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TheBody.com/TheBodyPRO.com covers The 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012)

Press Release

Sangamo Presents New Clinical Data at CROI 2012 Demonstrating Persistent Positive Effects of ZFN Therapeutic for "Functional Cure" of HIV/AIDS

Data Highlight Positive Effects of SB-728-T on Immune System and Viral Load Reduction and Further Validate Strategy of Ongoing Phase 2 Trials

March 8, 2012

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Richmond, Calif. -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced that new data from its program to develop a 'functional cure' for HIV/AIDS were described in two presentations at the 19th Conference on Retroviruses and Opportunistic Infections (CROI), held in Seattle from March 5 to March 8, 2012.

"These data differentiate SB-728-T from other novel therapies as a feasible approach to controlling HIV/AIDS," said Ronald Mitsuyasu, M.D., Professor of Medicine, David Geffen School of Medicine at UCLA and a principal investigator in Sangamo's SB-728-T studies. "The results suggest that SB-728-T has a positive effect on immune health of HIV-infected patients and this effect is persistent for over a year in some subjects. Most importantly, SB-728-T treatment provides HIV-resistant T-cells that are capable of mounting an immune response to an inflammatory event in lymphoid tissues and has yielded encouraging effects on HIV viral load when antiretroviral drugs are withdrawn during a treatment interruption."

"These data add to our understanding of the positive viral load changes in SB-728-T-treated subjects, and suggest that an early cytokine burst may initiate the dramatic and prolonged increase in CD4 counts observed following SB-728-T treatment," said Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "They also confirm that SB-728-T meets key requirements for our strategy for a 'functional cure' for HIV, by demonstrating durable engraftment and prolonged trafficking and dynamic immunological responsiveness in the gut mucosa. Together, these data further validate our strategy for the continued development of this ZFP Therapeutic as a 'functional cure' for HIV in two ongoing Phase 2 clinical trials designed to extend the observation of a statistically significant correlation between levels of bi-allelic modification of CD4 T cells and viral load reductions during treatment interruptions in HIV infection. The first study builds on the approximate doubling of bi-allelic engraftment that can be achieved in CCR5 delta-32 heterozygotes and seeks to confirm the occurrence of aviremia during treatment interruption as observed in one such patient in our Phase 1 program. The other clinical trial will examine the ability of a lymphopenic preconditioning regimen to enhance bi-allelic engraftment, and reduce viral load during treatment interruption, in non-CCR5-mutated HIV subjects."


Clinical Trial Data Summary

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Abstract # 155 "Induction of Acquired CCR5 Deficiency with Zinc Finger Nuclease (ZFN) Modified Autologous CD4 T-cells (SB-728-T) Correlates with Increases in CD4 Count and Effects on Viral Load (VL) in HIV-infected Subjects" -- Thursday, March 8, 2012

21 HIV-infected subjects were enrolled in Phase 1 clinical studies at the University of Pennsylvania and in California (SB-728-902) and received a single dose of SB-728-T (5 to 30 billion cells). All subjects were taking highly active antiretroviral therapy (HAART) and had stably controlled undetectable levels of HIV in their blood. Subjects were classified into two groups based on their CD4+ T-cell counts: one group of 15 subjects, with CD4+ T-cell counts below 500 cells/ ul designated Immune Non-Responders (INR), and a second group of six subjects with CD4+ T-cell counts of greater than 450 cells/ ul designated Immune Responders (IR). One month after SB-728-T treatment, six subjects in the INR group enrolled in the University of Pennsylvania study underwent a 12-week treatment interruption (TI) of their HAART.

The studies 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. In addition, viral DNA and changes in viral load (VL), as measured by HIV-RNA, were measured during the TI in the six INR subjects.

These studies demonstrated:

  • During the TI, the viral load, as measured by HIV-RNA levels, initially increased as expected in all six subjects. Subsequently, a 0.8 to > 2.0-log reduction in VL from peak achieved during the TI was observed in 3 of 6 subjects with the highest estimated circulating levels of cells with biallelic modification of their CCR5 gene. In one subject (Subject 205) VL decreased to undetectable levels such that the subject was aviremic at the end of the TI period. This subject entered the study carrying the natural CCR5 delta-32 mutation on one copy of his CCR5 gene resulting in an estimated percentage of biallelically-disrupted CCR5 genes that was twice that of subjects entering the study with wild-type CCR5 genes.
  • Control of HIV-RNA (suppression of VL) correlates significantly (p < 0.05) with calculated levels of circulating CD4+ T-cells that have undergone biallelic modification (i.e. modification of both copies) of the CCR5 gene.
  • The level of circulating viral DNA, a measure of the viral reservoir, exhibited a limited increase in five of six subjects over this period and was elevated in only one subject whose SB-728-T engraftment was the lowest of the group.
  • Confirmation and extension of previous observations of unprecedented improvements in overall CD4+ T-cell counts and CD4+ to CD8+ T-cell ratios, a measure of immune health, for over a year post administration of SB-728-T.
  • Elevated levels of certain T-cell cytokines (IL-2, IL-7 and IL-15) in the blood in the first few days post SB-728-T infusion which may have a role in the dramatic post-infusion expansion of CD4+T-cells. The magnitude of this increase was marked in Subject 205, who had an undetectable VL at the end of the TI.
  • Durable engraftment and persistence of ZFN-CCR5-modified cells (SB-728-T) in the peripheral blood for over a year (range: 90-738 days).
  • Ability of SB-728-T to traffic to the gut mucosa, an important reservoir of active HIV infection.
  • SB-728-T treatment continues to be safe and well tolerated with only mild, reversible symptoms typical of infusion reactions.
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This article was provided by Sangamo BioSciences, Inc. .
 


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Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.

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