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March 6, 2013 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced new data from its program to develop a 'functional cure' for HIV/AIDS in two presentations at the 20
th Conference on Retroviruses and Opportunistic Infections (CROI), held in
March 3 to 6, 2013.
The first presentation described data from the SB-728-T Phase 1 study (SB-728-902, Cohorts 1-3) demonstrating that SB-728-T treatment of HIV-infected subjects leads to durable reconstitution of the immune system driven by increases in total CD4+ central memory T-cells (T
CM) and CCR5-protected T
CM are long-lived, self-renewing cells that have the ability to remember and react against foreign antigens including HIV. The data also showed that certain cell surface marker and gene expression profiles may predict which patients will likely respond best to SB-728-T treatment.
"These important data extend our understanding of why SB-728-T treatment improves the immune system as well as the conditions required for optimal engraftment of ZFN-modified T-cells," said
Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "They confirm that SB-728-T meets the key immunologic requirements for immune reconstitution in HIV-infected individuals. In addition, analysis of cell surface marker and gene expression profiles of immune system cells in subjects who show superior responses to treatment in terms of increased T-cell counts provides us with important indicators that will aid us in the optimization of our clinical trials."
"The ability of SB-728-T to durably reconstitute the immune system in HIV-infected subjects after a single treatment has never been observed before with any other therapeutic approach," commented
Rafick-Pierre Sekaly, Ph.D., Co-Director & Chief Scientific Officer, The Vaccine & Gene Therapy Institute of
Florida (VGTI Florida), whose laboratory carried out the analysis. "Improvement in the overall health of the immune system of HIV-infected individuals, as demonstrated by treatment with SB-728-T, is a key step along the path to developing an immunologic approach to controlling and potentially eliminating the virus. We have analyzed the cells that constitute this unprecedented elevation of total CD4+ cell counts, extending our previous observations that the increase is primarily due to durable expansion of the central memory T-cells. Importantly, the level of ZFN-dependent CCR5 gene disruption is sustained in these cells, which is critical for the durable success of this approach."
HIV destroys the immune system by killing CD4+ T cells. The current standard of care for HIV/AIDS is daily treatment with antiretroviral therapy (ART), which suppresses viral load in the blood of most subjects but does not eliminate the reservoir of HIV-infected cells. In addition, a significant proportion of treated HIV-infected individuals do not experience a restoration of CD4+ T-cell counts to normal levels. SB-728-T treatment, by eliminating the co-receptor, CCR5, which is necessary for HIV entry to CD4+ cells, is designed to provide a CCR5-negative population of CD4+ T-cells that cannot be infected by HIV but are able to fight opportunistic infections and enable the immune system to control and eliminate the virus. Sangamo's clinical studies have demonstrated successful ZFN-dependent CCR5 gene modification of T-cell populations, including critical cell types such as the T
CM. Studies to date have demonstrated that engraftment of SB-728-T is safe, the modified cells are durable and demonstrate prolonged trafficking and dynamic immunological responsiveness in the gut mucosa, an important HIV reservoir. The data presented today demonstrate that SB-728-T treatment leads to unprecedented durable increases in total CD4+ T cells that are correlated with increases in T
CM and ZFN-mediated CCR5-modified T
"These exciting data support our development program for SB-728-T as a potential functional cure for HIV/AIDS," stated
Edward Lanphier, Sangamo's president and CEO. "We have ongoing Phase 2 clinical trials designed to build on our early studies in which we observed a significant correlation between the number of infused CD4+ T cells in which both copies of the CCR5 gene are modified, so-called biallelic modification, and reduction in viral load during a treatment interruption. We intend to present data from these trials this year."
The first of these ongoing trials (SB-728-902 Cohort 5) evaluates the approximate doubling of bi-allelic engraftment that can be achieved in individuals that have a natural mutation of one of their CCR5 gene copies, CCR5 delta-32 heterozygotes, and seeks to confirm an observation of the occurrence of aviremia during ART treatment interruption (TI). The second trial (SB-728-1101) examines the ability of a lymphopenic preconditioning regimen to enhance bi-allelic engraftment and reduce viral load during a TI in subjects in which CCR5 is not mutated.