Sangamo BioSciences Presents Clinical Data From SB-728-T HIV Studies

(RTTNews) - Sangamo BioSciences Inc. (SGMO) announced the presentation of data from all dose cohorts in the Company's ongoing clinical trials (SB-728-1101 and SB-728-902 Cohort 5) of SB-728-T, which is being developed for the functional control of HIV/AIDS.

Sangamo's Phase 1 data suggested that if a threshold level of engraftment of SB-728-T was achieved, specifically of CD4 cells fully protected from HIV entry by zinc finger nuclease (ZFN)-mediated modification of both CCR5 genes (biallelic modification), then functional control of HIV infection may be possible.

The company said new data from the SB-728-1101 study demonstrating a clear relationship between increasing the dose of Cytoxan and increased levels of both engrafted SB-728-T and total CD4 T-cell counts further support this hypothesis and suggest that with these, or higher doses, levels of SB-728-T that will enable functional control of the virus may be reliably attained.

Each of the two trials addressed a different approach to maximizing engraftment of infused SB-728-T that had undergone biallelic modification of the CCR5 gene. Inclusion of newly eligible subjects in the analysis strengthened previous data demonstrating a statistically significant correlation (p=0.008) between estimated number of engrafted biallelically modified cells and the reduction in viral load or VL during a treatment interruption or TI from antiretroviral therapy (ART).

In the SB-728-902 Cohort 5 study, bialleic modification of the infused CD4 cells could be approximately doubled by treating subjects heterozygous for the naturally occurring CCR5 delta-32 mutation. Three of eight evaluable CCR5 delta-32 heterozygous subjects with high levels of engraftment achieved a VL at or below the limit of quantification during a TI. This includes two of seven subjects that had initiated TI in the SB-728-902 Cohort 5 study and an additional CCR5 delta-32 heterozygote subject from an earlier Phase 1 clinical trial of SB-728-T.

The company noted that the SB-728-1101 study aimed to demonstrate enhanced engraftment of SB-728-T modified CD4 cells following cyclophosphamide (Cytoxan) preconditioning. Cytoxan is a drug that is used to transiently reduce the numbers of T-cells in the body, which then rapidly repopulate once the drug is discontinued and it is into this "growth" environment that SB-728-T is infused. This study was successful in showing a Cytoxan-dose dependent increase in both SB-728-T and total CD4 T-cells at the beginning of the treatment interruption, which in the top dose tested (1g/m2) approached the engraftment levels observed in CCR5 delta 32 heterozygote VL responders, and resulted in up to a two-log decrease in VL in one of three subjects who remains on TI and a 0.8-log decrease in a second subject.

The viral reservoir is a source of chronic HIV infection that is not addressed by current ART. All nine subjects enrolled in Sangamo's Phase 1 study (SB-728-902 Cohorts1-3) experienced a long term reduction in the reservoir over three years, as measured by HIV DNA in peripheral blood mononuclear cells (median 0.9 log decrease at Month 36).

Collectively, data from clinical studies demonstrate that in all trial subjects, SB-728-T treatment results in a durable increase in total CD4 T-cells and sustained levels of SB-728-T which correlate with ZFN-modification of long lived central memory and memory stem cell subsets.

Data from immunological analyses of subjects in both Phase 1 and Phase 2 studies of SB-728-T suggest that certain cell surface marker and gene expression profiles may predict which patients will likely respond best to SB-728-T treatment.