A Study of ALG-000184 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects

Inclusion Criteria for All Subjects:

1. Female subjects must have a negative serum pregnancy test at screening

2. Subjects must have a 12-lead electrocardiogram (ECG) that meets the protocol criteria

   Inclusion Criteria for Healthy Volunteers:

   In addition to inclusion criteria 1-2, the following inclusion criteria also apply to HV's (Parts 1 and 2)

3. Male or female between 18 and 55 years of age, extremes included.
4. Subjects must have a body mass index (BMI; weight in kg divided by the square of height in meters) of 18.0 to 32.0 kg/m2, extremes included.

CHB Subjects:

In addition to inclusion criteria 1-4, the following inclusion criteria also apply to CHB subjects:

All of the Following criteria apply to Part 3 at screening:

5 .Subjects must be 18 to 65 years of age, extremes included.

6.CHB subjects must have a BMI of 18.0 to 35.0 kg/m2, extremes included.

7.CHB subjects who at screening, have not received treatment with an approved or investigational medicine, or have never received treatment with HBV antiviral medicines

All of the following criteria apply to Part 4 Cohorts A \& B, unless otherwise specified, at Screening:

8.Subjects must be 18 to 65 years of age, extremes included.

9.Subjects must have a BMI of 18.0 to 35.0 kg/m2, extremes included

10.Subjects must be HBeAg positive (HBeAg ≥LLOQ and HBeAb negative)

11.Subjects enrolled in Part 4 Cohort A and B must have a history of Chronic Hepatitis B

12. Subjects must have ALT and AST must have ≤1.2×ULN or ≤5×ULN

All of the following criteria apply to Part 5 at Screening

13.Subjects must be 18 to 65 years of age, extremes included.

14. Subjects have a BMI of 17.0 to 35.0 kg/m2, extremes included

15.Subjects could belong to any of the following treatment categories: treatment naïve (TN), currently not treated (CNT) , virologically suppressed.

Exclusion Criteria

Exclusion Criteria for All Subjects:

1. Subjects with any previous or current illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject, or pose an additional risk in administering study drug to the subject, or that could prevent, limit, or confound the protocol specified assessments or study results' interpretation
2. Subjects with a past history of cardiac arrhythmias, risk factors for Torsade de Pointes syndrome (e.g., hypokalemia, family history of long QT syndrome, or history of clinical evidence at screening of significant or unstable cardiac disease etc.
3. Subjects with a history of clinically significant drug allergy
4. Subject with a current history of clinically significant (as determined by investigator) skin disease requiring intermittent or chronic treatment
5. Excessive use of alcohol, defined as regular consumption of ≥14 standard drinks/week for women and ≥21 standard drinks/week for men

6. Subjects with Hepatitis A, B, C, D, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection

   Exclusion Criteria for Healthy Volunteers (Parts 1 and 2):

   In addition to exclusion criteria 1-6, the following exclusion criteria also apply to HV's (Parts 1 and 2)

7. Unwilling to abstain from alcohol use for 48 hours prior to start of dosing through end of study follow up.
8. Positive alcohol or cotinine test at screening and Day -1.

9. Subjects with renal dysfunction (e.g., estimated creatinine clearance \<90 mL/min/1.73 m2at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula).

   Exclusion Criteria for CHB Subjects (Parts 3, 4, and 5):

   All exclusion criteria listed above for healthy volunteers apply also to CHB subjects, except for exclusion Criteria 9 (requirement relative to cotinine).All the following exclusion criteria apply to Parts 3, 4, and 5, unless otherwise specified.

10. Subjects who are positive for anti-HBs antibodies.
11. For HBeAg-positive subjects, they should be negative for anti-HBe antibodies (Parts 4 and 5)
12. Subject with any history or current evidence of hepatic decompensation such as: variceal bleeding, spontaneous bacterial peritonitis, ascites, hepatic encephalopathy, or active jaundice (within the last year).
13. History or current evidence of cirrhosis.
14. Subjects with liver fibrosis that is classified as Metavir Score ≥F3 liver disease
15. Subjects with signs of hepatocellular carcinoma