FVIII-CAART for Hemophilia A with Factor VIII Alloantibodies

Our CABA platform may be applicable in other instances where B cell antibody production is implicated. There are cases where the immune system has or produces antibodies against therapies, which is known as an alloimmune response. These alloantibodies can prevent a particular therapy from being delivered effectively because the therapy is degraded by the immune response. Our approach may address the alloantibody response by specifically ablating the B cells responsible for producing the alloantibodies through a similar mechanism seen in autoimmune disease. Currently, there is no effective treatment to eradicate FVIII inhibitors in patients who possess them.

Preliminary FVIII CAAR and CAAR-like constructs have been engineered that target parts, but not all, of the FVIII domains. A visual schematic depicting FVIII, which is a large glycoprotein consisting of six domains that interact with each other to form the full complex is below

Internally, we are conducting additional studies to optimize our FVIII-CAART development. The focus of these studies will be to fully characterize any additional pathogenic epitopes and construct a FVIII-CAART that includes additional FVIII domains. Given the size of the FVIII protein, this will likely require us to incorporate additional technologies to reduce the size of the final CAAR construct. An evaluation of potential technologies to achieve this objective is ongoing.