Sangamo Biosciences Reports Presentation of Clinical Data from Alzheimer's Program

Sangamo BioSciences, Inc. SGMO announced today the presentation of positive data from the Phase 1 clinical trial of CERE-110 (AAV-NGF), a gene therapy approach designed to deliver nerve growth factor (NGF) for the treatment of Alzheimer's disease (AD). This novel product was developed by Ceregene, Inc., which was recently acquired by Sangamo. The data were presented at the Sixth Clinical Trials on Alzheimer's Disease (CTAD) Meeting, which is being held in San Diego from November 14-16, 2013.  (Logo: http://photos.prnewswire.com/prnh/20130102/SF35903LOGO) The data from this dose escalation study demonstrate that surgical delivery of CERE-110 to the brain results in the long-term expression of bioactive NGF, the therapeutic protein.  Clinicians also observed apparent stabilization of brain cell metabolic activity in treated subjects, as determined by PET-scans measuring glucose use, which may reflect a slowing of cell deterioration. The treatment was well-tolerated at all dose levels. "These early clinical data demonstrate that this therapeutic approach is feasible, well-tolerated and results in appropriate delivery of the therapeutic, NGF protein, to the intended target cells in the brain," said Paul Aisen, M.D., Project Director of the ongoing Phase 2 clinical trial of CERE-110 and director of the Alzheimer's Disease Cooperative Study (ADCS) at the University of California San Diego, a preeminent research consortium for testing new treatments for Alzheimer's disease. "We are very pleased to be involved in the Phase 2 clinical trial, which is a placebo-controlled study, and will enable further evaluation of the efficacy of CERE-110. Alzheimer's disease has few effective treatment options, and this therapy could help the over five million people in the U.S. currently living with the disease." The Phase 2 clinical study of CERE-110 is being carried out in collaboration with the ADCS and is funded by a grant from the National Institute on Aging (NIA), part of the National Institutes of Health (NIH). "We are very encouraged by the Phase 1 data from the CERE-110 study," stated Edward Lanphier, Sangamo's president and CEO. "These positive data supported the further testing of this novel approach in a Phase 2 clinical trial to evaluate efficacy. The Phase 2 study is fully-funded and fully-enrolled and currently in the two year follow-up phase. We look forward to presenting data from the clinical trial in 2015." The data, which have been accepted for publication in Alzheimer's and Dementia, the official publication of The Alzheimer's Association (Rafii et al., 2013), were presented by Raymond Bartus, Ph.D., who led the preclinical and early clinical development of CERE-110. It is well-documented that cholinergic nerve cells in the brain degenerate early in AD and are linked to initial memory loss and cognitive decline. Current therapies for AD include a class of small molecule drugs called cholinesterase inhibitors, which aim to preserve or enhance the chemical signaling in cholinergic nerves. However, these drugs have dose-limiting side-effects, do not change the underlying disease process or its progression, are effective for some but not all people, and may help only for a limited time. Research in animal models suggests that growth factors, such as NGF, which promote nerve growth, nerve repair and protect nerves against damage, may improve AD symptoms and slow disease progression. However, delivery of proteins to the appropriate part of the brain, in a manner that enables them to have a therapeutic effect, has proved challenging due to the blood brain barrier. Gene therapy with AAV, combined with stereotactic surgery, enables delivery of the gene encoding a biologically active protein such as NGF to a precise location in the brain.  The nucleus basalis of Meynert (NBM), a structure near the base of the brain, is considered to be the best target for delivery of a gene-based therapeutic for AD as its cells represent the primary source of cholinergic nerves projecting to the brain cortex. Thus, a single treatment of CERE-110 into this structure is expected to provide a safe long-term source of NGF protein that may protect and preserve cholinergic cells in the brains of AD patients and potentially slow disease progression.