Sangamo BioSciences Announces Presentation of Preliminary Data From Phase 2 Study of SB-509

Sangamo BioSciences Announces Presentation of Preliminary Data From Phase 2 Study of SB-509 at International ALS Symposium
Early Data Demonstrates Improvement in Muscle Function with SB-509 Treatment Compared to Historic Controls

RICHMOND, Calif., Dec 09, 2009 /PRNewswire-FirstCall via COMTEX News Network/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the presentation of preliminary data from the Phase 2 clinical trial of its ZFP Therapeutic(TM) program to develop SB-509 as a treatment for amyotrophic lateral sclerosis (ALS) at a Work in Progress session at the 20th International Symposium on ALS/MND held in Berlin, Germany.

The preliminary data were from the first subjects enrolled in Sangamo's Phase 2 clinical trial, SB-509-801, and demonstrate an approximate doubling of frequency of improved muscle function in subjects with ALS who received two treatments of SB-509 (32%) compared to matched historic controls (17%). In early stage ALS clinical trials, an historic control is frequently used rather than a placebo to maximize the number of subjects receiving the drug.

Muscle function was assessed by muscle manual testing (MMT), a commonly used ALS endpoint which uses a manual method of functional assessment of 34 muscles over the whole body. In addition, a subset of subjects that showed an increase in muscle function over this period also demonstrated improvement in one or more additional end-points. These end-points include the Revised ALS Functional Rating Scale (ALSFRS-R) which is a validated rating instrument for monitoring the quality of life and progression of disability in patients with ALS and whose scores correlate significantly with survival, and forced vital capacity (FVC), a measure of lung function.

"We desperately need new therapeutics that will alter the relentless deterioration of muscle function that is characteristic of ALS," commented Jeffrey Rothstein, M.D., Ph.D., Director of the Robert Packard Center for ALS Research, Co-Director of the MDA/ALS Clinic and professor of Neurology at the Johns Hopkins University School of Medicine. "The ability to maintain muscle strength or delay its deterioration could have a significant impact on quality of life for persons with ALS."

SB-509 is a transcriptional activator of vascular endothelial growth factor (VEGF-A) which has been demonstrated to have a significant role in ALS. Mutations that reduce levels of VEGF-A expression are linked with progression to ALS and VEGF-A levels are reduced in the spinal fluid of patients with ALS. In addition, in an apparent compensatory response, VEGF receptor levels are increased in both the blood vessels and the spinal cord in ALS patients.

"Preclinical data as well as clinical observations from our studies of SB-509 in diabetic neuropathy demonstrated that this ZFP Therapeutic has an effect on muscle function and we are very pleased to see evidence of a similar effect in subjects with ALS," stated Dale Ando, M.D., Sangamo's Vice President of Therapeutic Development and Chief Medical Officer. "Our primary goal for this study was to assess the safety and tolerability of SB-509 in subjects with ALS and to evaluate a dosing schedule and pattern of drug administration as well as to look for indications of efficacy of the drug. At this point we have full data sets from only a handful of the subjects enrolled in the trial and thus have not completed a full analysis of all of the endpoints. Significant improvements in muscular function have not been seen in previous ALS trials. Any progress in this endpoint may translate into an important benefit in the quality of life of these patients. The drug continues to have an excellent safety profile and these initial results are encouraging not only for ALS but potentially for application in other neuromuscular diseases such as dystrophies and myopathies."

About SB-509

SB-509 is an injectable plasmid encoding a Zinc Finger DNA-binding Protein (ZFP) Transcription Factor (ZFP TF(TM)) designed to upregulate the endogenous expression of the gene encoding vascular endothelial growth factor (VEGF-A). VEGF-A has been demonstrated to have direct angiogenic, 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 the Study, SB-509-801

A total of 45 subjects with ALS were enrolled in this trial and randomized into one of two treatment cohorts. The first cohort (38 subjects) received 60 mg of SB-509 in a divided dose into muscles in the neck, arms and legs. The second cohort (7 subjects) received 60 mg of SB-509 in a divided dose into the muscles in the lower limb in both legs. Each subject receives a total of two treatments of 60 mg of SB-509 intramuscularly three months apart on Day 0 and Day 90 and is followed for six months after administration of the final dose.

Details of Presentation of Preliminary Data from SB-509-801 Study

Wednesday, December 9, 2009

    --  "Plasmid Gene Transfer of Zinc Finger Protein VEGF-A Transcription
        Activator (SB-509) for Treatment of Amyotrophic Lateral Sclerosis - A
        Phase 2 Clinical Trial of SB-509 in ALS." *E. Benaim, S. Hamilton, D.
        Moore and D. Ando, Sangamo BioSciences, Inc., Richmond, California.

Preliminary data were presented from Sangamo's open-label, repeat dosing, Phase 2 clinical study (SB-509-801) in which subjects with ALS were treated at 0 and 90 days with SB-509 in one of two injection patterns. All subjects will be followed for up to 270 days post initial treatment. A total of 45 subjects are enrolled in the study; data are presented here from 22 subjects up to a time point of 120 days post treatment. There were no drug related severe adverse events and the drug was well-tolerated.

In manual muscle testing (MMT), a widely used method of evaluation of muscle function in subjects with ALS, 32% of SB-509 treated subjects in cohort 1 (6/19) demonstrated an improvement in muscle function as assessed by an overall positive slope in their MMT score from day 0 - day 120 compared to historical controls in which 17% improved (26/153). Of the subjects within the intent to treat group who showed improvement in MMT slope across all visit days, 5 also showed parallel improvement in one or more endpoints (ALS-FRS-R and FVC).

A variety of data supporting the use of SB-509 in ALS were presented. These included preclinical experiments from a rat transgenic SOD1 model of ALS that demonstrated improved motor performance and hindlimb grip strength in SB-509-treated compared to placebo-treated animals as well as clinical observations from Sangamo's clinical study of SB-509 in subjects with diabetic neuropathy (SB-509-601). Data from the SB-509-601 study included previously reported dose-related improvements in the muscle testing component of the neurologic exam in the lower limb, or NIS-LL, as well as statistically significant improvements in intraepidermal nerve fiber density (IENFD) in SB-509 treated subjects. In addition, data were also presented demonstrating retrograde neuronal transport in the sciatic nerve back to the dorsal root ganglia of VEGF-A which had been produced in the muscle after IM administration of SB-509 in a diabetic rat model.

About Amyotrophic Lateral Sclerosis (ALS)

More than 30,000 Americans have ALS, according to the ALS Association, a nonprofit organization that supports ALS research and public and patient education about the disease. 3,000 to 5,000 new cases of the disease are diagnosed every year. Men and women of all ethnic and racial groups are equally affected, usually between the ages of 40 and 70. The disease attacks the motor nerves, nerve cells in the brain and spinal cord that control the body's voluntary muscles. As the motor nerves begin to die, the muscles weaken and shrink. Early symptoms of ALS may include unusual tiredness and clumsiness, muscle weakness, slurred speech, and difficulty swallowing. As the disease progresses, patients gradually lose the use of their hands, arms, legs, and neck muscles, ultimately becoming paralyzed. They can speak and swallow only with great difficulty. About half of people with ALS die within three to five years of diagnosis.

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. Sangamo also has two Phase 1 clinical trials to evaluate safety and clinical effect of a ZFP Therapeutic for the treatment of HIV/AIDS. Other therapeutic development programs are focused on cancer, 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) that can control gene expression and, consequently, cell function. Sangamo is also developing sequence-specific ZFP Nucleases (ZFN) for gene modification. Sangamo has established strategic partnerships with companies in non-therapeutic applications of its technology including Dow AgroSciences, Sigma-Aldrich Corporation and several companies applying its ZFP technology to engineer cell lines for the production of protein pharmaceuticals. For more information about Sangamo, visit the company's web site at

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 in ALS, research and development of novel ZFP TFs and ZFNs and therapeutic applications and efficacy of Sangamo's ZFP technology platform for treatment of ALS. 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 company's Annual Report on Form 10-K and 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.
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