Sangamo expects to present preliminary data in the first half of 2013 and the full data set from both trials by the end of 2013.
Abstract #126 "The Central Memory T-cell is the Critical Component for Sustained CD4+ Reconstitution in HIV Subjects Receiving ZFN CCR5 Modified CD4+ T-cells (SB-728-T)"
Wednesday, March 6, 2013 HIV-infected subjects were enrolled in a Phase 1 clinical trial (SB-728-902, Cohorts 1-3) and received a single dose of SB-728-T (5 to 30 billion cells). All subjects were on ART and had stably controlled undetectable levels of HIV in their blood.
The study evaluated safety and tolerability, changes in CD4+ T-cell counts and the ratio of CD4+ to CD8+ T-cells, as well as persistence of SB-728-T in the blood and trafficking of these ZFN-modified cells into gut-associated lymph tissue.
Analysis of data from subjects in the study presented today demonstrated:
- Treatment of HIV subjects with SB-728-T leads to both acute and long term increases in total CD4+ T-cell counts.
- Observed level of CD4+ T-cell reconstitution is significantly greater than in previously published T-cell infusion studies without CCR5 modification.
- Long term increases in total CD4+ T-cell counts correlate with increased T
CM and increased ZFN-mediated CCR5 disrupted T
- Levels of CCR5 disrupted T
CM were stable or increased over time compared to other T-cell sub-populations.
- In addition, analysis of immune cells of treated individuals provided a specific cell-surface marker profile and "gene expression signature" that characterized individuals who showed superior responses to treatment in terms of increased CD4+ T-cell counts.
In the same oral session, data were also presented from a research stage study conducted in collaboration with scientists in the laboratory of Dr.
James A. Hoxie
, Professor of Medicine at the
University of Pennsylvania
and Director of the Penn Center for AIDS Research.
Abstract #129 "T-Cells Edited to Express CCR5 or CXCR4 Fused to the C34 Peptide from gp41 Heptad Repeat-2 Exhibit Robust Protection from Diverse HIV-1 Isolates"
Wednesday, March 6, 2013
The data demonstrate potent inhibition of HIV infection in cells expressing a chimeric protein comprising a portion of the HIV envelope fused to either the CXCR4 or CCR5 HIV co-receptors. Scientists fused the C34 peptide from the gp41 portion of the HIV envelope to the amino terminus of either the CXCR4 (C34-X4) or CCR5 (C34-R5) proteins. Importantly, both C34-X4 and C34-R5 demonstrated potent inhibition of infection by either an X4-tropic or R5-tropic HIV-1 isolate in primary CD4+ T cells, the natural target of HIV.
Webcasts of all the presentations at CROI 2013 can be accessed via the following link:
SB-728-T is an autologous CD4+ T-cell product in which the gene for CCR5, a co-receptor for HIV entry, is modified via ZFN-mediated genome editing to disrupt the CCR5 protein. T-cells with a disrupted CCR5 protein are resistant to infection by the most common strain of HIV.
Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and genome editing. The Company has ongoing Phase 2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic
for the treatment of HIV/AIDS. Sangamo's other therapeutic programs are focused on monogenic diseases, including hemophilia, Huntington's disease and hemoglobinopathies such as beta-thalassemia and sickle cell anemia. Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). Engineering of ZFPs that recognize a specific DNA sequence enables the creation of sequence-specific ZFP Nucleases (ZFNs) for gene modification and ZFP transcription factors (ZFP TFs) that can control gene expression and, consequently, cell function. Sangamo has entered into a strategic collaboration with Shire AG to develop therapeutics for hemophilia, Huntington's disease and other monogenic diseases and has established strategic partnerships with companies in non-therapeutic applications of its technology including Dow AgroSciences and Sigma-Aldrich Corporation. For more information about Sangamo, visit the company's website at
is a registered trademark of Sangamo BioSciences, Inc.
This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references relating t
o research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo's ZFP technology platform for the treatment of HIV/AIDS, including a potential functional cure of HIV/AIDS, the expansion of clinical studies of SB-728-T in HIV-infected individuals, expected timing for the presentation of clinical trial data and the initiation of additional preclinical and clinical studies of ZFN-gene modification. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to the initiation and completion of stages of our clinical trials, whether the clinical trials will validate and support the tolerability and efficacy of ZFNs, technological challenges, Sangamo's ability to develop commercially viable products and technological developments by our competitors. For a more detailed discussion of these and other risks, please see Sangamo's SEC filings, including the risk factors described in its Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo BioSciences, Inc. assumes no obligation to update the forward-looking information contained in this press release.
SOURCE Sangamo BioSciences, Inc.