The primary purpose of this study is to assess the safety and tolerability of single and multiple intravenous (IV) doses of GIGA-2339 in participants with chronic Hepatitis B Virus (HBV) infection.

Key Inclusion Criteria:

• Hepatitis B envelope antigen (HBeAg) negative chronic HBV infection for ≥ 6 months, defined as presence of Hepatitis B surface antigen (HBsAg) in serum for ≥ 6 months.
• Serum HBsAg concentration between ≥ 100 international units per milliliter (IU/mL) and 2000 IU/mL at screening.
• Currently on stable dose of nucleot(s)ide analogues (NAs) (≥ 6 months) and expected to continue while participating in the study, or are not received NAs.
• Have serum HBV deoxyribonucleic acid (DNA) concentration ≤ 50 IU/mL at screening (for those who are on NAs); or have serum HBV DNA concentration ≤ 2000 IU/mL at screening (for those who are NOT on NAs).
• Male participants must refrain from donating spermatozoa and agree to use highly effective contraception.
• Female participants must not be pregnant, or breastfeeding; either should not be a woman of childbearing potential (WOCBP) or if WOCBP should use highly effective contraceptive methods.

Key Exclusion Criteria:

• Positive for co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), and/or hepatitis D virus (HDV) at screening.
• Participants that weigh less than 50 kilograms (kg) and/or have a body mass index (BMI) less than 18.5.
• History of documented liver cirrhosis at screening. Patients under liver cirrhosis evaluation at screening will not be eligible until cirrhosis is ruled out.
• Liver stiffness > 8 kilopascal (kPa) at screening.
• History of chronic liver disease from another cause, immune complex disease, or autoimmune diseases that in the opinion of the investigator would preclude participation.
• Family history of hepatocellular carcinoma (HCC).
• Alpha fetoprotein > 20 nanograms per milliliter (ng/mL).
• Presence of a liver imaging reporting and data system (LI-RADS) 4 or 5 liver lesion on imaging 12 months prior to Screening OR, LI-RADS-US findings of US-3 grade on imaging 12 months prior to Screening, OR LIRADS-US grade 3 done prior to the D1 infusion visit, if prior LI-RADS or LI-RADS-US results are not available at Screening.
• History of hematopoietic stem cell transplant or solid organ transplant.
• Receipt of anti-HBV monoclonal antibody (mAb)/pAb therapy of any kind in the past (including hepatitis B immunoglobulin [HBIG]).
• History of cardiovascular disease (e.g., coronary artery disease, cardiomyopathy, congestive heart failure, family history of congenital long QT syndrome). Stable hypertension is allowed.
• Malignancy diagnosed and/or treated within 5 years prior to Screening, and/or with ongoing treatment for malignancy, with the exception of localized non-metastatic basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix excised with curative intent.
• Participants requiring anti-coagulation therapies (for example warfarin, Factor Xa inhibitors, or anti-platelet agents like clopidogrel).
• Male participants with a corrected QT interval using Fridericia's formula (QTcF) > 450 milliseconds (msec) and female participants with QTcF > 470 msec on ECG recorded at screening. if the participant has evidence of an intraventricular conduction delay, defined as QRS interval greater than 110 msec, a QTcF is > 500 msec for both males and females will be excluded.
• Known hypersensitivity to any GIGA-2339 excipients or any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (nonactive hay fever is acceptable), or a history of drug or other allergy that, in the opinion of the Investigator, contraindicates participation.
• Received or will receive live-attenuated virus vaccinations such as measles, mumps, rubella or varicella within 4 weeks before and up to three months after administration of investigational product (IP).