Empasiprubart is engineered as a human IgG1 anti-C2 “sweeping” antibody. Generally, serum proteins like antibodies, are transported from the serum into the cell’s endosome then to the lysosome where they are degraded. Empasiprubart is designed with an Fc backbone that is equipped with the proprietary NHance™ mutation, which is intended to enhance the binding of the antibody to FcRn in the endosome and prevent the antibody going into the lysosome for degradation.

(1) Empasiprubart binds at its variable domain to the target C2 with high affinity in the serum but lower affinity in the endosome due to the pH and Ca2+ dependent nature of the binding.

(2) The lower affinity allows C2 to dissociate from Empasiprubart in the endosome and cycle into the lysosome for destruction (3).

(4) Empasiprubart still bound to FcRn can cycle back to circulation and bind new C2 – repeating the cycle in a “sweeping” manner to continuously destroy the C2 target. With sweeping recycling properties, it is expected that Empasiprubart will remain longer in circulation and can remove several C2 molecules from circulation resulting in enhanced C2 clearance from the bloodstream.