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."
SOURCE Sangamo BioSciences, Inc.