Sangamo Biosciences, Inc. (NASDAQ:SGMO), the leader in therapeutic genome editing, announced the presentation of Phase 2 data from two of the Company’s ongoing clinical trials (SB-728-1101 Cohort 3* and SB-728-mR-1401) of SB-728-T, which is being developed for the functional control of HIV/AIDS. The preliminary comparative data suggest that adenoviral delivery of zinc finger nucleases (ZFNs) to T-cells may be uniquely immune-stimulatory for both acute control of infection, and importantly, HIV reservoir reduction.

“The preliminary Phase 2 data suggest superiority of the SB-728-T product produced using adenoviral delivery to both CD4 and CD8 cells with two of three initially treated subjects remaining off ART for over one year,” stated Dale Ando, M.D., Sangamo’s vice president of therapeutic development and chief medical officer. “The adenovirus used to deliver the CCR5-modifying ZFNs to the T-cells may act somewhat like an “adjuvant,” providing additional immune stimulation beyond Cytoxan preconditioning, and enhancing expansion of CD8 cells once they are infused back into the subject.  This expansion may improve the likelihood of viral load control in the absence of ART, particularly in HIV-infected individuals who may have only a narrow repertoire of anti-HIV activity.”

“The proportion of treated subjects in the adenoviral modified Cohort 3* who have responded and established sustained control of viral load in the absence of ART is very striking and may reflect reprogramming of the immune system,” stated Rafick Pierre Sékaly, Ph.D., co-director, CHAR Proteomics and Systems Biology Core, Department of Pathology, Case Western Reserve University. “These data suggest that Sangamo has developed a product that can potentially protect the immune system, restore T-cell homeostasis and CD4 T-cell function thereby enabling durable immunological control of HIV by CD8 killer T-cells.”

“The observation of functional control in some Cohort 3* subjects complements the observation of significant reduction of HIV reservoir in the immunologic non-responder cohort (SB-728-0902 trial).  In that study, infusion of CCR5 modified T-cells led to restoration of T-cell homeostasis and an HIV resistant subset of memory stem T-cells that effectively diluted and reduced the HIV reservoir over time,” Dr. Sékaly further commented.

The data demonstrate that SB-728-T manufactured using both mRNA and adenoviral delivery of CCR5-modifying ZFNs to CD4 and CD8 T cells were safe and well-tolerated following a Cytoxan conditioning regimen. The mRNA product showed greater accumulation of total CD4, CD8 and CCR5-modified cells with 3 compared to 2 repeat doses, with persistence of modified cells in the circulation.  However, preliminary data suggest that adenoviral delivery may enhance the expansion of CD8 cells compared with mRNA delivery. In addition, a higher proportion of HIV infected subjects treated with the adenoviral SB-728-T product achieved durable control of viral load during a treatment interruption (TI) of their ART than those dosed with a product generated using mRNA delivery or adenoviral delivery to only CD4 cells. Both delivery methods achieved similar levels of CCR5 modification of T-cells.

Preliminary data from the two Phase 2 studies were presented by Dr. Ando at the 7th International Workshop on HIV Persistence during Therapy, considered to be the reference workshop on HIV reservoirs and eradication strategies, which is being held inMiami, FL, December 8-11, 2015. Analyses exploring the potential mechanism of action of SB-728-T in promoting reduction of the HIV reservoir in immune non-responder patients with HIV infection will be summarized in a presentation given by Dr. Sékaly today titled, “The Anti-inflammatory Response and the HIV Cure.”

Sangamo’s earlier studies of this ZFP Therapeutic®, generated using adenoviral delivery of ZFNs, used an SB-728-T product that was depleted of CD8 cells and thus enriched in CD4 cells.  Previously published reports have suggested that individuals who naturally control their HIV infection, so called elite controllers, have activated CD8 cells with low CCR5 expression.  For this reason, the SB-728-T product evaluated in both studies described in the presentation was manufactured to contain both ZFN-modified CD4 and CD8 T-cells.

The studies compared two cohorts of subjects that both received a Cytoxan preconditioning treatment, and similar doses of CD4 and CD8 T-cells that were ZFN-modified to disrupt expression of CCR5, a critical co-receptor for HIV entry. One group of subjects (SB-728-1101 Cohort 3*), received a single dose of cells that were modified using ZFNs delivered in an adenoviral formulation and the second group (SB-728-mR-1401, n=8) received an equivalent total dose of modified cells spread over two or three treatments that had been manufactured using electroporation of ZFNs delivered as mRNA. In Cohort 3* four subjects have been treated (of a planned total of eight subjects) and three subjects have completed the protocol’s 16-week TI. Both methods generate products with similar levels of ZFN-mediated disruption of the CCR5 gene and both treatments were safe and well-tolerated.  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.

“We have previously demonstrated that delivery of ZFNs to both T-cells and hematopoietic stem cells using mRNA and electroporation results in high levels of genome editing at clinical scale and we continue to use this method for all other ex vivoapplications,” stated Geoff Nichol, M.B., Ch.B., Sangamo’s executive vice president of research and development. “Adenoviral delivery of ZFNs to T cells may be uniquely immune-stimulatory for both acute control of infection and, based on our earlier studies, reservoir reduction, in HIV. We look forward to receiving data from an additional five Cohort 3* subjects in 2016.” (Original Source)

Shares of Sangamo Biosciences closed yesterday at $9.2, down $0.15 or -1.60%. SGMO has a 1-year high of $19.25 and a 1-year low of $5.30. The stock’s 50-day moving average is $7.84 and its 200-day moving average is $8.56.

On the ratings front, Sangamo has been the subject of a number of recent research reports. In a report issued on December 7, Wedbush analyst Liana Moussatos reiterated a Buy rating on SGMO, with a price target of $30, which represents a potential upside of 226.1% from where the stock is currently trading. Separately, on December 2, J.P. Morgan’s Cory Kasimov assigned a Buy rating to the stock and has a price target of $16.

According to, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Liana Moussatos and Cory Kasimov have a total average return of 20.7% and -2.7% respectively. Moussatos has a success rate of 46.6% and is ranked #47 out of 3638 analysts, while Kasimov has a success rate of 41.8% and is ranked #3193.

Sangamo BioSciences Inc is a clinical stage biopharmaceutical company. The Company is engaged in the research, development & commercialization of engineered DNA-binding proteins for the development of novel therapeutic strategies for unmet medical needs.