Iptacopan (LNP023) is a highly potent, reversible, selective inhibitor of factor B (IC50=10 nM), the proteolytically active component of the C3 and C5 convertases.
Iptacopan (LNP023) shows direct, reversible, and high-affinity binding to human FB with Kd of 7.9 nM in SPR assays, demonstrates potent inhibition of AP-induced MAC formation in 50% human serum with IC50 of 0.13 uM.
Iptacopan (LNP023) shows no inhibition of factor D (FD), as well as classical or lectin complement pathway activation (up to 100 uM), and no significant effects (up to 10 μM) in a broad assay panel of receptors, ion channels, kinases, and proteases.
Iptacopan (LNP023) blocks zymosan-induced MAC formation membrane attack complex (MAC) with IC50 of 0.15 uM, prevents KRN-induced arthritis in mice and is effective upon prophylactic and therapeutic dosing in an experimental model of membranous nephropathy in rats afer oral adminstration.
Iptacopan (LNP023) also prevents complement activation in sera from C3 glomerulopathy patients and the hemolysis of human PNH erythrocytes.