May 15, 2013
Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the presentation of new clinical data from its program to develop a ZFP Therapeutic
for HIV/AIDS. The data, which demonstrate that SB-728-T treatment results in a reduction in the HIV reservoir in HIV-infected subjects, are being presented at the 16
Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT). The meeting is being held in
Salt Lake City
May 15-18, 2013
HIV-infected subjects enrolled in Sangamo's ongoing SB-728-902 clinical trial (Cohorts 1-3) received a single infusion of SB-728-T which resulted in a durable increase in total CD4 T-cells driven by increased ZFN-modified CD4 central memory T-cells. The extent of exposure of subjects to circulating zinc finger nuclease (ZFN) CCR5 protected CD4 T cells correlated with a long term decrease in the peripheral blood mononuclear cell (PBMC) HIV reservoir as measured by proviral DNA. In addition, two of four evaluable subjects in Cohort 5 of this study showed a decrease of greater than one log in their viral load during a sixteen week treatment interruption (TI) with one of the subjects achieving a transiently undetectable viral load during the TI period. In subjects in which viral load decreased, a measureable anti-HIV response was observed, specifically a multi-functional response of CD8 T-cells to elements of HIV core proteins.
"These data are quite remarkable," commented
, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "In previous clinical studies, a decline in the HIV reservoir has never been observed in subjects on long-term anti-retroviral therapy (ART) and any increase in the levels of CD4 cells in HIV-infected subjects is often associated with a concomitant increase in the size of the reservoir. In contrast, a single SB-728-T treatment of subjects on long-term ART produced a significant and durable improvement in CD4 count and, in the majority of subjects, a notable decrease in the HIV reservoir over time. An observed correlation with circulating ZFN CCR5 protected CD4 cells is extremely promising."
Summary of Clinical Data
SB-728-0902 Cohorts 1-3 in Immunologic Non-Responders (INR)
SB-728-0902 Cohort 5 (CCR5 delta-32 Heterozygotes)
- Treatment of HIV subjects with a single infusion of SB-728-T leads to long term increases in CD4 counts (up to 3 years in some subjects).
- Long-term increases in CD4 counts correlate with increased CD4 central memory and increased ZFN CCR5 protected central memory T-cells.
- The extent of long-term exposure to circulating ZFN-CCR5 protected CD4 cells correlates with long-term decreases in the PBMC HIV reservoir.
SB-728-1101 Immunologic Responders with Cytoxan Conditioning
- Post SB-728-T infusion, a 16-week ART TI can lead to viral load reduction from initial peak.
- Two out of four subjects showed reduction in viral load during TI
- One subject achieved transient undetectable viral load during TI
- The best viral load reduction responses are seen in subjects with CD8 T-cell HIV gag immune responses that are polyfunctional (expression of multiple cytokines) and the highest levels of bi-allelic modification of the CCR5 gene.
Viral load decreases correlate with highest levels of estimated biallelic CCR5 modification
- Accrual and treatment in progress with ten subjects infused to date.
- Analysis of numbers of modified SB-728-T cells and viral load during TI is in progress.
- Decreases in viral load from peak to the end of TI correlated with mean circulating bi-allelic ZFN CCR5 protected CD4 cells during the TI for all patients to date who fully completed TI per protocol in SB-728-Penn, 902 Cohort 5(CCR5 delta-32 Heterozygotes) and 1101 studies.
"These data continue to demonstrate the important link between SB-728-T-driven immune reconstitution and HIV viral load depletion," said
, Ph.D., Co-Director & Chief Scientific Officer, The Vaccine & Gene Therapy Institute of
(VGTI Florida), whose laboratory carried out the immunologic analyses. "Specifically, SB-728-T treatment protects long-term central memory CD4 T-cells from HIV-infection which is key for the successful development of an immunologic approach to HIV. ZFN-protected central memory cells are driving positive effects on total CD4 T-cell counts in treated subjects and appear to also play a role in breaking the cycle of HIV reservoir maintenance. "
"We are very encouraged by our data to date and by our continued progress in understanding the factors required to maximize the potential of this novel immunologic approach to a functional cure for HIV," stated
, M.B., Ch.B
Sangamo's executive vice president of research and development. "Sangamo has demonstrated that we have the necessary factors for success: SB-728-T is well-tolerated; the modified cells engraft and traffic throughout the body, appear to be immunologically active, and importantly, persist.
We observe an unprecedented increase in total CD T-cell levels which correlates with the levels of ZFN-protected CD4 central memory T-cells, and a related long-term decrease in the viral reservoir. We have also observed reduction in viral loads during TI, to undetectable levels transiently in one of four subjects, providing a second example of this observation. Viral load changes during TI continue to correlate with circulating bi-allelic ZFN CCR protected CD4 cells. In addition, we have identified key immunologic markers of inflammation that correlate with the degree of engraftment and can potentially aid in the selection of subjects for which SB-728-T may be most effective."