Inhaled RB042 in Healthy Adult Volunteers, Healthy Adult Smokers and Patients With Chronic Obstructive Pulmonary Disease

Inclusion criteria

• Part A, B, C only: Participants must be 18 to 55 years of age inclusive.
• Part D only: Patients must be 40 to 80 years of age inclusive.
• Part A, B, C only: Participants must be overtly healthy as determined by medical evaluation.
• Part C only: have a ≥10 pack years smoking history, have smoked tobacco products (cigarettes, cigars, or equivalent) regularly for the past 12 months, and currently smoke daily.
• Part D only: Former smokers (smoked a total of 100 or more cigarettes in their lifetime but has not smoked in the past 6 months to over a year).
• Part A, B, C only: Have forced expiratory volume (FEV1) ≥80% predicted and FEV1 to FVC ratio (FEV1/FVC) ≥0.7 at Screening and on Day -1.
• Part D only: Have forced expiratory volume (FEV1) between ≥30% and \<80% predicted and FEV1 to FVC ratio (FEV1/FVC) \<0.7 post-bronchodilation at Screening.
• Part D only: Documented clinical diagnosis of COPD per 2026 Global Initiative for Chronic Obstructive Lung Disease (GOLD) for greater than ≥1 year and a history of chronic bronchitis as evidenced by frequent productive cough in the 2-year period immediately before Screening.
• Part D only: Have clinically stable COPD with no moderate to severe exacerbations in the past 3 months.
• Part D only: Must be on stable assigned maintenance COPD therapy.
• Body weight at least 50 kg and have a body mass index (BMI) within the range 18.0 and 32.0 kg/m2 (inclusive)
• Women of childbearing potential (WOCBP) must have a negative pregnancy test and must not be lactating.
• Participants must agree to use an approved method(s) of highly effective contraception as defined in the protocol.

Exclusion criteria

• Part A, B and C only: Clinically significant history or presence of gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, neurologic, hematologic, metabolic, autoimmune, or oncologic disorders that may affect safety or study outcomes.
• Part D only: Current unstable clinically significant history or presence of gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, neurologic, hematologic, metabolic, autoimmune, or oncologic disorders that may affect safety or study outcomes.
• Part A, B and C only: Chronic or active respiratory disease (e.g., asthma, COPD) or history of angioedema within 3 years.
• Part D only: Patients with other respiratory conditions other than COPD (for example, clinically significant asthma, active tuberculosis, pulmonary fibrosis) are excluded if these conditions are the primary cause of their respiratory symptoms.
• Active or chronic liver disease, or abnormal liver function tests (ALT, AST, or bilirubin outside reference range, except Gilbert's syndrome).
• QTcF \>450 msec (males) or \>470 msec (females).
• Renal impairment (creatinine clearance \<90 mL/min) or thrombocytopenia (\<150 × 10⁹/L).
• Positive test for hepatitis B surface or core antigen, hepatitis C (unless HCV-RNA negative), or HIV.
• Active respiratory infection within 5 days before study start.
• Recent or concurrent use of medications, herbal supplements, vaccines, or blood products that could interfere with study safety or interpretation.
• Participation in another investigational study within 30 days, or blood donation \>400 mL within 30 days.
• Parts A, B and D only: Regular smoking (≥1 day per week) within 6 months prior to dosing, or a positive urine cotinine test at screening or Day -1.
• Excessive alcohol consumption (\>21 drinks/week for males or \>14 for females).
• History of severe drug reaction or anaphylaxis.
• Part B and C only: Contraindication to, or unwillingness to undergo, bronchoscopy.
• Any psychiatric or medical condition that, in the investigator's opinion, could compromise safety or compliance.