Data From Sangamo BioSciences, Inc.' Diabetic Neuropathy Program Published In Diabetes
RICHMOND, Calif., May 26 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc. announced today publication in Diabetes, a journal of the American Diabetes Association, of preclinical animal data demonstrating the efficacy of the Company's ZFP Therapeutic(TM), SB-509, for the treatment of diabetic neuropathy. The positive data reported in the peer-reviewed article, suggest that SB-509 may provide a promising, new approach to treating this condition, one of the most common complications of diabetes. The data also support Sangamo's ongoing clinical program in diabetic neuropathy. The Company has announced that it expects to initiate a Phase 2 study of SB-509 in the second half of 2006. The Diabetes article entitled, "Gene Transfer of an Engineered Transcription Factor Promoting Expression of VEGF-A Protects Against Experimental Diabetic Neuropathy" is available on line at http://diabetes.diabetesjournals.org/.
SB-509 is 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), which has been shown to have direct neurotrophic and neuroprotective properties. In the preclinical study published in Diabetes, single and repeat intramuscular injections of SB-509 in rats with diabetes resulted in protection of nerve function in the treated limb as measured by sensory and motor nerve conduction velocities. The study was conducted in the laboratory of Professor David Tomlinson of the University of Manchester, U.K.
Philip Gregory, D. Phil., Sangamo's vice president of research and an author on the Diabetes paper, commented, "Intramuscular injection of SB-509 in an animal model of diabetic neuropathy preserved nerve conduction velocity, a key measure of nerve function. Remarkably, a single administration of SB-509 resulted in a positive outcome 28 days after administration and even more robust effects on nerve conduction velocities were observed with multiple dosing of the animals. In addition, in previous preclinical studies, we have demonstrated that Sangamo's VEGF ZFP TF activates all major forms of the VEGF gene, which we believe is important in replicating the full biological role of this growth factor. These encouraging preclinical findings provided a firm foundation for initiating Sangamo's clinical program in patients with diabetic neuropathy."
Sangamo recently announced the completion of the treatment portion of a Phase 1a dose-escalation study of SB-509 in subjects with mild to moderate diabetic neuropathy. The results of this trial were reported at the 58th Annual Meeting of the American Academy of Neurology in San Diego in April 2006. Additional data from ongoing clinical trials will be presented at the American Diabetes Association 66th Annual Scientific Sessions, which will be held June 9-13, 2006 in Washington, DC.
According to Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer, "SB-509 is designed to directly address the underlying problem of nerve damage in diabetic neuropathy, an important advance over current therapies which only address pain symptoms. Our Phase 1a study demonstrated that a single administration of SB-509 is well tolerated in humans. Importantly, we were able to treat subjects within the pharmacologically effective dose range demonstrated to be efficacious in the preclinical animal studies that are being published in our Diabetes paper. In addition, we saw anecdotal evidence of improvement in clinical symptoms in some subjects. Encouraged by these data, we initiated a Phase 1b study that will enable us to extend these observations. We also plan to initiate a multi-center Phase 2 clinical trial using a similar design with a repeat dosing protocol in the second half of this year. We intend to present our clinical data, when appropriate, at upcoming meetings over the coming year including the American Diabetes Association Scientific Sessions in June."
"We are delighted by the progress of our clinical program in diabetic neuropathy and by the reception that the data have received from the medical and scientific community," said Edward Lanphier, Sangamo's president and CEO. "We believe that SB-509 may provide a novel and much-needed therapeutic approach to diabetic neuropathy and optimistically look forward to the next stage of development of this novel therapeutic."
About Sangamo's Clinical Program in Diabetic Neuropathy
Sangamo's Phase 1a dose-escalation study enrolled twelve subjects with mild to moderate diabetic neuropathy, each of whom 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. The subjects were examined at 1, 2, 3 and 6 months post-treatment. Most of the subjects had type 2 diabetes. There were no subject dropouts, and the only adverse events reported were mild injection site reaction in four of the twelve subjects that resolved quickly.
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. The study demonstrated that a single treatment of SB-509 in one leg was well tolerated and associated with improvements in pain, numbness and neurological symptoms in approximately 50 percent of subjects.
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, Total Neuropathy Score (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 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.
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 patients 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 research and development of novel ZFP TFs and ZFNs, applications of Sangamo's ZFP TF technology platform and clinical trials of ZFP Therapeutics. Actual results may differ materially from these forward-looking statements due to a number of factors, including technological challenges, uncertainties relating to the initiation and completion of stages of the ZFP Therapeutic clinical trials, 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.Sangamo BioSciences, Inc.
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