Groundbreaking clinical data shows drug protects against HIV

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 was 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 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 optimisation 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 maximise 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.”

(Source: Sangamo BioSciences, Inc.: 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC))