The California Institute for Regenerative Medicine (CIRM) has granted the Sangamo BioSciences, Inc. a $6.4 million Strategic Partnership Award to develop a potentially curative ZFP Therapeutic for beta-thalassemia based on the application of its zinc finger nuclease (ZFN) gene-editing technology in hematopoietic stem cells (HSCs).

The four year grant provides matching funds for preclinical work that will support an Investigational New Drug (IND) application and a Phase 1 clinical trial in transfusion-dependent beta-thalassemia patients.  The grant application entitled "A Treatment for Beta-thalassemia via High Efficiency Targeted Genome Editing of Hematopoietic Stem Cells" won the highest scientific score and was the only application recommended for funding in this round of CIRM's Strategic Partnership Awards.

"Sangamo's powerful and precise ZFN-genome editing technology enables modification of a patient's own stem cells and potentially provides a safer approach to current therapies for haemoglobinopathies such as beta-thalassemia and sickle cell disease," said Mark Walters,  Director of Blood and Marrow Transplantation at Children's Hospital & Research Center Oakland and a member of the clinical team that will be conducting the phase 1 clinical trial of this ZFP Therapeutic. "We have known for some time that the persistence of fetal haemoglobin beyond the newborn stage mitigates the severity of these haemoglobin disorders.  We are very pleased to have the opportunity to develop a clinical protocol that uses Sangamo's technology to permanently raise fetal haemoglobin levels in red blood cells to a sufficient degree to have a strong beneficial effect.  If successful, this could eliminate the need for life-long medications and red blood cell transfusions that are currently the standard of care for these disorders."

Beta-thalassemia is a genetic disease of the blood caused by mutations in the beta-globin gene. This gene defect leads to impaired production of haemoglobin, the iron-containing protein in red blood cells (RBCs) that carry oxygen from the lungs to the tissues. Individuals with thalassemia are dependent on blood transfusions for survival as they fail to make sufficient healthy RBCs.  The unmet medical need in transfusion-dependent beta-thalassemia is significant, with reduced life expectancy due to multi-organ failure caused by iron overload, blood-borne infections and other disease complications.  A bone marrow transplant (BMT) of HSCs from a "matched" related donor (allogeneic BMT) is curative. However, this therapy is limited due to the scarcity of matched donors and the significant risk of graft-versus-host disease (GvHD) after transplantation of the foreign cells.

Sangamo is taking a different approach. During development, a fetal form of haemoglobin is made. In infancy, it fully protects beta-thalassemia patients from developing disease symptoms. Later in childhood however, production of fetal hemoglobin ceases and is replaced by synthesis of adult-type beta-globin chains that are defective in beta-thalassemia patients. Sangamo's approach uses its proprietary ZFN genome-editing technology to enable the permanent production of therapeutic fetal haemoglobin to achieve normal levels of hemoglobin and RBCs, with the goal of eliminating, or greatly reducing, the need for chronic blood transfusions.  Moreover, by performing this genome editing in HSCs isolated and returned to the same patient (so called autologous BMT), Sangamo's approach eliminates both the need for a matched donor and the risk of GvHD.

"CIRM support for this program is yet another major validation of our ZFP Therapeutics platform," said Edward Lanphier, Sangamo's president and CEO. "The award will assist the development of our stem cell-based ZFP Therapeutic for the potential cure of thalassemia.  Importantly, this same approach can be directly applied to related hemoglobinopathies such as sickle cell disease.  We look forward to working with a team of world-renowned experts in this field, including the team at Children's Hospital & Research Center Oakland and our colleagues at CIRM, to bring this treatment through IND application and into a Phase 1 clinical trial."

Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and genome editing.