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

Inclusion criteria

• Provides written informed consent before any study procedures
• Age 23 to 59 years, inclusive
• Body weight ≥50 kg at Screening
• Body mass index (BMI) 18.5-29.9 kg/m² at Screening
• In good health with no medically significant conditions, in the opinion of the Investigator
• Current smoker, ≥10 cigarettes per day for ≥2 years, with no abstinence \>6 months
• Female participants must agree not to donate ova during the study and for 90 days after dosing
• 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
• Female participants of non-childbearing potential must be surgically sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation) or postmenopausal (≥1 year without menses)
• Male participants must agree to use contraception and not donate sperm for 90 days after dosing
• Willing to abstain from all other tobacco products from Day -2 through Day 84
• Willing to abstain from all other nicotine products from Day -2 through Day 84
• Willing to abstain from smoking regular cigarettes:
• Approximately 18 hours from evening of Day -2
• Approximately 42 hours from evening of Day -1

Exclusion criteria

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