RICHMOND, Calif., Jan. 19 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today that preliminary data from the University of Pennsylvania investigator sponsored Phase 1 safety study of Sangamo's zinc finger nuclease (ZFN) based product, SB-728-T, for HIV/AIDS were presented on Friday, January 15, 2010 at the Keystone Symposium Session "HIV Biology and Pathogenesis." Sangamo's collaborator, Carl June, M.D., Director of Translational Research at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine, presented the data as an invited speaker in an NIAID Workshop entitled "The Next Challenge: Elimination of HIV Reservoirs."
"While only representative of a single individual in the trial, these data are very exciting," said Dr. June. "They demonstrate that the ZFN-modified T-cells were well tolerated by the body and persisted in the circulation at stable levels for the duration of our monitoring. In fact, we calculate that more ZFN-modified cells were present at 20 weeks than were initially infused. Total CD4+ T-cell counts were also stable during this time. Interestingly, we also observed ZFN-modified cells in the gut associated lymphoid tissue (GALT) which is a major reservoir of immune cells and a critical reservoir of HIV infection and suggests that the modified cells are functioning and trafficking normally in the body."
Dr. June described data from a single HIV- positive subject treated with SB-728-T who, as part of the study, began a structured treatment interruption (STI) from his antiviral drug therapy four weeks after SB-728-T treatment. Twelve weeks later, the STI ended and the subject resumed antiviral therapy. During the study, the subject's CD4+ T-cell count, the number of circulating ZFN-modified cells and viral loads were measured periodically. In addition, rectal biopsies were taken prior to treatment and at the end of the STI period to monitor levels of CD4+ and ZFN-modified T-cells in the GALT.
The subject entered the STI period with stable CD4+ and ZFN-modified T-cell levels and an undetectable viral load. Viral load was monitored with biweekly testing and it was observed that the subject experienced a delay in the return of virus, which was first detectable at six weeks post STI initiation. Previous studies have shown that in subjects undergoing an STI, the average time to detection of an increase in viral load is two to four weeks. At twelve weeks post STI, in accordance with the trial protocol, the subject resumed antiretroviral medication and his viral load decreased. During the monitoring period, the subject continued to demonstrate stable CD4+ T-cell counts and stable levels of ZFN-modified T-cells. In rectal biopsy samples taken at the end of the STI period, ZFN-modified cells were found in GALT suggesting that these cells circulate and traffic normally.
"These are the first human data from a ZFN-based therapeutic and, although preliminary, are very encouraging and recapitulate observations that we have made in preclinical studies," stated Dale Ando, Sangamo's vice president of therapeutic development and chief medical officer. "Importantly, ZFN-modified cells expanded over the period that we monitored the subject and were well tolerated. As expected, the subject's viral load increased during the STI. However, the kinetics of this subject's viral rebound was delayed. Presence of ZFN-modified cells in the GALT, an important HIV reservoir, demonstrates that we are achieving our pharmacologic biodistribution target. GALT HIV persistence in CD4+ T-cells is the reason that HIV is not eradicated in patients who are fully suppressed on highly active anti-retroviral treatment, or HAART. Ultimately, having a protected CD4+ T-cell population in the GALT may be extremely important in combating this disease.
"Our ZFN-based technology provides a totally new approach to HIV/AIDS with the aim of providing a reservoir of functional T-cells that are resistant to infection by HIV and available to fight opportunistic infections, and these data are an early indication that this may be possible."
SB-728-T is a cell product based on Sangamo's ZFN technology. CD4+ T-cells are removed from the subject's blood and treated with Sangamo's ZFNs designed to modify the DNA sequence encoding the CCR5 gene. This modification can occur directly in T-cells with only a brief exposure to the ZFNs. Once the CCR5 gene is modified, the gene is permanently disrupted in these cells.
CCR5 is a co-receptor that enables HIV to enter and infect cells of the immune system. About ten years ago, it was observed that individuals carrying a natural mutation of their CCR5 gene, CCR5-delta32, were highly resistant to infection by HIV. These individuals, lacking a functional CCR5 (approximately 1-2% of the general population), are immunologically "normal". A variety of small molecule and antibody antagonists of CCR5 have been tested and developed as potential therapeutic agents for the treatment of HIV infection. In addition, there is a recent report of a patient who had both HIV and leukemia and received a bone marrow transplant from a donor carrying the CCR5 mutation. After the successful bone marrow transplant, HIV treatment was discontinued and the virus could not be found in the circulating blood several months after the procedure.
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 a Phase 2b clinical trial for evaluation of safety and clinical effect in patients with diabetic neuropathy and a Phase 2 trial in ALS. Sangamo also has two Phase 1 clinical trials to evaluate safety and clinical effect of a treatment for HIV/AIDS and another Phase 1 trial to evaluate safety and clinical effect of a treatment for recurrent glioblastoma multiforme. Other therapeutic development programs are focused on 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 and Sigma-Aldrich Corporation. 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-728-T, tolerability and efficacy of SB 509-728-T, 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 small size of the data set, completion of stages of the SB-728-T clinical trials, whether the SB-728-T clinical trials will validate and support tolerability and efficacy of SB-728-T, 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.