Figure 2.

MOA of batoclimab. (A) FcRn maintains levels of IgG in circulation by preventing IgG degradation. (1) IgG enters cells via fluid-phase pinocytosis; (2) FcRn binds antibodies in a pH-dependent manner with high binding affinity at mild acidic conditions (pH 6.0) present in the endosome; (3) FcRn-IgG complexes are sorted from unbound proteins; (4) unbound proteins are trafficked to the lysosome for degradation; (5) IgG is recycled back to the cell surface and released into circulation. (B) Selective depletion and lysosomal degradation of pathogenic IgG antibodies via FcRn inhibition with batoclimab. (1) IgG and batoclimab are taken up into cells via endocytosis. (2) Batoclimab preferentially binds to FcRn in endosomes (batoclimab has high binding affinity at high and low pH). (3) FcRn-batoclimab complexes are sorted from unbound proteins including unbound IgG. (4) Non-receptor bound IgG are degraded in the lysosomes. (5) Batoclimab may remain bound to FcRn, further inhibiting IgG recycling. FcRn, neonatal fragment crystallisable receptor; IgG, immunoglobulin G; MOA, mechanism of action.