Table 1.
Viral and Host Targets, Mechanism of Action, and Novel Compounds in Development for Chronic Hepatitis B
| Target | Mechanism of Action | Class | Compounds in Development |
|---|---|---|---|
| Viral entry | Antibodies targeting pre‐S1 or small surface protein | Monoclonal antibodies | GC1102 |
| Attachment inhibitors that prevent viral interaction with entry receptors | Heparin | ||
| Poly‐L‐lysine | |||
| Reversibly/irreversibly block the NTCP receptor | Conjugated bile salts | ||
| Synthetic N‐acylated pre‐S1 | Myrcludex B | ||
| Cyclosporine | |||
| cccDNA | Inactivate cccDNA | Zinc finger nucleases | |
| Transcription activator‐like effector nuclease | |||
| CRISPR/cas9 system | EBT106 HBV CRISPR‐CAS9 lipid nanoparticle | ||
| Degrade cccDNA | Interferon , , | ||
| Tumor necrosis factor‐ | |||
| Lymphotoxin‐ receptor agonists | |||
| Functionally silence cccDNA | Epigenomic modifiers | ||
| Viral transcripts | Degrade mRNA | siRNA |
ARB‐1467 ARB‐1740 ALN‐HBV Hepbarna (BB‐HB‐331) Lunar‐HBV |
| Bind viral mRNA to prevent viral protein production | Antisense oligonucleotides |
IONIS‐HBVRx (GSK3228836) IONIS‐HBVLRx (GSK33389404) |
|
| Cause degradation of HBV RNA in the nucleus | DHQ |
AB452 RG7834 |
|
| Downregulate viral mRNA | Farnesoid X receptor agonist | EYP001 | |
| Core assembly modulators | Inhibit encapsidation of pregenomic RNA or nucleocapsid assembly | Heteroaryldihydropyrimidines (HAPS) | Morphothiadin (GLS4) |
| Phenylpropenamide | AT‐61; AT‐130 | ||
| Pyridazinone derivatives | 3711 | ||
| Sulfamoylbenzamide |
AB‐423 JNJ56136379 NVR 3‐778 |
||
| Isothiafludine | NZ‐4 | ||
| 2‐Amino‐n‐(2,6‐dichloropyridin‐3‐yl) acetamide derivatives | BCM‐599 | ||
| 5,5′‐bis[8‐(phenylamino)‐1‐ naphthalenesulfonate] | Bis‐ANS | ||
| HBsAg release inhibitors | Synthetic oligonucleotides that bind HBsAg | Nucleic acid polymers |
Rep 2139 Rep 2165 |
| Boost innate immunity | Agonists of sensing arm of innate immune system | Toll‐like receptor‐7 agonist | RO6864018 (RG7795, ANA773 |
| Toll‐like receptor‐8 agonist | GS‐9688 | ||
| RIG‐I and NOD2 agonist | Inarigivir (SB9200) | ||
| STING agonists | |||
| TCR‐like antibodies | |||
| Boost humoral immunity | Anti‐HBs | ||
| Boost adaptive immunity | Checkpoint inhibitors | Anti‐CTLA‐4 | |
| Anti‐PD‐1 | Nivolumab | ||
| Engineering new HBV‐specific T cells | TCR gene transfer | LTCR‐H2‐1 | |
| CAR‐T cells | |||
| Therapeutic vaccines | Induction of HBV‐specific B and T cells | T cell vaccines | HepTcell |
| DNA vaccines |
HB‐110 INO‐1800 |
||
| Viral vectors expressing HBV proteins |
TG1050 TomegaVax HBV |