Rare Daily Staff

Sangamo Therapeutics and Bioverativ said the U.S. Food and Drug Administration has accepted their application to begin human clinical studies of ST-400, a gene-edited cell therapy candidate for people with transfusion-dependent beta-thalassemia.

Beta-thalassemia is an inherited blood disorder caused by mutations in the beta-globin gene that leads to reduced or absent production of adult hemoglobin, the protein in red blood cells that carries oxygen to cells throughout the body. The disorder causes the destruction of red blood cells, which results in severe anemia and reduced oxygen transport to various tissues in the body. There are approximately 100,000 treated beta-thalassemia patients worldwide, according to the World Health Organization. About 19,000 of those patients are in the United States and Europe.

“We believe the precision, efficiency, and specificity of zinc finger nuclease gene editing technology will differentiate ST-400 among other genomic therapies in development for beta-thalassemia,” said Edward Conner, chief medical officer at Sangamo.

Sangamo expects to open several clinical sites across the United States and begin enrolling patients in the first half of 2018.

ST-400 is an autologous cell therapy that involves gene editing of a patient’s own hematopoietic stem cells using Sangamo’s zinc finger nuclease technology. It is being developed with the aim of providing a one-time treatment for people with transfusion-dependent beta-thalassemia by increasing production of fetal hemoglobin, which can more effectively carry oxygen, potentially eliminating the need for chronic blood transfusions.

As part of the phase 1/2 clinical trial protocol, a patient’s hematopoietic stem cells are isolated from the blood, and the cells then undergo ex-vivo gene editing using zinc finger nuclease proteins to modify a specific sequence of the BCL11A gene that suppresses fetal hemoglobin production in erythrocytes.

Following a conditioning regimen, patients will be infused with their own modified hematopoietic stem cells, with the goal of producing increased amounts of fetal hemoglobin to compensate for the decrease in functional beta-globin levels, potentially resolving the need for chronic blood transfusions and ameliorating the complications from major organ failure that frequently arise from the disease.

Sangamo and Bioverativ have an exclusive worldwide collaboration to develop and commercialize zinc finger nuclease-mediated gene-edited cell therapies for the treatment of beta-thalassemia and sickle cell disease. Under the agreement, Sangamo is responsible for conducting the ST-400 Phase 1/2 clinical trial, and Bioverativ will be responsible for subsequent worldwide clinical development, manufacturing, and commercialization.

October 2, 2017

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