Study of ARO-MUC5AC in Healthy Subjects and Patients With Muco-Obstructive Lung Disease

Inclusion Criteria:

• Normal pulmonary function tests at Screening (NHVs only)

• Confirmed diagnosis of asthma or COPD based on source verifiable medical record (asthma and COPD patients only)

• No abnormal finding of clinical relevance at Screening (NHVs only)

• Stable dose of asthma controller medications for at least 28 days prior to Screening (asthma patients only)

• Documented treatment with an inhaled corticosteroid and at least 1 additionalmaintenance asthma controller medication for at least 3 months prior to Screening (asthma patients only)

• Non-smoking (NHVs and asthma patients)

• Current smoker or ex-smoker with smoking history of ≥ 10 pack-years (COPD patientsonly)

• All COPD treatments have been stable for at least one month prior to Screening (COPDpatients only)

• Able to produce an induced sputum sample at Screening

• Women of childbearing potential must have a negative pregnancy test, cannot bebreastfeeding, and must be willing to use contraception. Males must not donate spermduring the study and for at least 90 days following the last dose of study drug

• 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 acuteupper respiratory infection within 7 days prior to first dose

• Positive COVID-19 test during Screening window

• Any history of chronic pulmonary disease (NHVs only)

• Any concomitant pulmonary disease in asthma or COPD patients that could interferewith the evaluation of the study drug or interpretation of patient safety or studyresults

• Use of theophylline within 30 days prior to first dose

• History of lung volume reduction surgery or pneumonectomy (COPD patients)

• Need for chronic oxygen support at Screening

• Clinically significant health concerns (other than asthma in asthma patients)

• Human immunodeficiency virus (HIV) infection, seropositive for hepatitis B virus (HBV), seropositive for hepatitis C virus (HCV)

• Uncontrolled hypertension

• Unwilling to limit alcohol consumption to within moderate limits for the duration ofthe study

• Use of illicit drugs

• Use of an investigational agent or device within 30 days prior to first dose

Note: additional inclusion/exclusion criteria may apply per protocol