RICHMOND, Calif., May 15, 2017 /PRNewswire/ -- Sangamo
Therapeutics, Inc. (NASDAQ: SGMO) today highlighted data from
research and clinical-stage programs presented over the past week
at the 20th Annual Meeting of the American Society of
Gene & Cell Therapy (ASGCT). Research from Sangamo scientists
and collaborators was selected for 10 oral presentations and nine
poster presentations during the conference.
"This year at ASGCT we showcased several exciting research and
clinical programs emerging from Sangamo's laboratories," said Dr.
Sandy Macrae, Sangamo's CEO.
"Sangamo is known for its leading research in genome editing, and
over time we have developed additional expertise in gene therapy,
gene regulation and cell therapy. We are also rapidly advancing our
viral and non-viral delivery capabilities which have the potential
to broaden our applications of genomic therapies. Such range of
expertise allows us to be selective as we pair technology platforms
with therapeutic applications, and compels us to make strategic
choices about our product candidates. We will develop and
commercialize certain products ourselves, while others, such as our
gene therapy for hemophilia A now in collaboration with Pfizer, or
our CNS or oncology programs, we may advance with a partner to
leverage the right disease area focus, skills and resources."
Selected Highlights from ASGCT 2017
Zinc Finger Nuclease Technology
Improvements
Ed Rebar, Ph.D.,
Sangamo's vice president of technology, presented recent
enhancements to the Company's zinc finger nuclease (ZFN) genome
editing technology that substantially improve specificity while
maintaining very high levels of on-target modification. These
include the removal of positively charged amino acids in the zinc
finger beta-sheet that make non-specific contacts with the DNA
phosphate backbone, as well as the substitution of key residues
within the Fok-1 cleavage domain. Dr. Rebar showed that these
refinements could be applied broadly to ZFN reagents to
substantially reduce off-target cleavage without sacrificing
on-target cutting efficiency.
Dr. Rebar concluded with a detailed specificity analysis of a
ZFN pair, in which these approaches were combined, which identified
no significant off-target modification with an assay sensitivity of
approximately 0.1%. Importantly, this study was performed on
samples generated using clinically relevant delivery conditions,
transfection scales and cell types, and with an on-target
modification level of greater than 80%.
Gene Therapy for Fabry Disease
Thomas Wechsler, Ph.D., Sangamo's director and
lead scientist for rare diseases, presented new data from the
Company's preclinical AAV-cDNA gene therapy program for Fabry
disease. Earlier in the week, Sangamo announced that it will
advance this program toward human clinical development with
preclinical studies enabling an Investigational New Drug
Application (IND) in the second half 2018.
Fabry is an X-linked lysosomal storage disorder caused by
mutations in the GLA gene that encodes for the alpha-galactosidase
A enzyme (α-Gal A). This mutation results in the buildup of Gb3 and
Lyso-Gb3 lipid molecules in the body's cells, resulting in a range
of symptoms and life-threatening complications that affect multiple
tissues and organ systems in the body.
Dr. Weschler presented data from GLAKO mouse models of Fabry
disease demonstrating that a single infusion of Sangamo's AAV
vector containing an α-Gal A transgene and a liver specific
promoter successfully transduced the liver, resulting in episomal
expression of α-Gal A in the plasma and various tissues for the
duration of the study, out to 60 days. From a single treatment, the
AAV-cDNA vector achieved enzyme activity levels in the plasma of up
to 100 fold greater than wildtype and 10 to 100 fold greater than
wildtype in tissues including the liver, heart, kidney and spleen.
Importantly, α-Gal A secreted from the liver led to a significant
reduction in the levels of accumulated Gb3 and Lyso-Gb3 lipid
substrates, in target tissues such as the kidney and heart.
Gene Regulation Treatment for Reduction of Tau
Sangamo
Scientist Bryan Zeitler, Ph.D.,
presented recent data demonstrating significant reduction of tau
expression using Sangamo's proprietary zinc finger protein
transcription factor (ZFP-TF) gene-regulation technology. The
research was conducted in conjunction with Dr. Brad Hyman, Director of the Alzheimer's Disease
Research Center at Massachusetts General Hospital. The reduction of
tau expression has been shown to help reduce neurofibrillary
tangles in the brain and provide neuronal protection and reversal
of pathology in Alzheimer's disease and other tauopathy disease
models.
The presentation included data from in vivo studies in
wild-type mice demonstrating up to 90% reduction of tau mRNA and
protein in the mouse hippocampus, as well as up to 70% tau
reduction across all regions of the brain, including the cortex,
midbrain, cerebellum, thalamus, hypothalamus and striatum.
In addition, data from in vivo studies in an amyloid
mouse model of Alzheimer's disease suggest that a single
administration of ZFP-TFs significantly reduced neuronal
dystrophies in mice with established disease pathology. This is the
first time that a tau lowering agent has demonstrated a reduction
in neuritic dystrophy. Specificity and off-target analysis in
ZFP-TF-treated primary neurons revealed that tau was the only
gene suppressed out of more than 26,000 coding transcripts
analyzed. New data in Dr. Zeitler's presentation demonstrated that
the effect of ZFP-TF treatment in lowering tau was durable out to
the last measurement, at 11 months.
These experiments were conducted using Sangamo's novel,
proprietary AAV serotype for improved CNS transduction.
Sangamo intends to seek a partner with disease area expertise
for the development and commercialization of its gene regulation
approach for certain central nervous system applications including
Alzheimer's disease and other tauopathies.
In Vivo Genome Editing Treatments for MPS I and
MPS II
Sangamo Scientist Russell
DeKelver, Ph.D., presented additional preclinical data from
the Company's in vivo genome editing clinical programs in
MPS I and MPS II demonstrating phenotypic correction of disease in
mouse models following a single administration of Sangamo's genome
editing treatments. Newly presented histopathological analysis
demonstrated reduced cellular vacuolation in various secondary
tissues, as well as in the bone marrow, and central nervous system
tissues such as the spinal cord and pituitary gland in treated MPS
I and MPS II mice, four months after dosing. Furthermore, newly
presented mass spectrometry analysis confirmed significant
reduction of dermatan sulfate, a type of GAG biomarker, in the
brains of MPS I and MPS II mice treated with Sangamo's genome
editing treatments.
Sangamo recently initiated two Phase 1/2 clinical trials
evaluating SB-318 and SB-913, ZFN-mediated in vivo genome
editing treatments for MPS I and MPS II, respectively. Data are
expected in late 2017 or early 2018.
Cell Therapy
Research by Brigit Riley,
Ph.D., Sangamo's director of discovery and translational
research, was presented demonstrating high levels of homology
driven genome editing of human B cells by ZFN mRNA and AAV6
transgene delivery. The data demonstrated robust ZFN-mediated,
site-specific modification of B cells at targeted loci, including
AAVS1, CCR5 and TRAC locus. The data also demonstrated high levels
of targeted transgene insertion, driven by homology directed
repair, using a B cell specific promoter. Analysis of AAV serotype
transduction showed the superiority of AAV6 in transducing B cells
compared to several other serotypes.
The data demonstrate the potential for using genome editing to
genetically modify B cells ex vivo and harness their natural
ability to produce large amounts of antibodies to generate protein
production reservoirs. This novel approach for using genome editing
to harness the protein production capacity of B cells could be
relevant for multiple indications, including immune disorders,
cancer immunotherapies and other monogenic disorders.
Delivery
Sangamo Scientist Anthony Conway, Ph.D., presented new data from
the Company's research into a next-generation delivery platform
using lipid nanoparticles (LNPs). ZFN mRNA delivery via LNPs
allowed for accumulation of genome modification within the mouse
liver following repeat administration, with progressive increases
in genomic modification out to six repeat doses tested. LNP
delivery of new ZFN architectures led to greater than 85% on-target
modification in vitro and greater than 60% on-target
modification in vivo, resulting in greater than 90% protein
knockdown of TTR and PCSK9 in wildtype mice. Repeat dosing of ZFNs
using LNP-mRNA in combination with a single human AAV-IDS donor
vector resulted in efficient targeted insertion of the IDS gene
into the albumin locus and accumulative enzymatic activity levels
in mouse plasma after each subsequent dose.
About Sangamo
Sangamo Therapeutics, Inc. is focused on
translating ground-breaking science into genomic therapies that
transform patients' lives using the company's industry leading
platform technologies in genome editing, gene therapy, gene
regulation and cell therapy. The Company is advancing Phase 1/2
clinical programs in Hemophilia A and Hemophilia B, and lysosomal
storage disorders MPS I and MPS II. Sangamo has a strategic
collaboration with Pfizer, Inc. for Hemophilia A, with Bioverativ
Inc. for hemoglobinopathies, including beta thalassemia and sickle
cell disease, and with Shire International GmbH to develop
therapeutics for Huntington's disease. In addition, it has
established strategic partnerships with companies in
non-therapeutic applications of its technology, including
Sigma-Aldrich Corporation and Dow AgroSciences. For more
information about Sangamo, visit the Company's website at
www.sangamo.com.
Forward Looking Statements
This press release
contains forward-looking statements regarding Sangamo's current
expectations. These forward looking statements include, without
limitation, references to the potential of novel delivery systems
to broaden applications of genomic therapies, the ability to
bring research and preclinical studies to clinical development, the
expected timing of filing INDs and releasing data from ongoing
clinical programs, the intent to seek partners and collaborators to
develop and commercialize gene regulation treatment, and the
research and development of ZFNs and ZFP-TFs, clinical trials and
therapeutic applications of Sangamo's ZFP technology. These
statements are not guarantees of future performance and are subject
to certain risks, uncertainties and assumptions that are difficult
to predict. Factors that could cause actual results to differ
include, but are not limited to, the dependence on the success of
clinical trials of lead programs, the lengthy and uncertain
regulatory approval process, uncertainties related to the timing of
initiation and completion of clinical trials, whether clinical
trial results will validate and support the safety and efficacy of
Sangamo's therapeutics, and the ability to establish strategic
partnerships. Further, there can be no assurance that the necessary
regulatory approvals will be obtained or that Sangamo and its
partners will be able to develop commercially viable gene-based
therapeutics. Actual results may differ from those projected in
forward-looking statements due to risks and uncertainties that
exist in Sangamo's operations and business environments. These
risks and uncertainties are described more fully in Sangamo's
Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q as
filed with the Securities and Exchange Commission. Forward-looking
statements contained in this announcement are made as of this date,
and Sangamo undertakes no duty to update such information except as
required under applicable law.
Contact
Sangamo Therapeutics,
Inc.
McDavid
Stilwell
(510) 970-6000, x219
mstilwell@sangamo.com
Varant Shirvanian
(510) 970-6000, x205
vshirvanian@sangamo.com
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