Manufacturing Process Development for Bioengineered FVIII

DESCRIPTION (provided by applicant): The manufacturing of recombinant coagulation factor VIII is a complex, labor and capital intensive endeavor. Of the recombinant proteins currently marketed, coagulation factor VIII is manufactured with the lowest efficiency and is by far the most expensive on a per unit mass basis with a pharmacy price of 10,000,000 per gram. The goal of the current application is to develop a product technology and a manufacturing process that can improve the production volume and pharmacy price of factor VIII biologics. Expression Therapeutics has developed two technologies, a bioengineered factor VIII transgene that demonstrates 100-fold greater expression than standard human factor VIII, and a new baby hamster kidney-derived (BHK) cell line, designated BHK-MS, that can be cultured and expanded indefinitely and at high density in serum and blood product-free medium under suspension bioreactor conditions. In the current application, we propose to optimize the fermentation and purification processes and conduct a scaled up production run that will demonstrate proof of concept of the manufacturing process and generate a substantial supply of bulk drug substance qualified for subsequent preclinical safety, efficacy and stability testing necessary to submit an Investigational New Drug application during phase II of the SBIR mechanism. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The long-term commercial objective of the current project is to commercialize a novel product for the treatment of persons with hemophilia A. Expression Therapeutics has acquired or developed multiple technologies that, when integrated, provide a highly efficient biomanufacturing platform designed for improved volumetric productivity of recombinant coagulation factor VIII, a complex and hard to manufacture biologic. Low-yield commercial manufacturing processes currently utilized have resulted in exorbitant product costs and therefore, limited patient access to treatment. The studies proposed herein are designed to provide proof-of-concept of the efficiency and scalability, as well as, rigorous preclinical validation and characterization of this novel recombinant factor VIII product and manufacturing process platform.