Sangamo BioSciences Presents Clinical Data Demonstrating HIV Reservoir Reduction in HIV-Infected Subjects Treated with ZFP

    Sangamo BioSciences Presents Clinical Data Demonstrating HIV Reservoir
  Reduction in HIV-Infected Subjects Treated with ZFP Therapeutic®, SB-728-T

Unprecedented Immune Reconstitution Drives HIV Viral Reservoir Depletion

Encouraging Preliminary Anti-Viral HIV Data during Treatment Interruption in
Ongoing SB-728-T Phase 2 Trials

PR Newswire

RICHMOND, Calif., May 15, 2013

RICHMOND, Calif., May 15, 2013 /PRNewswire/ --Sangamo BioSciences, Inc.
(Nasdaq: SGMO) announced today the presentation of new clinical data from its
program to develop a ZFP Therapeutic^® for HIV/AIDS. The data,
whichdemonstrate that SB-728-T treatment results in a reduction in the HIV
reservoir in HIV-infected subjects, are being presented at the 16^th Annual
Meeting of the American Society of Gene and Cell Therapy (ASGCT). The meeting
is being held in Salt Lake City from May 15-18, 2013.


HIV-infected subjects enrolled in Sangamo's ongoing SB-728-902 clinical trial
(Cohorts 1-3) received a single infusion of SB-728-T which resulted in a
durable increase in total CD4 T-cells driven by increased ZFN-modified CD4
central memory T-cells. The extent of exposure of subjects to circulating
zinc finger nuclease (ZFN) CCR5 protected CD4 T cells correlated with a long
term decrease in the peripheral blood mononuclear cell (PBMC) HIV reservoir as
measured by proviral DNA. In addition, two of four evaluable subjects in
Cohort 5 of this study showed a decrease of greater than one log in their
viral load during a sixteen week treatment interruption (TI) with one of the
subjects achieving a transiently undetectable viral load during the TI period.
In subjects in which viral load decreased, a measureable anti-HIV response was
observed, specifically a multi-functional response of CD8 T-cells to elements
of HIV core proteins.

"These data are quite remarkable," commented Dale Ando, M.D., Sangamo's vice
president oftherapeutic development and chief medical officer. "In previous
clinical studies, a decline in the HIV reservoir has never been observed in
subjects on long-term anti-retroviral therapy (ART) and any increase in the
levels of CD4 cells in HIV-infected subjects is often associated with a
concomitant increase in the size of the reservoir. In contrast, a single
SB-728-T treatment of subjects on long-term ART produced a significant and
durable improvement in CD4 count and, in the majority of subjects, a notable
decrease in the HIV reservoir over time. An observed correlation with
circulating ZFN CCR5 protected CD4 cells is extremely promising."

Summary of Clinical Data

SB-728-0902 Cohorts 1-3 in Immunologic Non-Responders (INR)

  oTreatment of HIV subjects with a single infusion of SB-728-T leads to long
    term increases in CD4 counts (up to 3 years in some subjects).
  oLong-term increases in CD4 counts correlate with increased CD4 central
    memory and increased ZFN CCR5 protected central memory T-cells.
  oThe extent of long-term exposure to circulating ZFN-CCR5 protected CD4
    cells correlates with long-term decreases in the PBMC HIV reservoir.

SB-728-0902 Cohort 5 (CCR5 delta-32 Heterozygotes)

  oPost SB-728-T infusion, a 16-week ART TI can lead to viral load reduction
    from initial peak.

       oTwo out of four subjects showed reduction in viral load during TI
       oOne subject achieved transient undetectable viral load during TI

  oThe best viral load reduction responses are seen in subjects with CD8
    T-cell HIV gag immune responses that are polyfunctional (expression of
    multiple cytokines) and the highest levels of bi-allelic modification of
    the CCR5 gene.

SB-728-1101 Immunologic Responders with Cytoxan Conditioning

  oAccrual and treatment in progress with ten subjects infused to date.
  oAnalysis of numbers of modified SB-728-T cells and viral load during TI is
    in progress.

Viral load decreases correlate with highest levels of estimated biallelic CCR5

  oDecreases in viral load from peak to the end of TI correlated with mean
    circulating bi-allelic ZFN CCR5 protected CD4 cells during the TI for all
    patients to date who fully completed TI per protocol in SB-728-Penn, 902
    Cohort 5(CCR5 delta-32 Heterozygotes) and 1101 studies.

"These data continue to demonstrate the important link between SB-728-T-driven
immune reconstitution and HIV viral load depletion," said Rafick-Pierre
Sekaly, Ph.D., Co-Director & Chief Scientific Officer, The Vaccine & Gene
Therapy Institute of Florida (VGTI Florida), whose laboratory carried out the
immunologic analyses. "Specifically, SB-728-T treatment protects long-term
central memory CD4 T-cells from HIV-infection which is key for the successful
development of an immunologic approach to HIV. ZFN-protected central memory
cells are driving positive effects on total CD4 T-cell counts in treated
subjects and appear to also play a role in breaking the cycle of HIV reservoir
maintenance. "

"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 a functional cure for HIV," stated Geoff Nichol, M.B.,
Ch.B., Sangamo's executive vice president of research and development.
"Sangamo has demonstrated that we have the necessary factors for success:
SB-728-T is well-tolerated; the modified cells engraft and traffic throughout
the body, appear to be immunologically active, and importantly, persist.

We observe an unprecedented increase in total CD T-cell levels which
correlates with the levels of ZFN-protected CD4 central memory T-cells, and a
related long-term decrease in the viral reservoir. We have also observed
reduction in viral loads during TI, to undetectable levels transiently in one
of four subjects, providing a second example of this observation. Viral load
changes during TI continue to correlate with circulating bi-allelic ZFN CCR
protected CD4 cells. In addition, we have identified key immunologic markers
of inflammation that correlate with the degree of engraftment and can
potentially aid in the selection of subjects for which SB-728-T may be most

Dr. Nichol continued, "In our ongoing studies, we will continue to investigate
these parameters including the threshold engraftment levels of biallelically
modified T-cells and the types of HIV-reactive cells necessary to mount an
immune response to the virus. We look forward to presenting the results of
these completed studies at the end of 2013."

The data were presented today by Dale Ando, M.D., Sangamo's vice president of
therapeutic development and chief medical officer in a Scientific Symposium
entitled "Challenges and Success of Gene Therapy Product Approval." Dr. Ando
also chaired the symposium.

Data will also be presented from Sangamo's Phase 1 clinical trial SB-728-902
Cohorts 1-3 in a second presentation at 2:15 pm MT, on Thursday, May 16, 2013,
Abst.#: 58 "Long Term CD4 Reconstitution in HIV Subjects Receiving ZFN CCR5
Modified CD4 T-Cells (SB-728-T) May Be Attributed to the Sustained Durability
of the Central Memory T-Cell Subset."

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). The trial enrolled nine HIV-infected subjects
(three cohorts of three subjects each) who have sub-optimal T-cell levels and
no detectable viral load on long-term ART. Subjects remained on their
existing antiviral therapy while receiving treatment with SB-728-T.

About SB-728-902 Cohort 5
Up to 20 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
are being enrolled and will receive a single intravenous infusion of SB-728-T
(5 to 30 billion modified cells). Two months after SB-728-T treatment,
subjects undergo a 16 week TI during which time their anti-retroviral therapy
is discontinued. ART will be reinstituted in subjects whose CD4 T-cell counts
drop to <350 cells/ mm^3 and/or whose HIV-RNA increases to >100,000 /mL for
three consecutive weekly measurements. At the end of the TI, subjects with a
sustained detectable HIV viral load are reinstituted on ART. Subjects with an
undetectable viral load can remain off ART until HIV RNA levels are detectable
or their CD4 T-cell count drops below 350 cell/mm^3 for three 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 one day 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. 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.

At least 9 HIV-infected subjects on ART are being enrolled into 3
dose-escalating cohorts (3 subjects/cohort), and will receive intravenous
Cytoxan (200 mg, 500 mg/m^2 or 1000 mg/m^2). Within each cohort, treatment is
staggered so that each subsequent subject cannot be infused with Cytoxan until
at least 2 weeks after the preceding subject. One day after receiving Cytoxan,
subjects are infused with SB-728-T (5 to 30 billion cells). Six weeks after
SB-728-T infusion, subjects with CD4 cell counts ≥500 cells/ mm^3undergo a 16
week TI during which time their anti-retroviral therapy is discontinued. ART
will be reinstituted in subjects whose CD4 T-cell counts drop to <500
cells/mm^3and/or whose HIV-RNA increases to >100,000 copies/ mL for three
consecutive weekly measurements. At the end of the TI, subjects with a
sustained detectable viral load or CD4 T-cell count <500 cells/ mm^3are
reinstituted on ART. Subjects with an undetectable viral load can remain off
ART until HIV RNA levels are detectable or their CD4 T-cell count drops below
500 cells/mm^3 for three consecutive weekly measurements.

Additional Presentations at ASGCT
Twelve additional presentations from Sangamo and its collaborators will be
featured later in the week and include data from preclinical and
research-stage human therapeutic programs. Therapeutic areas include
additional presentations on HIV/AIDS, ZFP-based approaches for monogenic
diseases such as hemophilia, including applications of Sangamo's proprietary
In Vivo Protein Replacement Platform, hemoglobinopathies, and oncology.
Developments in gene-editing technology applications will also be featured in
presentations at the meeting.

All abstracts for the meeting are available online at 2013 ASGCT Meeting

About Sangamo
Sangamo BioSciences, Inc. is focused on research and development of novel
DNA-binding proteins for therapeutic gene regulation and genome editing. It
has ongoing Phase 2 and Phase 1/2 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 and hemoglobinopathies such as sickle cell anemia and
beta-thalassemia, and a program in Parkinson's disease. 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 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

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 research and development of novel ZFP TFs and ZFNs as ZFP
Therapeutics and therapeutic applications and the scope of such applications
of Sangamo's ZFP technology platform to specific human diseases and unmet
medical needs, including a potential functional cure of HIV/AIDS, the
expansion of clinical studies of SB-728-T in HIV-infected individuals,
expected timing for the presentation of clinical trial data, the development
of ZFP Therapeutics for monogenic diseases and stem cell applications. Actual
results may differ materially from these forward-looking statements due to a
number of factors, including uncertainties relating to whether clinical trials
will validate and support tolerability and efficacy of ZFP Therapeutic
approaches, technological challenges, Sangamo's ability to develop
commercially viable products and technological developments by our
competitors. See Sangamo's SEC filings, and in particular, the risk factors
described in the Company's Annual Report on Form 10-K and 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.

Contact: Elizabeth Wolffe, Ph.D., Sangamo BioSciences, Inc., 510-970-6000
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