Inhaled RB042 in Healthy Adult Volunteers and Healthy Adult Smokers

Exclusion Criteria

• •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.
• •Chronic or active respiratory disease (e.g., asthma, COPD) or history of angioedema within 3 years.
• •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 and B 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.
• •Contraindication to, or unwillingness to undergo, bronchoscopy.
• •Any psychiatric or medical condition that, in the investigator's opinion, could compromise safety or compliance.