Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants With Chronic Hepatitis B (B-Well 2)

Inclusion Criteria:

• Participants who have documented chronic HBV infection ≥6 months prior to screeningand currently receiving stable NA therapy defined as no changes to their NA regimenfrom at least 6 months prior to Screening and with no planned changes to the stableregimen over the duration of the study.

• Plasma or serum HBsAg concentration >100 IU/mL, but no greater than ≤3000 IU/mL.

• Plasma or serum HBV DNA concentration must be adequately suppressed, defined asplasma or serum HBV DNA <90 IU/mL.

• Alanine aminotransferase (ALT) ≤2 × upper limit of normal (ULN).

• Participants who are willing and able to cease their NA treatment in accordance withthe protocol.

Exclusion Criteria:

• Clinically significant abnormalities, aside from chronic HBV infection in medicalhistory (e.g., moderate severe liver disease other than chronic HBV, acute coronarysyndrome within 6 months of screening, major surgery within 3 months of screening,significant/unstable cardiac disease, uncontrolled diabetes, bleeding diathesis orcoagulopathy) or physical examination.

Co-infection with:

a) Current history of Hepatitis C infection or participants that have been cured for <12 months at the time of screening b) Human immunodeficiency virus (HIV), c) Hepatitis D virus.

• History of or suspected liver cirrhosis and/or evidence of cirrhosis.

• Diagnosed or suspected hepatocellular carcinoma.

• History of malignancy within the past 5 years except for specific cancers that arecured by surgical resection (e.g., skin cancer). Participants under evaluation forpossible malignancy are not eligible.

• History of vasculitis or presence of symptoms and signs of potential vasculitis (e.g., vasculitic rash, skin ulceration, repeated blood detected in urine withoutidentified cause) or history/presence of other diseases that may be associated withvasculitis condition (e.g., systemic lupus erythematosus, rheumatoid arthritis,relapsing polychondritis, mononeuritis multiplex).

• History of extrahepatic disorders possibly related to HBV immune conditions (e.g.,nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa,cryoglobulinemia, uncontrolled hypertension).

• History of alcohol or drug abuse/dependence.

• Currently taking, or took within 3 months of screening, any immunosuppressing drugs (e.g., prednisone), other than a short course of therapy (≤2 weeks) ortopical/inhaled steroid use.

• Participants to whom immunosuppressive treatment, including therapeutic doses ofsteroids is contraindicated, should not be considered for enrolment in the study.

• Currently taking, or has taken within 12 months of Screening, any interferoncontaining therapy.

• Participants requiring anti coagulation therapies (e.g., warfarin, Factor Xainhibitors) or anti-platelet agents (like clopidogrel or aspirin) unless treatmentcan safely be discontinued throughout duration of the study, by the discretion ofthe investigator. Occasional use is permitted.

• Prior treatment with any oligonucleotide or siRNA within 12 months prior to thefirst dosing day.

• Prior treatment with bepirovirsen.