First-in-Human Study of VNT-101: Safety, Tolerability, and Pharmacokinetics

Inclusion criteria

• Provides written informed consent prior to the initiation of any trial procedures.
• Able to understand and agrees to comply with all planned trial procedures and be available for all study visits.
• Healthy, adult, male or female (of non-childbearing potential only\*), 18-59 years of age, inclusive, at the screening visit. \
• Female participants of non-childbearing potential must be either surgically sterile (i.e., hysterectomy, bilateral tubal ligation, bilateral tubal occlusion \[hysteroscopic sterilization\], salpingectomy, and/or bilateral oophorectomy at least 26 weeks before Screening) or post-menopausal, defined as spontaneous amenorrhea for at least a year, with follicle-stimulating hormone (FSH) in the post-menopausal range at Screening, based on the central laboratory ranges.
• Continuous non-smoker who has not used nicotine-, tobacco-, cannabis-, or cannabidiol-containing products\*\
• prior to the first dosing based on participant self-reporting. \*\*The period before first dose is at least 3 months for tobacco and associated products and at least 60 days for cannabis and associated products.
• Body mass index (BMI)\>/=18.0 and \</= 30.0 kg/m\^2 at the screening visit.
• Medically healthy\*\*\
• with no clinically significant medical history, physical examination, laboratory profiles, vital signs, and ECGs, as deemed by the Principal Investigator (PI) or designee, \*\*\*Including the following:
• Supine diastolic blood pressure is \>/= 40 mmHg and \</= 90 mmHg at the screening visit.
• Supine systolic blood pressure is \>/= 90 mmHg and \</= 140 mmHg at the screening visit.
• Supine heart rate is \>/= 60 bpm and\</= 100 bpm at the screening visit.
• QTcF interval is \</= 460 msec (males) and \</=470 msec (females) and has ECG findings considered normal or not clinically significant by the PI or designee at the screening visit.
• Estimated creatinine clearance \>/= 80 mL/min based on the Cockroft-Gault equation and creatinine \<1.50 mg/dL at the screening visit.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is not greater than 1.1 times the upper limit of normal (ULN), as specified by the testing laboratory.
• Other clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the PI or designee.
• Must agree to refrain from using tanning salons, saunas, sunbathing, or prolonged sun exposure during participation in the study through the follow-up visit.
• Male participants must agree not to donate sperm during the study and for 90 days following the last administration of Study Product.
• Male participants must agree to use a medically accepted contraceptive regimen\*\*\*\
• during participation and for 30 days after last administration of the study product or be vasectomized.
• Acceptable methods of contraception include abstinence from intercourse with a female of childbearing potential or use of male condoms with spermicide or surgical sterilization (vasectomy) of participant at least 26 weeks before the Screening.

Exclusion criteria

• History or presence of clinically significant medical or psychiatric condition or disease, making the participant unsuitable for enrollment in the opinion of the PI or designee.
• History of severe allergic or anaphylactic reactions to any prescription or non-prescription drug or vaccine.
• Participants who took any prescription medications within 14 days of first dosing or within 5 half-lives of the drug, whichever is longer.
• Participants who took any over the counter (OTC) medication/vitamins/herbal supplements\
• in the last 7 days prior to first dosing. \*Exception for occasional use of OTC acetaminophen (paracetamol) 325 to 500 mg every 4 hours not to exceed 3000 mg/day.
• History or diagnosis of a cardiovascular disease condition, including myocardial infarction, angina, congenital heart disease, cardiomyopathy, hypertension, or hypercholesteremia\*\*. \*\*Defined as: clinically significant hypercholesteremia with high low-density lipoprotein (LDL) cholesterol (\>/= 160 mg/dL)
• Increased risk for peptic ulcer\*\*\
• \*\*\*Defined as: participants with a history of gastric or duodenal ulcer, chronic non-steroidal anti-inflammatory drug use in the past 3 months, current smokers, alcohol consumption of \> 21 alcoholic units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit or a 125 mL of wine) or chronic atrophic gastritis,
• Female participant with a positive pregnancy test at the screening visit or at baseline or who is lactating.
• Positive urine drug toxicology test (or cotinine or alcohol results) at the screening visit or check-in.
• Has been on a diet incompatible with the on-study diet\*\*\*\*, in the opinion of the PI or designee, within the 30 days prior to the first dosing, \*\*\*\*including consumption of grapefruit/Seville orange within 14 days prior to first dosing,
• For Cohorts S2, S3, and S5 only, is known to be intolerant of a high fat/high calorie diet.
• Participants who are unlikely to comply with the study protocol OR those who would not be suitable candidates for participation in the opinion of the investigator.
• Participants who donated blood or plasma recently\*\*\*\*\
• \*\*\*\*\*Recently defined as within 30 days prior to Day -1, or loss of whole blood of more than 500 mL within 30 days prior to Day-1, or receipt of a blood transfusion within 1 year of study enrollment.
• Participated in a clinical study involving administration of an investigational drug in the past 30 days (90 days for injectable biological agent) before screening.