Rozanolixizumab (RYSTIGGO) is a high-affinity humanized immunoglobulin G4 monoclonal antibody targeting Fc receptors (FcRn) in human newborns for the study of pathogenic IgG in autoimmune and alloimmune diseases.

FcRn (monkey):25 pM(Kd), FcRn (human):23 pM(Kd), MDCK cells:0.98 nM

Demonstrating similar affinity at both pH 6.0 (Kd 23 pM and 25 pM for human and cynomolgus monkey, respectively) and pH 7.4 (34 pM and 53 pM for human and cynomolgus monkey, respectively), Rozanolixizumab binds to human FcRn and cynomolgus monkey FcRn[1].In a dose-dependent manner, Rozanolixizumab is observed to inhibit the recycling of human IgG by human FcRn-transfected MDCK cells, with an IC50 of 0.41 nM. The recycling of IgG is similarly inhibited in cynomolgus monkey FcRn-transfected MDCK cells (IC50 0.98 nM)[1].Additionally, Rozanolixizumab causes an increase in intracellular IgG AF647[1].

Demonstrating non-linear pharmacokinetics indicative of target-mediated drug disposition, intravenous (IV) dosing of rozanolixizumab in cynomolgus monkeys showed that single IV doses (30 mg/kg) reduced plasma IgG concentration by 69% by Day 7 post-administration. Throughout the treatment period of 42 days, daily IV administration of rozanolixizumab (initial 30 mg/kg loading dose; 5 mg/kg daily thereafter) consistently reduced plasma IgG concentrations in all cynomolgus monkeys, maintaining low concentrations[1].