RICHMOND, Calif., Sept. 12, 2013 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the presentation of new data from its ongoing Phase 2 clinical trial (SB-728-902 Cohort 5) to evaluate a single infusion of Sangamo's novel ZFP Therapeutic ®, SB-728-T, for the treatment of HIV/AIDS. The data demonstrate functional control of the virus at or below the limit of detection in CCR5 delta-32 heterozygote HIV-infected subjects treated with SB-728-T. The abstract was selected as a "late-breaker" presentation at the 53 rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). On Wednesday, September 11, data were also presented demonstrating depletion of the HIV viral reservoir in SB-728-T treated subjects in cohorts 1-3 of the SB-728-902 study.
Data from the late-breaking presentation demonstrate that viral load (VL) became undetectable during a treatment interruption (TI) from antiretroviral therapy (ART) in three of seven evaluable CCR5 delta-32 heterozygote HIV-infected subjects, including two of six subjects that had completed TI in the ongoing SB-728-902 Cohort 5 study and an additional subject from an earlier Phase 1 clinical trial of SB-728-T. In one SB-728-902 Cohort 5 subject, VL has remained undetectable (at or below the limits of quantification (LOQ) of the current ultra-sensitive assays for HIV) for seven weeks (to last measurement taken) and the TI is ongoing. Reduction in VL from peak during TI showed a statistically significant correlation (p=0.015) with estimated numbers of engrafted ZFN modified cells (SB-728-T) in which both copies of the CCR5 gene had been disrupted (biallelic modification), in line with previously presented data from this program.
"The data presented today demonstrate that a single infusion of SB-728-T can lead to profound suppression of viral load in the blood and sustained functional control of the virus," stated Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "This is the first evidence that sustained functional control of HIV in the absence of ART is possible. The fact that three of the seven evaluable CCR5 delta-32 subjects achieved undetectable levels is a major step toward immunological functional control of HIV. We look forward to following these Cohort 5 subjects and presenting a complete data set from this study by the end of the year."In a presentation on September 11, 2013 entitled " Host Immune Environment Significantly Impact the Level of CD4 Reconstitution and the Effects on Latent Reservoir in HIV Subjects Receiving ZFN CCR5 Modified CD4 T-cells (SB-728-T)," data were presented that demonstrated that treatment of HIV infected subjects with SB-728-T leads to a long term increase in CD4 counts. The effect on total CD4 counts in SB-728-T-treated subjects was significantly greater than those observed in previously published T-cell infusion studies without CCR5 modification and correlated with increased CD4 central memory and increased CCR5-disrupted central memory cells. In addition, a median 0.6 log reduction decrease in the size of the HIV reservoir at twelve months was observed, as demonstrated by measurement of HIV total DNA in peripheral blood mononuclear cells (PBMCs). The decrease in reservoir showed a statistically significant correlation with the improvement in CD4 count. Finally, data were presented describing possible predictors of robust CD4 T-cell reconstitution and immunological response post SB-728-T infusion. "These data are extremely important and suggest that an immunological approach to control of HIV infection is obtainable," commented Rafick-Pierre Sekaly, Ph.D., Co-Director & Chief Scientific Officer of the Vaccine & Gene Therapy Institute of Florida (VGTI Florida), and a collaborator on the study. "SB-728-T treatment results in an unprecedented and durable increase in CD4+ cells primarily due to the expansion of central memory cells - CD4+ T-cell types that are vital for the successful reconstitution of the immune system in HIV-infected individuals. This enables functional control of virus and effects on the latent reservoir of HIV-infected cells that cannot be cleared by ART." Central and transitional memory T-cells remember previously encountered foreign invaders, such as viruses or bacteria. These cells can survive in the body for the individual's lifetime and reactivate when they re-encounter the same antigen. On reactivation they produce a faster and stronger immune response than the previous encounter. SB-728-T seems to both expand the total memory pool and, by CCR5 modification, protect a proportion of that pool from HIV entry, suggesting that SB-728-T treatment has the potential to durably reconstitute and protect an effective immune system in HIV-infected individuals.