A Study to Evaluate the Safety and Efficacy of AHB-137 in Healthy Participants and HBeAg-negative Chronic Hepatitis B (CHB) Patients

Inclusion Criteria:

• Healthy participants are required to meet all the following inclusion criteria inorder to be enrolled in the study (Part Ia):

1. The participants voluntarily participate in the study, and sign the InformedConsent Form (ICF) prior to screening;

2. The participants are able to comply with all the protocol requirements;

3. The participants (and partners) are willing to take effective contraceptivemeasures from the screening until at least 6 months after the last dosing;

4. Male or female aged 18-55 when signing ICF;

5. Body Mass Index (BMI) between 18 to 28 kg/m2 (inclusive) and body weight equalto or over 50 kg for male and 45 kg for female;

6. Vital signs and physical examination are normal, or abnormal values are notclinically significant.

• CHB participants are required to meet all the following inclusion criteria in orderto be enrolled in the study (Part Ib and part IIa):

1. The participants voluntarily participate in the study, and sign the InformedConsent Form (ICF) prior to screening;

2. The participants are able to comply with all the protocol requirements;

3. The participants (and partners) are willing to take effective contraceptivemeasures from the screening until at least 6 months after the last dosing;

4. Male or female aged 18-65 when signing ICF;

5. Body Mass Index (BMI) between 18 to 32 kg/m2 (inclusive) and body weight equalto or over 45 kg for male and 40 kg for female;

6. participants who have documented chronic HBV infection equal to or above 6months prior to screening.

7. Stable treatment of HBeAg negative CHB participants;

8. Currently receiving single-agent treatment with stable NAs (TDF, TAF, or ETV)for at least 6 months and no changes in the NAs treatment regimen are plannedduring the trial;

9. Serum ALT≤2×ULN, HBV DNA < 100 IU/mL. Dose increasing stage of Ib: 100 IU/mL <HBsAg≤1000 IU/mL; Dose expansion stage of Ib: 1000 IU/ml < HBsAg≤3000 IU/mL atscreening; IIa phase: 100 IU/ml < HBsAg≤ 3000 IU/mL at screening;

10. Participants who are willing and able to terminate NA treatment according tothe protocol in IIa stage.

Exclusion Criteria:

• Healthy participants are required to not meet any of the exclusion criteria in orderto be enrolled in the study (Part Ia):

1. Any suspicat screening ion of drug component allergy, or allergic constitution (various drug and food allergy, and judged by the investigator to be clinicallysignificant) in participants;

2. Blood donation or blood loss not less than 400 mL within 12 weeks beforescreening;

3. Drug administration that change the activity of liver enzymes within 28 daysprior to screening;

4. Receipt of another investigational drug or device within 3 months before firstdosing (interventional treatment);

5. Clinically significant electrocardiogram (ECG) abnormalities on screening ECG;

6. TdP high-risk factors (hypokalemia, hypomagnesemia, decompensated heart failureand acute myocardial infarction), and QTc interval above 450 msec inparticipants (judged by investigator based on actual screening conditions);

7. Pregnant (positive pregnancy test), recently ready to conceive, or lactatingfemale;

8. Clinically significant lab examination abnormalities, or other clinicallysignificant diseases discovered within 12 months before screening, includingbut not limited to gastrointestinal, renal, hepatic, neurological,hematological, endocrinological, tumor, pulmonary, immune, mental, orcardiovascular and cerebrovascular diseases;

9. Any acute disease or concomitant medication occurred during screening to thefirst dosing;

10. Alcohol consumption, or positive alcohol test 24 hours before drug dosing;

11. Positive test for urinalysis (including Morphine, Cannabis) in participants;

12. Other factors resulting in participant becoming unsuitable for the study,determined by the investigator.

• CHB participants are required to not meet any of the exclusion criteria in order tobe enrolled in the study (Part Ib and Part IIa):

1. Any suspicion of drug component allergy, or allergic constitution (various drugand food allergy, and judged by the investigator to be clinically significant)in participants;

2. Blood donation or blood loss more than 400 mL within 12 weeks before screening;Blood transfusion; Blood donation or blood loss not less than 200 mL within 1month before screening;

3. Any oligonucleotide or siRNA treatments within 12 months before first dosing;

4. Any immunosuppressing, immunomodulator (e.g. Thymosin) or cytotoxic drugadministrations within 6 months before first dosing; Vaccination within 1 monthin prior of screening, or plan to take any vaccines during the study;

5. Receiving anticoagulant therapy for Ib phase (e.g., Warfarin, Factor XaInhibitors or antiplatelet drugs such as Clopidogrel);

6. Any clinically significant liver diseases, including but not limited tohepatitis caused by other pathogenic infections, hemochromatosis, Wilsondisease, primary biliary cirrhosis, autoimmune liver diseases, alcoholic liverdisease, severe non-alcoholic fatty liver disease, Drug-induced liver injury,etc.;

7. Personal history of cirrhosis or progressive hepatic fibrosis (e.g., theparticipant undergoes hepatic histopathological examination, which indicatescirrhosis, or undergoes endoscopic examination indicating esophagogastricvarices);

8. Confirmation or suspicion of decompensated hepatitis B cirrhosis, including butnot limited to hepatic encephalopathy, hepatorenal syndrome, esophageal andgastric variceal bleeding, ascites, primary hepatocellular carcinoma, etc.;

9. History of malignancy within the past 5 years, except for certain tumors thatcan be cured by surgical resection (e.g., non-melanoma skin cancer, cervicalintraepithelial neoplasia, thyroid neoplasm, breast tumor, etc. that have beentreated without signs of recurrence);

10. Combined sever diseases of circulation, digestion, respiration, urinary, blood,metabolism, immune, nervous system, etc.;

11. Participants for IIa phase with high-risk factors for TdP (hypokalemia,hypomagnesemia, decompensated heart failure, and acute myocardial infarction),baseline QTc interval longer than 450 ms (determined by the researchers basedon actual screening);

12. Acute infection within 2 weeks prior to screening;

13. Receipt of another investigational drug or device within 1 month beforescreening (interventional treatment);

14. Laboratorial examination: blood platelet counts<90 x 10^9/L, absoluteneutrophil count<1.3 x 10^9/L, hemoglobin<90 g/L, serum total bilirubin ≥2 xULN, albumin<30 g/L, creatinine clearance rate (calculated by MDRD formula) ≤60mL/min, PT/INR>1.5;

15. Alpha-fetoprotein (AFP) >70 ug/L, or imaging suspicion of malignant hepaticspace-occupying;

16. HCV antibody/HCcAg positive, AIDS antigen/antibody positive, or TreponemaPallidum antibody positive and Rapid Plasma Reagin (RPR) or Toluidine RedUnheated Serum Test (TRUST) positive, or Hepatitis D antibody positive;

17. LSM≥12.4 kPa when screening;

18. Pregnant (positive pregnancy test) or lactating female;

19. Positive test for urinalysis (including Morphine, Cannabis) or alcohol test inparticipants;

20. Other factors results in unsuitable for the study, determined by theinvestigator.