Presentation Details Encouraging Clinical Results for SB-509 in Development
for Treatment of Diabetic Neuropathy
WASHINGTON, June 12 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc.,
(Nasdaq: SGMO) announced today the presentation of encouraging Phase 1b
clinical data from its ZFP Therapeutic(TM) program in a presentation at the
66th Scientific Sessions of the American Diabetes Association (ADA). Sangamo
is developing SB-509, a formulation of 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), for the
treatment of diabetic neuropathy. In the presentation entitled, "Single
Treatment, Phase 1b Trial of a Zinc Finger DNA-binding Protein (ZFP) Activator
(SB-509) of Vascular Endothelial Growth Factor (VEGF) in Subjects with
Diabetic Neuropathy (DN) Shows Clinical Tolerability and Improvements in Pain
and Neurologic Effects," researchers reported positive findings from Sangamo's
Phase 1a and 1b clinical trial in subjects with diabetic neuropathy.
Data presented at ADA demonstrate that a single treatment of SB-509 was
well tolerated and that no severe adverse events were observed. Importantly,
subjects in the Phase 1b study and in the top dose cohorts of the Phase 1a
trial were treated within the pharmacologically effective dose range that had
been demonstrated to be efficacious in preclinical animal studies. Injection
site reactions were the most common adverse events reported and were mild and
reversible.
Clinicians also observed anecdotal clinical improvements in quantitative
sensory testing (QST) which measures perception of vibration, and improvements
in average total neuropathy score (TNS), a composite of several measurements
including neurologic exam, QST, electrophysiologic studies and neurologic
symptoms. A placebo group of 6 subjects, treated in both legs, provides an
important control group and showed a mean deterioration in their average TNS
over two months. In contrast, all subjects treated with SB-509 in one leg in
the Phase 1a portion of the study, and all subjects treated in both legs in
the Phase 1b portion of the study showed anecdotal improvements in neurologic
exam with improved average TNS from baseline. This positive trend in
neurologic function highlights the potential for SB-509 to address the nerve
damage and its potential for nerve regeneration in the treatment of diabetic
neuropathy. The top dose level of 60 mg of SB-509 will be extended to treat
nine subjects with SB-509 and nine subjects with placebo to provide additional
clinical data on the effects of SB-509 in DN patients.
"While we have so far treated a relatively small number of subjects with
SB-509 in our Phase 1a and 1b studies, we continue to observe that the drug is
well-tolerated and are seeing encouraging improvements in the neurologic exam,
as determined by positive changes in the average TNS for treated versus
placebo groups, and in quantitative sensory testing," stated Dale Ando, M.D.,
Sangamo's vice president of therapeutic development and chief medical officer.
"Importantly, we have not observed any severe adverse events or dose-limiting
toxicity in the study, and have been able to treat subjects within the
pharmacologically effective dose range that we had demonstrated to be
efficacious in preclinical animal studies. We expect to treat a further 18
subjects in our Phase 1b study and are optimistically looking forward to
initiating a Phase 2 repeat-dosing study in the second half of this year. "
"We are pleased that our SB-509 diabetic neuropathy program update was
selected for a late-breaking poster presentation during the year's most
significant conference on diabetes," said Edward Lanphier, Sangamo's president
and CEO. "We believe that SB-509 represents a new therapeutic approach for
diabetic neuropathy, designed to directly protect and restore nerve function,
in contrast to the current standard of care designed to address the pain
associated with this condition. The value of this presentation is the release
of our most up-to-date clinical results and the preclinical underpinnings of
this promising research. We are encouraged by the data so far and are swiftly
moving forward with the next stage of clinical development, a Phase 2 clinical
trial that we expect to initiate later this year."
About the SB-509 Clinical Program
Phase 1a
All subjects in the Phase 1a dose-escalation study received a single
treatment of SB-509 in one leg (four dose levels of drug were tested -- 1, 5,
15 and 30 milligrams) and placebo in the other leg and were examined at 1, 2,
3 and 6 months post-treatment. Twelve subjects with mild to moderate diabetic
neuropathy were enrolled and treated in the study. Most of the subjects had
type 2 diabetes. There were no subject dropouts, and the only adverse event
reported was mild injection site reaction in four of the twelve subjects that
resolved quickly. This trial has been completed.
In addition to assessments of clinical and laboratory safety, subjects
were evaluated for changes in pain, numbness, perception of vibration,
strength, sensation, reflexes and nerve conduction studies. Pain was assessed
using one of the most frequently used measurement scales in health care
research, the Visual Analog Scale (VAS). The VAS is an 11-point scale from 0
to 10 with 0 being equivalent to "no pain at all" and 10 being "worst possible
pain." Although five of the subjects continued to see a worsening of their
pain, we observed that fifty percent of subjects experienced a 2-point
decrease in their VAS score over the course of the study. When questioned
about their perception of feeling, fifty percent of subjects also reported
that they were no longer experiencing numbness. Total neuropathy scores (TNS)
were also assessed for each subject. The TNS represents is a composite score
that combines measurements of neurologic symptoms, neurologic examination,
nerve conduction velocity studies (NCV) and quantitative sensory tests (QST),
each assessed on a 5-point scale and is designed to provide a single measure
to quantify neuropathy. Fifty percent of subjects showed 2-point improvements
in their TNS. Nine of the 12 subjects showed 2-point improvements in their
QST scores, four subjects in the SB-509 treated leg alone, three subjects in
both legs and two subjects in the placebo treated leg alone. Studies to
evaluate these bilateral clinical effects are ongoing and include measurements
of serum VEGF levels as well as retrograde or neurovascular transport of
SB-509 and/or VEGF.
Phase 1b
A Phase 1b extension of this study is in progress to assess the safety and
clinical effects of administration of SB-509 to subjects in both legs.
Subjects are randomized and administered either SB-509 or placebo in both legs
by intramuscular injection. Two dose levels of SB-509 are being tested. At
the first dose level, three subjects were administered placebo and three
subjects were treated with a total of 30 mg of SB-509, 15 mg per leg. Accrual
of these subjects is complete. A further eight subjects have been treated at
the second dose level, four with placebo and four with a total dose of 60 mg
of SB-509, administered as 30 mg per leg. Sangamo expects to enroll a further
sixteen subjects to this top dose cohort, eight treated with placebo and eight
treated with SB-509 in both legs. Subjects in this Phase 1b study will be
monitored for both the safety and tolerability of SB-509 treatment as well as
evaluation of pain and clinical effects on lower limb diabetic neuropathy at
one, two, three and six months post-treatment.
Sangamo also plans to initiate a placebo-controlled, multi-treatment Phase
2 study in diabetics with mild to moderate sensory/motor neuropathy in the
second half of this year. Safety will be monitored throughout the study.
Clinical evaluations will include evaluation of pain intensity, TNS,
neurological examination and electrophysiological testing. The Phase 2 study
will be conducted at multiple centers and subject enrollment is expected to
take approximately twelve months.
About SB-509
SB-509 is administered as an injectable formulation of plasmid DNA that
encodes a ZFP TF, designed to upregulate the VEGF-A gene. VEGF-A has been
demonstrated to have direct neurotrophic and neuroprotective properties. In
preclinical animal efficacy studies in a diabetic rat model recently published
in the journal Diabetes, SB-509 has proven effective in protecting motor and
sensory nerve function from disease-induced nerve damage.
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 the period from 2000 to 2001,
this translated to approximately 82,000 amputations. The American Diabetes
Association estimates that there are approximately 18.3 million people with
diabetes in the United States and that of those about 60 percent to 70 percent
have mild to severe forms of neuropathy. According to the Centers for Disease
Control, diabetes is becoming more common in the United States. From 1980
through 2002, the number of Americans with diabetes more than doubled.
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 programs are currently in
Phase 1 clinical trials for evaluation of safety in subjects with diabetic
neuropathy and peripheral artery disease. Other therapeutic development
programs are focused on macular degeneration, ischemic heart disease,
congestive heart failure, neuropathic pain, and infectious 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 therapeutic gene modification as a treatment for a
variety of monogenic diseases, such as sickle cell anemia, and for infectious
diseases, such as HIV. Sangamo has established several Enabling Technology
Agreements with companies to apply 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 trial, whether the SB-509 clinical trial 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 the company's SEC filings, and in
particular, the risk factors described in the company's Annual Report on Form
10-K and its most recent 10-Q. Sangamo BioSciences, Inc. assumes no obligation
to update the forward-looking information contained in this press release.
SOURCE Sangamo BioSciences, Inc.
-0- 06/12/2006
/CONTACT: Elizabeth Wolffe, Ph.D., of Sangamo BioSciences, Inc.,
+1-510-970-6000, ext. 271, ewolffe@sangamo.com; Media, Justin Jackson of Burns
McClellan, Inc. for Sangamo BioSciences, Inc., +1-212-213-0006,
jjackson@burnsmc.com/
/Web site: http://www.sangamo.com /
(SGMO)
CO: Sangamo BioSciences, Inc.; American Diabetes Association
ST: District of Columbia, California
IN: BIO MTC HEA
SU: TDS TRI
AM
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0516 06/12/2006 07:30 EDT http://www.prnewswire.com