Sangamo changes path in Beta-Thanlassemia program- delays trial to 2016

RICHMOND, Calif., May 13, 2015 /PRNewswire/ -- Sangamo BioSciences, Inc. (NASDAQ: SGMO) announced that it will consolidate development paths for the zinc finger nuclease (ZFN)-mediated genome editing programs targeting beta-thalassemia and sickle cell disease (SCD). This decision was based on preclinical data that support the development of the "BCL11A Enhancer" target for these clinical programs, indicating that it has the potential to provide the most efficient path to clinical proof of concept and subsequent development. While the beta-thalassemia program was initiated with a BCL11a knockout strategy, the SCD program already employs the BCL11A Enhancer approach. The decision to consolidate the strategy for these two programs was made by the joint steering committee (JSC) governing the programs, including Sangamo's collaborator Biogen.
Biogen's experience in the development of novel therapeutics has been critical as we work to advance these ZFP Therapeutics into the clinic," said Edward Lanphier, Sangamo's president and chief executive officer. "While our joint decision will result in a delay in the initiation of the beta-thalassemia Phase 1 clinical trial, we believe that the efficiency of the consolidated development path and potential benefit to patients clearly support this decision."
Mr. Lanphier added, "We are committed to rapidly moving this exciting new therapeutic approach powered by our ZFN genome editing technology into human clinical trials. The alignment of the beta-thalassemia and SCD programs to use the same specific ZFN reagent will enable more rapid and efficient co-development and provide both beta-thalassemia and sickle cell disease patients with a potentially safe and efficacious single-administration treatment with a life-long therapeutic effect."
"The quality of the clinical candidate and a focus on patient benefit drives our development decisions," said Olivier Danos, Ph.D., Biogen's senior vice president of gene therapy. "Sangamo's ability to rapidly move from identification of a new DNA target to a highly specific genome editing therapeutic lead candidate has enabled us to quickly deploy the latest scientific knowledge against both of these important genetic diseases."
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 Philip Gregory, D.Phil., Sangamo's senior vice president of research and chief scientific officer. "While the discovery of the BCL11A Enhancer as a potential target was made relatively recently, the team generated critical data that supported the Enhancer approach in time for this strategy to be used for both the beta-thalassemia and the sickle cell disease programs."
Preclinical data supporting the Enhancer program will be presented at 4:15 pm ET, today, Wednesday, May 13, 2015 at the 18th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT). Abstract #53 "From GWAS to the Clinic: Genome-Editing the Human Bcl11a Erythroid Enhancer for Fetal Globin Elevation in the Hemoglobinopathies