In an oral presentation made on Monday, September 10 th, 2012 at ICAAC, data were presented from all dosing cohorts of Sangamo's Phase 1 dose-escalation study (SB-728-902) in subjects on highly active antiretroviral therapy (HAART). The data demonstrate that SB-728-T infusion in HIV-infected subjects is well-tolerated, and results in significant and sustained increases in CD4+ T-cells above baseline throughout the year-long period reported in the study. Statistically significant improvement in CD4 counts were observed even at 12 months post infusion (p<0.038). In particular, CD4 counts improved to greater than 500 cells/mm 3 in five of nine subjects in the study at one year post-treatment, which is the usual T-cell count threshold for initiation of HAART in HIV-infected subjects.
Analysis of the specific types of CD4 T-cells that comprise the initial increase in CD4+ T-cells post-infusion revealed that they were primarily transitional memory T-cells (T TM). The frequency of T TM expressing CD25 (a marker that identifies activated T-cells) within the SB-728-T product correlated with the peak CD4 count post-infusion (r=0.733, p=0.0172). This suggests that replication of activated T TM SB-728-T cells post-infusion accounts for the initial peak improvement in CD4+ T-cells. As the infused cells consist of only 1-10% of total memory cells at six months post-treatment, the prolonged increase in absolute numbers of CD4+ T-cells may be accounted for by the enhanced survival and differentiation of host central memory T-cells (T CM). Specifically, while the magnitude of the increase in T TM positively correlated with the peak of CD4+ T-cells in the first weeks post-infusion (r= 0.9, p=0.083), the increase in T CM correlated with the maintenance of high CD4+ T cell counts at later time points (r= 0.9, p=0.083). Proliferation of the SB-728-T product post-infusion was sustained over the year-long period reported in the study with median modified circulating cell numbers measured to be 2.04-fold relative to input at 7 days, 0.96-fold at 6 months and 1.15-fold at 1 year post-infusion.
These preliminary data confirm the prolonged engraftment of SB-728-T, and suggest that SB-728-T has the attributes to provide sustained improvement in the CD4 memory compartment and the potential to reconstitute the immune system in immune non-responders.