Biogen's experience in the development of novel therapeutics has been critical as we work to advance these ZFP Therapeutics into the clinic," said
"The quality of the clinical candidate and a focus on patient benefit drives our development decisions," said
Sangamo intends to file a new Investigational New Drug (IND) application for the "BCL11A Enhancer" approach for beta-thalassemia and anticipates initiating a Phase 1 clinical trial in 2016.
About the BCL11A Enhancer and BCL11A Knockout approachesBoth beta-thalassemia and SCD manifest several months after birth, when patients' cells switch from producing functional fetal globin to a mutant form of adult beta-globin, which causes their condition. Naturally occurring increased levels of fetal hemoglobin have been shown to reduce the severity of both SCD and beta-thalassemia disorders in adulthood. The collaborative development program uses ZFN-mediated genome editing of a patient's own hematopoietic stem and progenitor cells (HSPCs) to increase production of fetal globin in cells that will ultimately become red blood cells (RBCs). This novel approach uses the targeted specificity of ZFNs which need to be expressed in the cell only transiently to have a permanent effect.
Building upon recent data on the regulation of fetal hemoglobin, Sangamo and Biogen have developed two related but distinct ZFN-mediated genome editing approaches to disrupt critical aspects of the regulatory pathway that, in early infancy, leads to the switch in production from fetal to adult globin.
Initially, Biogen and Sangamo developed a strategy for beta-thalassemia that specifically knocked out the gene encoding the BCL11A transcription factor, a critical regulator of the switch from fetal to adult globin production. A second approach was initiated for the SCD program, which involved the disruption of the more recently described erythroid-specific "Enhancer" of BCL11A expression, a regulatory DNA sequence in the genome that is essential for expression of BCL11A but that is functional exclusively in cells destined to become RBCs. Both ZFN-mediated approaches were found to be equally specific and efficient leading to similar increases in fetal globin production. However, the Enhancer approach was found to have certain advantages, including its specificity for RBC producing cells, making it a preferable therapeutic strategy for hemoglobinopathies. Thus, the determination was made that the beta-thalassemia program should follow BCL11A Enhancer approach, like the SCD program.
"Sangamo's design and selection process enables rapid optimization of highly specific lead ZFN therapeutics," commented
Preclinical data supporting the Enhancer program will be presented at
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