RICHMOND, Calif., Jan. 9, 2012 /PRNewswire/ -- Sangamo
BioSciences, Inc. (Nasdaq: SGMO) announced today the initiation of
two new Phase 2 clinical studies (SB-728-1101 and SB-728-902,
Cohort 5) in its program to develop a "functional cure" for
HIV/AIDS. Sangamo's ZFP Therapeutic® approach
(SB-728-T) generates T-cells that are resistant to HIV infection
using its zinc finger nuclease (ZFN) technology to permanently
disrupt the DNA sequence encoding CCR5, a co-receptor used by HIV
to enter cells. The company expects to present data from its
SB-728-T HIV clinical trials at appropriate medical meetings in
2012.
"We are delighted to be able to open these two important
clinical studies ahead of schedule," said Geoff Nichol, M.B. Ch.B., Sangamo's executive
vice president, research and development. "Data from earlier Phase
1 trials demonstrated a statistically significant relationship
between the number of circulating T-cells in which both CCR5 genes
are modified and the reduction in HIV viral load in infected
subjects during an interruption of anti-retroviral
therapy. Both of these new Phase 2 clinical trials are
specifically designed to confirm and further investigate these
findings."
The new studies employ two approaches to increase the number of
engrafted T-cells in which both CCR5 gene copies are modified
(biallelically modified) in SB-728-T-treated, HIV-infected
subjects. The first, an extension of an ongoing trial (SB-728-902,
Cohort 5), is designed to further investigate the effect of
SB-728-T treatment on HIV viral load in subjects that are naturally
heterozygous for the CCR5 delta-32 gene mutation (i.e. one of their
two CCR5 gene copies has the mutation and one is normal). The
second study (SB-728-1101), in HIV-infected subjects without the
CCR5 delta-32 mutation, employs a conditioning pretreatment
designed to significantly enhance the number of engrafted
biallelically modified T-cells.
The rationale for the Phase 2 studies is based on data obtained
in a Phase 1 trial of SB-728-T that demonstrated a statistically
significant relationship between the number of engrafted
biallelically modified T-cells and the reduction in HIV viral load
in treated subjects. In this earlier trial, the viral load of
an SB-728-T treated-subject decreased to undetectable levels during
a scheduled treatment interruption (TI). This subject was
heterozygous for the CCR5 delta-32 gene mutation, thus doubling the
number of biallelically modified T-cells after SB-728-T
treatment.
"We are focused on applying our ZFP Technology platform to
develop novel therapeutics to address unmet medical needs," stated
Edward Lanphier, Sangamo's president
and CEO. "In addition to the rapid progress that we are making in
our clinical program to develop a "functional cure" for HIV/AIDS,
we are advancing our preclinical ZFP Therapeutic programs to
engineer genetic cures for monogenic diseases including
hemophilias and hemoglobinopathies such as sickle cell anemia.
Sangamo enters 2012 with a solid cash position which allows us to
aggressively pursue our goals while maintaining our historic
control on cash burn. As such, we plan to end 2012 with at
least $60 million in cash. We look
forward to providing further financial guidance for 2012 as well as
an update on our clinical and preclinical programs and our
corporate partnering activities on our fourth quarter and end of
year 2011 call in early February."
Mr. Lanphier will also provide an update on Sangamo's ZFP
Therapeutic pipeline and an overview of the Company's business
strategy and objectives for 2012 during his presentation at the
30th Annual J.P. Morgan Healthcare Conference at 7:30 am PT, on Thursday,
January 12, 2012. The presentation will be webcast and
available at http://investor.sangamo.com/events.cfm.
About the SB-728-T Program
Sangamo is developing SB-728-T, a ZFN approach to the treatment
of HIV/AIDS. In addition to the newly initiated Phase 2 studies,
SB-728-T is being evaluated in an ongoing Phase 1/2 and two Phase 1
clinical trials to evaluate the safety and clinical efficacy of
this approach in CD4+ T-cells. Sangamo's ZFNs are designed to
permanently modify the DNA sequence encoding CCR5, a co-receptor
that enables HIV to enter and infect cells of the immune system.
Individuals carrying a naturally occurring mutation in both of
their CCR5 genes (homozygotes), a variant known as CCR5 delta-32,
have been shown to be resistant to HIV infection. Building on
this observation, a study published in Blood in December 2010 reported an effective cure when an
AIDS patient with leukemia, the so-called "Berlin Patient,"
received a bone marrow transplant from a "matched" donor homozygous
for the CCR5 delta-32 mutation. This approach transferred
hematopoietic stem cells (HSCs) from the bone marrow of the
delta-32 donor providing a self-renewable and potentially lifelong
source of HIV-resistant immune cells. After transplantation, the
HIV patient was able to discontinue all anti-retroviral drug
treatments, CD4 T-cell counts increased, and HIV viral load dropped
to an undetectable level, demonstrating effective transplantation
of protection from HIV infection.
About SB-728-902 Cohort 5 – Phase 2 Study
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 Highly Active Anti-retroviral
Therapy (HAART) will be 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 will undergo a 16
week TI during which time their anti-retroviral therapy will be
discontinued. HAART will be reinstituted in subjects whose CD4
T-cell counts drop to 100,000 /mL for three consecutive weekly
measurements. At the end of the TI, subjects with a sustained
detectable HIV viral load will be reinstituted on HAART. Subjects
with an undetectable viral load will remain off HAART until HIV RNA
levels are detectable or their CD4 T-cell count drops below 350
cell/mm3 for three consecutive weekly measurements.
About SB-728-1101 – Phase 1/2 Study
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 will evaluate the effect of
escalating doses of Cytoxan on SB-728-T engraftment, the effect of
SB-728-T treatment on viral load following HAART 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 HAART will be enrolled into
3 dose-escalating cohorts (3 subjects/cohort), and will receive
intravenous Cytoxan (200 mg, 500 mg or 1000 mg). Within each
cohort, treatment will be 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 will
be infused with SB-728-T (5 to 30 billion cells). Six weeks after
SB-728-T infusion, subjects with CD4 cell counts >500 cells/mm3
will undergo a 16 week TI during which time their anti-retroviral
therapy will be discontinued. HAART will be reinstituted in
subjects whose CD4 T-cell counts drop 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