A First in Human Single Ascending Dose (SAD) Study of ATI-1013 in Healthy Smokers

Inclusion Criteria

1. Provides written informed consent before any study procedures
2. Age 23 to 59 years, inclusive
3. Body weight ≥50 kg at Screening
4. Body mass index (BMI) 18.5-29.9 kg/m² at Screening
5. In good health with no medically significant conditions, in the opinion of the Investigator
6. Current smoker, ≥10 cigarettes per day for ≥2 years, with no abstinence \>6 months
7. Female participants must agree not to donate ova during the study and for 90 days after dosing
8. Female participants of childbearing potential must use an acceptable, effective method of birth control from 30 days prior to Screening through 90 days after dosing
9. Female participants of non-childbearing potential must be surgically sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation) or postmenopausal (≥1 year without menses)
10. Male participants must agree to use contraception and not donate sperm for 90 days after dosing
11. Willing to abstain from all other tobacco products from Day -2 through Day 84
12. Willing to abstain from all other nicotine products from Day -2 through Day 84
13. Willing to abstain from smoking regular cigarettes:

    1. Approximately 18 hours from evening of Day -2
    2. Approximately 42 hours from evening of Day -1

Exclusion Criteria

1. Pregnant, breastfeeding, or planning pregnancy
2. Positive serum pregnancy test at Screening or urine pregnancy test on Day -2 (women only)
3. Prior exposure to any anti-nicotine vaccine or antibody
4. Use of mentholated tobacco products within 30 days before Screening, unwilling to refrain during the study
5. History of severe allergic reaction to antibodies or vaccines (including Guillain-Barré syndrome)
6. Received any vaccination within 90 days prior to Screening
7. Clinically significant allergic adverse reaction (seasonal allergies allowed)
8. Use of systemic steroids or immunomodulating drugs within 90 days (inhaled steroids allowed)
9. History of cancer (except treated basal/squamous cell skin cancer), HIV, other immunodeficiency, or autoimmune disease
10. History of drug (excluding nicotine) or alcohol use disorder (DSM-5 criteria)
11. Clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, or psychiatric disorder, as determined by the Investigator
12. Clinically significant abnormal clinical chemistry, hematology, or urinalysis at Screening or Day -2, in the opinion of the Investigator
13. COVID-19 within the past 6 months or ongoing symptoms likely attributable to COVID-19
14. Use of varenicline, bupropion, nicotine replacement therapy (NRT), or other anti-smoking pharmacologic treatments (including off-label nortriptyline, clonidine, or cytisinicline) within 90 days prior to Screening
15. Received an investigational product within 30 days (90 days for biologics) or 5 half-lives (whichever is longer) prior to Screening
16. Exhaled carbon monoxide (CO) \<8 ppm at Screening
17. Positive test for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody at Screening
18. Positive urine alcohol test at Screening and/or Day -2
19. Positive urine drug test (e.g., cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids) at Screening and/or Day -2
20. Unwilling to abstain from xanthine-containing products (coffee, tea, cola, chocolate, energy drinks) within 24 hours prior to admission until discharge
21. Unwilling to abstain from alcohol or alcohol-containing products within 24 hours prior to admission until discharge
22. Significant blood donation or blood loss \>500 mL within 56 days before Screening
23. Plasma donation or loss within 30 days prior to Screening through Day 84
24. Hypersensitivity to the study drug, its excipients, or similar products
25. Unable or unwilling to comply with protocol requirements, restrictions, or instructions
26. Currently enrolled in another clinical study