Subcutaneous administration of Cp40 in NHPs. (A) Pharmacokinetic profile of Cp40 in plasma samples collected 2, 5, and 30 minutes and 1, 2, 4, 6, and 24 hours after a single subcutaneous injection (2 mg/kg) in cynomolgus monkeys. Baseline levels of plasma C3 (measured by ELISA) are depicted as dotted lines for each animal. (B) Dose scheme for optimized Cp40 administration study: 4 doses of Cp40 (1 mg/kg each) were injected subcutaneously into 2 cynomolgus monkeys at a time interval of 12 hours (green arrows) and blood samples were collected 30 minutes, and 4, 8, and 12 hours after each injection, with an additional collection 72 hours after the start of the experiment (red arrows). (C) Monitoring of Cp40 plasma concentrations as determined by ultra performance liquid chromatography-high definition mass spectrometry (after SPE). Baseline levels of plasma C3 (measured by ELISA in T0 sample) are depicted as dotted lines for each animal. The dependence of the Cp40 concentration profiles on the baseline C3 level of each animal is expected to be caused by target-dependent elimination kinetics, as suggested in previous studies.18 (D) Plasma levels of C3 (top) and transferrin (internal standard; bottom) during the treatment with Cp40 as determined by western blot analysis (in analogy to Figure 3C). Panel shows a representative blot from at least 2 independent analyses of samples from 2 animals each.
