This is a randomized, controlled, open-label, 6 parallel arms study to assess reduced exposure of biomarkers of exposure (BoE) of selected HPHC in smokers switching to TP18 (a prototype heated tobacco device) or THS relative to smokers who continue smoking CIG after 5 days of confinement period, followed by 2 days of pharmacokinetic (PK) period of single use of THS/TP18 and CIG, and followed by an ambulatory period.

This randomized, controlled, open-label study comprises six parallel arms and is designed to evaluate reductions in biomarkers of exposure (BoE) to selected HPHCs in adult smokers switching toTP18 (a prototype heated tobacco device with four variants: THS1, THS2, THS3, THS4) or THS5 relative to smokers who continue smoking CIG after 5 days of confinement period followed by 2 days of pharmacokinetic (PK) period of single use of THS/TP18 and CIG, and followed by an ambulatory period.

During the 5-day confinement period, participants will be randomized to use only their assigned product and will operate their assigned devices (THS1, THS2, THS3, THS4, or THS5) with their corresponding sticks or continue smoking CIG ad libitum (6 arms in total).

In the subsequent 2-day PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. Participants randomized to the CIG arm at Baseline will not participate in this period.

During the ambulatory period, participants randomized to one of the TP18 versions at Baseline will be free to choose and use any TP18 variant at any time, ad libitum. Participants randomized at Baseline to TP18 will continue using THS ad libitum. Participants randomized to the CIG arm will only be smoking cigarettes, ad libitum.

Inclusion Criteria:

• Participant has signed the ICF and understands the information provided in it.
• Participant is male or female and between 21 and 65 years old (inclusive).
• Participant has been a smoker for at least 2 years prior to the screening visit and is willing to switch to THS and TP18.
• Participant has smoked on average ≥10 commercially available CIGs/day over the last 30 days. Smoking status will be verified based on a urinary cotinine test (cotinine ≥200 ng/mL).
• Participant does not plan to quit smoking within the next three months.
• Participant is available for the entire study period and willing to comply with the study procedures, including product use assignments and periods of abstinence from any nicotine/tobacco-containing products, and willing to adhere to a standardized diet (during confinement period and during overnight stays on Day 30 and Day 60).

Exclusion Criteria:

• As per the Investigator's judgment, the participant cannot participate in the study for any reason other than medical (e.g., psychological, social reason).
• Participant is legally incompetent, or physically or mentally incapable of giving consent (e.g., in emergency situations, under guardianship, prisoners).
• Participant has a health condition which requires medication or any other clinically relevant finding based on available assessments from the Screening period (e.g., safety panel, pulmonary function test, vital signs, physical examination, ECG, and medical history), as determined by the Principal Investigator or designee.
• Participant experienced within 30 days prior to screening/admission a body temperature >37.9°C or an acute illness (e.g., upper respiratory-tract infection, viral infection, etc.).
• According to the Investigator's judgment, the participant has medical conditions that require or will require medical intervention (e.g., initiation of treatment, surgery, hospitalization) during the study period, which may interfere with study participation and/or study results.
• Participant uses medication that aids in smoking cessation.
• Participant experiences difficulty with venipuncture and/or poor venous access.
• Participant has a hemoglobin level < 11.0 g/dL for females and < 12.0 g/dL for males at the Screening visit.
• Participant has a positive nitrite urinary test at screening or on admission day (Day -2)
• Participant has donated blood or received whole blood or blood products within the past 3 months.
• BMI < 18.5 kg/m2 or ≥ 32.0 kg/m2.
• Positive serology test for HIV 1/2, HBV, or HCVa.
• Participant has a positive alcohol breath test and/or has a history of alcohol disorder that could interfere with their participation in the study.
• The participant has a positive urine drug test.
• Participant or one of their family members is a current or former employee of the tobacco industry, manufacturing or distributing e-cigarettes or other nicotine/tobacco-containing products.
• A participant or a family member is an employee of the investigational site or of any other parties involved in the study.
• Participant has participated in another clinical study within 30 days or within a period equivalent to five half-lives of the investigational product from that study, whichever is longer. .
• Participant has been previously screened or enrolled in this study (unless they are alternate subjects).
• Female participant is pregnant (does not have negative pregnancy tests at screening and/or at admission) or is breastfeeding.
• For women of childbearing potential only and males: participant does not agree to use an acceptable method of effective contraception.