Phase 1/Phase 2a Study of AERO-007 Inhalation Solution, a Nebulized LABA/LAMA Combination for Maintenance Treatment of COPD

Cohort 1 (Healthy Subjects)

Inclusion Criteria:

• Male or female aged 18 to 55 years

• FEV1 > 80% of predicted normal (using the Global Lung Function Initiative GLI 2012reference values)

• Body mass index > 18 and < 32 kg/m2

• Female subjects of childbearing potential must not be pregnant, breast feeding orlactating and use, with their partner, a male condom plus an approved method ofhighly effective birth control method

• Female subjects of childbearing potential must have a negative serum or urinepregnancy test at the Screening Visit

• Male subjects who are sexually active with a partner of childbearing potential mustuse, with their partner, a male condom plus an approved method of highly effectivecontraception from the time of informed consent

• Participants must be in good health as determined by medical history, physicalexamination, vital signs, 12-lead ECG and clinical laboratory assessments at thetime of screening, as judged by the Investigator

• Willing and able to provide written informed consent

Exclusion Criteria:

• Any condition or abnormality (including medical history, clinical laboratory, ECG,physical examination, or vital sign abnormalities), current or past, that, in theopinion of the Investigator

• Lower respiratory tract infection within 6 weeks prior to the Screening Visit

• History of malignancy of any organ system, except for localized skin cancers, within 5 years prior to the Screening Visit

• Major surgery (requiring general anaesthesia) within 6 weeks prior to the ScreeningVisit

• Positive serum hepatitis B surface antigen (HbsAg), hepatitis C virus antibodies (HCV Ab) or human immunodeficiency virus (HIV) 1 and/or 2 antibodies

• Chronic viral infection or immunodeficiency condition

• History of any drug and/or alcohol abuse in the past 2 years

• Current or previous use of tobacco, nicotine products or e-cigarettes within 6months

• Smoking history of > 5 pack years

• Regular alcohol consumption in males >21 units per week and females >14 units perweek

• Positive urine drugs of abuse test and/or alcohol breath test

• Donation of 450 mL of blood within 8 weeks

• Known hypersensitivity to any ingredients in the formulation for AERO-001, AERO-002,and AERO-007

• Participation in another investigational drug study within 30 days, 5 half-lives ortwice the duration of the biological effect

Cohort 2 (Subjects with COPD)

Inclusion Criteria:

• Male or female aged 40 to 75 years

• Clinical diagnosis of COPD according to the Global Initiative for ChronicObstructive Lung Disease [GOLD] Report, 2024 for at least 12 months

• Post-bronchodilator spirometry (within 30 minutes following 4 puffs of salbutamol)demonstrating the following:

• FEV1 > 40 and < 80% of predicted normal (using the Global Lung Function InitiativeGLI 2012 reference values)

• FEV1/FVC ratio < 0.70

• ≥ 150 mL increase from pre-bronchodilator FEV1

• Ability to change current COPD therapy and discontinue long-acting bronchodilatorsfor the duration of the study and short-acting bronchodilators for 8 hours prior todosing at each treatment visit

• Current or former-smokers with at least 10 pack-year smoking history (eg, at least 1pack/day for 10 years, 10 packs/day for 1 year)

• Ability to perform reproducible spirometry according to the American ThoracicSociety (ATS)/European Respiratory Society (ERS) guidelines

• Female subjects of childbearing potential must not be pregnant, breast feeding orlactating and use, with their partner, a male condom plus an approved method ofhighly effective birth control method

• Willing and able to provide written informed consent

Exclusion Criteria:

• Female subjects who are pregnant, breast-feeding or lactating

• Current evidence or recent history of significant comorbidities; includingcardiovascular disease (such as myocardial infarction, cardiac failure, uncontrolledhypertension, or life-threatening arrhythmias), uncontrolled diabetes, neurologic,psychiatric, hepatic, renal, immunological, or haematological conditions within thelast 6 months

• Positive serum HbsAg, HCV Ab or HIV 1 and/or 2 antibodies

• Lower respiratory tract infection within 6 weeks

• Recent history of hospitalization due to an exacerbation of airway disease or acuteworsening of COPD requiring antibiotic or corticosteroid treatment within 6 months

• Other respiratory disorders: Current diagnosis of predominant asthma, lung cancer,bronchiectasis, interstitial lung disease, tuberculosis, pulmonary hypertension, orother non-specific pulmonary diseases

• Prior lung volume reduction surgery or history of chest/lung irradiation

• Daily oxygen therapy for > 12 hours per day

• Body mass index >35 kg/m2

• Current or recent history of medical conditions that are contraindicated for use ofan inhaled LAMA (such as urinary retention or bladder neck obstruction typesymptoms, prostatic hypertrophy, or narrow-angle glaucoma) within the last 6 months

• Current or recent history (previous 12 months) of excessive use or abuse of alcohol (males >21 units per week and females >14 units per week)

• Current evidence or history (within the past 2 years) of abusing legal drugs or useof illegal drugs or substances

• Donation of 450 mL of blood within 8 weeks

• Major surgery (requiring general anaesthesia) within 6 weeks

• History of malignancy of any organ system, except for localized skin cancers, within 5 years

• Known hypersensitivity to any ingredients in the formulation for AERO-001, AERO-002,and AERO-007

• Participation in another investigational drug study within 30 days, 5 half-lives ortwice the duration of the biological effect, whichever is longer