Sangamo BioSciences Announces Initiation of Two New Phase 2 HIV Clinical Trials

RICHMOND, Calif., Jan. 9, 2012 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the initiation of two new Phase 2 clinical studies (SB-728-1101 and SB-728-902, Cohort 5) in its program to develop a "functional cure" for HIV/AIDS. Sangamo's ZFP Therapeutic^® approach (SB-728-T) generates T-cells that are resistant to HIV infection using its zinc finger nuclease (ZFN) technology to permanently disrupt the DNA sequence encoding CCR5, a co-receptor used by HIV to enter cells. The company expects to present data from its SB-728-T HIV clinical trials at appropriate medical meetings in 2012.

"We are delighted to be able to open these two important clinical studies ahead of schedule," said Geoff Nichol, M.B. Ch.B., Sangamo's executive vice president, research and development. "Data from earlier Phase 1 trials demonstrated a statistically significant relationship between the number of circulating T-cells in which both CCR5 genes are modified and the reduction in HIV viral load in infected subjects during an interruption of anti-retroviral therapy. Both of these new Phase 2 clinical trials are specifically designed to confirm and further investigate these findings."

The new studies employ two approaches to increase the number of engrafted T-cells in which both CCR5 gene copies are modified (biallelically modified) in SB-728-T-treated, HIV-infected subjects. The first, an extension of an ongoing trial (SB-728-902, Cohort 5), is designed to further investigate the effect of SB-728-T treatment on HIV viral load in subjects that are naturally heterozygous for the CCR5 delta-32 gene mutation (i.e. one of their two CCR5 gene copies has the mutation and one is normal). The second study (SB-728-1101), in HIV-infected subjects without the CCR5 delta-32 mutation, employs a conditioning pretreatment designed to significantly enhance the number of engrafted biallelically modified T-cells.

The rationale for the Phase 2 studies is based on data obtained in a Phase 1 trial of SB-728-T that demonstrated a statistically significant relationship between the number of engrafted biallelically modified T-cells and the reduction in HIV viral load in treated subjects. In this earlier trial, the viral load of an SB-728-T treated-subject decreased to undetectable levels during a scheduled treatment interruption (TI). This subject was heterozygous for the CCR5 delta-32 gene mutation, thus doubling the number of biallelically modified T-cells after SB-728-T treatment. 

"We are focused on applying our ZFP Technology platform to develop novel therapeutics to address unmet medical needs," stated Edward Lanphier, Sangamo's president and CEO. "In addition to the rapid progress that we are making in our clinical program to develop a "functional cure" for HIV/AIDS, we are advancing our preclinical ZFP Therapeutic programs to engineer genetic cures for monogenic diseases including  hemophilias and hemoglobinopathies such as sickle cell anemia. Sangamo enters 2012 with a solid cash position which allows us to aggressively pursue our goals while maintaining our historic control on cash burn. As such, we plan to end 2012 with at least $60 million in cash. We look forward to providing further financial guidance for 2012 as well as an update on our clinical and preclinical programs and our corporate partnering activities on our fourth quarter and end of year 2011 call in early February."

Mr. Lanphier will also provide an update on Sangamo's ZFP Therapeutic pipeline and an overview of the Company's business strategy and objectives for 2012 during his presentation at the 30th Annual J.P. Morgan Healthcare Conference at 7:30 am PT, on Thursday, January 12, 2012. The presentation will be webcast and available at http://investor.sangamo.com/events.cfm.

About the SB-728-T Program

Sangamo is developing SB-728-T, a ZFN approach to the treatment of HIV/AIDS. In addition to the newly initiated Phase 2 studies, SB-728-T is being evaluated in an ongoing Phase 1/2 and two Phase 1 clinical trials to evaluate the safety and clinical efficacy of this approach in CD4+ T-cells. Sangamo's ZFNs are designed to permanently modify the DNA sequence encoding CCR5, a co-receptor that enables HIV to enter and infect cells of the immune system. Individuals carrying a naturally occurring mutation in both of their CCR5 genes (homozygotes), a variant known as CCR5 delta-32, have been shown to be resistant to HIV infection. Building on this observation, a study published in Blood in December 2010 reported an effective cure when an AIDS patient with leukemia, the so-called "Berlin Patient," received a bone marrow transplant from a "matched" donor homozygous for the CCR5 delta-32 mutation. This approach transferred hematopoietic stem cells (HSCs) from the bone marrow of the delta-32 donor providing a self-renewable and potentially lifelong source of HIV-resistant immune cells. After transplantation, the HIV patient was able to discontinue all anti-retroviral drug treatments, CD4 T-cell counts increased, and HIV viral load dropped to an undetectable level, demonstrating effective transplantation of protection from HIV infection.

About SB-728-902 Cohort 5 – Phase 2 Study

Up to 20 HIV-infected subjects heterozygous for the CCR5 delta-32 mutation (i.e. with one CCR5 gene that is naturally modified) who are currently on Highly Active Anti-retroviral Therapy (HAART) will be enrolled and will receive a single intravenous infusion of SB-728-T (5 to 30 billion modified cells). Two months after SB-728-T treatment, subjects will undergo a 16 week TI during which time their anti-retroviral therapy will be discontinued. HAART will be reinstituted in subjects whose CD4 T-cell counts drop to <350 cells/mm3 and/or whose HIV-RNA increases to >100,000 /mL for three consecutive weekly measurements. At the end of the TI, subjects with a sustained detectable HIV viral load will be reinstituted on HAART. Subjects with an undetectable viral load will remain off HAART until HIV RNA levels are detectable or their CD4 T-cell count drops below 350 cell/mm3 for three consecutive weekly measurements.

About SB-728-1101 – Phase 1/2 Study

SB-728-1101 is an open-label, dose escalation, multi-center study designed primarily to evaluate the safety and tolerability of escalating doses of cyclophosphamide (Cytoxan®) administered one day prior to SB-728-T infusion. Cytoxan is a drug that is used to transiently reduce the numbers of T-cells in the body which then rapidly repopulate once the drug is discontinued. Such lymphodepletive treatment has been used to enhance engraftment of adoptively transferred T-cells in the treatment of cancer and as therapy for numerous autoimmune diseases. The drug has been previously used in HIV-infected individuals and studies demonstrate that, while the drug was transiently lymphodepleting, it did not significantly reduce total CD4 T-cell counts over the long term and was adequately tolerated.

In addition to safety, the study will evaluate the effect of escalating doses of Cytoxan on SB-728-T engraftment, the effect of SB-728-T treatment on viral load following HAART interruption, the change in CD4+ T-cell counts in peripheral blood and the long-term persistence of SB-728-T.

At least 9 HIV-infected subjects on HAART will be enrolled into 3 dose-escalating cohorts (3 subjects/cohort), and will receive intravenous Cytoxan (200 mg, 500 mg or 1000 mg). Within each cohort, treatment will be staggered so that each subsequent subject cannot be infused with Cytoxan until at least 2 weeks after the preceding subject. One day after receiving Cytoxan, subjects will be infused with SB-728-T (5 to 30 billion cells). Six weeks after SB-728-T infusion, subjects with CD4 cell counts >500 cells/mm3 will undergo a 16 week TI during which time their anti-retroviral therapy will be discontinued. HAART will be reinstituted in subjects whose CD4 T-cell counts drop to <500 cells/ mm3 and/or whose HIV-RNA increases to >100,000 copies/ mL for three consecutive weekly measurements. At the end of the TI, subjects with a sustained detectable viral load or CD4 T-cell count <500 cells/mm3 will be reinstituted on HAART. Subjects with an undetectable viral load will remain off HAART until HIV RNA levels are detectable or their CD4 T-cell count drops below 500 cells/ mm3 for three consecutive weekly measurements.

About Sangamo's HIV Pipeline of Programs

As part of a collaboration with scientists at City of Hope and the University of Southern California, under a $14.5 million CIRM Disease Team Research Award, Sangamo is also developing an approach to modify a patient's own HSCs to circumvent the need to find matched donors that carry the delta-32 CCR5 mutation while providing a renewable and long-lasting source of HIV-resistant cells. Specifically, the grant funds the development up to submission of a an Investigational New Drug (IND) Application of a ZFN approach to treat AIDS patients by first isolating their HSC, modifying them using CCR5-specific ZFNs, and then re-infusing them to reconstitute the immune system with CCR5-negative, HIV-resistant immune cells.

About HIV/AIDS

HIV stands for Human Immunodeficiency Virus. HIV infection kills or impairs cells of the immune system progressively destroying the body's ability to fight infections and certain cancers resulting in AIDS (Acquired Immune Deficiency Syndrome). Individuals diagnosed with AIDS are susceptible to opportunistic infections, infections that usually are not as frequent or severe in healthy individuals. At the end of 2008, an estimated 1,178,000 persons aged 13 and older were living with HIV infection in the United States. Of those, 20% had undiagnosed HIV infections. In 2009, the estimated number of persons diagnosed with AIDS in the United States was 35,000. According to UNAIDS/WHO, over 2.6 million people were infected with HIV in 2009. There are now over 33 million people living with HIV and AIDS worldwide.

About Sangamo

Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and genome editing. Sangamo has a Phase 2 clinical trial and two Phase 1 / 2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic^® for the treatment of HIV/AIDS. Other therapeutic programs are focused on monogenic diseases, including hemophilia and hemoglobinopathies. 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 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 to clinical trials of ZFP Therapeutics in HIV/AIDS, the timing and availability of clinical data, the research and development of novel ZFP TFs and ZFNs as ZFP Therapeutics, applications of Sangamo's ZFP Therapeutics  to treat specific human disease as well as establishing strategic partnerships for therapeutic programs and references to anticipated cash and investment balance. Actual results may differ materially from these forward-looking statements due to a number of factors, including technological challenges, uncertainties relating to the initiation, completion and outcome of stages of ZFP Therapeutic clinical trials, Sangamo's ability to develop commercially viable products and technological developments by our competitors. See Sangamo's SEC filings, and in particular, the risk factors described in Sangamo's Annual Report on Form 10-K and most recent Quarterly Reports on its Form 10-Q. Sangamo BioSciences, Inc. assumes no obligation to update the forward-looking information contained in this press release.

SOURCE Sangamo BioSciences, Inc.