FDA accepts Sangamo's IND for repeat-dosing in Phase 1 clinical trial of SB-728-T ZFN-based therapeutic

Sep 23 2009

Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today that the US Food and Drug Administration (FDA) has reviewed and accepted an Investigational New Drug (IND) application to initiate an open-label, repeat-dosing Phase 1 clinical trial (SB-728-T-902) of the company's ZFN-based therapeutic, SB-728-T. A single dose Phase 1 clinical study of SB-728-T was initiated in February 2009 and is ongoing at the University of Pennsylvania. Both Phase 1 studies are designed primarily to evaluate the safety and tolerability of this ZFP Therapeutic(TM) approach, however subjects' CD4 T-cell counts, levels of CCR5-modified T-cells and viral burden will also be monitored.

"Opening a second Phase 1 clinical trial of this exciting new approach to HIV/AIDS treatment enables us to expedite clinical and commercial development of SB-728-T. We are very pleased with the FDA's decision enabling us to expand this program and move forward quickly with a repeat-dosing trial," said Dale Ando, M.D., Sangamo's chief medical officer and vice president of therapeutic development.

"The best approach to controlling HIV is by preventing infection of cells in the first place. Since 1996, when CCR5 was validated as a target for HIV therapy, the goal has been to recapitulate the naturally-occurring protection against viral infection exhibited by individuals who have the CCR5-delta32 mutation. We have the ability to disrupt the CCR5 gene and make human T-cells resistant to infection by CCR5-specific strains of HIV. In this trial we will be evaluating SB-728-T in subjects that have well-controlled levels of virus but have sub-optimal recovery of CD-4+ T-cell counts despite long-term triple drug therapy. This group represents approximately thirty percent of all HIV-infected patients in the US and may particularly benefit from this novel T-cell ZFP Therapeutic approach."

Based on Sangamo's zinc finger DNA-binding protein nuclease (ZFN) technology, SB-728-T has been shown in an animal model of HIV infection to lead to an increase in CD4+ T-cell counts, a reduction in viral load and expansion of CCR5-modified T-cells, suggesting resistance to HIV.

"Although it is still early days, we are encouraged by what we have seen in pre-clinical experiments and in the ongoing Phase 1 clinical trial that is being run by collaborators at the University of Pennsylvania," commented Edward Lanphier, Sangamo's president and CEO. "This new study is another important step in our mission to establish ZFP Therapeutics as a major new therapeutic product development platform. Moving our first ZFN technology-based product efficiently through the development process is vital to that goal. SB-728-T represents a new treatment paradigm for the treatment of HIV and we are very excited to expand its clinical development."

CCR5 is a co-receptor that enables HIV to enter and infect cells of the immune system. It has been observed that individuals carrying a natural mutation of their CCR5 gene, CCR5-delta32, are highly resistant to infection by HIV, despite high-risk behaviors. These individuals, lacking a functional CCR5 (approximately 1-2% of the general population), are otherwise immunologically "normal". A variety of small molecule and antibody antagonists of CCR5 binding have been tested and developed as potential therapeutic agents for the treatment of HIV infection. In addition, there is a recent report of a patient who had both HIV infection and leukemia and received a bone marrow transplant from a donor carrying the CCR5 mutation. After the successful bone marrow transplant, HIV treatment was discontinued and the virus could not be found in the circulating blood several months after the procedure. Sangamo's ZFNs are designed to modify the DNA sequence encoding CCR5. This modification can occur directly in T-cells with only a brief exposure to the ZFNs. Once the modification is made to the T-cell's CCR5 gene it is permanently disrupted.

Source: http://www.sangamo.com