<< Back
Sangamo BioSciences Announces 'Late-Breaking' Presentation of Phase 1b ZFP Therapeutic Data at American Diabetes Association Meeting
 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
-- NYM146 --
0516 06/12/2006 07:30 EDT http://www.prnewswire.com
"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release regarding Sangamo BioSciences's business which are not historical facts are "forward-looking statements" that involve risks and uncertainties. For a discussion of such risks and uncertainties, which could cause actual results to differ from those contained in the forward-looking statements, see "Risk Factors" in the Company's Annual Report or Form 10-K for the most recently ended fiscal year.