MIAMI, May 19 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc. announced today the presentation of data from a Phase 1 clinical trial of a zinc finger DNA-binding protein activator of vascular endothelial growth factor (ZFP-VEGF) in subjects with critical limb ischemia (CLI). The data demonstrate that administration of ZFP-VEGF resulted in a statistically significant increase in circulating progenitor or stem cells in the peripheral blood. In addition, within a subgroup in which bone marrow cells were examined before and after treatment, the data suggests that subjects who showed the most marked clinical improvements, as judged by limb salvage, ulcer healing, reduction in pain and increased oxygen concentrations in the tissues, also showed the greatest increase in bone marrow stem cells. The trial was conducted by principal investigator Brian Annex, M.D., Director, Vascular Medicine and his colleagues at Duke University Medical Center.
“The data obtained in this clinical trial are very interesting and may have important implications for assessing biological activity and efficacy of this therapeutic strategy,” commented the presenter, Robert Mitchell, M.D., of the department of medicine at Duke University Medical Center. “Several of the subjects in this trial were already scheduled for amputation but chose to enroll in this important trial. Within a subgroup analysis, the data demonstrate that the best clinical responders had the largest fold increase in bone marrow stem cells twelve days after dosing. Increased mobilization of stem cells, which may be involved in tissue regeneration and repair, may provide an early indication of a biological response to this therapy.”
“These data, and other clinical and preclinical observations of natural mobilization of stem cells in a response to our ZFP activator of VEGF, are very interesting and form the basis of our most recently initiated Phase 2 study (SB-509-703),” commented Dale Ando, M.D. Sangamo’s vice president of therapeutic development and CMO. “In this Phase 2 clinical trial we are monitoring changes in the numbers of stem cells in the circulation of subjects with mild to moderate diabetic neuropathy after treatment with our ZFP Therapeutic. We believe that the study may provide us with valuable pharmacodynamic data on the relationship between stem cell mobilization and treatment.”
Clinical Results Presented at the ISCT Meeting
The data presented at the ISCT meeting on Sunday, May 18, 2008, were collected from a single arm, open-label, Phase 1 clinical trial in subjects (n=20) with critical limb ischemia (Rutherford Grade 4/5). Qualifying subjects were assigned to receive dose-escalating, intra-muscular injections of ZFP-VEGF in the ischemic leg (index leg). Subjects were clinically classified as significant responders, minimal responders or non-responders based on their tissue oximetry readings. Circulating progenitor cells were measured and quantitated by FACS analysis based on aldehyde dehydrogenase activity (ALDH+) and expression of CD34 in 11 subjects. These measures were subsequently compared with clinical outcomes. Additionally, bone marrow samples from 8 patients were evaluated for ALDH+ cells on Day 0 and Day 12 post treatment to determine the effects of ZFP-VEGF on progenitor cell mobilization.
Clinicians observed a mean increase in circulating CD34+/ ALDH + cells of 1.3 fold from Day 0 to Day 30 post-treatment and 1.9 fold from Day 0 to Day 90 post-treatment. In addition, subjects with 7 to 9 fold increases in bone marrow stem cells were also the best clinical responders as assessed by increased tissue oxygen perfusion, improved pain scores, ulcer healing and amputation rates.
Aldehyde bright stem cells can be identified in the subject’s blood or bone marrow 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.
“We are pleased to have an opportunity to highlight several of our ZFP Therapeutic programs at this meeting focused on development of novel cell therapies,” said Edward Lanphier, Sangamo’s president and CEO. “The stem cell data that Dr. Mitchell presented align well with observations that we and our collaborators have made in both preclinical animal models of angiogenesis and in our early clinical studies of our ZFP activator of VEGF, SB-509. We look forward to the data from our ongoing Phase 2 clinical trial, SB-509-703 which is designed to investigate this potentially useful effect of our ZFP Therapeutic as a means of mobilizing cells that have a function in tissue repair and regeneration.”
Other Presentations of Data from Sangamo Programs at the ISCT Meeting
In addition, preclinical data is being presented from Sangamo’s ZFP Therapeutics programs in glioblastoma and HIV/AIDS.
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 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.
CONTACT: Elizabeth Wolffe, Ph.D. of Sangamo BioSciences, Inc.,
+1-510-970-6000, x271, ewolffe@sangamo.com
Web site: http://www.sangamo.com//
