JNJ-73763989 + JNJ-64300535 + nucleoside and nucleotide analogs

This is a **combination regimen** comprising three agents for the treatment of **chronic hepatitis B virus (HBV) infection**: - **JNJ-73763989 (also called JNJ-3989):** a liver-targeted small interfering RNA (siRNA) molecule that degrades all HBV RNAs, leading to reduced production of viral proteins including hepatitis B surface antigen (HBsAg)[4][3][1][7]. - **JNJ-64300535 (also called JNJ-0535):** a DNA vaccine encoding for HBV core and polymerase proteins, delivered by electroporation-based intramuscular injection, designed to induce HBV-specific T-cell immune responses[4][1][6][8]. - **Nucleoside and nucleotide analogs (NUCs):** standard-of-care oral antiviral therapies (e.g., entecavir, tenofovir) that inhibit HBV DNA polymerase, suppressing viral replication[1][2][3]. The rationale for the combination is that siRNA-induced antigen reduction may allow the vaccine to more effectively stimulate immune responses, while ongoing NUC therapy maintains control over viral replication[4][1]. These combinations are in early-phase clinical trials for the goal of achieving a functional cure for chronic hepatitis B.