Sangamo BioSciences, Inc. Presents Postive Data Showing Pain Reduction by Novel ZFP Therapeutic

SAN DIEGO, Calif., Nov. 5 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc. announced today the presentation of data demonstrating that treatment with a zinc finger DNA-binding protein (ZFP) Therapeutic targeting TrkA, a validated pain receptor, significantly reduced the perception of pain in a mouse model of bone cancer pain. The presentation of in vivo data from this novel therapeutic program was made at Neuroscience 2007, the 37th annual meeting of the Society for Neuroscience in San Diego.

"These positive, proof of principle data highlight the potential for our ZFP technology in the treatment of chronic pain," commented Philip Gregory, D. Phil. Sangamo's vice president of research. "The TrkA-NGF pathway is a well- validated pain target which is the focus of intense effort for the development of new pain therapeutics. Our approach of targeting TrkA at the DNA level using a ZFP repressor delivered directly into the relevant tissue, the affected nerve, derives specificity at two levels and thus avoids possible non-specific effects of a systemic treatment."

Sangamo has developed a ZFP transcription factor (ZFP TF) that represses the expression of the TrkA receptor (neurotrophic tyrosine kinase receptor type 1). TrkA is a high affinity receptor for nerve growth factor (NGF) and has been demonstrated to have a role in pain perception. Mutations in the TrkA gene have been shown to be responsible for congenital insensitivity to pain with anhidrosis (CIPA), a rare genetic disorder characterized by a lack of pain sensation.

"Persistent pain, particularly pain associated with certain cancers, remains an unmet medical need," stated Edward Lanphier, Sangamo's president and chief executive officer. "Approved analgesic approaches have drawbacks. For example, opioids, which are widely prescribed to treat cancer pain, have side-effects that significantly affect a patient's quality of life. There is an urgent need to develop more specifically efficacious drugs directed against new molecular targets, which has thus far proven difficult. We believe that by 'turning off' the expression of pain receptors directly in the affected tissue, our ZFP Therapeutics potentially have significant advantages over approaches that are currently available and under development."

Data Reported in the Neuroscience 2007 Presentation

The reported results demonstrate that Sangamo's ZFP TF represses expression of TrkA in cells in culture. ZFP TF treated cells no longer respond to nerve growth factor stimulation demonstrating that the expression of the TrkA receptor has been turned off. To test whether ZFP-mediated TrkA repression can block pain signaling in a mouse model of bone cancer pain, scientists delivered a gene encoding the ZFP TF using a modified, non-replicating vector derived from the herpes virus (HSV). HSV enables specific and efficient delivery to local nerves (specifically the dorsal root ganglia) through skin injection.

Mice with experimental bone cancer in the right limb were subcutaneously injected in the right foot pad with ZFP TF TrkA-repressor, or positive or negative control vectors and pain behavior assessed one and two weeks later. Pain was assessed in two ways; using a subjective spontaneous ambulatory pain score (SAPS) and via measurement of mechanical allodynia (MA). Tumor-bearing mice inoculated with the ZFP vector had statistically significantly reduced SAPS and MA at both the 1- and 2-week time points compared to tumor-bearing control animals.

Abstract # 904.23/AA27: "An Engineered Zinc Finger Protein Transcriptional Repressor of TrkA Reduces Nociception in a Mouse Model of Bone Cancer Pain"

*H. S. Zhang(1), D. Krisky(2), A. R. McNamara(1), Y. Jouvenot(1), S. Tan(1), S. Huang(3), D. Wolfe(2), J. B. Wechuck(2), S. K. Spratt(1), J. C. Glorioso(3), P. D. Gregory(1), J. R. Goss(3)

(1) Sangamo BioSciences Inc., Richmond, CA; (2) Diamyd Inc., Pittsburgh, PA (a wholly-owned subsidiary of Diamyd Medical, Stockholm, Sweden); (3) Dept. of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA.

About Chronic Pain

As many as 90 million people in the United States suffer from pain with as many as 8 million suffering from severe chronic pain and a further 3 million suffering from severe cancer-related pain. Studies have shown that 90% of patients with advanced cancer experience severe pain, and that pain occurs in 30% of all cancer patients regardless of the stage of the disease. The most common cancer pain is from tumors that metastasize to the bone, the second most common cancer pain is caused by tumors infiltrating nerves. Effective management of such pain remains inadequate. The few drugs currently being used can have very significant side effects and severely affect a patient's quality of life. Chronic pain is a major and underserved market opportunity. The discovery of several new pain-related pathways and drug targets has increased the pharmaceutical industry's focus on this area.

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 research and development of novel ZFP TFs and ZFNs as ZFP Therapeutics, applications of Sangamo's ZFP TF technology platform, strategic partnerships with collaborators 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 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 Quarterly Report on Form 10-Q. Sangamo BioSciences, Inc. assumes no obligation to update the forward-looking information contained in this press release.

CONTACT: Elizabeth Wolffe, Ph.D. of Sangamo BioSciences, Inc.,
+1-510-970-6000, ext. 271, ewolffe@sangamo.com

Web site: http://www.sangamo.com//

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