SAN DIEGO, Nov. 6 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the presentation of additional Phase 1b clinical data from its ZFP Therapeutic(TM) program at Neuroscience 2007, the 37th annual meeting of the Society for Neuroscience. The data demonstrate statistically significant improvements in quantitative measurements of neurological health in subjects with diabetic neuropathy (DN), suggesting an alteration of disease progression.
Additional data were presented suggesting that a single treatment with SB- 509 may increase the mobilization of stem cells into a subject's blood. These circulating stem cells may have implications for the nerve regeneration and nerve and blood vessel growth that have been reported from SB-509 treatment. Sangamo plans to further investigate this observation and evaluate the kinetics of mobilization in a new Phase 2 trial that the Company expects to initiate in the first quarter of 2008 in subjects with mild to moderate DN.
"The data obtained in this clinical trial demonstrate that, six months after a single treatment, SB-509 appears to have not only a neuroprotective but also possibly a neuroregenerative effect," commented the presenter, Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "We are very pleased with these data. We are also excited by the observation of mobilization of aldehyde bright stem cell into the blood stream of subjects with diabetic neuropathy after a single treatment with SB-509. VEGF ZFP TF(TM) treatment appears to mobilize between 100 and 1000-fold more stem cells than are typically being introduced into patients in many of the stem cell therapeutic approaches that are currently being tested.
We believe that exploring this observation of natural mobilization of stem cells in a new Phase 2 trial in subjects with diabetic neuropathy may provide us with valuable mechanistic data that could aid in the ultimate development of this product for a number of neurological and vascular indications. In addition, this may provide us with a pharmacodynamic surrogate biomarker that enables easy monitoring of the response of subjects to SB-509."
SB-509 is a formulation of a zinc finger DNA-binding protein transcription factor (ZFP TF) designed to upregulate the expression of the gene encoding vascular endothelial growth factor (VEGF-A). Sangamo is currently evaluating SB-509 in two ongoing Phase 2 clinical trials for the treatment of diabetic neuropathy.
"We continue to be very pleased and impressed by the disease-altering improvements that we have observed in several measurements of nerve health in subjects with mild to moderate diabetic neuropathy treated with SB-509," said Edward Lanphier, President and CEO of Sangamo BioSciences. "We are also very excited to be evaluating SB-509 in models of spinal cord injury, traumatic brain injury, and in a major new initiative, a Phase 2 clinical trial in Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's disease). We will provide more details about trial design and timing for both our stem cell mobilization and ALS Phase 2 trials at our Analyst Briefing in early December."
Clinical Results Presented at Neuroscience 2007
The data presented at the Society for Neuroscience meeting were collected from subjects with mild to moderate diabetic peripheral neuropathy enrolled in Sangamo's Phase 1b study of SB-509. Subjects received a single treatment in both legs of either placebo (10 subjects) or SB-509 (10 subjects who received 60 mg total dose or 30 mg per leg). All of the subjects completed six-month follow-up testing. Clinicians observed statistically significant clinical improvements in quantitative sensory testing (QST) which quantifies perception of vibration. Specifically, mean QST testing compared to baseline in SB-509 treated patients showed a 25.9% improvement compared to 5.4% worsening in the placebo group (a delta in QST of 31.3%, p
In addition, preliminary data were presented demonstrating a four-fold increase in "aldehyde bright" stem cells in the bloodstream of subjects at 30 days post a single intramuscular treatment with SB-509. This represents an increase of 0.05%-0.1% of circulating blood mononuclear cells corresponding to approximately one billion stem cells in vivo. VEGF ZFP TF treatment appears to mobilize 100-1000-fold more stem cells than are typically being introduced into patients in many of the stem cell therapeutic approaches that are currently being tested. Aldehyde bright stem cells can be identified in the subject's blood by staining with a substrate of aldehyde dehydrogenase, an enzyme that is highly expressed in stem cells. Stem cells can self-renew through cell division giving rise to more stem cells and, under certain conditions, can be induced to become cells with a special function in the body such as nerves and blood vessels. It is believed that in response to long-range signals, stem cells are able to migrate from the blood circulation into areas of injury or degeneration and participate in the repair response. Aldehyde bright stem cell populations of human bone marrow have been shown to be highly enriched in cell types thought to mediate tissue repair, including endothelial, mesenchymal, neural and hematopoietic progenitor cells. Sangamo expects to initiate a Phase 2 clinical trial to further investigate this observation in the first half of 2008.
Preclinical Results from Sangamo's DN program Presented at
Neuroscience 2007
In addition, preclinical animal data will be presented by Sangamo's collaborators in the laboratory of Professor David Tomlinson, Ph.D., Faculty of Life Sciences, University of Manchester, U.K., on Wednesday, November 7, 2007 in a presentation entitled "Effect of Engineered VEGF-A Zinc Finger DNA-Binding Transcription Factor on Diabetic Neuropathy Molecular Markers (MAP kinases). A role for Gp38/Podoplanin?"
About the SB-509 Clinical Program
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 (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 1
The Phase 1b study to assess the safety and clinical effects of a single administration of SB-509 to subjects is ongoing. Subjects were randomized and administered either SB-509 or placebo in both legs by intramuscular injection. Two dose levels of SB-509 have been 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 twenty-two subjects have been treated at the second dose level with either placebo or a total dose of 60 mg of SB-509, administered as 30 mg per leg. 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.
Phase 2
Phase 2 study of SB-509 for mild to moderate DN
The clinical trial is a double-blind, placebo-controlled, repeat-dosing study designed to evaluate the clinical safety and clinical effects of repeat administration of SB-509 in diabetics with mild to moderate diabetic peripheral sensory motor neuropathy in the legs. The trial is being conducted at 19 sites.
Approximately 100 subjects will be enrolled into the trial. Subjects will be randomized to one of two groups in a 2:1 ratio. The larger group (approximately 66 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 33 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 a distribution pattern that targets the skeletal muscle adjacent to the major peripheral nerves in the legs and feet.
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. Investigators will primarily use the total neuropathy score (TNS) to assess signs and symptoms of the condition. A composite scoring system such as the TNS, is widely regarded by neurologists as the most comprehensive approach to evaluating changes in nerve health. In addition to qualitative assessment of symptoms, the TNS includes electrophysiological testing using nerve conduction velocity (NCV) to assess the rate at which a nerve can conduct an electrical signal, and quantitative sensory testing (QST) with the Vibratron II instrument, to assess the threshold of detection of vibration. In addition, skin biopsies will be taken to evaluate the direct therapeutic effect of SB-509 on nerve regrowth. This test is a very sensitive marker of DN severity and may provide an important mechanistic marker for efficacy. Individuals interested in participating in this trial should visit http://www.clinicaltrials.gov/ or the Sangamo website at http://www.sangamo.com/.
The Juvenile Diabetes Research Foundation, or JDRF, the major charitable funding organization of research leading to a cure for type 1 diabetes and its complications, is providing up to $3 million of funding towards this Phase 2 clinical trial pursuant to a research agreement between Sangamo and JDRF.
Sangamo has stated that it expects to complete accrual of this trial by the end of 2007 and to have data in the second half of 2008.
Phase 2 study of SB-509 for moderate to severe DN
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, so-called "blocked nerves". The trial is being conducted at multiple sites.
Approximately 45 subjects will be enrolled in the trial. Subjects will 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 3 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 two treatments (Day 0 and 90). Subjects will receive injections in a distribution pattern that targets the skeletal muscle adjacent to the major peripheral nerves in the legs and feet.
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 use the total neuropathy score (TNS) to assess signs and symptoms of the condition.
Individuals interested in participating in this trial should visit http://www.clinicaltrials.gov/ or the Sangamo website at http://www.sangamo.com/. Sangamo expects to have data from this trial by the end of 2008.
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 (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.
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 20.8 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 program is currently in Phase 2 clinical trials for evaluation of safety and clinical effect in patients with diabetic neuropathy. Phase 1 clinical trials are ongoing to evaluate a ZFP Therapeutic for peripheral artery disease. Other therapeutic development programs are focused on cancer and 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 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 Quarterly Reports 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.
