Abuse Liability of Four Modern Oral Nicotine Products

1. Able to read, understand, and willing to sign an informed consent form (ICF) and complete questionnaires written in English.
2. Generally healthy males or females, 21 to 60 years of age, inclusive, at the time of consent.
3. Smokes combustible, filtered, non-menthol or menthol cigarettes, 83 mm to 100 mm in length as primary source of tobacco and who also use MST. Participant's usual brand MST product needs to be a moist snuff tobacco product and not a Snus oral tobacco product.
4. Smokes an average of at least 10 cigarettes per day (CPD) and inhales the smoke, for at least 6 months prior to Screening. Brief periods of abstinence due to illness, quit attempt (occurring 30 days prior to Screening), or clinical study participation (occurring 30 days prior to Screening) will be allowed at the discretion of an investigator.
5. Agrees to smoke the same UB cigarette throughout the study period. The UB cigarette is defined as the reported cigarette brand and style currently smoked most frequently by the participant.
6. Reports daily use of MST products and agrees to use the same UB MST throughout the study period. The UB moist snuff is defined as the reported moist snuff brand and style currently used most frequently by the participant.
7. Expired breath carbon monoxide (eCO) level is ≥ 10 ppm and ≤ 100 ppm at Screening and at check-in (Day 1).
8. Response at Screening to the Fagerström Test for Nicotine Dependence (FTND) Question 1 ("How soon after you wake up do you smoke your first cigarette?") is either "Within 5 minutes" or "6-30 minutes" (Heatherton et al., 1991) OR response at Screening to "How soon after you wake up do you place your first dip?" is either "Within 5 minutes" or "6-30 minutes" from the Fagerström Test for Nicotine Dependance-Smokeless Tobacco (FTND-ST) (Ebbert et al., 2006).
9. Positive urine cotinine test (i.e., ≥200 ng/mL) at Screening and at Check-in Day 1.
10. Willing to use Study IPs, their UB cigarette and UB moist snuff (Product S) during the study period.
11. Willing to abstain from tobacco and nicotine use for at least 12 hours prior to the start of each of six Test Sessions.

12. Females must be willing to use a form of contraception acceptable to an investigator from the time of signing the ICF until End-of-Study.

    Examples of acceptable means of birth control are, but not limited to:

    1. Surgical sterilization (hysterectomy, bilateral tubal ligation/occlusion, bilateral oophorectomy, bilateral salpingectomy);
    2. physical barrier method (e.g., condom, diaphragm/sponge/cervical cap) with spermicide;
    3. abstinence;
    4. non-hormone releasing intrauterine devices (IUD);
    5. vasectomized partner; or
    6. post-menopausal and not on hormone replacement therapy.
13. Agrees to an in-clinic confinement of seven days (six nights).
14. BMI within 18.0 to 40.0 kg/m2, inclusive (minimum weight of at least 50.0 kg at Screening)

Exclusion Criteria:

1. Allergic to or cannot tolerate mint or wintergreen flavoring agents.
2. Individuals or their family members that have ongoing litigation with tobacco company(ies).
3. Have used electronic nicotine delivery system (e.g., Vuse Alto, JUUL) or tobacco heating device (e.g., iQOS) within the 30 days prior to screening.
4. Presence of clinically significant uncontrolled cardiovascular, pulmonary, renal, hepatic, endocrine, gastrointestinal, psychiatric, hematological, neurological disease, or any other concurrent disease or medical condition that, in the opinion of an investigator, makes the study participant unsuitable to participate in this clinical study.
5. History, presence of, or clinical laboratory test results indicating diabetes.
6. Scheduled treatment for asthma currently or within the past consecutive 12 months prior to the Screening Visit. As-needed treatment, such as inhalers, may be included at an investigator discretion.
7. History or presence of bleeding or clotting disorders.
8. Any history of cancer, except for primary cancers of skin such as localized basal cell/squamous cell carcinoma that has been surgically and/or cryogenically removed.
9. Systolic blood pressure of > 160 mmHg or a diastolic blood pressure of > 95 mmHg, measured after being seated for five minutes at Screening or at check-in Day 1.
10. Hemoglobin level is \< 12.5 g/dL for females or \< 13.0 g/dL for males at Screening.
11. Females who have a positive pregnancy test, are pregnant, breastfeeding, or intend to become pregnant during the course of the study.
12. Has positive urine drug screen (UDS) or alcohol test (urine or breath) at Screening or at Check-in to the Assessment Phase (Day 1), with the exception of positive results for tetrahydrocannabinol (THC). If positive for THC at check-in (Day 1), a cannabis intoxication evaluation will be performed, and inclusion will be at the discretion of an investigator.
13. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV).
14. Use of any medication or substance that aids in smoking cessation, including but not limited to any NRT (e.g., nicotine gum, lozenge, patch), varenicline (Chantix®), bupropion (Wellbutrin®, Zyban®), GLP-1 agonists (e.g., Wegovy®, Mounjaro®, and Ozempic®), or lobelia extract within 30 days prior to signing the informed consent form.
15. Postpones a decision to quit using tobacco- or nicotine-containing products in order to participate in this study or self-reports a previous quit attempt within (≤) 30 days prior to signing the informed consent.
16. Any use of daily aspirin (≥ 325 mg) or any use of other anticoagulants.
17. Individuals ≥ 35 years of age currently using systemic, testosterone, estrogen-containing contraception or hormone replacement therapy.
18. Whole blood donation or lost blood or blood products in excess of 500 mL within 8 weeks (≤ 56 days) prior to signing the informed consent and between Screening and check-in Day 1.
19. Plasma donation within (≤) 7 days prior to signing the informed consent and between Screening and check-in Day 1.
20. Employed by a tobacco or nicotine company, the study site, or handles raw, unpackaged tobacco- or nicotine-containing products as part of their job.
21. Has used an investigational drug, device, biologic, or tobacco/nicotine product in a previous clinical study within 30 days or 5 times the half-life of the product (whichever is longer) prior to Screening.
22. Drinks more than 21 servings of alcoholic beverages per week.
23. Determined by an investigator to be inappropriate for this study.