The long-term objective of current project is to commercialize a novel coagulation factor product manufactured using a novel production cell line, designated ET3i/BHK-M with a primary indication of treatment of anti-drug antibodies that develop following the treatment of congenital hemophilia A with factor VIII (fVIII) replacement products. Expression Therapeutics has developed multiple technologies that, when integrated, provide a highly efficient biomanufacturing platform designed for improved volumetric productivity. In the phase I SBIR project periods, Expression Therapeutics generated and validated a research cell bank demonstrating the highest levels of recombinant factor VIII reported to date, completed upstream and downstream process development, and successfully transferred the technology to a contract manufacturing organization for production of phase I clinical test material. The current application seeks to complete all manufacturing, nonclinical, clinical planning, and regulatory activities required to conduct a phase I first-in-man trial of ET3i/BHK-M, with the primary endpoint of safety and tolerability.
Despite many advances toward the control and prevention of bleeding in hemophilia A through coagulation factor VIII infusion therapy, 25 ? 35% of severe patients develop anti-drug antibodies termed ?inhibitors? that block treatment efficacy. In the US, Canada and Western Europe, the majority of inhibitor patients are treated off-label with higher, more frequent administration of expensive coagulation factor VIII products in protocols collectively referred to as ?Immune Tolerance Induction? therapy. The goal of the current project is to commercialize the first product using our novel commercial cell production system, which will be a coagulation factor VIII product with a primary label indication for the treatment of fVIII inhibitors through Immune Tolerance Induction therapy.
