Inclusion Criteria:
1. At least 21 years of age at the time of signing the informed consent.
2. Documented to be HBsAg positive for ≥ 6 months prior to Screening.
3. Currently receiving stable NA therapy (defined as no changes to their NA regimen from at least 6 months prior to Screening and with no planned changes to the stable regimen over the duration of the study), or not receiving any Hepatitis B treatment for at least 6 months, or Hepatitis B treatment naïve.
4. qHBsAg ≤1000 IU/ml
5. Alanine aminotransferase (ALT) ≤2x ULN
6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:
* Is a woman of non-childbearing potential
* Is a woman of childbearing potential and using a contraceptive method
7. Capable of giving signed informed consent
Exclusion Criteria:
1. qHBsAg \> 1000 IU/ml
2. Do not consent to participate in the Bepirovirsen Liver Biopsy study
3. Clinically significant abnormalities or clinically significant physical examination findings (e.g. major surgery within 3 months of screening)
4. Past history of or current co-infection with Hepatitis C infection, Human immunodeficiency virus (HIV) or Hepatitis D virus
5. History of or liver cirrhosis as determined by:
1. Fibroscan \> 12kPa
2. Participant's historic record of either/both liver biopsy or liver stiffness measurements in their medical records where their results are Liver biopsy Metavir Score is F4, they will be excluded from the study(If the participant has inconsistent clinical picture of cirrhosis, confirm and discuss eligibility with an investigator)
6. Diagnosed with hepatocellular carcinoma as evidenced by Alpha-fetoprotein concentration ≥200 ng/mL or if the screening alpha fetoprotein concentration is ≥50 ng/mL and \<200 ng/mL, the absence of liver mass must be documented by imaging within 6 months of or at screening. Cases should be discussed with an investigator.
7. History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer). Participants under evaluation for possible malignancy are not eligible.
8. History of vasculitis or presence of symptoms and signs of potential vasculitis, current or history of an autoimmune condition or history/presence of other diseases that may be associated with vasculitis condition
9. History of extrahepatic disorders possibly related to HBV immune conditions
10. Current/History of alcohol or drug abuse/dependence as judged by the investigator to potentially interfere with participant compliance
11. Currently taking, or took within 3 months of screening, any immunosuppressing drugs, other than a short course of therapy (≤2 weeks) or topical/inhaled steroid use.
12. Participants requiring anti-coagulation therapies or anti-platelet agents unless treatment can safely be discontinued throughout duration of Bepirovirsen treatment, by the discretion of the investigator. Occasional use is permitted.
13. The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives (if known) or twice the duration (if known) of the biological effect of the study treatment (whichever is longer) or 90 days (if half-life or duration is unknown).
14. Prior treatment with any oligonucleotide or siRNA within 12 months prior to the first dosing day
15. Prior treatment with Bepirovirsen within 6 months
16. Fridericia's QT correction formula (QTcF) ≥450 msec (if single ECG at screening shows QTcF ≤450 msec, a mean of triplicate measurements should be used to confirm that participant meets exclusion criterion).
17. Laboratory results as follows:
1. Serum albumin ≤3.5 g/dL
2. Glomerular filtration rate (GFR) ≤60 mL/min/1.73m2 as calculated by the CKD-EPI formula
3. INR \>1.25
4. Platelet count \<140 x 109/L
5. Total bilirubin \>1.25x ULN (For participants with benign unconjugated hyperbilirubinemia with total bilirubin \>1.25x ULN, discussion for inclusion to the study is required with the investigator)
6. Urine albumin to creatinine ratio (uACR) \>0.3 mg/mg (or \>300 mg/g). (In the event of an uACR above this threshold, eligibility may be confirmed by a second measurement. In cases where results are shown as unable to perform (UTP), please check the individual labs and confirm that the participant has urine albumin and/or urine creatinine within normal levels. The investigator should confirm that the participant does not have a history of medical conditions or other risk factors that may affect renal function)
18. History of/sensitivity to Bepirovirsen or components thereof or a history of drug or other allergy that, in the opinion of the investigator, contraindicates their participation.
