Sangamo BioSciences Presents Clinical Data From HIV Study Demonstrating Sustained Control Of Viremia

Data were presented at the Annual Meeting of the European Society of Gene and Cell Therapy (ESGCT and SETGyC Collaborative Congress) which is being held in Madrid from October 25-28, 2013.

“These data demonstrate that sustained functional control of HIV in the absence of ART is possible with a single SB-728-T treatment,” stated Geoff Nichol, M.B., Ch.B., Sangamo’s executive vice president of research and development. “Our aim is to provide a population of immune memory cells that are protected from HIV infection and are capable of generating an effective immune response against the virus throughout the body. These data represent a further step toward demonstrating the efficacy and durability of this therapeutic approach.”

Dr. Nichol added, “We continue to follow these Cohort 5 subjects and look forward to presenting a complete data set from this study, and a second ongoing trial (SB-728-1101), designed to maximize the engraftment of SB-728-T in subjects who are not CCR5 delta-32 heterozygotes, later this year.”

Data from Sangamo’s Phase 1 and 2 studies demonstrate that VL became undetectable during a TI from ART in three of seven evaluable CCR5 delta-32 heterozygote HIV-infected subjects, including two of six subjects that had completed TI in the ongoing 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.  In one SB-728-902 Cohort 5 subject, VL has remained undetectable (at or below the limits of quantification of the current ultra-sensitive assays for HIV) for 14 weeks (to last measurement taken) and the TI is ongoing.  Reduction in VL from peak during TI showed a statistically significant correlation (p=0.015) with estimated numbers of engrafted ZFN modified cells (SB-728-T) in which both copies of the CCR5 gene had been disrupted (biallelic modification), in line with previously presented data from this program.

Collectively, data from these studies demonstrate that in all trial subjects, SB-728-T treatment results in a durable increase in total CD4 T-cells.  In addition, seven of nine subjects enrolled in Sangamo’s Phase 1 study (SB-728-902 Cohorts1-3) experienced a longer term reduction in the viral reservoir as measured by HIV DNA in peripheral blood mononuclear cells, a source of chronic HIV infection not addressed by current ART.

Sangamo scientists and collaborators also presented data from preclinical and research programs in hemophilia and lysosomal storage disorders, hemoglobinopathies, cancer, cystic fibrosis, immunodeficiencies and the application of ZFN-mediated CCR5 modification in stem cells for HIV.

“The presentations at the ESGCT meeting demonstrate the diversity and breadth of potential therapeutic applications of Sangamo’s ZFP technology,” said Edward Lanphier, Sangamo’s president and CEO. “We look forward to continuing to update on our progress in the coming months at a translational medicine meeting organized by The Lancet entitled, ‘What Will it Take to Achieve an AIDS-free World?’ in San Francisco, from November 3-5, as well as at the Sixth International Workshop on HIV Persistence, Reservoirs & Eradication Strategies in Miami in early December.  In addition, we will present data from Sangamo’s preclinical programs at the Annual Meetings of the Society for Neuroscience in November and the American Society of Hematology (ASH) in early December.”

Presentations at the ESGCT Meeting
Saturday, October 26

• “TCR gene editing for the treatment of hematological malignancies.” Chiara Bonini, San Raffaele Telethon Institute for Gene Therapy, Milan
• “Efficient site-specific integration and in situ gene correction of human long-term repopulating hematopoietic stem cells by zinc finger nucleases.” Pietro Genovese, San Raffaele Telethon Institute for Gene Therapy, Milan
• “Allele-preferred targeted correction of CFTR gene in Cystic Fibrosis induced pluripotent stem cells.” Brian Davis, University of Texas

Sunday, October 27

• “Gene therapy for sickle cell disease.” Donald Kohn, University of California, Los Angeles
• “Genome editing with zinc finger nucleases.” Michael Holmes, Sangamo BioSciences, Inc.
• “Targeted transgene integration in human hematopoietic stem cells and induced pluripotent stem cells from normal donors and SCID-X1 patients.” Angelo Lombardo, San Raffaele Telethon Institute for Gene Therapy, Milan
• “Zinc finger nucleases targeting the beta-globin locus drive efficient correction of the sickle mutation in CD34+ cells.” Megan Hoban, University of California, Los Angeles
• “Rescue of T-cell deficiency in Prkdc mice by transplantation of gene-edited hematopoietic cells.” Rafael Yanez, Royal Holloway, University of London
• “ZFN mediated targeting of albumin: a platform for expression of multiple therapeutic genes in vivo.” Xavier Anguela, The Children’s Hospital of Philadelphia
• “Development of ZFN-based preclinical in vitro cell model in human embryonic stem cells for Wiskott-Aldrich syndrome.”Pilar Munoz-Fernandez, GENYO, Pfizer-University of Granada.

Monday, October 28

• “Infusion of ZFN CCR5-modified CD4 T-cells (SB-728-T) led to long term reconstitution of CD4 T-cells and reduction of HIV-DNA levels in HIV-infected subjects on ART.” Dale Ando, Sangamo BioSciences, Inc.

Summary of Clinical Trial Design
About SB-728-902 Cohort 5
Ten HIV-infected subjects heterozygous for the CCR5 delta-32 mutation (i.e. with one CCR5 gene that is naturally modified) who are currently on ART have been enrolled and have received a single intravenous infusion of SB-728-T (5 to 30 billion modified cells). Two months after SB-728-T treatment, subjects undergo a 16 week TI during which time their ART is discontinued. ART is 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 a sustained detectable HIV viral load are reinstituted on ART. Subjects with an undetectable viral load can remain off ART until HIV RNA levels are detectable or their CD4 T-cell count drops below 350 cell/mm 3 for three consecutive weekly measurements.

A total of ten subjects have been treated in this cohort.

Of the six evaluable subjects, we observed two subjects in which their VL became undetectable during TI from ART:

• In one subject, VL suppression at, or below, the limit of quantification (LOQ) of virus was sustained from week 11 — 25 of TI and the TI is ongoing.
• In the second subject there was a transient suppression of VL at or below LOQ.
• A third subject completed the TI with 1-log decrease in VL from peak.

In three subjects, there was no reduction in VL during the TI, one completed the TI and in two the TI was terminated early due to their viral loads exceeding the upper limit allowed in the protocol. A seventh subject has not completed TI and is still being evaluated.

About SB-728-902 Cohorts 1-3
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 enrolled 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 ART.  Subjects remained on their existing antiviral therapy while receiving treatment with SB-728-T.

About SB-728-T
Sangamo’s drug, SB-728-T, is generated by ZFN-mediated modification of the gene encoding the CCR5 receptor in a patient’s own T-cells.  ZFN modification disrupts the expression of this key co-receptor for HIV entry and renders cells resistant to HIV infection. The approach is based on the observation that a naturally occurring mutation in the CCR5 gene, CCR5 delta-32, provides protection from HIV infection. Individuals in whom both copies of the CCR5 gene carry the delta-32 mutation are generally not susceptible to the most common strain of HIV.

About Sangamo
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 and Phase1/2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic® for the treatment of HIV/AIDS. As part of its acquisition of Ceregene Inc., Sangamo acquired a fully-enrolled and funded, double-blind, placebo-controlled Phase 2 trial to evaluate NGF-AAV (CERE-110) in Alzheimer’s disease. 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 AgroSciencesand Sigma-Aldrich Corporation. For more information about Sangamo, visit the company’s website at www.sangamo.com.

ZFP Therapeutic® 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 to 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 for HIV/AIDS, the ability of a ZFP Therapeutic to control HIV infection, projected timing of release of SB-728-T clinical data, the expansion of clinical studies for HIV-infected individuals and the initiation of additional preclinical 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 public filings with the Securities and Exchange Commission, including the risk factors described in its Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.

SOURCE Sangamo BioSciences, Inc.