Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the presentation of positive preliminary clinical data from its Phase 1 trial (SB-728-902). The trial is being conducted in immunologic non-responders, HIV-infected subjects who are currently on highly active antiretroviral therapy (HAART) and have undetectable levels of virus but suboptimal CD4+ T-cell counts. The study is designed to evaluate safety and clinical outcomes of Sangamo's zinc finger nuclease (ZFN)-generated CCR5-modified, autologous T-cell product (SB-728-T) for the treatment of HIV/AIDS. CCR5 is the major co-receptor used by HIV to infect cells of the immune system.
"These compelling data provide a mechanistic 'proof of concept' for this novel approach to HIV therapy which shows the most promise of any yet tested," stated Carl June M.D., Director of Translational Research at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine, and an investigator in a second SB-728-T Phase 1 trial that is led by Pablo Tebas, M.D. at the University of Pennsylvania.
"From a single infusion of ZFN-modified cells, substantial and sustained increases in total CD4+ T-cell counts were observed in most subjects. This improvement is greater than we have seen in any previous adoptive T-cell approach. The data are consistent with CCR5-ZFN-modified T-cells being resistant to HIV infection and having a selective advantage in the presence of the virus – just as we saw in the preclinical studies. This is very encouraging as we continue to evaluate the drug in HIV-infected subjects with active infections."
Summary of Clinical Data
The data demonstrate that a single infusion of SB-728-T was well tolerated; the CCR5-modified cells successfully engrafted in all subjects and resulted in a durable improvement in total CD4+ T-cell counts in five of six of the subjects analyzed. In addition, five of the six subjects also exhibited sustained improvements in their CD4:CD8 T-cell ratio, which is an indicator of immunologic health. The ZFN-CCR5-modified cells also exhibited normal T-cell growth kinetics and trafficking and were observed to undergo selective expansion in the gut mucosa, a major reservoir of virus in the body, suggesting, as predicted, that the cells were resistant to HIV infection. These data represent the necessary first steps in the development of a "functional cure" for HIV/AIDS by providing a protected CD4+ T-cell population in these subjects that is resistant to HIV infection.
The presentation will be made at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) which is being held in Boston from February 27 to March 2, 2011. In a late-afternoon session on Wednesday, March 2, 2011, Dr. June will present further data from Sangamo's Phase 1 trials of SB-728-T and Paula Cannon, Ph.D., Associate Professor of Molecular Microbiology & Immunology at the Keck School of Medicine of the University of Southern California (USC), will present preclinical data from Sangamo's program of ZFN-modification of the CCR5 receptor in hematopoietic stem cells. Also at CROI, Sangamo's collaborators at the University of Pennsylvania will describe preclinical data from a program to modify the CXCR4 gene in human CD4+ T-cells. More information about these presentations will be available later in the week.
"These data represent the beginning of a new hope for HIV therapy," said Jacob Lalezari, M.D., the Director of Quest Clinical Research, Assistant Clinical Professor of Medicine at Mount Zion Hospital, UCSF, and one of the principal investigators of the study. "This approach aims to provide a protected reservoir of HIV-resistant T-cells that are available to fight infections including the virus. I look forward to completing the follow-up of this initial study and to working with Sangamo as it expands these studies to include the full range of HIV-infected populations."
Study uncovers key mechanism behind HIV latency