Sangamo Presents New Clinical Data at CROI 2013 Demonstrating Persistent Immune System Improvements After Treatment With ZFN Therapeutic® SB-728-T

RICHMOND, Calif., March 6, 2013 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced new data from its program to develop a 'functional cure' for  HIV/AIDS  in two presentations at the 20^th Conference on Retroviruses and Opportunistic Infections (CROI), held in Atlanta from March 3 to 6, 2013. 

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The first presentation described data from the SB-728-T Phase 1 study (SB-728-902, Cohorts 1-3) demonstrating that SB-728-T treatment of HIV-infected subjects leads to durable reconstitution of the immune system driven by increases in total CD4+ central memory T-cells (T_CM) and CCR5-protected T_CM. T_CM are long-lived, self-renewing cells that have the ability to remember and react against foreign antigens including HIV.  The data also showed that certain cell surface marker and gene expression profiles may predict which patients will likely respond best to SB-728-T treatment.

"These important data extend our understanding of why SB-728-T treatment improves the immune system as well as the conditions required for optimal engraftment of ZFN-modified T-cells," said Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "They confirm that SB-728-T meets the key immunologic requirements for immune reconstitution in HIV-infected individuals. In addition, analysis of cell surface marker and gene expression profiles of immune system cells in subjects who show superior responses to treatment in terms of increased T-cell counts provides us with important indicators that will aid us in the optimization of our clinical trials."

"The ability of SB-728-T to durably reconstitute the immune system in HIV-infected subjects after a single treatment has never been observed before with any other therapeutic approach," commented Rafick-Pierre Sekaly, Ph.D., Co-Director & Chief Scientific Officer, The Vaccine & Gene Therapy Institute of Florida (VGTI Florida), whose laboratory carried out the analysis. "Improvement in the overall health of the immune system of HIV-infected individuals, as demonstrated by treatment with SB-728-T, is a key step along the path to developing an immunologic approach to controlling and potentially eliminating the virus. We have analyzed the cells that constitute this unprecedented elevation of total CD4+ cell counts, extending our previous observations that the increase is primarily due to durable expansion of the central memory T-cells. Importantly, the level of ZFN-dependent CCR5 gene disruption is sustained in these cells, which is critical for the durable success of this approach."

HIV destroys the immune system by killing CD4+ T cells. The current standard of care for HIV/AIDS is daily treatment with antiretroviral therapy (ART), which suppresses viral load in the blood of most subjects but does not eliminate the reservoir of HIV-infected cells.  In addition, a significant proportion of treated HIV-infected individuals do not experience a restoration of CD4+ T-cell counts to normal levels.  SB-728-T treatment, by eliminating the co-receptor, CCR5, which is necessary for HIV entry to CD4+ cells, is designed to provide a CCR5-negative population of CD4+ T-cells that cannot be infected by HIV but are able to fight opportunistic infections and enable the immune system to control and eliminate the virus. Sangamo's clinical studies have demonstrated successful ZFN-dependent CCR5 gene modification of T-cell populations, including critical cell types such as the T_CM.  Studies to date have demonstrated that engraftment of SB-728-T is safe, the modified cells are durable and demonstrate prolonged trafficking and dynamic immunological responsiveness in the gut mucosa, an important HIV reservoir.  The data presented today demonstrate that SB-728-T treatment leads to unprecedented durable increases in total CD4+ T cells that are correlated with increases in T_CM and ZFN-mediated CCR5-modified T_CM. 

"These exciting data support our development program for SB-728-T as a potential functional cure for HIV/AIDS," stated Edward Lanphier, Sangamo's president and CEO. "We have ongoing Phase 2 clinical trials designed to build on our early studies in which we observed a significant correlation between the number of infused CD4+ T cells in which both copies of the CCR5 gene are modified, so-called biallelic modification, and reduction in viral load during a treatment interruption.  We intend to present data from these trials this year."

The first of these ongoing trials (SB-728-902 Cohort 5) evaluates the approximate doubling of bi-allelic engraftment that can be achieved in individuals that have a natural mutation of one of their CCR5 gene copies, CCR5 delta-32 heterozygotes, and seeks to confirm an observation of the occurrence of aviremia during ART treatment interruption (TI).  The second trial (SB-728-1101) examines the ability of a lymphopenic preconditioning regimen to enhance bi-allelic engraftment and reduce viral load during a TI in subjects in which CCR5 is not mutated. 

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.

Data Summary

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_CM.
• 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: http://webcasts.retroconference.org/m/2013

About SB-728-T
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.

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 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 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 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.