Effect of Switching From Cigarette Smoking to THS on Disease Progression in Mild to Moderate COPD Subjects With Chronic Bronchitis Symptoms.

Main Inclusion Criteria:

• Subjects have read, understood, and signed the written informed consent form (ICF)

• Diagnosis of COPD GOLD Stage 1 or 2 (FEV1/FVC <0.70 & FEV1 ≥60% predicted [post-BD])

• Current symptoms of chronic bronchitis (sputum and cough) based on CAT questionnairescores for CAT1 (cough) item ≥ 3 and CAT2 (sputum) item ≥ 3

• Body mass index (BMI) 17.6-40.0 kg/m2 and body weight > 50 kg (male) or 40 kg (female).

• Subject has a smoking history of at least 10 years.

• Subject has been smoking ≥ 10 commercially available cigarettes/day on average (nobrand restriction) for at least 1 year prior to V1 (based on self-reporting).

• Subject has not used other tobacco and nicotine products apart from cigarettes on adaily basis over the past year prior to V1.

• For subjects not willing to quit smoking only: have been advised to quit smoking,informed of smoking risks and of cessation programs and is still not willing to quitduring the study duration.

• Subjects willing to quit smoking only: willing to set a target quit date (TQD)within the next 28 days at V1 as assessed by self-reported questions.

Main Exclusion Criteria:

• Subjects with any (mild, moderate or severe) COPD exacerbation that has not resolvedat least four weeks prior to V1

• Subjects with active cancer or history of any cancer

• Subjects with pneumonia or other lower respiratory tract infections that have notresolved at least four weeks prior to V1

• Subjects with other active systemic infections that have not resolved at least 4weeks prior to V1

• Subjects with other active respiratory disorders such as, but not limited to,tuberculosis, bronchiectasis, sarcoidosis, asthma2, pulmonary hypertension,interstitial lung diseases (e.g., idiopathic pulmonary fibrosis [IPF]). No newexamination is required if the subject can present at V1, at a minimum, a Chest XRay (CXR) (or Computed Tomography (CT) of the chest, if available) not older than 6months with anterior-posterior and left lateral views

• The subject is confirmed or suspected with active SARS-CoV-2 infection (as per siteand per country recommendation)

• Clinically significant ECG alterations that will not allow subject to participate inthe study, per Investigator's discretion

• Any concomitant disease that in the opinion of the investigator would interfere withthe study procedures

• Subjects with diagnosed alpha-1 antitrypsin deficiency (AATD)

• History of alcohol and/or drug abuse which as per judgment of the Investigator wouldjeopardize either the participation in an investigational study or safety of thesubject

• Positive serology test (HIV 1/2, hepatitis B or C).

• Inability to cooperate with the study procedures

• Previous participation in this study, or participation in an investigational study (drug or medical device) within 4 weeks before V1 (participation in observationalstudies/registries allowed)

• Close affiliation with the investigational site: a close relative of theinvestigator, a person dependent on the investigational site (e.g., employee orstudent of the investigational site)

• Subject is a current or former employee of the tobacco industry or theirfirst-degree relatives (parent, child, spouse)

• Subjects have re-initiated smoking in the six months prior to V1

• Subjects have used in the past 3 months, or are currently daily using THS

• Any oral/injectable corticosteroids (acute or chronic treatments) or oxygen therapyin the last 2 months excluding short term use for a COPD exacerbation

• Female subject is pregnant or breastfeeding, (a urine pregnancy test will beperformed at V1 and V2)

• For women of childbearing potential, female subject who does not agree to using anacceptable method of effective contraception during the entire study.