Part A of this study is a Phase 1, First-in-human (FiH), randomized, single-blind, placebo controlled study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD3366 following single intravenous (IV) ascending doses.

Part B of this study is a randomized, single-blind, parallel group placebo-controlled study to assess the safety, tolerability and PD of a single IV administration of AZD3366 with concomitant loading doses followed by repeated maintenance dosing of ticagrelor and acetylsalicylic acid (ASA).

The study will provide data on safety, tolerability, PK, and PD of AZD3366 in healthy subjects. Three populations (healthy subjects, healthy Japanese subjects and healthy Chinese subjects) will be enrolled into this study.

This study will be conducted at a single study center in United States of America (USA).

Part A of the study will investigate the safety, tolerability, PK, and PD (inhibition of platelet aggregation and capillary bleeding time [CBT]) of an IV administration of single ascending doses (SAD) of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects.

Part B of the study will investigate the safety, tolerability, and PD (inhibition of platelet aggregation and CBT) of a single IV dose of AZD3366 or placebo with concomitant administration of ticagrelor and ASA by a parallel group cohort consisting of of healthy subjects. Furthermore, the potential effect of AZD3366 on the PK of ticagrelor will be investigated. Co-medication with ASA and ticagrelor is chosen based on the Standard of Care anti-platelet treatment regimen in patients with myocardial infarction.

Inclusion Criteria:

1. Healthy men and women of non-childbearing potential

2. Females must have a negative pregnancy test at Screening and on admission to the study center, must not be lactating, and must be of non-childbearing potential, confirmed at Screening, by fulfilling one of the below criteria:

   • Postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and Follicle stimulating hormone levels in the postmenopausal range.
   • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not bilateral tubal ligation.

3. Subjects described as healthy subjects are defined as not having origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent [for example, Cambodia, China, India, Indonesia, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam] except for subjects enrolled into the Japanese (subject for whom both parents and all grandparents are Japanese; born in Japan and not lived outside Japan for more than 10 years) and Chinese (a subject for whom both parents and all grandparents are Chinese and not lived outside of China for more than 10 years) cohorts.

4. Body mass index: 18 and 30 kg/m^2, and weigh minimum 50 kg and not >100 kg.

Exclusion Criteria:

1. Subjects having history of the following are excluded:

   • Any clinically important disease or disorder which, may put the subject at risk, or influence the results or the subject's ability to participate in the study.
   • History or presence of gastrointestinal, hepatic or renal disease or other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
   • Hemophilia, von Willebrand´s disease, lupus anticoagulant or other diseases/syndromes that can either alter or increase the propensity of bleeding.
   • Any clinically significant non-traumatic bleed or clinically significant enhanced bleeding.
   • Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
   • History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD3366 or to ASA or ticagrelor.

2. Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results, coagulation parameters, including but not limited to the list below:

   • Alanine aminotransferase > upper limit of normal (ULN)
   • Aspartate aminotransferase > ULN
   • Creatinine > ULN
   • White blood cell count < lower limit of normal (LLN)
   • Hemoglobin < LLN
   • Platelet count < 150,000/µL
   • Total bilirubin 1.2 x > ULN

3. Subjects with positive serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus.

4. Any abnormal vital signs, after 10 minutes supine rest, as defined in the list below, at the Screening Visit and/or Day -1:

   • Systolic blood pressure (BP) < 90 mmHg or > 140 mmHg.
   • Diastolic BP < 50 mmHg or > 90 mmHg.
   • Heart rate <45 or >85 beats per minute.

5. Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG, which may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology.

6. Current smokers or those who have smoked or used nicotine products within the previous 3 months, or history of alcohol abuse or excessive intake of alcohol.

7. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.

8. Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, mega-dose vitamins and minerals during the 2 weeks prior to the first administration of IMP or 5 x the half-life of the drug (whichever is longer).

9. Plasma donation within one month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months prior to the Screening Visit.

10. COVID-19 vaccination has been administered and a period of less than 14 days has elapsed after the second dose of the vaccine prior to randomization.

11. Received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days (or 5 half-lives, whichever is longer) of the first administration of IMP in this study.

12. Scheduled surgery, including dental surgery, within 8 weeks of the scheduled completion date of the study.

13. Anti-platelet therapy, anticoagulation therapy (i.e., warfarin, factor Xa inhibitors, direct thrombin inhibitors, or heparin), or thrombolytic use, in the past month prior to randomization or planned use during the duration of the study.

14. Use of non-steroidal anti-inflammatory drugs (including ibuprofen) within 3 days prior to the randomization.

15. Use of potent cytochrome 3A4/3A5 and/or P-glycoprotein inhibiting or inducing drugs during the 2 weeks prior to the first administration of IMP or 5 x the half-life of the drug (whichever is longer).

16. Subjects who are vegans.

17. Subjects who cannot communicate reliably with the investigator.

18. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please re-refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Staff will remain blinded. For this single-blind study (in which the study center staff have remained blinded during the dosing phase of the study), the randomization code will be available at the SRC meeting and the data will be reviewed unblinded.

The pharmacokineticist will remain unblinded during the study conduct, unless otherwise required based on study findings.

The following personnel will have access to the randomization list:

1. The AstraZeneca personnel carrying out the labeling and packaging of subject specific treatments
2. The pharmacy personnel preparing study drug at the site
3. The personnel performing the bioanalyses of the plasma/urine samples. The randomization list should be kept in a secure location until the end of the study.

In the event of a medical emergency, the treatment received may be revealed by personnel authorized by the principal investigator (PI), after discussing with AstraZeneca.