Sangamo BioSciences Announces Presentation of Preliminary Data From Phase 1 Safety Trial of SB-728-T for HIV/AIDS
First Human Data from ZFN Clinical Program ZFN-Modified Cells Well Tolerated and Able to Expand
RICHMOND, Calif., Jan. 19 /PRNewswire-FirstCall/ -- Sangamo
BioSciences, Inc. (NASDAQ:SGMO) announced today that preliminary
data from the University of Pennsylvania investigator sponsored
Phase 1 safety study of Sangamo's zinc finger nuclease (ZFN) based
product, SB-728-T, for HIV/AIDS were presented on Friday, January
15, 2010 at the Keystone Symposium Session "HIV Biology and
Pathogenesis." Sangamo's collaborator, Carl June, M.D., Director of
Translational Research at the Abramson Family Cancer Research
Institute at the University of Pennsylvania School of Medicine,
presented the data as an invited speaker in an NIAID Workshop
entitled "The Next Challenge: Elimination of HIV Reservoirs."
"While only representative of a single individual in the trial,
these data are very exciting," said Dr. June. "They demonstrate
that the ZFN-modified T-cells were well tolerated by the body and
persisted in the circulation at stable levels for the duration of
our monitoring. In fact, we calculate that more ZFN-modified cells
were present at 20 weeks than were initially infused. Total CD4+
T-cell counts were also stable during this time. Interestingly, we
also observed ZFN-modified cells in the gut associated lymphoid
tissue (GALT) which is a major reservoir of immune cells and a
critical reservoir of HIV infection and suggests that the modified
cells are functioning and trafficking normally in the body."
Dr. June described data from a single HIV- positive subject
treated with SB-728-T who, as part of the study, began a structured
treatment interruption (STI) from his antiviral drug therapy four
weeks after SB-728-T treatment. Twelve weeks later, the STI ended
and the subject resumed antiviral therapy. During the study, the
subject's CD4+ T-cell count, the number of circulating ZFN-modified
cells and viral loads were measured periodically. In addition,
rectal biopsies were taken prior to treatment and at the end of the
STI period to monitor levels of CD4+ and ZFN-modified T-cells in
the GALT.
The subject entered the STI period with stable CD4+ and
ZFN-modified T-cell levels and an undetectable viral load. Viral
load was monitored with biweekly testing and it was observed that
the subject experienced a delay in the return of virus, which was
first detectable at six weeks post STI initiation. Previous studies
have shown that in subjects undergoing an STI, the average time to
detection of an increase in viral load is two to four weeks. At
twelve weeks post STI, in accordance with the trial protocol, the
subject resumed antiretroviral medication and his viral load
decreased. During the monitoring period, the subject continued to
demonstrate stable CD4+ T-cell counts and stable levels of
ZFN-modified T-cells. In rectal biopsy samples taken at the end of
the STI period, ZFN-modified cells were found in GALT suggesting
that these cells circulate and traffic normally.
"These are the first human data from a ZFN-based therapeutic
and, although preliminary, are very encouraging and recapitulate
observations that we have made in preclinical studies," stated Dale
Ando, Sangamo's vice president of therapeutic development and chief
medical officer. "Importantly, ZFN-modified cells expanded over the
period that we monitored the subject and were well tolerated. As
expected, the subject's viral load increased during the STI.
However, the kinetics of this subject's viral rebound was delayed.
Presence of ZFN-modified cells in the GALT, an important HIV
reservoir, demonstrates that we are achieving our pharmacologic
biodistribution target. GALT HIV persistence in CD4+ T-cells is the
reason that HIV is not eradicated in patients who are fully
suppressed on highly active anti-retroviral treatment, or HAART.
Ultimately, having a protected CD4+ T-cell population in the GALT
may be extremely important in combating this disease.
"Our ZFN-based technology provides a totally new approach to
HIV/AIDS with the aim of providing a reservoir of functional
T-cells that are resistant to infection by HIV and available to
fight opportunistic infections, and these data are an early
indication that this may be possible."
About SB-728-T
SB-728-T is a cell product based on Sangamo's ZFN technology.
CD4+ T-cells are removed from the subject's blood and treated with
Sangamo's ZFNs designed to modify the DNA sequence encoding the
CCR5 gene. This modification can occur directly in T-cells with
only a brief exposure to the ZFNs. Once the CCR5 gene is modified,
the gene is permanently disrupted in these cells.
CCR5 is a co-receptor that enables HIV to enter and infect cells
of the immune system. About ten years ago, it was observed that
individuals carrying a natural mutation of their CCR5 gene,
CCR5-delta32, were highly resistant to infection by HIV. These
individuals, lacking a functional CCR5 (approximately 1-2% of the
general population), are immunologically "normal". A variety of
small molecule and antibody antagonists of CCR5 have been tested
and developed as potential therapeutic agents for the treatment of
HIV infection. In addition, there is a recent report of a patient
who had both HIV and leukemia and received a bone marrow transplant
from a donor carrying the CCR5 mutation. After the successful bone
marrow transplant, HIV treatment was discontinued and the virus
could not be found in the circulating blood several months after
the procedure.
About Sangamo
Sangamo BioSciences, Inc. is focused on the research and
development of novel DNA-binding proteins for therapeutic gene
regulation and modification. The most advanced ZFP Therapeutic(TM)
development program is currently in a Phase 2b clinical trial for
evaluation of safety and clinical effect in patients with diabetic
neuropathy and a Phase 2 trial in ALS. Sangamo also has two Phase 1
clinical trials to evaluate safety and clinical effect of a
treatment for HIV/AIDS and another Phase 1 trial to evaluate safety
and clinical effect of a treatment for recurrent glioblastoma
multiforme. Other therapeutic development programs are focused on
neuropathic pain, nerve regeneration, Parkinson's disease and
monogenic diseases. Sangamo's core competencies enable the
engineering of a class of DNA-binding proteins known as zinc finger
DNA-binding proteins (ZFPs). By engineering ZFPs that recognize a
specific DNA sequence Sangamo has created ZFP transcription factors
(ZFP TF) that can control gene expression and, consequently, cell
function. Sangamo is also developing sequence-specific ZFP
Nucleases (ZFN) for gene modification. Sangamo 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 web site at http://www.sangamo.com/.
This press release may contain forward-looking statements based
on Sangamo's current expectations. These forward-looking statements
include, without limitation, references to the clinical trials of
SB-728-T, tolerability and efficacy of SB 509-728-T, research and
development of novel ZFP TFs and ZFNs and therapeutic applications
of Sangamo's ZFP technology platform. Actual results may differ
materially from these forward-looking statements due to a number of
factors, including uncertainties relating to the small size of the
data set, completion of stages of the SB-728-T clinical trials,
whether the SB-728-T clinical trials will validate and support
tolerability and efficacy of SB-728-T, 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 BioSciences, Inc. assumes no
obligation to update the forward-looking information contained in
this press release.
Source: Sangamo BioSciences, Inc.
CONTACT: Elizabeth Wolffe, Ph.D. of Sangamo BioSciences,
Inc.,
+1-510-970-6000, ext. 271, ewolffe@sangamo.com
Web Site: http://www.sangamo.com/
Posted: January 2010
