ARGX-117 is designed to be a humanized sweeping antibody that binds specifically to C2 in a pH- and Ca2+- dependent manner. C2 is a protein in the complement cascade which, when activated, leads to cell destruction. Binding of ARGX-117 is intended to inhibit the function of C2 and downstream complement activation.
By blocking complement activity, ARGX-117 has the potential to reduce tissue inflammation and the adaptive immune response. Through this proposed mechanism, ARGX-117 could represent a broad pipeline opportunity across severe autoimmune indications.
- ARGX-117 is designed to block complement activity with potential to reduce tissue inflammation and the adaptive immune response
- IV ARGX-117 and SC ARGX-117 (enabled with Halozyme's ENHANZE® drug delivery technology)
ARGX-117 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. ARGX-117 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) ARGX-117 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 ARGX-117 in the endosome and cycle into the lysosome for destruction (3).
(4) ARGX-117 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 ARGX-117 will remain longer in circulation and can remove several C2 molecules from circulation resulting in enhanced C2 clearance from the bloodstream.