Clinical Trials


We have an ongoing Phase 2 clinical trial to evaluate safety and tolerability of our ZFN-CCR5-gene modification approach in T-cells in subjects that are HIV-infected. Several trials have been completed, including a Phase 1 single-dose, investigator-sponsored trial at the University of Pennsylvania. Data from this trial were published in a report in the New England Journal of Medicine in 2014 (N.Eng. J. Med. 2014: 370:897-906 “Gene Editing of CCR5 in Autologous CD4 T-cells of Persons Infected with HIV.”)

We also have a Phase 1 clinical stage program to investigate this ZFN-mediated approach in hematopoietic stem progenitor cells (SB-728-HSPC). With our collaborators at City of Hope and the University of Southern California, we have been granted a $14.5 million Disease Team Research Award by the California Institute for Regenerative Medicine (CIRM) to fund this program. In May 2014, Sangamo was also granted a $5.6 million Strategic Partnership Award. The four-year grant provides matching funds to support a clinical trial in HIV-infected individuals at City of Hope. We expect preliminary data from this program in 2016.

For complete details of our clinical trials of SB-728 please refer to


Our ongoing Phase 2 clinical trial, SB-728-mR-1401 (1401), is designed to provide further evidence of functional control of HIV in additional subjects. The protocol incorporates a number of methods to increase the engraftment of CD4 and CD8 T-cells that have undergone biallelic CCR5 gene modification, including certain criteria for subject selection, optimal Cytoxan preconditioning and a number of process improvements such as mRNA delivery of the ZFNs, which will allow the administration of multiple doses of the modified cells. The Company has completed subject enrollment for this study and initial data are expected by the end of 2015.


A dose escalation Phase 1/2 study designed primarily to evaluate the safety and tolerability of escalating doses of cyclophosphamide (Cytoxan®) administered one day prior to SB-728-T infusion. 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. Such lymphodepletive treatment has been used to enhance engraftment of adoptively transferred T-cells in the treatment of cancer and as therapy for numerous autoimmune diseases. The drug has been previously used in HIV-infected individuals and studies demonstrate that, while the drug was transiently lymphodepleting, it did not significantly reduce total CD4 T-cell counts over the long term and was adequately tolerated.

In addition to safety, the study was designed to evaluate the effect of escalating doses of Cytoxan on SB-728-T engraftment, the effect of SB-728-T treatment on viral load following highly active antiretroviral therapy (ART) interruption, the change in CD4+ T-cell counts in peripheral blood and the long-term persistence of SB-728-T.

A total of 18 HIV-infected subjects on ART have being enrolled into 5 dose-escalating cohorts (3-6 subjects/cohort), and receive intravenous Cytoxan (200 mg, 500 mg/m2, 1000 mg/m2,1500 mg/m2 or 2000 mg/m2). Within each cohort, treatment was staggered so that each subsequent subject could not be infused with Cytoxan until at least 2 weeks after the preceding subject. One day after receiving Cytoxan, subjects were infused with SB-728-T (5 to 30 billion modified cells). Six weeks after SB-728-T infusion, subjects with CD4 cell counts ≥500 cells/mm3 underwent a 16 week treatment interruption (TI) during which time their anti-retroviral therapy was discontinued. At the end of the TI subjects with an undetectable viral load are allowed to remain off ART until HIV RNA levels are detectable or their CD4 T-cell count drops below 500 cells/mm3 for three consecutive weekly measurements.

We presented preliminary data from these trials in May 2013 and the full data set from all cohorts in September 2014 at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). It was determined that the optimal dose of Cytoxan was 1000 mg/m2.

An additional cohort (Cohort 3*) of three subjects was added to the SB-728-1101 study, in which subjects received a ZFN-mediated CCR5 modified SB-728-T product containing both CD4 and CD8 T-cells.  The CD8 cells are directly involved in clearance of the virus with "help" from CD4 cells.  A subset of the HIV population, termed 'Elite Controllers', have shown elevated levels of CD8 T-cells that express low levels of CCR5 and have good anti-viral responses, a characteristic shared by those SB-728-T treated subjects in which the greatest effectgs on the virus have been seen to date. The addition of CD8 cells to SB-728-T will potentially mimic this characteristic of the 'Elite Controller' subpoopuation by improving the anti-viral effect of the treatment, as well as significantly simplify the Company's therapeutic product manufacturing process. The new clinical data from Cohort 3* was presented in February 2015 at the Conference on Retroviruses and Opportunistic Infections (CROI), and updated subject data were presented in May 2015 at the Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT).


We have completed and continue to follow subjects treated with SB-728-T in a Phase 1 clinical trial (SB-728-902) of SB-728-T in subjects known as “immunologic non-responders". These individuals constitute approximately 20% of the HIV infected population and while they have well-controlled levels of virus on ART, they have suboptimal CD4+ T-cell counts.

This Phase 1 trial was carried out in HIV-infected individuals on ART and was primarily designed to evaluate the safety and tolerability of this ZFP Therapeutic approach, however subjects’ CD4 T-cell counts, levels of CCR5-modified T-cells, viral load and levels of viral reservoir (as measured by viral DNA in the peripheral blood) were also monitored. We have presented positive preliminary data from both trials at several scientific meetings. These data have provided valuable information for the design of additional studies.

We added a fifth cohort to our SB-728-902 study (SB-728-902-Cohort 5 – a Phase 2 study) which enrolled HIV-infected subjects who were heterozygous for the CCR5 delta-32 mutation (i.e. with one CCR5 gene that is naturally modified) and are currently on ART. Subjects received a single intravenous infusion of SB-728-T (5 to 30 billion modified cells) and undergo a 16 week TI two months after SB-728-T treatment, during which time their anti-retroviral therapy is discontinued. ART will be reinstituted in subjects whose CD4 T-cell counts drop to <350 cells/mm3 and/or whose HIV-RNA increases to >100,000/mL for three consecutive weekly measurements. At the end of the TI, subjects with an undetectable viral load will remain off ART until HIV RNA levels are detectable or their CD4 T-cell count drops below 350 cell/mm3 for three consecutive weekly measurements.