Positive Interim Data from Ongoing SB-509-701 Study in Subjects with Moderate to Severe Diabetic Neuropathy and Additional Data from Phase 1b Clinical Trial SB-509-401 RICHMOND, Calif., Sept. 15
RICHMOND, Calif., Sept. 15 /PRNewswire-FirstCall/ -- Sangamo BioSciences,
Inc. (Nasdaq: SGMO) announced today the presentation of positive interim Phase
2 clinical data from its ZFP Therapeutic(TM) program (SB-509-701) at the
International Society for Cellular Therapy (ISCT) Europe Regional Meeting in
Antwerp, Belgium. The data presented demonstrate an improvement in nerve
conduction velocity (NCV) in SB-509 treated subjects with moderate to severe
diabetic neuropathy (DN), a patient population that until now has been
considered impossible to treat.
Sangamo management will host a conference call at 11:00 a.m. ET today to
discuss these data.
In addition, on September 8, 2008, new data were presented from Sangamo's
Phase 1b study (SB-509-401) at the 44th Annual Meeting of the European
Association for the Study of Diabetes (EASD) demonstrating a statistically
significant (p= 0.0016) positive correlation of 2 or more response endpoints
in the SB-509 treated group compared with placebo treated subjects at day 180
post-treatment. Response endpoints were defined as greater than a 14%
improvement in quantitative sensory testing (QST), greater than 0.8
meters/second (m/sec) improvement in NCV and greater than a 3 point
improvement as judged by the Neuropathy Impairment Scale -- Lower Limbs
(NIS-LL). Data have previously been presented from this trial demonstrating a
statistically significant improvement in NIS-LL and QST and trends for
improvement in NCV. Sangamo has a larger, repeat-dosing clinical trial
(SB-509-601) in this population of subjects with mild to moderate DN.
Data presented today at ISCT from the study SB-509-701 were collected from
subjects with moderate to severe diabetic peripheral neuropathy. All subjects
entered the trial with between one and six nerves in the lower limb that were
"blocked" or for which no NCV could be measured. The majority of the subjects
had at least one blocked sural nerve, the most relevant in DN. Subjects
received two treatments in both legs of either placebo (n=10 subjects) or
SB-509 (n=17) (60 mg total dose, 30 mg per leg) one at Day 0 and one at Day
90. Recovery of NCV during 180 days post treatment in subjects who entered the
trial with blocked sural nerves was observed in 75% of the SB-509-treated
subjects compared to 25% of the placebo-treated group. SB-509 was well
tolerated and no drug-related severe adverse events were observed.
"While these are interim data, we are very pleased and excited by the
return of NCV in such a high percentage of these subjects," commented Dale
Ando, M.D., Sangamo's vice president, therapeutic development and CMO. "This
is a patient population for which historically there have been absolutely no
treatment options. This sural nerve recovery data in subjects in the Phase 2
study reinforces our preliminary and surprising data in 3 subjects in the
Phase 1 trial.
The sural nerve on the foot is a sensory nerve and one of the first nerves
to be affected as diabetic neuropathy progresses. However, some of the
subjects enrolled in this study had quite severe neuropathy with all six
nerves of the nerves that we are monitoring blocked. Not surprisingly, we
found that subjects entering the study with fewer blocked nerves showed the
highest rates of response to these two treatments with SB-509.
When we began this trial we chose a more conservative two dose regimen as
this is a sicker population than that originally tested in the Phase 1b study.
The data suggest that two doses are well tolerated and that our observations
from the Phase 1 trial were worth pursuing. We have expanded the trial to
include a third treatment with SB-509 and believe that the increased dose and
increased subject numbers will provide us with valuable information in
determining how well more severely affected DN patients will respond."
A total of 45 subjects have been enrolled in the trial (SB-509-701) who
were randomized to one of two groups in a 2:1 ratio and received 2 treatments
at (Day 0 and Day 90). The trial has also been expanded to include a further
45 subjects randomized in the same ratio who will receive three treatments
(Day 0, Day 60 and Day 120), the same dosing schedule as that used in
Sangamo's Phase 2 trial of SB-509 in subjects with mild to moderate DN
(SB-509-601).
"While these data are from a relatively small number of subjects, we are
very encouraged by the safety of SB-509 in a repeat dosing situation and the
greater evidence for clear improvements that are unprecedented in this
moderate to severe DN population," said Edward Lanphier, Sangamo's president
and CEO. "SB-509 is designed to address nerve damage and these data
demonstrate that SB-509 may have both a neuroprotective and a
neuroregenerative effect and confirm earlier analyses which showed similar
trends. Based on these data and data from our Phase 1b study we expanded the
SB-509-701 trial. Additional data from this expanded trial may provide
important information which could expedite the design of a Phase 3 study. We
also look forward to presenting data from our double blind Phase 2 clinical
trial (SB-509-601) later this year."
Conference Call
Sangamo will host a conference call today, September 15, 2008 at 11:00
a.m. ET, which will be open to the public. The call will also be webcast live
and can be accessed via a link on the Sangamo BioSciences website in the
Investor Relations section under "Events and Presentations"
http://investor.sangamo.com/events.cfm . The webcast replay will also be
available for two weeks after the call. During the conference call, the
company will review the data presented today.
The conference call dial-in numbers are 877-719-9810 for domestic callers
and 719-325-4751 for international callers. The passcode for the call is
4708168. For those unable to listen in at the designated time, a conference
call replay will be available for one week following the conference call, from
approximately 2:00 p.m. ET on September 15, 2008 to midnight, Monday September
22, 2008. The conference call replay numbers for domestic and international
callers are 888-203-1112 and 719-457-0820, respectively. The conference ID
number for the replay is 4708168.
About SB-509
SB-509 is an injectable formulation of a plasmid encoding a zinc finger
DNA-binding protein transcription factor (ZFP TF(TM)) designed to upregulate
the expression of the gene encoding vascular endothelial growth factor
(VEGF-A). VEGF-A has been demonstrated to have direct neurotrophic and
neuroprotective properties. In preclinical animal efficacy studies in a
diabetic rat model (Diabetes, June 1, 2006; 55(6): 1847-1854), SB-509 has
proven effective in protecting motor and sensory nerve function from
disease-induced nerve damage.
Phase 2 study of SB-509 for moderate to severe DN (SB-509-701)
The clinical trial is a single-blind, placebo-controlled, repeat-dosing
study designed to evaluate the clinical safety and clinical effects of repeat
administration of SB-509 in diabetics with moderate to severe diabetic
peripheral sensory motor neuropathy in the legs. The trial is being conducted
at multiple sites, accrual has been completed and plans recently announced to
expand the study and enroll additional subjects.
Accrual of the first part (Part A) of SB-509-701 is complete with 45
subjects enrolled who were randomized to one of two groups in a 2:1 ratio.
The larger group (approximately 30 subjects) was treated by intramuscular
injection of 60 mg of SB-509 (30 mg of SB-509 per leg) into the lower limb and
will be treated every 3 months. The remaining group (approximately 15
subjects) received an equal volume of placebo on the same schedule. Each
subject will receive a total of two treatments (Day 0 and 90). Subjects
receive injections in a distribution pattern that targets the major peripheral
nerves in the legs and feet.
As announced on June 6, 2008, Sangamo will expand the Phase 2 study by
enrolling approximately 45 additional subjects in the trial (Part B). Subjects
will again be randomized to one of two groups in a 2:1 ratio. The larger group
(approximately 30 subjects) will be treated by intramuscular injection of 60
mg of SB-509 (30 mg of SB-509 per leg) into the lower limb every 2 months.
The remaining group (approximately 15 subjects) will receive an equal volume
of placebo on the same schedule. Each subject will receive a total of three
treatments (Day 0, 60 and 120). Subjects will receive injections in the same
pattern used in the initial part of the trial.
The symptoms of diabetic peripheral neuropathy and any changes that occur
during the trial will be evaluated based on neurological examination data,
electrophysiological testing data, subject neurological questionnaire, and
subject pain assessment. Specifically, investigators will measure NCV, will
assess pain using VASPI, and use scoring systems such as a modified NIS-LL and
TNS to quantify neurologic exam and assess signs and symptoms of the
condition.
For each subject the trial is expected to take approximately fourteen
months: two months for screening, three months for subject treatment and a
further nine months for subject follow-up. Individuals interested in
participating in this trial should visit http://www.clinicaltrials.gov/ .
About Diabetic Neuropathy
Diabetic peripheral neuropathy is one of the most frequent complications
of diabetes. Symptoms include numbness, tingling sensations and pain
particularly in the toes or feet. This gradually evolves to loss of sensation
and motor function as nerve damage progresses. Ulcers and sores may appear on
numb areas of the foot because pressure or injury goes unnoticed. Despite
adequate treatment, these areas of trauma frequently become infected and this
infection may spread to the bone, necessitating amputation of the leg or foot.
More than 60 percent of non-traumatic lower-limb amputations in the United
States occur among people with diabetes. In 2004, this translated to
approximately 71,000 amputations. Diabetes is a growing problem, the Centers
for Disease Control estimates that from 1980 through 2007, the number of
Americans with diabetes increased from 5.6 million to 23.6 million and that of
those about 60 percent to 70 percent have mild to severe forms of neuropathy.
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
Phase 2 clinical trials for evaluation of safety and clinical effect in
patients with diabetic neuropathy and ALS. Other therapeutic development
programs are focused on cancer, HIV/AIDS, 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(TM)) that can control gene expression and, consequently, cell
function. Sangamo is also developing sequence-specific ZFP Nucleases
(ZFN(TM)) for gene modification. Sangamo has established strategic
partnerships with companies outside of the human therapeutic space including
Dow AgroSciences, Sigma-Aldrich Corporation and several companies applying its
ZFP Technology to enhance the production of protein pharmaceuticals. 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-509, 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 initiation and completion of stages of the
SB-509 clinical trials, whether the SB-509 clinical trials will validate and
support tolerability and efficacy of SB-509, 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 it's 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.
