A Study to Assess Changes in Cigarette Consumption During a Switch to Very Low Nicotine Cigarettes

Very low nicotine (VLN) cigarettes contain a 'non-additive' level of nicotine. This study
will switch smokers from their usual brand to VLN cigarettes. Periodically during the study
the investigators will collect blood and measure nicotine exposure and also other biomarkers
to see what effect switching has. The participants will also use a diary to record number of
cigarettes smoked. Cigarette butts will also be collected.

Inclusion Criteria:

Potential subjects must fulfill all of the following inclusion criteria to be eligible for
participation in the study.

1. Is a healthy adult male or female adult smoker, 26 to 65 years of age, inclusive, at
Screening.

2. Has been a smoker for at least 5 years prior to Screening. Brief periods of non
smoking (e.g., up to 7 consecutive days due to illness, trying to quit, participation
in a study where smoking was prohibited) during that time will be permitted at the
discretion of the Investigator.

3. Reports smoking an average of 10 or more manufactured combustible cigarettes per day
at Screening.

4. Usual brand (UB) of cigarette is a filtered king size cigarette (with an approximate
length of 84 mm (± 3 mm)).

5. Has a positive urine cotinine (≥ 500 ng/ml) at Screening.

6. Has an exhaled Carbon Monoxide > 10 ppm at Screening.

7. If female, has a negative serum pregnancy test at Screening.

8. A female subject of childbearing potential must have been using one of the following
forms of contraception and agree to continue using it through completion of the study:

- hormonal (e.g., oral, vaginal ring, transdermal patch, implant, or injection)
consistently for at least 3 months prior to Screening;

- double barrier method (e.g., condom with spermicide, diaphragm with spermicide)
consistently for at least 14 days prior to Screening;

- intrauterine device for at least 3 months prior to Screening;

- Essure® or similar nonsurgical sterilization procedure at least 6 months prior to
Screening

- a partner who has been vasectomized for at least 6 months prior to Screening;

- abstinence beginning at least 14 days prior to Screening and through the End of
Study.

9. A female subject of non childbearing potential must have undergone one of the
following sterilization procedures at least 6 months prior to Screening:

- hysteroscopic sterilization;

- bilateral tubal ligation or bilateral salpingectomy;

- hysterectomy;

- bilateral oophorectomy; Or be postmenopausal with amenorrhea for at least 1 year
prior to Day 1 and follicle stimulating hormone (FSH) levels consistent with
postmenopausal status.

10. Willing to comply with the requirements of the study, including a willingness to use
the test products.

11. Voluntary consent to participate in this study documented on the signed informed
consent form (ICF).

12. Subject is not planning to leave the area during the course of the study.

Exclusion Criteria:

Subjects may be excluded from the study if there is evidence of any of the following
criteria at Screening, start of Week -1 (first clinic visit), or during the study as noted,
in the opinion of the Investigator.

1. History or presence of clinically significant gastrointestinal, renal, hepatic,
neurologic, hematologic, endocrine, oncologic, urologic, pulmonary (especially
bronchospastic diseases and asthma), immunologic, psychiatric, or cardiovascular
disease, or any other condition that, in the opinion of the Investigator, would
jeopardize the safety of the subject or impact the validity of the study results.

2. Clinically significant abnormal findings on the physical examination, medical history,
ECG, or clinical laboratory results, in the opinion of the Investigator.

3. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen
(HBsAg), or hepatitis C virus (HCV).

4. An acute illness (e.g., upper respiratory infection, viral infection) requiring
treatment with prescription medication(s) within 14 days prior to Screening or first
clinic visit.

5. Fever (>100.5 degrees F) at Screening or first clinic visit.

6. Body mass index (BMI) greater than 40.0 kg/m2 or less than 18.0 kg/m2 at Screening.

7. History of drug or alcohol abuse or has used medical/recreational marijuana within 12
months of Screening.

8. Diabetes mellitus that is not controlled by diet/exercise alone, in the opinion of the
Investigator.

9. Seated heart rate is lower than 40 bpm or higher than 99 bpm at Screening, unless
deemed not clinically significant by the PI.

10. Seated systolic blood pressure <90 mmHg or >150 mmHg, diastolic blood pressure <40
mmHg or >95 mmHg at Screening, unless deemed not clinically significant by the PI.

11. Positive urine screen for drugs of abuse or alcohol at Screening or at the first
clinic visit.

12. Female subjects who are pregnant, lactating, or intend to become pregnant from
Screening through the End of Study.

13. Use of medications known to interact with cytochrome p450 2A6 (including, but not
limited to, amiodarone, desipramine, isoniazid, ketoconazole, miconazole,
phenobarbital, rifampin, tranylcypromine, methoxsalen) within 3 months prior to
Screening and throughout the study.

14. Use of inhalers to treat any medical condition within 3 months prior to Screening and
throughout the study.

15. Use of nicotine-containing products other than factory manufactured cigarettes [e.g.,
roll-your-own cigarettes, e-vapor products, bidis, snuff, nicotine inhaler, pipe,
cigar, chewing tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine
gum] within 28 days prior to Screening.

16. Use of any prescription smoking cessation treatments, including, but not limited to,
varenicline (Chantix®) or buproprion (Zyban®) within 3 months prior to Screening.

17. Self-reported puffer/non-inhaler (i.e., a smoker who draws smoke from the cigarette
into the mouth and throat but does not inhale).

18. Planning to quit smoking during the study period or postponing a quit attempt in order
to participate in the study.

19. Plasma donation within 7 days prior to Screening or at any time during the study.

20. Donation of blood or blood products (with the exception of plasma as noted above), had
significant blood loss, or received whole blood or a blood product transfusion within
56 days prior to Screening.

21. Participation in a previous clinical study for an investigational drug, device,
biologic, or tobacco product within 30 days prior to Screening.

22. Subject or a first-degree relative (i.e., parent, sibling, child) is a current or
former employee of the tobacco industry or a named party or class representative in
litigation with the tobacco industry.

23. Subject or a first-degree relative (i.e., parent, sibling, child) is a current
employee of the clinic sites.