Preliminary results from Sangamo Therapeutics’ Phase I/II THALES clinical trial of ST-400 have demonstrated a favourable profile of the gene therapy in treating transfusion-dependent beta thalassemia (TDT) patients.

Beta thalassemia is a rare blood disorder that develops due to a beta-globin gene mutation and negatively affects the production of red blood cells.

ST-400 is an ex-vivo gene-edited cell therapy that leverages the company’s zinc finger nuclease (ZFN) genome editing technology to alter a patient’s own hematopoietic stem cells (HSCs) to generate functional red blood cells using foetal haemoglobin.

Sangamo is developing the drug candidate in alliance with Sanofi. ST-400 secured grant support from the California Institute for Regenerative Medicine (CIRM).

The single-arm, multi-site THALES trial is designed to evaluate the safety, efficacy and tolerability of ST-400 autologous hematopoietic stem cell transplant in six TDT patients.

Initial data from three participants showed ‘prompt’ hematopoietic reconstitution when treated with the gene therapy. Results also found neutrophil engraftment from days 14-22 and platelet engraftment from days 22-35.

Investigators did not report any clonal haematopoiesis, which is determined using on-target indel pattern monitoring. Adverse events (AEs) were observed to be consistent with the known mobilisation, apheresis and myeloablative busulfan conditioning toxicities.

One ST-400-associated serious adverse event (SAE) was reported. One of the three participants had hypersensitivity during ST-400 infusion but the event was resolved by the completion of the infusion.

Sangamo Therapeutics Research and Development head Adrian Woolfson said: “The early experiences with the first three patients enrolled in this first-in-human study of ST-400 are providing useful insights into the patient characteristics, product characteristics and outcomes, including the relationship between patient genotype, phenotype, age, CD34+ cell dose, editing efficiency, and induction of foetal haemoglobin.

“Our understanding of ST-400 will continue to evolve as we follow the progress of these and additional patients in the coming year, and those dosed in Sanofi’s BIVV003 clinical trial, which is evaluating the same gene-editing approach in sickle cell disease.”

Sangamo and its partner Pfizer also reported new, positive follow-up data from the Phase I/II Alta study of SB-525 gene therapy in severe haemophilia A patients.