Sangamo BioSciences Announces Presentation of Groundbreaking Clinical Data From ZFN Therapeutic for HIV/AIDS at ICAAC 2011

Data Represents "Significant Progress Toward a 'Functional Cure' for HIV/AIDS"

Statistically Significant Correlation between SB-728-T and Viral Load Reduction

Sep 18, 2011, 12:15 ET from Sangamo BioSciences, Inc.

RICHMOND, Calif., Sept. 18, 2011 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced that data from its Phase 1 clinical programs to develop SB-728-T, a novel therapeutic approach for the treatment of HIV/AIDS, were discussed in two presentations at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).  The meeting is being held in Chicago from September 17-20, 2011.  

"The data obtained in our treatment interruption studies are very exciting and represent significant progress toward a 'functional cure' for HIV/AIDS," said Carl June, M.D., Director of Translational Research at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine, who with Pablo Tebas, M.D., is an investigator in the Phase 1 studies of SB-728-T at that institution. "The statistically significant relationship between estimated modification of both copies of the CCR5 gene and viral load during the treatment interruption suggests that the next step is to increase the frequency of the modified cells in HIV-infected patients with the ultimate hope that if we do, we will achieve a 'functional cure' and eliminate the need for continued HAART."

In an oral presentation made on Saturday, September 17th at ICAAC, data were presented from all dosing cohorts of Sangamo's Phase 1 dose escalation study (SB-728-902) in subjects on highly active antiretroviral therapy (HAART) who entered the study with CD4+ T-cells counts of <500 cells/mm3 after several years of therapy ("immunologic non-responders").  A presentation made today described data from the second cohort of a Phase 1 clinical study of the same drug, conducted at the University of Pennsylvania and Albert Einstein College of Medicine, in subjects who entered the study with CD4+ T-cell counts of  >450 cells/mm3 and underwent a treatment interruption (TI) of HAART following treatment with SB-728-T.

Data from these presentations demonstrate:

  • A statistically significant relationship (p<0.05) between suppression of HIV viral load (VL) and calculated levels of circulating CD4+ T-cells that have undergone biallelic modification (i.e. modification of both copies) of the CCR5 gene in SB-728-T-treated individuals who underwent a TI. CCR5 is the major co-receptor used by HIV to infect cells of the immune system.
  • The VL of one SB-728-T treated-subject decreased to undetectable levels during a TI. This subject was found to be heterozygous for the CCR5 delta-32 gene mutation, i.e. half that subject's CCR5 genes were naturally disrupted.  
  • Confirmation and extension of previous observations of unprecedented improvements in overall CD4+ T-cell counts and CD4+ : CD8+ T-cell ratios, as well as engraftment, expansion, trafficking and persistence of the ZFN modified cells.
  • SB-728-T treatment continues to be safe and well tolerated.

"We are very encouraged by both this early demonstration of an antiviral effect of SB-728-T as well as the marked improvement in the overall CD4+ T-cell counts in treated subjects in the SB-728-902 trial," said Ronald Mitsuyasu, M.D., Professor of Medicine, David Geffen School of Medicine at UCLA and a principal investigator of Sangamo's SB-728-902 study.  "While their viral loads are well controlled on HAART, these subjects experienced incomplete restoration of their T-cell counts.  Improvement and preservation of the immune system is of paramount importance in HIV and those seen in this study show an improvement over that seen after several years of HAART."

"There is no other drug that has been shown to have the same dramatic effect on the immune system in this setting," stated Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "SB-728 treatment results in unprecedented improvement in immune system health as measured by increased CD4+ T-cell levels and improved CD4+: CD8+ T-cell ratios, even in subjects that entered the trial with poor CD4+ counts. Moreover, the interesting kinetics in viral load that we observed in the first few subjects that underwent a treatment interruption has been borne out and has allowed us to correlate a statistically significant effect of the rate of biallelic ZFN-modification of the CCR5 gene on viral load during treatment interruption."

"Data presented this weekend at ICAAC suggest that, with sufficiently high levels of circulating biallelically  modified cells and good engraftment, SB-728-T can provide a 'functional cure' for HIV," said Geoff Nichol, M.B., Ch.B., Sangamo's executive vice president of research and development.  "We continue to collect valuable data about the parameters essential for optimization of this novel drug candidate. Based on these data, Sangamo plans to continue to expand our clinical trials and carry out confirmatory studies in subjects who are natural heterozygotes for the CCR5 delta-32 mutation.  We will also explore other mechanisms to enhance engraftment and maximize the impact of the HIV resistant cells on viral load and the overall immune system of HIV patients. The ground-breaking clinical data that we and our collaborators are generating continue to validate our highly specific ZFN technology as a platform for development of novel therapeutic products."

Clinical Trial Data Summary

Abst.# H2-794a: "HAART Treatment Interruption following Adoptive Transfer of Zinc Finger Nuclease (ZFN) Modified Autologous CD4+ T-cells (SB-728-T) to HIV-infected Subjects Demonstrates Durable Engraftment and Suppression of Viral Load" Presenters: Dale Ando, M.D., Vice President, Therapeutic Development and CMO and Geoffrey Nichol, M.B., Ch.B., Executive Vice President, Research and Development, Sangamo BioSciences, Inc.

In a late-breaker session on Sunday, September 18, 2011 data were presented from the six subjects enrolled in cohort 2 of the Phase 1 clinical trial of SB-728-T conducted at the University Pennsylvania and Albert Einstein College of Medicine.  These subjects entered the clinical trial with CD4+ T-cell counts of >450 cells/mm3 and underwent a twelve week HAART TI four weeks after treatment with a single dose of SB-728-T.

The data demonstrate that:  

  • A statistically significant relationship between VL and the calculated percentage of circulating CD4+ T-cells that have  undergone ZFN-mediated modification of both copies (biallelic) of the CCR5 gene within a cell (P= 0.0001 for VL at the end of TI, and 0.037 for area under the curve of VL over the TI period).
  • A 0.8 to >2.0-log reduction in VL from peak during TI was observed in the 3 of 6 subjects with the highest estimated circulating levels of cells with biallelic modification.  
  • One subject's VL decreased to undetectable levels such that the subject was considered to be 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.
  • Persistent engraftment of ZFN-modified T-cells, overall improvement in total CD4+ T-cell levels and CD4+:CD8+ T-cell ratios as well as normal trafficking of the cells and the safety and tolerability of the treatment.

These data provide important new information of the design of future clinical studies including enhanced engraftment strategies.

Abst.# H1-375: "Adoptive Transfer of Zinc Finger Nuclease (ZFN) Modified Autologous CD4+ T-Cells to Aviremic HIV-Infected Subjects with Suboptimal CD4+ Counts" Presenter: R. Mitsuyasu, M.D., Professor of Medicine, David Geffen School of Medicine, UCLA.

In a presentation on Saturday, September 17, 2011, Dr. Mitsuyasu discussed data from the full complement of subjects in Sangamo's ongoing Phase 1 dose-escalation study (SB-728-902) in aviremic subjects with CD4+ T-cell counts <500 cells/mm3.  These subjects are often classified as immunologic non-responders because, while they have their virus levels well-controlled by HAART, their immune systems have not responded well and levels of CD4+ cells remain depressed.

The data demonstrate that:

  • SB-728-T is safe and well tolerated in this patient population with only mild, reversible symptoms typical of infusion reactions.
  • ZFN CCR5-modified cells engrafted, expanded, and persisted for the duration of the study to date (Median of 337 days, range: 115-561).
  • The modified cells trafficked to the gut mucosa, an important reservoir of active HIV infection.
  • Notably, an increase in total CD4+ T-cells was observed in all subjects and a normalization of the ratio of CD4+:CD8+ T-cells, a measure of immunologic health, was observed in the majority of subjects that entered the study with a ratio below one.  These immunologic improvements were persistent over the study period.  
  • These data confirmed and extended preliminary data that were previously reported from the first two dosing cohorts of the trial at the Conference on Retroviral and Opportunistic Infections (CROI) in March 2011.  
  • In addition, data were presented from one subject in this trial who has undergone an extended treatment interruption one year after SB-728-T infusion and saw a VL reduction from peak during TI of >1-log, suggesting a potential antiviral effect  of the treatment.

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; those with only one copy of the delta-32 mutation are identified as "Elite Controllers" for their immune systems' ability to resist progression of HIV without the need for HAART.

Dr. Mitsuyasu and Dr. June have 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. Sangamo also has a Phase 1 / 2 clinical trial and two ongoing Phase 1 clinical trials to evaluate safety and clinical effect of a treatment for HIV/AIDS as well as a Phase 1 trial of a 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.

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 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 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.