Sangamo BioSciences Announces Presentation of Positive Clinical Data From Novel ZFN Therapeutic Approach for HIV/AIDS Treatment

Sangamo BioSciences Announces Presentation of Positive Clinical Data From Novel ZFN Therapeutic Approach for the Treatment of HIV/AIDs at Conference for Retroviral and Opportunistic Infections

First Steps in Development of a 'Functional Cure' for HIV/AIDS: Demonstration of Successful Engraftment and Expansion of ZFN- CCR5-Modified T-Cell Product, SB-728-T, with Durable Improvement in Total CD4+ T-cell Counts and CD4:CD8 Ratios

RICHMOND, Calif., Feb. 28, 2011 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the presentation of positive preliminary clinical data from its Phase 1 trial (SB-728-902).  The trial is being conducted in immunologic non-responders, HIV-infected subjects who are currently on highly active antiretroviral therapy (HAART) and have undetectable levels of virus but suboptimal CD4+ T-cell counts.  The study is designed to evaluate safety and clinical outcomes of Sangamo's zinc finger nuclease (ZFN)-generated CCR5-modified, autologous T-cell product (SB-728-T) for the treatment of HIV/AIDS. CCR5 is the major co-receptor used by HIV to infect cells of the immune system.

"These compelling data provide a mechanistic 'proof of concept' for this novel approach to HIV therapy which shows the most promise of any yet tested," stated Carl June M.D., Director of Translational Research at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine, and an investigator in a second SB-728-T Phase 1 trial that is led by Pablo Tebas, M.D. at the University of Pennsylvania.

"From a single infusion of ZFN-modified cells, substantial and sustained increases in total CD4+ T-cell counts were observed in most subjects.  This improvement is greater than we have seen in any previous adoptive T-cell approach.  The data are consistent with CCR5-ZFN-modified T-cells being resistant to HIV infection and having a selective advantage in the presence of the virus - just as we saw in the preclinical studies.  This is very encouraging as we continue to evaluate the drug in HIV-infected subjects with active infections."

Summary of Clinical Data

The data demonstrate that a single infusion of SB-728-T was well tolerated; the CCR5-modified cells successfully engrafted in all subjects and resulted in a durable improvement in total CD4+ T-cell counts in five of six of the subjects analyzed.  In addition, five of the six subjects also exhibited sustained improvements in their CD4:CD8 T-cell ratio, which is an indicator of immunologic health. The ZFN-CCR5-modified cells also exhibited normal T-cell growth kinetics and trafficking and were observed to undergo selective expansion in the gut mucosa, a major reservoir of virus in the body, suggesting, as predicted, that the cells were resistant to HIV infection. These data represent the necessary first steps in the development of a "functional cure" for HIV/AIDS by providing a protected CD4+ T-cell population in these subjects that is resistant to HIV infection.

The presentation will be made at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) which is being held in Boston from February 27 to March 2, 2011.  In a late-afternoon session on Wednesday, March 2, 2011, Dr. June will present further data from Sangamo's Phase 1 trials of SB-728-T and Paula Cannon, Ph.D., Associate Professor of Molecular Microbiology & Immunology at the Keck School of Medicine of the University of Southern California (USC), will present preclinical data from Sangamo's program of ZFN-modification of the CCR5 receptor in hematopoietic stem cells.  Also at CROI, Sangamo's collaborators at the University of Pennsylvania will describe preclinical data from a program to modify the CXCR4 gene in human CD4+ T-cells. More information about these presentations will be available later in the week.

"These data represent the beginning of a new hope for HIV therapy," said Jacob Lalezari, M.D., the Director of Quest Clinical Research, Assistant Clinical Professor of Medicine at Mount Zion Hospital, UCSF, and one of the principal investigators of the study. "This approach aims to provide a protected reservoir of HIV-resistant T-cells that are available to fight infections including the virus.  I look forward to completing the follow-up of this initial study and to working with Sangamo as it expands these studies to include the full range of HIV-infected populations."

About SB-728-T

SB-728-T is an autologous CD4+ T-cell product modified with Sangamo's ZFN technology to specifically and permanently modify the cell's own DNA sequence encoding CCR5. CCR5 is the major co-receptor used by HIV to infect cells. A naturally occurring mutation of the CCR5 gene, CCR5-delta32, has been shown to provide protection against HIV infection. Sangamo scientists have demonstrated that CCR5-specific ZFNs can be used to disrupt the CCR5 gene and make human CD4+ T-cells resistant to HIV infection.  Sangamo's SB-728-902 Phase 1 study is designed to evaluate single escalating doses of SB-728-T in subjects that have sub-optimal CD4+ T-cell counts despite long-term HAART and no detectable viral load.  This group represents approximately thirty percent of all HIV-infected patients in the US.  The trial has recently been expanded to add an additional cohort of subjects that are failing HAART and have active viral infections.  In addition, Sangamo has an ongoing Phase 1 / 2 clinical trial, SB-728-1002, in HIV-infected subjects that are viremic but not currently on HAART. 

"While preliminary, these data are very encouraging and an early validation of the feasibility of our novel gene modification approach for the treatment of HIV/AIDS," said Dale Ando, M.D, Sangamo's vice president of therapeutic development and chief medical officer. "The SB-728-902 trial was designed to provide answers to several important questions.  We have confirmed that we have a scalable manufacturing process and that from a single apheresis we can manufacture doses of SB-728-T of 10 to 30 billion cells. We have also learned that a single infusion of these cells is well-tolerated and that the cells engraft, multiply and persist in the body.  The modified cells behave like unmodified cells and traffic to the gut mucosa. In addition, we observed selective expansion of ZFN-modified cells in the gut mucosa, a major reservoir of HIV in the body, suggesting that these cells are protected from HIV and selectively enrich in the presence of the virus. These data are consistent with our preclinical findings†. The data also underscore our decision to expand our clinical studies to populations of HIV-infected individuals that have active viral replication and thus higher viral loads and retain immune reactivity to HIV.  From such studies we will be able to assess the effect of ZFN-CCR5-modified T- cells on overall T-cell numbers and the course of the viral infection."

"This presentation is a terrific beginning to a transformational year of clinical data for Sangamo," stated Edward Lanphier, Sangamo's president and chief executive officer. "Later in 2011, we expect to present additional clinical data from our ZFP Therapeutic® programs in HIV/AIDs as well as data from our Phase 2b clinical trial (SB-509-901) of a first-in-class, disease modifying-approach to diabetic neuropathy. The data presented at CROI are the latest example of our substantial progress towards our goal of establishing ZFP Therapeutics as a new and highly differentiated class of human pharmaceuticals to address unmet medical needs."

† (Nat Biotechnol. 2008 Jul;26(7):808-16  Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases).

About the SB-728-T Clinical Trial (SB-728-902)

The study is an open-label Phase 1 clinical trial to evaluate the safety and tolerability of single infusions of an escalating dose of an autologous (a patient's own) CD4+ T-cell product genetically modified at the CCR5 gene by CCR5-specific ZFNs (SB-728-T). The trial will enroll a total of nine HIV-infected subjects (three cohorts of three subjects each) who have sub-optimal T-cell levels and no detectable viral load on long-term HAART.  The trial has three dosing cohorts.  Subjects will remain on their existing antiviral therapy while receiving treatment with SB-728-T. A fourth cohort, of up to four subjects who have failed HAART and have measureable viral loads, was recently added to the study.  No data from subjects in the last two cohorts of this study were reported in today's CROI presentation. The primary objective of the study is to evaluate the safety and tolerability of SB-728-T. In addition to safety monitoring, data are being collected on the expansion, trafficking and persistence of SB-728-T, total CD4+ T-cell counts, CD4:CD8 T-cell ratios and viral load.

Dr. June has no financial relationship with Sangamo BioSciences, Inc.

About Sangamo

Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and modification.  The most advanced ZFP Therapeutic® development program is currently in a Phase 2b clinical trial for evaluation of safety and clinical effect in patients with diabetic neuropathy and a Phase 2 trial in ALS. Sangamo also has a Phase 1 / 2 clinical trial and two ongoing Phase 1 clinical trials to evaluate the safety and efficacy for the treatment of HIV/AIDS as well as a Phase 1 trial for the treatment for recurrent glioblastoma multiforme. Other therapeutic programs are focused on Parkinson's disease, monogenic diseases, neuropathic pain and nerve regeneration.  Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs).  By engineering ZFPs that recognize a specific DNA sequence Sangamo has created ZFP transcription factors (ZFP TFs) that can control gene expression and, consequently, cell function.  Sangamo is also developing sequence-specific ZFP Nucleases (ZFNs) for gene modification.  Sangamo 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

ZFP Therapeutic® is a registered trademark of Sangamo BioSciences, Inc.