bepirovirsen + GSK3528869A

bepirovirsen + GSK3528869A is an investigational sequential combination therapy under development for the treatment of chronic hepatitis B virus (HBV) infection. The combination involves two agents administered in sequence: - **bepirovirsen** (GSK3228836), an antisense oligonucleotide that binds to HBV RNA in infected hepatocytes, blocking the expression of viral proteins and reducing HBV replication and antigen production through targeted RNA degradation. It also acts as a Toll-like receptor 8 agonist, stimulating immune responses. - **GSK3528869A**, a therapeutic vaccine composed of three components: (1) ChAd155-hIi-HBV (a replication-defective chimpanzee adenovirus vector encoding HBV antigens), (2) MVA-HBV (a modified vaccinia Ankara vector encoding HBV antigens), and (3) HBc-HBs/AS01B-4 (adjuvanted HBV proteins) to induce robust immune responses against HBV proteins. The combination’s goal is to suppress HBV viral load and antigenemia while enhancing the host immune response to achieve sustained virologic response and possible functional cure. Clinical development is sponsored by GSK, building on a collaboration with Ionis Pharma for antisense technology[1][2][3][7].