Intrahepatic and Peripheral Responses to Imdusiran (AB-729) in Chronic Hepatitis B

Inclusion Criteria:

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for theduration of the study

3. Male or female, over 18 years of age on the date of screening

4. In good general health as evidenced by medical history

5. Documented evidence of chronic hepatitis B infection (HBsAg positive at screeningand for at least more than 6 months prior to screening)

6. For females of reproductive potential must have a negative serum pregnancy test atscreening and a negative urine pregnancy test at baseline prior to study drugadministration

7. Male and female subjects of childbearing potential who engage in heterosexualintercourse must agree to use protocol specified method(s) of contraception

8. Have been on commercially available HBV oral antiviral treatment(s) for at least 6months and willing to continue through the final study visit.

9. HBV Deoxyribonucleic acid (DNA) ≤ 20 IU/mL for 6 or more months prior to Screening.

10. Hepatitis B surface antigen titer ≥ 100 IU/mL.

11. Liver imaging without liver mass suggestive of hepatocellular carcinoma within 12months of day 0 AND Alpha fetoprotein <10 ng/mL within 3 months of screening.

Exclusion Criteria:

1. Known co-infection with any of the following:

2. Human immunodeficiency virus (HIV)

3. Hepatitis C virus (HCV), unless subjects are HCV Ab positive, but have adocumented history of completing HCV treatment and/or negative HCV RNA

4. Hepatitis D virus (HDV)

5. Any known preexisting medical or psychiatric condition that could interfere with thesubject's ability to provide informed consent or participate in study conduct, orthat may confound study

6. History of cirrhosis at any time, or evidence of decompensated liver diseaseincluding, but not limited to, a history or presence of clinical ascites, bleedingesophageal varices, hepatorenal syndrome, liver transplantation and/or hepaticencephalopathy.

7. Liver ultrasound or other imaging with findings suggestive of hepatocellularcarcinoma (HCC) at any time.

8. Clinically unstable medical condition ≤2 weeks prior to the first dose of studytreatment.

9. Clinical diagnosis of substance abuse with alcohol, narcotics, or cocaine within thepast 12 months except for those subjects monitored in an opioid substitutionmaintenance program.

10. Malignancy within 5 years prior to screening, with the exception of specific cancersthat are cured by surgical resection (e.g. basal cell skin cancer). Subjects underevaluation for possible malignancy are not eligible.

11. Extensive bridging fibrosis or cirrhosis as defined clinically, by imaging or by thefollowing: a. Metavir ≥ 3 or Ishak fibrosis score ≥ 4 by a liver biopsy within 3 years ofscreening, or, in the absence of an appropriate liver biopsy, either: i. ScreeningFibroTest score >0.48 and APRI >1, or ii. FibroScan with a result >9 kPa within 12months of screening

• If liver biopsy is available, the liver biopsy result supersedes (i) and (ii).

9. Subjects meeting any of the following laboratory parameters at screening:

10. Alanine aminotransferase (ALT) >3x Upper Limit of Normal (ULN)

11. Direct bilirubin (if total bilirubin elevated) >1.5 × ULN of the laboratoryreference range.

12. Prothrombin (PT) or Activated Partial Thromboplastin Clotting Time (APTT) overthe upper limit of normal.

13. Platelet count <100,000/microliters

14. Estimated glomerular filtration rate, calculated by the chronic kidney diseaseepidemiology collaboration formula: <60 mL/min/1.73 m2

15. Significant cardiovascular, pulmonary, or neurological disease in the opinion of theinvestigator.

16. Participation in any investigational drug, vaccine, or device study within 30 daysbefore study treatment administration, or 90 days for a biologic study, or at anytime during participation in the study.

17. Pregnancy or lactation

18. Believed by the Study Investigator to be inappropriate for study participation forany reason not otherwise listed