Sangamo BioSciences Presents Clinical Data From HIV Study Demonstrating
Sustained Control Of Viremia
Reduction of Viral Load at or Below Limit of Detection Ongoing at 14 Weeks
Additional Presentations of Preclinical Data at Annual Meeting of European
Society of Gene and Cell Therapy (ESGCT)
RICHMOND, Calif., Oct. 28, 2013
RICHMOND, Calif., Oct. 28, 2013 /PRNewswire/ -- Sangamo BioSciences, Inc.
(Nasdaq: SGMO) announced today the presentation of new data demonstrating
sustained control of HIV viral load (VL) at or below the limit of detection
for 14 weeks (at last measurement) in an SB-728-T- treated HIV-infected
subject who was not on antiretroviral therapy (ART). The CCR5 delta-32
heterozygote subject is enrolled in Sangamo's clinical trial (SB-728-902
Cohort 5) and, as part of the clinical trial protocol, is undergoing an ART
treatment interruption (TI), which is ongoing.
Data were presented at the Annual Meeting of the European Society of Gene and
Cell Therapy (ESGCT and SETGyC Collaborative Congress) which is being held in
Madrid from October 25-28, 2013.
"These data demonstrate that sustained functional control of HIV in the
absence of ART is possible with a single SB-728-T treatment," stated Geoff
Nichol, M.B., Ch.B., Sangamo's executive vice president of research and
development. "Our aim is to provide a population of immune memory cells that
are protected from HIV infection and are capable of generating an effective
immune response against the virus throughout the body. These data represent a
further step toward demonstrating the efficacy and durability of this
Dr. Nichol added, "We continue to follow these Cohort 5 subjects and look
forward to presenting a complete data set from this study, and a second
ongoing trial (SB-728-1101), designed to maximize the engraftment of SB-728-T
in subjects who are not CCR5 delta-32 heterozygotes, later this year."
Data from Sangamo's Phase 1 and 2 studies demonstrate that VL became
undetectable during a TI from ART in three of seven evaluable CCR5 delta-32
heterozygote HIV-infected subjects, including two of six subjects that had
completed TI in the ongoing 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. In one SB-728-902 Cohort 5 subject, VL has remained undetectable
(at or below the limits of quantification of the current ultra-sensitive
assays for HIV) for 14 weeks (to last measurement taken) and the TI is
ongoing. Reduction in VL from peak during TI showed a statistically
significant correlation (p=0.015) with estimated numbers of engrafted ZFN
modified cells (SB-728-T) in which both copies of the CCR5 gene had been
disrupted (biallelic modification), in line with previously presented data
from this program.
Collectively, data from these studies demonstrate that in all trial subjects,
SB-728-T treatment results in a durable increase in total CD4 T-cells. In
addition, seven of nine subjects enrolled in Sangamo's Phase 1 study
(SB-728-902 Cohorts1-3) experienced a longer term reduction in the viral
reservoir as measured by HIV DNA in peripheral blood mononuclear cells, a
source of chronic HIV infection not addressed by current ART.
Sangamo scientists and collaborators also presented data from preclinical and
research programs in hemophilia and lysosomal storage disorders,
hemoglobinopathies, cancer, cystic fibrosis, immunodeficiencies and the
application of ZFN-mediated CCR5 modification in stem cells for HIV.
"The presentations at the ESGCT meeting demonstrate the diversity and breadth
of potential therapeutic applications of Sangamo's ZFP technology," said
Edward Lanphier, Sangamo's president and CEO. "We look forward to continuing
to update on our progress in the coming months at a translational medicine
meeting organized by The Lancet entitled, 'What Will it Take to Achieve an
AIDS-free World?' in San Francisco, from November 3-5, as well as at the Sixth
International Workshop on HIV Persistence, Reservoirs & Eradication Strategies
in Miami in early December. In addition, we will present data from Sangamo's
preclinical programs at the Annual Meetings of the Society for Neuroscience in
November and the American Society of Hematology (ASH) in early December."
Presentations at the ESGCT Meeting
Saturday, October 26
o"TCR gene editing for the treatment of hematological malignancies." Chiara
Bonini, San Raffaele Telethon Institute for Gene Therapy, Milan
o"Efficient site-specific integration and in situ gene correction of human
long-term repopulating hematopoietic stem cells by zinc finger nucleases."
Pietro Genovese, San Raffaele Telethon Institute for Gene Therapy, Milan
o"Allele-preferred targeted correction of CFTR gene in Cystic Fibrosis
induced pluripotent stem cells." Brian Davis, University of Texas
Sunday, October 27
o"Gene therapy for sickle cell disease." Donald Kohn, University of
California, Los Angeles
o"Genome editing with zinc finger nucleases." Michael Holmes, Sangamo
o"Targeted transgene integration in human hematopoietic stem cells and
induced pluripotent stem cells from normal donors and SCID-X1 patients."
Angelo Lombardo, San Raffaele Telethon Institute for Gene Therapy, Milan
o"Zinc finger nucleases targeting the beta-globin locus drive efficient
correction of the sickle mutation in CD34+ cells." Megan Hoban, University
of California, Los Angeles
o"Rescue of T-cell deficiency in Prkdc mice by transplantation of
gene-edited hematopoietic cells." Rafael Yanez, Royal Holloway, University
o"ZFN mediated targeting of albumin: a platform for expression of multiple
therapeutic genes in vivo." Xavier Anguela, The Children's Hospital of
o"Development of ZFN-based preclinical in vitro cell model in human
embryonic stem cells for Wiskott-Aldrich syndrome." Pilar Munoz-Fernandez,
GENYO, Pfizer-University of Granada.
Monday, October 28
o"Infusion of ZFN CCR5-modified CD4 T-cells (SB-728-T) led to long term
reconstitution of CD4 T-cells and reduction of HIV-DNA levels in
HIV-infected subjects on ART." Dale Ando, Sangamo BioSciences, Inc.
Summary of Clinical Trial Design
About SB-728-902 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 (5
to 30 billion modified cells). Two months after SB-728-T treatment, subjects
undergo a 16 week TI during which time their ART is discontinued. ART is
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.
A total of ten subjects have been treated in this cohort.
Of the six evaluable subjects, we observed two subjects in which their VL
became undetectable during TI from ART:
oIn one subject, VL suppression at, or below, the limit of quantification
(LOQ) of virus was sustained from week 11 – 25 of TI and the TI is
oIn the second subject there was a transient suppression of VL at or below
oA third subject completed the TI with 1-log decrease in VL from peak.
In three subjects, there was no reduction in VL during the TI, one completed
the TI and in two the TI was terminated early due to their viral loads
exceeding the upper limit allowed in the protocol. A seventh subject has not
completed TI and is still being evaluated.
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.
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.
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
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, 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.
Contact: Sangamo BioSciences, Inc., Elizabeth Wolffe, Ph.D., 510-970-6000,
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