Sangamo BioSciences Presents Clinical Data From Key SB-728-T HIV Studies: Proof Of Concept For Ongoing Sustained Functional

  Sangamo BioSciences Presents Clinical Data From Key SB-728-T HIV Studies:
 Proof Of Concept For Ongoing Sustained Functional Control Of HIV Viral Load;
          Cytoxan Preconditioning Successfully Enhances Engraftment

Undetectable Viral Load Sustained Over 20 Weeks in SB-728-902 Study; Data
Demonstrate Dose Response in SB-728-1101 Cytoxan Study; Reduction of Viral
Reservoir Observed in All Immune Non-Responders Over Three Years

PR Newswire

RICHMOND, Calif., Dec. 6, 2013

RICHMOND, Calif., Dec. 6, 2013 /PRNewswire/ --Sangamo BioSciences, Inc.
(Nasdaq: SGMO) announced today the presentation of data from all dose cohorts
in the Company's ongoing clinical trials (SB-728-1101 and SB-728-902 Cohort 5)
of SB-728-T, which is being developed for the functional control of HIV/AIDS.
The data are being presented at the Sixth International Workshop on HIV
Persistence during Therapy, considered to be the reference workshop on HIV
reservoirs and eradication strategies, which is being held in Miami, FL,
December 3-6 2013.

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"The results announced today represent a major milestone," stated Geoff
Nichol, M.B., Ch.B., Sangamo's executive vice president of research and
development. "We have succeeded in achieving sustained control of HIV with
SB-728-T in CCR5 delta-32 heterozygotes, and we have shown that we can safely
use Cytoxan to potentially achieve threshold levels of engraftment for all
patients with HIV. Collectively, data from our clinical studies suggest that
protection of CD4 T-cells by ZFN mediated CCR5 disruption may provide helper
function to CD8 cells enabling the immune system to mount an anti-HIV response
that can also erode the HIV reservoir. The reservoir is a compartment of the
HIV-infected immune system that is not addressed by antiretroviral medication
and its depletion is key to the goal of complete eradication of HIV
infection."

Sangamo's Phase 1 data suggested that if a threshold level of engraftment of
SB-728-T was achieved, specifically of CD4 cells fully protected from HIV
entry by zinc finger nuclease (ZFN)-mediated modification of both CCR5 genes
(biallelic modification), then functional control of HIV infection may be
possible. New data from the SB-728-1101 study demonstrating a clear
relationship between increasing the dose of Cytoxan and increased levels of
both engrafted SB-728-T and total CD4 T-cell counts further support this
hypothesis and suggest that with these, or higher doses, levels of SB-728-T
that will enable functional control of the virus may be reliably attained.

Each of the two trials addressed a different approach to maximizing
engraftment of infused SB-728-T that had undergone biallelic modification of
the CCR5 gene. Inclusion of newly eligible subjects in the analysis
strengthened previous data demonstrating a statistically significant
correlation (p=0.008) between estimated number of engrafted biallelically
modified cells and the reduction in viral load (VL) during a treatment
interruption (TI) from antiretroviral therapy (ART).

"The decreases observed in viral load in several subjects on both of these
trials have been very impressive and are not something that one would expect
to happen by chance," stated Gary Blick, M.D., AAHIVS, Medical & Research
Director, CIRCLE CARE Center and an investigator on both studies.
"Furthermore, the data that have been generated in the course of the clinical
investigation of this novel therapy on reductions in viral load and the levels
of viral reservoir, as well as the increases in total CD4 cells, demonstrate
that a single SB-728-T treatment has the unique ability to enable sustained
immunological functional control of HIV in the absence of ART."

In the SB-728-902 Cohort 5 study, bialleic modification of the infused CD4
cells could be approximately doubled by treating subjects heterozygous for the
naturally occurring CCR5 delta-32 mutation. Three of eight evaluable CCR5
delta-32 heterozygous subjects with high levels of engraftment achieved a VL
at or below the limit of quantification during a TI. This includes two of
seven subjects that had initiated TI in the SB-728-902 Cohort 5 study and an
additional CCR5 delta-32 heterozygote subject from an earlier Phase 1 clinical
trial of SB-728-T. One SB-728-902 Cohort 5 subject, who had the highest levels
of estimated biallelically modified cells and measurable immunological
responses to the virus (polyfunctional anti-gag response), demonstrated
sustained control of VL at or below the limits of detection, which is ongoing
for more than 20 weeks into the TI.

The SB-728-1101 study aimed to demonstrate enhanced engraftment of SB-728-T
modified CD4 cells following cyclophosphamide (Cytoxan) preconditioning.
Cytoxan is a drug that is used to transiently reduce the numbers of T-cells in
the body, which then rapidly repopulate once the drug is discontinued and it
is into this "growth" environment that SB-728-T is infused. This study was
successful in showing a Cytoxan-dose dependent increase in both SB-728-T and
total CD4 T-cells at the beginning of the treatment interruption, which in the
top dose tested (1g/m^2) approached the engraftment levels observed in CCR5
delta 32 heterozygote VL responders, and resulted in up to a two-log decrease
in VL in one of three subjects who remains on TI and a 0.8-log decrease in a
second subject. In the study, a total of twelve subjects were treated in three
cohorts of escalating doses of Cytoxan (three subjects at 200 mg, six subjects
at 500 mg/m^2and three subjects at 1000 mg/m^2). All doses tested were safe
and well-tolerated although two of the first three subjects in the second
cohort experienced Grade 2 nausea, which was reversed using an improved
anti-emetic regimen that was further tested with an additional three subjects
(total of six subjects at this dose level). Cytoxan dose-dependent increases
were observed in both SB-728-T and total CD4 T-cells. The study has been
expanded to test an additional six subjects in two cohorts of three at Cytoxan
doses of 2.0 and 3.0 g/m^2.

The viral reservoir is a source of chronic HIV infection that is not addressed
by current ART. All nine subjects enrolled in Sangamo's Phase 1 study
(SB-728-902 Cohorts1-3) experienced a long term reduction in the reservoir
over three years, as measured by HIV DNA in peripheral blood mononuclear cells
(median 0.9 log decrease at Month 36). In addition, a reduction in the viral
reservoir, as measured by integrated HIV DNA in sorted CD4 cells, correlated
with increased numbers of functional HIV gag-responsive CD8 T-cells,
suggesting that these cells can mount an anti-HIV response with the help of
ZFN modified CD4 T-cells (SB-728-T).

Collectively, data from clinical studies demonstrate that in all trial
subjects, SB-728-T treatment results in a durable increase in total CD4
T-cells and sustained levels of SB-728-T which correlate with ZFN-modification
of long lived central memory and memory stem cell subsets. Data from
immunological analyses of subjects in both Phase 1 and Phase 2 studies of
SB-728-T suggest that certain cell surface marker and gene expression profiles
may predict which patients will likely respond best to SB-728-T treatment.

"We are very encouraged by our data to date and by our continued progress in
understanding the factors required to maximize the potential of this novel
immunologic approach to functional control of HIV," said Edward Lanphier,
Sangamo's president and CEO. "We look forward to continuing to update on our
progress in the coming months as we complete treatment in our expanded
SB-728-1101 study. We will also present preclinical data from several of
Sangamo's programs in monogenic diseases and other indications at the upcoming
Annual Meeting of the American Society of Hematology (ASH)."

Summary of Clinical Trial Design
About SB-728-902
Cohorts 1-3
The study is an open-label Phase 1 clinical trial to evaluate the safety and
tolerability of single infusions of an escalating dose of an autologous (a
patient's own) CD4+ T-cell product genetically modified at the CCR5 gene by
CCR5-specific ZFNs (SB-728-T). Nine HIV-infected subjects (three cohorts of
three subjects each) classified as immune non-responders (INR) with
sub-optimal T-cell levels and no detectable viral load on long-term ART were
enrolled into the trial. Subjects received SB-728-T at doses of approximately
5, 20 or 30 billion cells and remained on their existing antiviral therapy
throughout the study without undergoing a TI.
Cohort 5
Ten HIV-infected subjects heterozygous for the CCR5 delta-32 mutation (i.e.
with one CCR5 gene that is naturally modified) who are currently on ART have
been enrolled and have received a single intravenous infusion of SB-728-T
(12.6 to 23.5 billion cells). Two months after SB-728-T treatment, subjects
underwent a 16 week TI during which time their ART was discontinued. ART was
reinstituted in subjects whose CD4 T-cell counts dropped to <350 cells/ mm^3
and/or whose HIV-RNA increased to >100,000 /mL for three consecutive weekly
measurements. At the end of the TI, subjects with a sustained detectable HIV
viral load were reinstituted on ART. Subjects with an undetectable viral load
can remain off ART until HIV RNA levels are >10,000 copies/mL for three
consecutive weekly measurements or their CD4 T-cell count drops below 500
cell/mm^3 for two consecutive weekly measurements.

About SB-728-1101
SB-728-1101 is an open-label, dose escalation, multi-center study designed
primarily to evaluate the safety and tolerability of escalating doses of
cyclophosphamide (Cytoxan) administered prior to SB-728-T infusion. Cytoxan is
a drug that is used to transiently reduce the numbers of T-cells in the body,
which then rapidly repopulate once the drug is discontinued, and it is into
this "growth" environment that SB-728-T is infused. Such lymphodepletive
treatment has been used to enhance engraftment of adoptively transferred
T-cells in the treatment of cancer and as therapy for numerous autoimmune
diseases. The drug has been previously used in HIV-infected individuals and
studies demonstrate that, while the drug was transiently lymphodepleting, it
did not significantly reduce total CD4 T-cell counts over the long term and
was adequately tolerated.

In addition to safety, the study is evaluating the effect of escalating doses
of Cytoxan on SB-728-T engraftment, the effect of SB-728-T treatment on viral
load following ART interruption, the change in CD4+ T-cell counts in
peripheral blood and the long-term persistence of SB-728-T.

By protocol, nine HIV-infected subjects on ART were enrolled into three
dose-escalating cohorts (three subjects/cohort), and received intravenous
Cytoxan (200 mg, 500 mg/m^2 or 1000 mg/m^2). In cohort two, an additional
three subjects were evaluated on an improved anti-emetic protocol due to an
adverse event of Grade 2 nausea observed in two subjects at that dose level.
Within each cohort, treatment was staggered so that each subsequent subject
was infused with Cytoxan two weeks after the preceding subject. One to three
days after receiving Cytoxan, subjects were infused with SB-728-T (8.2 to 36.2
billion cells). Six weeks after SB-728-T infusion, subjects with CD4 cell
counts ≥500 cells/mm^3underwent a 16 week TI during which time their
anti-retroviral therapy was discontinued. ART was reinstituted in subjects
whose CD4 T-cell counts dropped to <500 cells/mm^3and/or whose HIV-RNA
increased to >100,000 copies/ mL for three consecutive measurements. At the
end of the TI, subjects with a sustained detectable viral load >10,000 copies/
mL or CD4 T-cell count <500 cells/mm^3 were reinstituted on ART. Subjects with
a viral load >10,000 copies/ mL and CD4 T-cell count >500 cells/mm^3 can
remain off ART until HIV RNA levels are >10,000 copies/ mL for three
consecutive weeks or their CD4 T-cell count drops below 500 cells/mm^3 for two
consecutive weekly measurements.

Two additional cohorts of three subjects each will be treated at doses of
2000mg/m^2 and 3000mg/m^2, respectively.

About SB-728-T
Sangamo's drug, SB-728-T, is generated by ZFN-mediated modification of the
gene encoding the CCR5 receptor in a patient's own T-cells. ZFN modification
disrupts the expression of this key co-receptor for HIV entry and renders
cells resistant to HIV infection. The approach is based on the observation
that a naturally occurring mutation in the CCR5 gene, CCR5 delta-32, provides
protection from HIV infection. Individuals in whom both copies of the CCR5
gene carry the delta-32 mutation are generally not susceptible to the most
common strain of HIV.

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 and Phase1/2 clinical trials to evaluate the
safety and efficacy of a novel ZFP Therapeutic® for the treatment of HIV/AIDS.
As part of its acquisition of Ceregene Inc., Sangamo acquired a fully-enrolled
and funded, double-blind, placebo-controlled Phase 2 trial to evaluate NGF-AAV
(CERE-110) in Alzheimer's disease. Sangamo's other therapeutic programs are
focused on monogenic diseases, including hemophilia, Huntington's disease and
hemoglobinopathies such as beta-thalassemia and sickle cell anemia. 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, references relating to research and development of novel ZFP TFs
and ZFNs and therapeutic applications of Sangamo's ZFP technology platform for
the treatment of HIV/AIDS, including a potential functional cure for HIV/AIDS,
the ability of a ZFP Therapeutic to control HIV infection, projected timing of
release of SB-728-T clinical data and preclinical data from Sangamo's
monogenic disease programs, the expansion of clinical studies for HIV-infected
individuals and the initiation of additional preclinical studies of ZFN-gene
modification. 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 public
filings with the Securities and Exchange Commission, including the risk
factors described in its Annual Report on Form 10-K and its most recent
Quarterly Report on Form 10-Q. Sangamo assumes no obligation to update the
forward-looking information contained in this press release.

SOURCE Sangamo BioSciences, Inc.

Website: http://www.sangamo.com
Contact: Sangamo BioSciences, Inc.,, Elizabeth Wolffe, Ph.D. 510-970-6000,
x271, ewolffe@sangamo.com
 
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