RICHMOND, Calif., May 27, 2014 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced that data from clinical, preclinical and research-stage programs focused on the development of ZFP Therapeutics® were outlined in several presentations and posters at the 17th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) from May 21-24, 2014.
The presentations included an update, given by Dale Ando., M.D., Sangamo's vice president of therapeutic development and chief medical officer, on subjects in Sangamo's completed clinical trials of SB-728-T for HIV/AIDS. One subject, enrolled in the SB-728-902 Cohort 5 study, has demonstrated continuing control of circulating viral load at low levels (under 300 copies) for 45 weeks of treatment interruption (TI) of their antiretroviral medication (ART). A second subject, enrolled in the SB-728-1101 Cytoxan pre-conditioning study at the 1 g/m2 dose, has experienced a two log decrease in circulating viral load from peak during TI, which has been maintained for 24 weeks. Both subjects remain off ART.
"We plan to initiate a Phase 2 clinical trial to further investigate the dramatic and sustained effects on viral load, reservoir reduction and immune reconstitution that we have observed in our early studies of SB-728-T," stated Geoff Nichol, M.B., Ch.B., Sangamo's executive vice president of research and development. "The data that we have generated in these early studies have provided valuable information for the design of this new trial in which we also plan to implement process improvements including the use of messenger RNA (mRNA) to deliver the CCR5 specific zinc finger nucleases (ZFNs)."
Sangamo expects to enroll 12 HIV-infected subjects in the Phase 2 study by the end of 2014. Subjects will undergo pre-conditioning with Cyclophosphamide (Cytoxan), at a dose determined to be optimal for enhancement of SB-728-T engraftment in the SB-728-1101 study. All subjects will undergo a TI from their ART during which the effect of SB-728-T treatment on viral load will be evaluated. The study will also evaluate the effect of SB-728-T on the viral reservoir, total CD4 levels, and other immunologic parameters. In addition, as ZFNs require only transient expression to achieve a permanent modification of their target gene, Sangamo will employ a new proprietary manufacturing process using mRNA delivery of the ZFNs used in CCR5 gene modification. This improved delivery method provides both process- and cost-saving advantages over viral delivery, will enable retreatment, if necessary, and offers the potential for greater CCR5 biallelic modification.
Additional presentations, given by Sangamo scientists and their collaborators included preclinical data from Sangamo's Huntington's disease program, which won an outstanding poster award, and preclinical and research stage programs in other monogenic diseases, cancer immunotherapy, and advancements in the technology.
New data provided further proof of concept for the potential of ZFN-mediated genome-editing to provide curative treatments for intractable monogenic diseases, such as severe combined immunodeficiency (SCID-X1), that are safer than approaches that use randomly integrating viruses. Sangamo scientists and collaborators described method using mRNA delivery of ZFNs and improved culture conditions that increased the efficiency of targeted gene insertion to therapeutically relevant levels in long-lived hematopoietic stem cells (HSCs).
"We have ongoing efforts to expand our internal delivery capabilities and to exploit non-viral delivery methods for our gene-based therapeutics," continued Dr. Nichol. "These include mRNA delivery in ex-vivo applications of the technology in our stem cell and T-cell program for HIV and our partnered hemoglobinopathies program. We are also exploring the possible use of RNA-based delivery directly to tissues and presented preclinical data at ASGCT on one such early example in the lung which could potentially open the door to new applications, and repeat-dosing to enhance ZFN activity in vivo."
The application of ZFNs to the lung was presented in a preclinical study in a mouse model of surfactant protein-B (SP-B) deficiency of the lung in which ZFNs targeting the SP-B gene (SFTPB) were delivered directly into the airways as a chemically modified messenger RNA, enabling short bursts of ZFN expression and efficient genome editing in vivo when combined with an Adeno-associated (AAV)-encoded repair template. Modified mRNA/AAV-template delivery generated constitutive production of protein from the SFTPB in the mice with SP-B deficiency, resulting in a significant improvement in survival. Sangamo's collaborators demonstrated successful use of modified mRNA as a new vector supporting transient delivery of ZFNs in vivo, providing the first report of therapeutic genome editing using ZFNs in the murine lung. The data raise the possibility of utilizing modified-mRNA and mRNA/AAV combinations for the treatment of other severe inherited lung diseases. [Abstract #248];In Vivo Genome Editing Using Nuclease-Encoding Chemically Modified mRNA,
"The ASGCT Annual Meeting is the premier scientific meeting for gene therapy and modified cell therapy and provides an important venue for the presentation and discussion of progress in research and our therapeutic programs," said Edward Lanphier, Sangamo's president and CEO " The scientific community, as demonstrated by the interest at critical conferences like the ASGCT, continues to appreciate the efficiency and precision of ZFP Therapeutics for modification for any disease-related gene as well as the platform's validation in clinical studies. These presentations demonstrate the progress that Sangamo scientists and our collaborators have made in the development of our ZFP technology platform for the generation of novel therapeutic approaches for the treatment of unmet medical needs, particularly those with a genetic basis."
Sangamo BioSciences, Inc. is focused on Engineering Genetic Curesfor monogenic and infectious diseases by deploying its novel DNA-binding protein technology platform in therapeutic gene regulation and genome editing. The Company has ongoing Phase 2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic® for the treatment of HIV/AIDS (SB-728-T) and NGF-AAV for Alzheimer's disease (CERE-110). Sangamo's other therapeutic programs are focused on monogenic and rare diseases. The company has formed a strategic collaboration with Shire International GmbH to develop therapeutics for hemophilia, Huntington's disease and other monogenic diseases, and with Biogen Idec for hemoglobinopathies, such as sickle cell disease and beta-thalassemia. It has also 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, the research and development of novel ZFP TFs and ZFNs as ZFP Therapeutics and therapeutic applications and the scope of such applications of Sangamo's ZFP technology platform to specific human diseases and unmet medical needs, including a potential functional cure of HIV/AIDS, the expansion and expected timing of clinical studies of SB-728-T in HIV-infected individuals, the development of ZFP Therapeutics for monogenic diseases and stem cell applications and the possible use and benefits of RNA-based delivery methods. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to whether clinical trials will validate and support tolerability and efficacy of ZFP Therapeutic approaches, technological challenges, 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 the Company's Annual Report on Form 10-K and most recent Quarterly Report on Form 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.
Logo - http://photos.prnewswire.com/prnh/20130102/SF35903LOGO
SOURCE Sangamo BioSciences, Inc.