The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-RAGE Injection in normal healthy volunteers.

Inclusion Criteria:

• Normal pulmonary function tests at Screening prior to sputum induction
• Normal 12-lead electrocardiogram (ECG) at Screening
• Non-smoking
• Able to produce an induced sputum sample at Screening
• Participants of child-bearing potential (male and female) must use highly effective contraception and cannot donate sperm or eggs during the study or for at least 12 weeks following the end of the study or last dose of study drug, whichever is later. Women must have a negative pregnancy test and cannot be breastfeeding
• Willing to provide written informed consent and to comply with study requirements

Exclusion Criteria:

• Acute lower respiratory infection within 30 days prior to first dose and/or acute upper respiratory infection within 7 days prior to first dose
• Positive COVID-19 test during Screening window
• Chronic or acute infection that is clinically significant or requires treatment with systemic antibiotics, antivirals, antifungals, or antiparasitics within 30 days prior to first dose
• Any history of chronic pulmonary disease
• Use of immunosuppressive medication within 90 days prior to first dose
• Receipt of any intranasal vaccine within 30 days prior to first dose
• Human Immunodeficiency virus (HIV) infection, seropositive fo Hepatitis B Virus (HBV), seropositive for Hepatitis C Virus (HCV)
• Uncontrolled hypertension
• Use of illicit drugs
• Unwilling to limit alcohol consumption to within moderate limits for the duration of the study
• Use of an investigational agent or device within 30 days prior to first dose
• Prior use of any formulation of ARO-RAGE

Note: additional inclusion/exclusion criteria may apply per protocol