EpiVax received a grant to reengineer Factor VIII (FVIII), the primary therapeutic used to control bleeding for individuals who have acquired or hereditary hemophilia. This project is funded by an SBIR grant from the National Heart Lung and Blood Institute (NHLBI), a component of the NIH. The grant will provide $528,313 to fund studies that will provide a first proof-of-principle for the redesign program. The studies are anticipated to show that a reengineered FVIII, a protein that is missing or at low levels in most hemophiliacs, does not cause antibody responses in special strains of mice with humanized immune systems and in a mouse model of FVIII.
"This is an entirely novel approach to improving factor VIII therapy," says Anne De Groot, M.D., president and CEO of EpiVax. "We hope to make it possible for persons living with hemophilia to avoid a common side effect of FVIII that is currently in use—the development of inhibitors to the life-saving therapy." Dr. De Groot indicated a whole range of effective and second-generation biologics such as toxins and mAbs might also benefit from the same approach. Research on a novel deimmunized Botox, to be developed by EpiVax, was reported earlier this Spring.
The approach used by EpiVax to redesign proteins is to modify the parts of the proteins that stimulate undesirable immune responses. The approach is called DeFT™, Demmunization of Functional Therapeutics. EpiVax uses computer algorithms to determine which part of the protein might be modified to diminish immune responses while retaining the protein's essential functions. EpiVax uses immunoinformatics and humanized mice in order to make safer, more effective human therapeutics. This approach also offers hope for individualizing deimmunized therapies, also known as immunopharmacogenomics.