RICHMOND, CA, USA I December 5, 2016 I Sangamo BioSciences, Inc. (SGMO), the leader in therapeutic genome editing, announced the presentation of preclinical and manufacturing data that support SB-525, its gene therapy program for hemophilia A, at the 58th Annual Meeting of the American Society of Hematology (ASH) being held in San Diego, CA, from December 3-6, 2016.
“We have developed an improved gene therapy vector for treatment of hemophilia A which we believe is highly competitive, and we remain on track to file an Investigational New Drug (IND) application for our clinical program by the end of 2016,” said Sandy Macrae, M.B., Ch.B., Ph.D., Sangamo’s president and chief executive officer. “This program illustrates Sangamo’s drug development capabilities beyond our ZFP platform. Moreover, it demonstrates the ability of our R&D and technical operations teams to rapidly develop a program from research data, through positive preclinical results in relevant animal models to a clinical program fully supported by a scalable manufacturing process. We have strengthened our clinical development capabilities with recent senior management changes and are committed to consistent achievement of planned milestones for our four clinical programs. We look forward to initiating a clinical trial in 2017 to evaluate SB-525.”
The development of adenovirus associated vector (AAV) cDNA gene therapy approaches for hemophilia A has been challenging due to a number of factors, including the large size of the native human Factor 8 gene (hF8), low levels of human Factor VIII protein (hFVIII) expression from conventional promoters, and low yields of vector in large scale manufacturing processes. Through an iterative process Sangamo scientists have developed an improved AAV construct that expresses an hF8 cDNA cassette (SB-525). A single intravenous administration of SB-525 results in the expression of significant levels of hFVIII in mice and non-human primates (NHPs) and correction of the bleeding defect in a mouse model of hemophilia A. The construct also resulted in greatly improved AAV yields during vector manufacturing.
Importantly, dosing studies in NHPs which evaluated SB-525 manufactured at GMP-clinical scale demonstrated a robust and reproducible dose response curve and the most potent dose response in NHPs thus far disclosed for an hF8 cDNA gene therapy program. In these animals, mean hFVIII levels ranged from 5% of normal at the lowest dose to 230% at the highest (AAV doses in the 6 x 1011 – 6 x 1012 vgs/kg range). The therapeutic levels of hFVIII that were observed in these studies support starting clinical doses in the E11 vg/kg range.
About Sangamo
Sangamo BioSciences, Inc. is focused on Pioneering Genetic Cures™ for monogenic and infectious diseases by deploying its AAV-based gene therapy platform, and therapeutic genome editing and gene regulation platforms based on its novel zinc finger DNA-binding protein technology. The Company’s proprietary zinc finger nuclease (ZFN)-mediated in vivo genome editing approach is focused on monogenic diseases, including hemophilia and lysosomal storage disorders MPS I and MPS II. Sangamo has initiated a Phase 1/2 clinical trial for hemophilia B, the first in vivo genome editing application cleared by the FDA. In addition, Sangamo has Phase 1/2 and Phase 2 clinical programs in HIV/AIDS (SB-728). The Company has a strategic collaboration with Bioverativ, Biogen’s planned spin-off company for rare blood disorders, for hemoglobinopathies, including sickle cell disease and beta-thalassemia, and with Shire International GmbH to develop therapeutics for Huntington’s disease. It 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.
SOURCE: Sangamo
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RICHMOND, CA, USA I December 5, 2016 I Sangamo BioSciences, Inc. (SGMO), the leader in therapeutic genome editing, announced the presentation of preclinical and manufacturing data that support SB-525, its gene therapy program for hemophilia A, at the 58th Annual Meeting of the American Society of Hematology (ASH) being held in San Diego, CA, from December 3-6, 2016.
“We have developed an improved gene therapy vector for treatment of hemophilia A which we believe is highly competitive, and we remain on track to file an Investigational New Drug (IND) application for our clinical program by the end of 2016,” said Sandy Macrae, M.B., Ch.B., Ph.D., Sangamo’s president and chief executive officer. “This program illustrates Sangamo’s drug development capabilities beyond our ZFP platform. Moreover, it demonstrates the ability of our R&D and technical operations teams to rapidly develop a program from research data, through positive preclinical results in relevant animal models to a clinical program fully supported by a scalable manufacturing process. We have strengthened our clinical development capabilities with recent senior management changes and are committed to consistent achievement of planned milestones for our four clinical programs. We look forward to initiating a clinical trial in 2017 to evaluate SB-525.”
The development of adenovirus associated vector (AAV) cDNA gene therapy approaches for hemophilia A has been challenging due to a number of factors, including the large size of the native human Factor 8 gene (hF8), low levels of human Factor VIII protein (hFVIII) expression from conventional promoters, and low yields of vector in large scale manufacturing processes. Through an iterative process Sangamo scientists have developed an improved AAV construct that expresses an hF8 cDNA cassette (SB-525). A single intravenous administration of SB-525 results in the expression of significant levels of hFVIII in mice and non-human primates (NHPs) and correction of the bleeding defect in a mouse model of hemophilia A. The construct also resulted in greatly improved AAV yields during vector manufacturing.
Importantly, dosing studies in NHPs which evaluated SB-525 manufactured at GMP-clinical scale demonstrated a robust and reproducible dose response curve and the most potent dose response in NHPs thus far disclosed for an hF8 cDNA gene therapy program. In these animals, mean hFVIII levels ranged from 5% of normal at the lowest dose to 230% at the highest (AAV doses in the 6 x 1011 – 6 x 1012 vgs/kg range). The therapeutic levels of hFVIII that were observed in these studies support starting clinical doses in the E11 vg/kg range.
About Sangamo
Sangamo BioSciences, Inc. is focused on Pioneering Genetic Cures™ for monogenic and infectious diseases by deploying its AAV-based gene therapy platform, and therapeutic genome editing and gene regulation platforms based on its novel zinc finger DNA-binding protein technology. The Company’s proprietary zinc finger nuclease (ZFN)-mediated in vivo genome editing approach is focused on monogenic diseases, including hemophilia and lysosomal storage disorders MPS I and MPS II. Sangamo has initiated a Phase 1/2 clinical trial for hemophilia B, the first in vivo genome editing application cleared by the FDA. In addition, Sangamo has Phase 1/2 and Phase 2 clinical programs in HIV/AIDS (SB-728). The Company has a strategic collaboration with Bioverativ, Biogen’s planned spin-off company for rare blood disorders, for hemoglobinopathies, including sickle cell disease and beta-thalassemia, and with Shire International GmbH to develop therapeutics for Huntington’s disease. It 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.
SOURCE: Sangamo
Post Views: 29
