"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
"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."
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
"These data represent the beginning of a new hope for HIV therapy," said
SB-728-T is an autologous CD4+ T-cell product modified with Sangamo's ZFN technology to specifically and permanently modify the cell's own DNA sequence encoding CCR5. CCR5 is the major co-receptor used by HIV to infect cells. A naturally occurring mutation of the CCR5 gene, CCR5-delta32, has been shown to provide protection against HIV infection. Sangamo scientists have demonstrated that CCR5-specific ZFNs can be used to disrupt the CCR5 gene and make human CD4+ T-cells resistant to HIV infection. Sangamo's SB-728-902 Phase 1 study is designed to evaluate single escalating doses of SB-728-T in subjects that have sub-optimal CD4+ T-cell counts despite long-term HAART and no detectable viral load. This group represents approximately thirty percent of all HIV-infected patients in the US. The trial has recently been expanded to add an additional cohort of subjects that are failing HAART and have active viral infections. In addition, Sangamo has an ongoing Phase 1 / 2 clinical trial, SB-728-1002, in HIV-infected subjects that are viremic but not currently on HAART.
"While preliminary, these data are very encouraging and an early validation of the feasibility of our novel gene modification approach for the treatment of HIV/AIDS," said
"This presentation is a terrific beginning to a transformational year of clinical data for Sangamo," stated
† (Nat Biotechnol. 2008 Jul;26(7):808-16 Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases).
About the SB-728-T Clinical Trial (SB-728-902)
The study is an open-label Phase 1 clinical trial to evaluate the safety and tolerability of single infusions of an escalating dose of an autologous (a patient's own) CD4+ T-cell product genetically modified at the CCR5 gene by CCR5-specific ZFNs (SB-728-T). The trial will enroll a total of nine HIV-infected subjects (three cohorts of three subjects each) who have sub-optimal T-cell levels and no detectable viral load on long-term HAART. The trial has three dosing cohorts. Subjects will remain on their existing antiviral therapy while receiving treatment with SB-728-T. A fourth cohort, of up to four subjects who have failed HAART and have measureable viral loads, was recently added to the study. No data from subjects in the last two cohorts of this study were reported in today's CROI presentation. The primary objective of the study is to evaluate the safety and tolerability of SB-728-T. In addition to safety monitoring, data are being collected on the expansion, trafficking and persistence of SB-728-T, total CD4+ T-cell counts, CD4:CD8 T-cell ratios and viral load.
Dr. June has no financial relationship with
ZFP Therapeutic® is a registered trademark of
This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references relating to research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo's ZFP technology platform for the treatment of HIV/AIDS, including a potential functional cure of HIV/AIDS the expansion of clinical studies for HIV-infected individuals, presentation of data from research collaborations and expected timing for clinical trial data. 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 our clinical trials, whether the clinical trials will validate and support the tolerability and efficacy of ZFNs, technological challenges, Sangamo's ability
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