A First-In-Human Study of ARO-033 in Adult Participants

Key Inclusion Criteria:

• NHV cohorts only: Adults 18 to 65 years of age who are not pregnant, not breastfeeding, and do not plan to become pregnant (or impregnate their partners) during the study and for at least 90 days following the end of the study.
• AMD cohorts only: Adults ≥50 years of age who are not pregnant, not breastfeeding, and do not plan to become pregnant (or impregnate their partners) during the study and for at least 90 days following the end of the study.
• Body mass index (BMI) between 18.0 and 35.0 kilograms (kg)/square meter (m^2), inclusive.
• No abnormal finding of clinical relevance at the Screening evaluation that in the opinion of the Investigator could adversely impact participant's safety during the study or adversely impact study results.
• AMD cohorts only: A clinical diagnosis of AMD in both eyes as determined by the Investigator and confirmed by the central reading center.

Key Exclusion Criteria:

All Cohorts:

• Human immunodeficiency virus (HIV) infection, as shown by the presence of anti-HIV antibody (seropositive).
• Seropositive for hepatitis B virus (HBV) (hepatitis B surface antigen positive at screening) or hepatitis C virus (HCV) (HCV antibody positive with reflex confirmation using HCV RNA amplification at Screening). Cured HCV (positive antibody test without detectable HCV RNA) is permitted if HCV RNA has been negative for at least 2 years.
• Uncontrolled hypertension (resting systolic blood pressure ≥160 millimeters of mercury [mmHg] or diastolic blood pressure ≥95 mmHg, confirmed by repeat measurement, at Screening).
• Evidence of clinically significant immunocompromising condition (for example, primary immunodeficiency syndrome, aplastic anemia, known or suspected complement factor deficiency, or any other condition resulting in significantly impaired immune response as evidenced by recurrent infections), or recent/ongoing treatment with immunosuppressive agents.
• History of major surgery within 90 days of Screening.
• Use of an investigational agent or device within 30 days or 5 half-lives (whichever is longer) prior to dosing or current participation in an investigational study. Participants recently participating in studies involving investigational agents with prolonged therapeutic effect (such as ribonucleic acid interference [RNAi] therapeutics, cell or gene therapies) and whose last dose was less than 12 months prior to the first dose of study intervention, should be discussed with the Medical Monitor.
• Any medical condition or clinically significant laboratory abnormality at Screening that in the opinion of the Investigator should exclude the participant from participation, preclude safe and successful completion of the study, or confound study results.

AMD Cohorts Only:

• Any ocular condition in the study eye that may be expected to progress and that may affect central vision or otherwise be a confounding factor during the study, as determined by the Investigator.
• Atrophic retinal disease due to causes other than AMD (for example, drug-induced, Stargardt disease, cone rod dystrophy) in either eye.

Note: Other protocol-defined inclusion and exclusion criteria may apply.