Table 1.
Novel agents against HBV and phase of development
| Mode of action | Target | Drug | Clinical phase |
|---|---|---|---|
| Direct acting antivirals | |||
| Polymerase inhibition | HBV polymerase | Tenofovir alafenamide | Phase 3 |
| Besifovir | Phase 3 | ||
| Entry inhibition | NTCP | Myrcludex-B | Phase 2a |
| Core inhibitors | Nucleocapsid assembly | NVR 3–778 | Phase 2 |
| AT-61, AT130, Bay 41–4109 | Preclinical | ||
| Cleavage of DNA | ccc-DNA | ZFNs,TALENs,CRISPR/Cas | Preclinical |
| Inhibition of ccc-DNA formation | CCC-0975 and CCC-0346 | Preclinical | |
| Non-cytolitic cccDNA degradation by inducing APOBEC3A and APOBEC3B | Lymphotoxin-b receptor agonist | Preclinical | |
| Apoptosis induction by inhibiting cIAPs | CIAPs | Birinapant | Phase 1 |
| Knock down HBV RNA, viral proteins and HBV DNA | HBV RNA | ARC-520, ARC-521 | Phase 2 |
| Block release of HBsAg | REP-2139 | Phase 2 | |
| Antisense nucleotides | Target RNA | ASOs | Preclinical |
| Host targeting agents | |||
| Exogenous interferon stimulation | Innate immunity TLR7 | Toll-like receptor (TLR) agonist (GS-9620) | Phase 2 |
| Stimulate IFN response | Innate immunity RIG-I | SB 9200 | Phase 2 |
| Therapeutic vaccination | Adaptive immunity | GS-4774 (Tarmogen) | Phase 2b |
| ABX203 | Phase 2b | ||
APOBEC apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3A and 3B, ASO antisense nucleotides, cccDNA covalently closed circular DNA, CIAPs Cellular inhibitor of apoptosis proteins, CRISPR/Cas clustered regulatory interspaced short palindromic repeats (CRISPR) and CRISPR associated (Cas) systems, NTCP sodium taurocholate co-transporting polypeptide, RIG-I Retinoic acid-inducible gene, TALENs transcription activator-like effector nucleases, ZFNs zinc-finger nucleases