The purpose is to assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS AGT-LRx in up to 82 Healthy Volunteers

Inclusion Criteria:

• Must have given written informed consent and be able to comply with all study requirements
• Healthy males or females aged 18-60 inclusive and weighing ≥ 50 kg at the time of Informed Consent
• Females must be non-pregnant and non-lactating, and either surgically sterile or post- menopausal
• Males must be surgically sterile, abstinent or using an acceptable contraceptive method
• BMI ≤ 35 kg/m
• Agree to conduct at home blood pressure monitoring (in triplicate using study provided device) every morning and every evening throughout study participation for Single-Dose Cohort subjects and every morning for Multiple-Dose Cohort subjects

Exclusion Criteria:

• Treatment with another Study Drug, biological agent, or device within one-month of Screening
• Subject with borderline orthostatic hypotension defined as a fall in systolic blood pressure of ≥ 17 mmHg or diastolic blood pressure of ≥ 7 mmHg when they assume a standing position (within 3 minutes of standing up)
• Use of nicotine-containing products or illicit drugs
• Considered unsuitable for inclusion by the Principal Investigator