT)
throughout the patient's life. The data were presented at the
54thAnnual Meeting of the American Society of Hematology
(ASH) which is being held in Atlanta.
"These data provide proof-of-concept for this broadly applicable
genome editing strategy," said Philip
Gregory. D. Phil., Sangamo's vice president of research and
CSO. "We show that a single systemic treatment enables stable
liver-specific production of human Factor IX protein, the clotting
factor absent in hemophilia B, reaching or exceeding 100% of normal
circulating levels. In addition, our data in multiple lysosomal
storage diseases serve to demonstrate the potential of this
approach for a broad range of other monogenic diseases."
Sangamo's In Vivo Protein Replacement Platform makes use of a
highly expressed and liver specific genomic "safe-harbor site" that
can be edited with ZFP nucleases (ZFNs) to accept and express any
therapeutic gene and thus permanently produce high levels of the
missing protein with a single treatment. The gene encoding albumin,
the most abundant protein in blood serum, was chosen as a safe
harbor site because it is highly expressed exclusively in the
liver, continuously producing large amounts of albumin protein
(approximately 15g/day). With such a large capacity for protein
production, targeting and co-opting a very small percentage of the
body's albumin production capacity is sufficient to safely produce
the needed replacement protein at therapeutically relevant levels.
The study was performed in collaboration with the laboratory of
Katherine A. High, M.D., director of
the Center for Cellular and Molecular Therapeutics at The
Children's Hospital of Philadelphia. Dr. High, a Howard Hughes
Medical Institute Investigator, is also a Professor of Pediatrics
at the Perelman School of Medicine at the University of Pennsylvania.
"This platform demonstrates our ability to leverage our ZFN
technology across multiple disease areas and enables us to rapidly
expand our ZFP Therapeutic pipeline," stated Edward Lanphier, Sangamo's president and chief
executive officer. "As these presentations at ASH demonstrate, our
ZFN gene-editing platform has broad utility with the potential to
provide a disruptive and broadly leverageable therapeutic approach
to a variety of diseases with unmet medical needs. Our In
Vivo Protein Replacement Platform has the potential to impact any
disease-relevant gene where enabling the liver to provide a stable
source of corrective replacement protein will be therapeutic."
The data were presented in an oral presentation:
Abst. #751 In Vivo Genome Editing of Liver Albumin for
Therapeutic Gene Expression: Rescue of Hemophilic Mice Via
Integration of Factor 9 (Oral Session:
801)
Monday, December 10,
2012: 4:30 PM
Scientists demonstrated efficient ZFN-mediated gene correction
in an adult mouse model of hemophilia B with a single systemic
administration of ZFNs and a donor DNA sequence encoding the
corrected human Factor IX gene. Efficient modification of the
albumin locus to insert a correct copy of the Factor IX gene was
achieved with a single treatment resulting in the production of
robust stable levels of circulating Factor IX protein that
normalize clotting times in hemophilic mice.
In addition, data were presented demonstrating the broad utility
of this method for the potential treatment of a wide range of
monogenic diseases. In these studies, this same
albumin-specific ZFN strategy was used in combination with
appropriately designed donor DNA sequences encoding a diverse range
of protein factors including alpha-galactosidase which is deficient
in Fabry disease, beta-glucosidase (Gaucher disease), Iduronate-2
Sulfatase (Hunter disease) and alpha-L-Iduronidase (Hurler
disease).
In a second study presented at the meeting, Sangamo's ZFP
technology was used to investigate the role of DNA structure in
regulation of the beta-globin gene.
Abst. # 280 Controlling Long-Range Genomic
Interactions to Reprogram the Beta-Globin
Locus
(Oral Session: 503)
Monday,
December 10, 2012: 7:45
AM
About Sangamo
Sangamo BioSciences, Inc. is focused on
research and development of novel DNA-binding proteins for
therapeutic gene regulation and genome editing. The Company has
ongoing Phase 2 clinical trials to evaluate the safety and efficacy
of a novel ZFP Therapeutic® for the treatment of HIV/AIDS.
Sangamo's other therapeutic programs are focused on monogenic
diseases, including hemophilia, Huntington's disease and
hemoglobinopathies such as sickle cell anemia and beta-thalassemia.
Sangamo's core competencies enable the engineering of a class of
DNA-binding proteins known as zinc finger DNA-binding proteins
(ZFPs). Engineering of ZFPs that recognize a specific DNA
sequence enables the creation of sequence-specific ZFP Nucleases
(ZFNs) for gene modification and ZFP transcription factors (ZFP
TFs) that can control gene expression and, consequently, cell
function. Sangamo has entered into a strategic collaboration with
Shire AG to develop therapeutics for hemophilia, Huntington's
disease and other monogenic diseases and has established strategic
partnerships with companies in non-therapeutic applications of its
technology including Dow AgroSciences and Sigma-Aldrich
Corporation. For more information about Sangamo, visit the
company's website at www.sangamo.com.
ZFP Therapeutic® is a registered
trademark of Sangamo BioSciences, Inc.
This press release may contain forward-looking statements
based on Sangamo's current expectations. These forward-looking
statements include, without limitation, the potential of ZFNs to
treat human monogenic diseases, including the treatment of
hemophilia B and other monogenic diseases, research and development
of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo's
ZFP technology platform. Actual results may differ materially from
these forward-looking statements due to a number of factors,
including uncertainties relating to the initiation and completion
of stages of our clinical trials, whether the clinical trials will
validate and support the tolerability and efficacy of ZFNs,
technological challenges, Sangamo's ability to develop commercially
viable products and technological developments by our competitors.
For a more detailed discussion of these and other risks, please see
Sangamo's SEC filings, including the risk factors described in its
Annual Report on Form 10-K and its most recent Quarterly Report on
Form 10-Q. Sangamo BioSciences, Inc. assumes no obligation to
update the forward-looking information contained in this press
release.
SOURCE Sangamo BioSciences, Inc.