Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced that data from its Phase 1 clinical programs to develop SB-728-T, a novel therapeutic approach designed to generate a "functional cure" for HIV/AIDS, were presented at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). The meeting is being held in San Francisco from September 9-12, 2012.
"The immunologic data presented at ICAAC have predictive implications for the success of this exciting new therapeutic approach to HIV and the realization of a 'functional cure' for the disease," commented Rafick-Pierre Sékaly, Ph.D., Co-Director & Chief Scientific Officer, the Vaccine & Gene Therapy Institute of Florida (VGTI Florida), whose laboratory carried out the analysis. "SB-728-T treatment results in an unprecedented and durable increase in CD4+ cells. Importantly, our analysis shows that this is primarily due to the expansion of CD4+ T-cell types that are vital for the successful reconstitution of the immune system in HIV-infected individuals - the central and transitional memory cells."
"These data are very important because CD4 T-cells, especially memory T-cells, are precisely the cell type that we would want to protect and expand to enable HIV-infected individuals to control infections, and HIV, without antiretroviral drugs," added Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "Our aim is to provide a protected reservoir of immune memory cells to replenish the cells killed by HIV and to generate an effective immune response against the virus and opportunistic infections. 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 when they re-encounter the same antigen they reactivate, producing 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 treatment has the potential to reconstitute and protect an effective and durable immune system in HIV-infected individuals."
SB-728-T is generated by ZFN-mediated modification of the gene encoding the CCR5 receptor in a patient's own T-cells, disrupting the expression of this key co-receptor for HIV entry and rendering the modified cells resistant to HIV infection.
In an oral presentation made on Monday, September 10th, 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/mm3 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 (TTM). The frequency of TTM 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 TTM 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 (TCM). Specifically, while the magnitude of the increase in TTM positively correlated with the peak of CD4+ T cells in the first weeks post-infusion (r= 0.9, p=0.083), the increase in TCM 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.
"Our Phase 1 trials continue to provide valuable insight into the durability and unprecedented effects of SB-728-T treatment on immune system health in HIV-infected individuals," said Geoff Nichol, M.B., Ch.B., Sangamo's executive vice president of research and development. "In addition we are making good progress in two Phase 2 clinical trials designed to maximize the engraftment of SB-728-T. We expect to present preliminary data in the first half of 2013 and a full data set in the second half of next year. The ground-breaking clinical data that we and our collaborators are generating continues to validate this treatment as a promising approach to provide a 'functional cure' for HIV/AIDS."
Affordability and supply remain critical to the success of long-lasting HIV drug