the Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects in Adult Subjects With Elevated LDL-C

Inclusion criteria

• Male and female subjects, aged 18 to 60 years, inclusive
• Body mass index between 18 and 32 kg/m2, inclusive, with body weight > 45 kg for females and >50 kg for males
• Serum LDL-C ≥100 mg/dL (2.6 mmol/L) at screening and Day -1
• Fasting triglycerides < 400 mg/dL (<4.52 mmol/L) at screening and Day -1

Exclusion criteria

• Known underlying disease or medical condition that may have a potential impact on general safety assessment, lipid metabolism, or glucose metabolism, or surgical condition (including, but not limited to, bariatric surgery) that, in the opinion of the investigator, may interfere with the interpretation of the results of the clinical study
• Received any medication including, but not limited to, statins, ezetimibe, or lipid-altering nutrients within 30 days prior to screening, or PCSK9 antibody within 90 days prior to screening, or any LDL-C-lowering siRNA therapy within 12 months prior to screening
• History of multiple drug allergies or allergic reactions to oligonucleotides or N-acetylglucosamine (GalNAc)
• Subjects with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 1.5 times the upper limit of normal (ULN) at the time of screening (one repeat of the screening assay is permitted) with clinically significant ALT and/or AST > ULN and ≤ 1.5 times the ULN as determined by the investigator
• Any medical condition that, in the opinion of the Investigator, makes the subject unsuitable for enrollment or may interfere with the subject's participation in or completion of the study. This includes, but is not limited to: history or presence of cardiovascular disease (including peripheral arterial and cerebrovascular disease); diabetes mellitus (except for diabetes mellitus of pregnancy in remission); cerebrovascular accidents; and abnormal thyroid function.