AIM Ropeginterferon alfa-2b is a new site-specific conjugated 40 kDa branched polyethylene-glycol recombinant interferon (IFN). The aim of the study was to determine its safety, pharmacokinetics (PK) and pharmacodynamic (PD). METHODS Ropeginterferon alfa-2b was evaluated first in human in 48 healthy male volunteers after a single dose subcutaneous injection by either 24, 48, 90, 180, 225, 270mcg of the product or 180mcg of marketed pegylated (peg)-IFN alfa-2a. Within each dosing group, 6 subjects received ropeginterferon alfa-2b and 2 subjects received peg-IFN alfa-2a. RESULTS Dose-related increases in ropeginterferon alfa-2b PK parameters (Cmax, AUC, and AUC0-t) were observed over the dose range 24 to 270mcg. The geometric mean values for these PK parameters of ropeginterferon alfa-2b were higher than that of peg-IFN alfa-2a at the 180mcg dose level of 176%, 166%, and 182%, respectively. Mean PD parameters (Emax, Tmax, and AUC0-t) for ropeginterferon alfa-2b increased with dose for both biomarkers neopterin and 2’, 5’-OAS. Ropeginterferon alfa-2b has similar PD profiles as peg-IFN alfa-2a. The treatment related adverse events are similar between the two study drugs, but the overall incidence was numerically lower for ropeginterferon alfa-2b (83%) than peg-IFN alfa-2a (100%) at the 180mcg dose level. CONCLUSIONS Single subcutaneous dose of Ropeginterferon alfa-2b of up to 270mcg is safe and well tolerated. It displays dose related increase in PK and PD parameters, potentially less frequent injection, and better safety profiles. Ropeginterferon alfa-2b is being developed for diseases in which previous peg-IFN use has been limited by side effects.