AIC649

**AIC649** is an investigational immunostimulant developed by AiCuris Anti-infective Cures GmbH, derived from chemically inactivated parapoxvirus ovis (PPVO) particles of strain NZ-2. It functions as a novel immunomodulator that stimulates toll-like receptor 9 (TLR9)-dependent and independent pathways, as well as CD14 signaling, leading to regulated release of type I interferons (IFN-α, IFN-β), TNF-α, IL-12, and IFN-γ, thereby activating antigen-presenting cells (dendritic cells, monocytes, pDCs), NK cells, and T cells to reconstitute antiviral immune responses deficient in chronic hepatitis B (CHB). Preclinical studies in HBV transgenic mice and woodchucks chronically infected with woodchuck hepatitis virus (WHV) demonstrated significant reductions in viral DNA and antigens, often comparable or superior to nucleoside analogs like tenofovir or entecavir when used in combination, with a characteristic biphasic response (initial antigen peak followed by durable decline) indicative of functional cure potential. Phase 1 trials confirmed safety and tolerability in CHB patients following single ascending intravenous doses, with plans for multiple-dose studies.