This study is an open-label, 2-Part (Single Ascending Dose [Part 1] And Dose Expansion) study that will evaluate the safety of EPI-003 administered to patients with chronic infection with HBV (CHB). EPI-003 is a liver-targeted antiviral therapeutic for intravenous (IV) injection that is capable of precise epigenetic modifications of the HBV genome without causing mutations in the gene sequence itself. This study is designed to determine the safety and pharmacokinetic (PK) and pharmacodynamic (PD) profile of EPI-003 in this patient population.

Inclusion Criteria:

1. Aged 18 to 65 years (inclusive) at the time of signing the informed consent.
2. Body mass index (BMI) ≥ 18 kg/m2 and ≤ 35 kg/m2 at Screening, and body weight of ≤ 120 kg.
3. Chronic HBV infection for ≥ 6 months prior to Screening (eg, positive for serum HBsAg, HBV DNA, HBeAg for ≥ 6 months ) or serum immunoglobulin M (IgM) anti-HBc (hepatitis B core antibody) negative at Screening; AND Baseline HBsAg positive at Screening.
4. Has received treatment with a NA (entecavir, tenofovir disoproxil fumarate or tenofovir alafenamide) as a stable dose for ≥ 6 months before Screening and plans to continue at the same dose level for the duration of the study. Participants may be on other NAs but require Sponsor approval before enrolment.
5. HBV DNA < LLOQ (according to local guidelines) for ≥ 6 months and at Screening
6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 × upper limit of normal (ULN) at Screening.
7. Able and willing to attend the necessary visits to the study site.
8. Able and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.

Exclusion Criteria:

1. Evidence or history of liver disease of non-HBV aetiology.
2. Previous history or current diagnosis of significant liver fibrosis or cirrhosis
3. Liver ultrasound or other imaging with findings suggestive of HCC at any time.
4. Participants with serum alpha-fetoprotein (AFP) ≥ 200 ng/mL at Screening.
5. Positive test result for HIV-1 or HIV-2 that suggests a concurrent infection at Screening.
6. History of acute febrile illness, symptomatic viral, bacterial, or fungal infection within 1 week before Day 1.
7. History of receiving HBV vaccine or other HBV-targeted therapeutic within the 6 months before Day 1.
8. Previous treatment with an HBV-targeted treatment other than NAs within the 6 months before Day 1 or planned use during the study.
9. Any of the laboratory values at Screening (Screening laboratory tests may be repeated once for values thought to be erroneous OR not clinically significant as per the PI):
10. Immunodeficient or autoimmune conditions due to disease.
11. Chronic treatment with immunosuppressants.
12. Any history of unexplained blackouts, fainting episodes, significant arrythmias, clinically significant abnormality of ECG, marked QT abnormalities, or any known risk factors for Torsade de Points
13. History of anaphylaxis, hypersensitivity, or significant drug allergies.
14. Received any antiplatelet or antithrombotic therapy.
15. History of thrombophilia or history of a positive genetic test for Factor V Leiden and/or prothrombin 20210.
16. Known or suspected intolerance or hypersensitivity to the IP components.
17. Have received any other IP within 30 days or 5 half-lives of Day 1.
18. Have received any vaccination within 14 days prior to Day 1 or vaccination planned for 3 months following administration of IP.
19. Received any medications or other treatments that may adversely affect the immune system.
20. Excess alcohol consumption within 3 months of Screening.
21. Significant drug abuse/addiction within 3 months of Screening.
22. Any safety concern or personal condition that is inappropriate for study participation per the Investigator's judgement.