Iptacopan (LNP023) is an inhibitor with high affinity to factor B, with a KD value of 7.9 nM and an IC50 value of 10 nM.

FB:7.9 nM (KD), Caspase-1:> 100 μM, FB:10 nM, Caspase-8:> 100 μM, Cathepsin B:> 100 μM, 5-LOX:> 30 μM, Cathepsin L:48 μM, CFB:0.01 μM, Cathepsin K:> 100 μM, Apopain:> 100 μM, Chymase:> 100 μM, DPP4:> 100 μM, CFB:0.012 μM, COX-2 receptor:> 30 μM, DPP2:> 100 μM, Cathepsin S:> 30 μM, Cathepsin G:> 100 μM, Chymotrypsin:> 100 μM, Cathepsin H:> 100 μM, Blood-coagulation factor Xa:> 100 μM, COX-1 receptor:> 30 μM

METHODS: Blood from three patients was analyzed in 2-14 replicates and Iptacopan was used at 1 μM. Hemolysis of PNH erythrocytes was determined by FACS analysis.
RESULTS LNP023 can block C3 deposition on the surface of CD59-negative red blood cells. [2]

METHODS: Iptacopan (LNP023) was tested in KRN-induced arthritis at doses of 20, 60 and 180 mg/kg by injection twice daily.
RESULTS Comprehensive disease protection was observed at 60 and 180 mg/kg, and LNP023 significantly inhibited complement activation in joints at all doses, with significant reductions in Ba, C3d, and C5a levels. [1]
METHODS: Sixty-eight patients with biopsy-proven C3G, decreased C3 (<77 mg/dl), proteinuria ≥1.0 g/g), and estimated glomerular filtration rate (eGFR) ≥30 ml/min per 1.73 m2 were recruited. Patients will be randomized 1:1 to receive iptacopan 200 mg twice daily or placebo for 6 months, followed by open-label treatment of all patients with iptacopan 200 mg twice daily for 6 months.
RESULTS Iptacopan slows disease progression by inhibiting FB and preventing excessive activation of AP and may become one of the first targeted therapies available for C3G patients. [3]