Evaluation of Biological and Functional Changes in Healthy Smokers After Switching to THS 2.2 for 26 Weeks

The clinical, biological and functional endpoints to be measured in this study ("smoker's
health profile") may characterize the modification of risk of smoking-related diseases.

Clinical risk endpoint to be assessed are selected based on a) their association to
smoking-related diseases b) their association to smoking status, c) their reversibility upon
smoking cessation, and d) their suitability to be measured with valid and robust methods in
clinical studies.

The biological markers, functional markers and biomarkers of exposure (BoExp) with the
strongest scientific evidence will constitute the 'smoker's health profile' and will be
measured as the primary objective of the study.

Additional endpoints involved in the mechanistic of smoking-related diseases will be studied
to provide additional scientific evidence to strengthen the primary objective.

The study will provide a perspective of product usage in a "real world setting" where smoking
CC in addition to THS 2.2 may be expected.

Inclusion Criteria:

- Current healthy smoker as judged by the Principal Investigator(s) or designee(s)

- Minimum age: 30 years old

- Have smoked for the last 10 years

- Have smoked more than 10 non menthol CC/day on average (no brand restriction) over the
past year

Exclusion Criteria:

- Clinically relevant medical conditions that in the opinion of the investigators would
jeopardize the safety of the participant.

- Subject who has (FEV1/FVC) < 0.7 and FEV1 < 80% predicted value at post-bronchodilator
spirometry

- Subject with asthma condition (post-bronchodilator FEV1/FVC < 0.75 and reversibility
in FEV1 ≥ 12% and > 200 mL from pre- to post-bronchodilator values)

- Subject who took or is taking concomitant medication which may have an impact on the
"smoker's heath profile"

- Female subject is pregnant or breast feeding.

- Female subject who does not agree to use an acceptable method of effective
contraception.