A Study to Assess the Safety, Tolerability, and Efficacy of Monthly Subcutaneous Administration of ION904 in Participants With Uncontrolled Hypertension

This is a Phase 2, multicenter, double-blind, randomized, placebo-controlled study. It will include up to approximately 48 participants with mild to moderate hypertension who have uncontrolled blood pressure (˃ 130 - ≤ 170 millimeters of mercury [mmHg] systolic) and have been on one or more anti-hypertensive medications for at least one month. Following an up to 4-week screening period, eligible participants will receive multiple doses of ION904 during a 13-week treatment period, followed by a 13-week post-treatment follow-up period.

General Inclusion Criteria:

• Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), she uses a highly effective contraceptive method. Aged 18 - 75 inclusive and weighing ≥ 50 kilograms (kg) at the time of informed consent
• Body mass index (BMI) ≤ 45.0 kilograms per square meter (kg/m^2) at screening
• History of uncontrolled hypertension (HTN) on one or more antihypertensive medications without changes in antihypertensive regimen within 4 weeks of screening and will be required to maintain this regimen throughout the Treatment Period

General Exclusion Criteria:

• History of secondary HTN including, but not limited to any of the following: renovascular HTN (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug induced HTN
• Unstable/underlying known cardiovascular disease defined as:

• Any history of congestive heart failure (New York Heart Association [NYHA] Class III-IV)
• Any history of previous myocardial infarction, coronary revascularization, unstable or stable angina pectoris ˂ 6 months prior to screening
• Any hemodynamically unstable atrial or ventricular arrhythmias
• Significant uncorrected valvular heart disease
• Any history of stroke or transient ischemic attack < 6 months prior to screening
• A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of screening