The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of single doses of RN5681 in Adult healthy subjects

Inclusion Criteria:

• Body mass index (BMI) 18 to 35 kg/m2
• Fasting LDL-C ≥70 mg/dL (1.81 mmol/L) (all SAD cohorts); fasting LDL-C ≥100 mg/dL (2.59 mmol/L) (POC cohort only)
• Lp(a) at Screening: SAD cohort: ≥25 nmol/L POC cohort: ≥100 nmol/L
• Fasting triglycerides <400 mg/dL (4.51 mmol/L) at Screening
• No clinically significant abnormalities of hepatic or renal function

Exclusion Criteria:

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5× the upper limit of normal at screening
• Hemoglobin A1c (HbA1c) ≥6.5% at screening
• Current regular smoker (defined as >2 cigarettes/day or >10 cigarettes/week) within 3 months prior to screening
• Use of any siRNA, antisense oligonucleotide (ASO), cell and gene therapy, or clustered regularly interspaced short palindromic repeats (CRISPR) agent in the prior 12 months
• Received any prescription lipid-lowering medication, including but not limited to statins, ezetimibe, and PCSK9 inhibitors to alter serum lipids within 30 days before screening