This Clinical trial is being done to understand how food and a common stomach-acid reducing medicine (called a proton pump inhibitor-PPI) affect how the body absorbs a new drug, VRN101099, in healthy adults.

Researchers will measure how much of the drug gets into the bloodstream and how fast it gets there in each situation.

This will help identify the most effective way for future patients to use VRN101099 in the treatment of solid tumors and cancers.

The main questions it aims to answer is:

1. Does food or a PPI change how the body absorbs a single dose of VRN101099?
2. Is a single dose of VRN101099 safe and well tolerated when taken with or without food or a PPI?
3. How is VRN101099 removed through urine when taken with or without food or a PPI?

This is a single-centre, 3-period, 2-sequence, open-label, randomized, crossover study to evaluate the effect of food and a PPI on the PK of a 160 mg oral dose of VRN101099 in healthy adult participants. The study will consist of approximately 24 participants, who will be enrolled and then randomized 1:1 into 2 cohorts (sequences).

This is a 3-period, 2-sequence, crossover study, which means every participant will receive VRN101099 three times-once in each condition, but in different orders depending on their assigned sequence.

Participants will be randomly assigned to one of two sequences:

Sequence 1: Fasted → Fed → Fed + PPI Sequence 2: Fed → Fasted → Fasted + PPI

All participants will take the same dose of VRN101099, but under different conditions:

• once after eating a meal,
• once while taking a PPI,
• and once on an empty stomach.

Each dose of VRN101099 will be 160 mg and taken once per period. There will be at least 7 days of washout between doses.

Blood samples may be taken up to 240 hours (10 days) after each dose to measure drug levels

Urine samples will be collected for 24 hours after each dose

Participants will be monitored for side effects and general safety throughout the study.

Inclusion Criteria:

1. Male or female aged between 18 and 65 years of age (inclusive at the time of informed consent).
2. In good general health, with no significant medical history, and have no clinically significant abnormalities on physical examination at Screening and/or before the first administration of IP (at the discretion of the PI or designee).
3. BMI between ≥ 18.0 and ≤ 32.0 kg/m2 and weight ≥ 50 kg at Screening.
4. Clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the PI or designee. Note: Repeat testing at Screening is acceptable for out-of-range values at the discretion of the Investigator.
5. Female participants must be either not of childbearing potential or if they are a woman of childbearing potential and are engaged in heterosexual intercourse, they must agree to use an acceptable, highly effective contraception method in conjunction with a condom for the male partner from Screening until 100 days after the last dose of IP (ie, 90 days plus 5 half-lives of the IP).
6. Male participants must not be of childbearing potential, or if they are engaged in sexual relations with WOCBP, they must agree to use a condom in conjunction with an acceptable, highly effective contraception method for the female partner from Screening until 100 days after the last dose of the IP.
7. Males must not donate sperm and females must not donate ova from the first dose of IP until at least 100 days after the last dose of IP (ie, 90 days plus 5 half-lives of the IP).
8. Able and willing to attend the necessary visits to the CRU.
9. Able and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.

Exclusion Criteria:

1. Underlying physical or psychological medical condition that, in the opinion of the PI or designee, would make it unlikely for the participant to comply with the protocol or complete the study per protocol. This includes but may not be limited to: medical histories (eg, hepatic/biliary, renal, cardiovascular, endocrine, respiratory, digestive, haematologic, oncologic [except for non-melanoma skin cancer, excised more than 2 years ago and cervical intraepithelial neoplasia that has been successfully cured more than 5 years prior to the first administration of IP], central nervous system, psychiatric, musculoskeletal) or past medical/surgical histories that may affect drug absorption, distribution, metabolism, or excretion (excluding simple appendectomy or herniorrhaphy).
2. Participants with known or suspected conditions or significant gastrointestinal disorders that may interfere with drug absorption (eg, inflammatory bowel disease, chronic diarhoea, malabsorption syndromes, or prior gastrointestinal surgery affecting absorption).
3. History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents.
4. History of hypersensitivity and/or intolerance to PPIs.
5. History of infections requiring parenteral antibiotics within 6 months prior to the first administration of IP.
6. Blood donations of ≥ 400 mL or significant blood loss within 60 days prior to the first administration of investigational product (IP), plasma donation within 7 days prior to the first administration of IP, or platelet donation within 30 days prior to the first administration of IP. Participants must also agree not to donate blood, plasma, or platelets during the study and for at least 30 days after the last dose of IP.
7. Abnormal findings on 12-lead (triplicate) ECG at Screening that are considered by the PI or designee to be clinically significant; or has a QTcF (Fridericia's formula) interval at Screening of > 450 msec for males or > 470 msec for females based on the average of the 3 readings. Repeat testing at Screening is acceptable for abnormal values at the discretion of the Investigator (once per parameter).
8. Abnormal vital sign findings at Screening that are considered clinically significant by the Principal Investigator (PI) or designee, including systolic blood pressure >140 mmHg or < 90 mmHg, diastolic blood pressure > 90 mmHg or < 50 mmHg, or a history of symptomatic hypotension. If a screening value falls outside these limits, repeat measurement is permitted at the discretion of the Investigator, with one repeat assessment allowed per parameter. Eligibility should be based on the repeat value.
9. Active liver disease, or AST and/or ALT > 1.5 × upper limit of normal at Screening. Note: Repeat testing at Screening is acceptable for out-of-range values at the discretion of the Investigator.
10. Estimated glomerular filtration rate (eGFR) of ≤ 80 mL/min/ 1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 formula.
11. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at Screening.
12. Use of (or anticipated use of) any prescription drugs (other than hormonal contraception; oral contraceptive pills, long-acting implantable hormones, injectable hormones, a vaginal ring, or an intrauterine device), within 14 days prior to the first administration of the IP; or use of any over the counter medication, herbal remedies, supplements, or vitamins within 7 days prior to the first administration of IP and during course of study. Note: Simple analgesia (eg, paracetamol) may be permitted at the discretion of the PI, provided they are used within the recommended maximum daily doses as specified in the package insert.
13. Use of any drugs, herbal supplements, or foods that are known to be strong or moderate inhibitors/inducers of CYP3A4 (eg, carbamazepine, rifampin, St. John's wort, ketoconazole, ginkgo biloba, grapefruit, grapefruit juice) from within 30 days prior to the first administration of IP until the end of the study.
14. Use of PPIs, histamine (H)2 blockers, potassium-competitive acid blockers, or locally-acting antacids within 8 weeks before the first dose of IP, or requiring these medications during the study (except for the planned use of rabeprazole specified in the protocol)
15. Vaccination with a live vaccine within 4 weeks prior to the first administration of IP (and up until 14 days after the last dose of the IP).
16. Use of any IP or investigational medical device within 30 days prior to the first administration of IP, or 5 half lives of the product (whichever is the longest), and during the course of the study.
17. Positive toxicology screening panel (urine test including qualitative identification of amphetamines, methamphetamines, methadone, barbiturates, benzodiazepines, cocaine, opiates, methylenedioxymethamphetamine, phencyclidine, tetrahydrocannabinol, and tricyclic antidepressants), or alcohol breath test at Screening. Note: A single repeat test in the event of a false positive is permitted for the drug of abuse urine test at the discretion of the Investigator.
18. History of regular alcohol consumption defined as > 14 standard drinks per week or > 3 standard drinks on any single day (where 1 standard drink = 10 g of alcohol) within 3 months prior to Screening.
19. Unwilling or unable to abstain from the consumption of alcohol and caffeine containing food or drinks beginning 72 hours prior to the first administration of IP and until the end of the study.
20. Unwilling to abstain from cigarettes or nicotine-containing products (eg, cigars, vapes, nicotine patches) for at least 7 days prior to first IP administration through to the end of the study, or is considered to be dependent on nicotine at the discretion of the PI. Note: Participants that are considered light or social smokers (defined as ≤ 5 cigarettes per week) will be considered eligible for entry into the study but must also adhere to these restrictions.
21. Unwilling to refrain from strenuous exercise (including weightlifting) from 48 hours prior to each admission (on Day -1, Day 11, and Day 28), during the inpatient stays, and for 48 hours prior to any outpatient visit (including the EOS visit).
22. Unable or unwilling to consume a high-fat meal.
23. Pregnant or lactating.
24. Poor peripheral venous access.
25. Anything that the PI considers that would jeopardize the safety of the participant, prevent complete participation in the study, or compromise interpretation of study data.