Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Dose escalation or repetition will be governed by pre-specified safety and activity rules. Subjects will be confined on days 1-3 and/or days 8-10. Follow-up visits are required periodically through day 43. Subjects with sustained reductions in HbsAg will be requested to return for additional follow-up follow-up visits at 3 and 6 months post last dose. Study procedures involve blood draws for pharmacokinetic, pharmacodynamic, virologic, and safety assessments

Inclusion Criteria:

• Chronic HBV infection for ≥ 6 months
• Currently on treatment with at least 1 HBV approved oral drug (i.e. lamivudine, telbivudine, entecavir, adefovir, tenofovir) ≥ 3 months prior to screening
• HBsAg ≥ 250 IU/mL
• HBV DNA at below the level of quantitation (BLQ; to be confirmed at screening)
• Absence of extensive bridging fibrosis (Metavir 3 or greater)or cirrhosis
• Creatinine clearance ≥ 70 mL/min

Exclusion Criteria:

• Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV
• History of Gilberts disease
• Laboratory parameters not within defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid-stimulating hormone (TSH), or other evidence of hepatic decompensation
• Diagnosis of autoimmune disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), malignancy, hemoglobinopathy, retinal disease, or patients who are immunosuppressed
• Evidence of hepatocellular carcinoma