Preclinical development of TAK-754, a high-performance AAV8-based vector expressing coagulation factor VIII

CP/kg were conducted in male C57BL/6J mice. The highest TAK-754 dose occurred without TAK-754-related adverse clinical signs. Biodistribution profiling showed predominant detection in the liver with a low occurrence of vector DNA in other tissues. Integration site analysis revealed minimal vector integration, with no observations of clonal outgrowth or preferred integrations in genes previously implicated in hepatocellular carcinoma formation within the observation period. These preclinical studies demonstrate a good safety and efficacy profile for TAK-754.