Sangamo Presents New Clinical Data at CROI 2013 Demonstrating Persistent
Immune System Improvements After Treatment With ZFN Therapeutic® SB-728-T
Data Demonstrate that SB-728-T Possesses Necessary Immunologic Properties to
Support a 'Functional Cure' for HIV/AIDS
RICHMOND, Calif., March 6, 2013
RICHMOND, Calif., March 6, 2013 /PRNewswire/ --Sangamo BioSciences, Inc.
(Nasdaq: SGMO) announced new data from its program to develop a 'functional
cure' for HIV/AIDS in two presentations at the 20^th Conference on
Retroviruses and Opportunistic Infections (CROI), held in Atlanta from March 3
to 6, 2013.
The first presentation described data from the SB-728-T Phase 1 study
(SB-728-902, Cohorts 1-3) demonstrating that SB-728-T treatment of
HIV-infected subjects leads to durable reconstitution of the immune system
driven by increases in total CD4+ central memory T-cells (T[CM]) and
CCR5-protected T[CM]. T[CM] are long-lived, self-renewing cells that have the
ability to remember and react against foreign antigens including HIV. The
data also showed that certain cell surface marker and gene expression profiles
may predict which patients will likely respond best to SB-728-T treatment.
"These important data extend our understanding of why SB-728-T treatment
improves the immune system as well as the conditions required for optimal
engraftment of ZFN-modified T-cells," said Dale Ando, M.D., Sangamo's vice
president of therapeutic development and chief medical officer. "They confirm
that SB-728-T meets the key immunologic requirements for immune reconstitution
in HIV-infected individuals. In addition, analysis of cell surface marker and
gene expression profiles of immune system cells in subjects who show superior
responses to treatmentin terms ofincreased T-cell counts provides us with
important indicators that will aid us in the optimization of our clinical
"The ability of SB-728-T to durably reconstitute the immune system in
HIV-infected subjects after a single treatment has never been observed before
with any other therapeutic approach," commented Rafick-Pierre Sekaly, Ph.D.,
Co-Director & Chief Scientific Officer, The Vaccine & Gene Therapy Institute
of Florida (VGTI Florida), whose laboratory carried out the analysis.
"Improvement in the overall health of the immune system of HIV-infected
individuals, as demonstrated by treatment with SB-728-T, is a key step along
the path to developing an immunologic approach to controlling and potentially
eliminating the virus. We have analyzed the cells that constitute this
unprecedented elevation of total CD4+ cell counts, extending our previous
observations that the increase is primarily due to durable expansion of the
central memory T-cells. Importantly, the level of ZFN-dependent CCR5 gene
disruption is sustained in these cells, which is critical for the durable
success of this approach."
HIV destroys the immune system by killing CD4+ T cells. The current standard
of care for HIV/AIDS is daily treatment with antiretroviral therapy (ART),
which suppresses viral load in the blood of most subjects but does not
eliminate the reservoir of HIV-infected cells. In addition, a significant
proportion of treated HIV-infected individuals do not experience a restoration
of CD4+ T-cell counts to normal levels. SB-728-T treatment, by eliminating
the co-receptor, CCR5, which is necessary for HIV entry to CD4+ cells, is
designed to provide a CCR5-negative population of CD4+ T-cells that cannot be
infected by HIV but are able to fight opportunistic infections and enable the
immune system to control and eliminate the virus. Sangamo's clinical studies
have demonstrated successful ZFN-dependent CCR5 gene modification of T-cell
populations, including critical cell types such as the T[CM]. Studies to date
have demonstrated that engraftment of SB-728-T is safe, the modified cells are
durable and demonstrate prolonged trafficking and dynamic immunological
responsiveness in the gut mucosa, an important HIV reservoir. The data
presented today demonstrate that SB-728-T treatment leads to unprecedented
durable increases in total CD4+ T cells that are correlated with increases in
T[CM ]and ZFN-mediated CCR5-modified T[CM].
"These exciting data support our development program for SB-728-T as a
potential functional cure for HIV/AIDS," stated Edward Lanphier, Sangamo's
president and CEO. "We have ongoing Phase 2 clinical trials designed to build
on our early studies in which we observed a significant correlation between
the number of infused CD4+ T cells in which both copies of the CCR5 gene are
modified, so-called biallelic modification, and reduction in viral load during
a treatment interruption. We intend to present data from these trials this
The first of these ongoing trials (SB-728-902 Cohort 5) evaluates the
approximate doubling of bi-allelic engraftment that can be achieved in
individuals that have a natural mutation of one of their CCR5 gene copies,
CCR5 delta-32 heterozygotes, and seeks to confirm an observation of the
occurrence of aviremia during ART treatment interruption (TI). The second
trial (SB-728-1101) examines the ability of a lymphopenic preconditioning
regimen to enhance bi-allelic engraftment and reduce viral load during a TI in
subjects in which CCR5 is not mutated.
Sangamo expects to present preliminary data in the first half of 2013 and the
full data set from both trials by the end of 2013.
Abstract #126 "The Central Memory T-cell is the Critical Component for
Sustained CD4+ Reconstitution in HIV Subjects Receiving ZFN CCR5 Modified CD4+
T-cells (SB-728-T)" Wednesday, March 6, 2013
HIV-infected subjects were enrolled in a Phase 1 clinical trial (SB-728-902,
Cohorts 1-3) and received a single dose of SB-728-T (5 to 30 billion cells).
All subjects were on ART and had stably controlled undetectable levels of HIV
in their blood.
The study evaluated safety and tolerability, changes in CD4+ T-cell counts and
the ratio of CD4+ to CD8+ T-cells, as well as persistence of SB-728-T in the
blood and trafficking of these ZFN-modified cells into gut-associated lymph
Analysis of data from subjects in the study presented today demonstrated:
oTreatment of HIV subjects with SB-728-T leads to both acute and long term
increases in total CD4+ T-cell counts.
oObserved level of CD4+ T-cell reconstitution is significantly greater than
in previously published T-cell infusion studies without CCR5 modification.
oLong term increases in total CD4+ T-cell counts correlate with increased
T[CM] and increased ZFN-mediated CCR5 disrupted T[CM].
oLevels of CCR5 disrupted T[CM] were stable or increased over time compared
to other T-cell sub-populations.
oIn addition, analysis of immune cells of treated individuals provided a
specific cell-surface marker profile and "gene expression signature" that
characterized individuals who showed superior responses to treatment in
terms of increased CD4+ T-cell counts.
In the same oral session, data were also presented from a research stage study
conducted in collaboration with scientists in the laboratory of Dr. James A.
Hoxie, Professor of Medicine at the University of Pennsylvania and Director of
the Penn Center for AIDS Research.
Abstract #129 "T-Cells Edited to Express CCR5 or CXCR4 Fused to the C34
Peptide from gp41 Heptad Repeat-2 Exhibit Robust Protection from Diverse HIV-1
Wednesday, March 6, 2013
The data demonstrate potent inhibition of HIV infection in cells expressing a
chimeric protein comprising a portion of the HIV envelope fused to either the
CXCR4 or CCR5 HIV co-receptors. Scientists fused the C34 peptide from the
gp41 portion of the HIV envelope to the amino terminus of either the CXCR4
(C34-X4) or CCR5 (C34-R5) proteins. Importantly, both C34-X4 and C34-R5
demonstrated potent inhibition of infection by either an X4-tropic or
R5-tropic HIV-1 isolate in primary CD4+ T cells, the natural target of HIV.
Webcasts of all the presentations at CROI 2013 can be accessed via the
following link: http://webcasts.retroconference.org/m/2013
SB-728-T is an autologous CD4+ T-cell product in which the gene for CCR5, a
co-receptor for HIV entry, is modified via ZFN-mediated genome editing to
disrupt the CCR5 protein. T-cells with a disrupted CCR5 protein are resistant
to infection by 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 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
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 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 and the initiation
of additional preclinical and clinical 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 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.
Contact: Sangamo BioSciences, Inc., Elizabeth Wolffe, Ph.D., +1-510-970-6000,
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