Study to Establish Safety, Tolerability and Pharmacokinetics of NRL-1049 in Healthy Adult Participants Following Multiple-Dose Administration

1. Provision of signed and dated informed consent form (ICF) prior to Screening
2. Stated willingness to comply with all study procedures and to follow site and local infectious disease safety protocols, and availability for the duration of the study
3. Healthy adult male or female

4. If female, meets one of the following criteria:

   1. Is of childbearing potential and agrees to use an acceptable contraceptive method. Acceptable contraceptive methods include:

      • Abstinence from heterosexual intercourse from 14 days prior to the Screening visit through to at least 90 days after the last dose of the study drug
      • One of the following highly-effective contraceptive methods, used from at least 28 days prior to the Screening visit through to at least 90 days after the last dose of the study drug:
      • Systemic contraceptives (combined birth control pills, injectable/implant/insertable hormonal birth control products, or transdermal patch)
      • Intrauterine device (with or without hormones)
      • Male partner vasectomized at least 6 months prior to the Screening visit
      • One of the following double-barrier contraceptive methods, used from the Screening visit through to at least 90 days after the last dose of the study drug:
      • Male condom plus spermicide, or
      • Diaphragm plus spermicide, or
      • Cervical cap plus spermicide

   2. Is of non-childbearing potential, defined as either:

      • Surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation), or
      • In a postmenopausal state:
      • At least 1 year without menses and without an alternative medical condition prior to the Screening visit and follicle-stimulating hormone (FSH) levels ≥ 40 mIU/mL at Screening; or
      • At least 1 year without menses and without an alternative medical condition prior to the Screening visit, FSH levels \< 40 mIU/mL and estradiol serum level ≤150 pmol/L at Screening

5. If male, meets one of the following criteria:

   1. Is able to procreate and agrees to use one of the accepted contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last study drug administration. An acceptable method of contraception includes one of the following:

      • Abstinence from heterosexual intercourse
      • Male condom with spermicide or male condom with a vaginal spermicide (gel, foam, or suppository)
   2. Is unable to procreate; defined as surgically sterile (i.e., has undergone a vasectomy at least 180 days prior to the first study drug administration)
6. Age of at least 18 years but not older than 65 years
7. Body mass index within 18.0 to 32.0 kg/m2 (inclusive)
8. Body weight between 50 and 111 kg (inclusive)
9. Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by an Investigator
10. Able to communicate effectively with the study personnel

Exclusion Criteria:

1. Female who is lactating
2. Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration
3. History of significant hypersensitivity to ROCK kinase inhibitors or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (e.g., angioedema) to any drugs
4. Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability
5. Presence or history of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease
6. History of surgery or major surgery within 30 days of Screening, or surgery planned during the study
7. Presence of clinically significant ECG abnormalities at the screening visit, as defined by medical judgment (e.g., QTcF > 450 msec for males and >470 msec for females)
8. Smoking and the use of tobacco products, tetrahydrocannabinol (THC), or cannabidiol (CBD) in the 6 months prior to the first dose of study drug
9. History of alcohol abuse (consumption of >10 standard drinks/week; 1 standard drink is defined as 12 ounces [360 mL] of beer or lager, 5 ounces [150 mL] of wine, or 1.5 ounces [45 mL] of liquor or a mixed drink), illicit drug use, physical dependence to any opiates, THC, CBD, or any history of drug abuse or addiction within 12 months of Screening.
10. Any clinically significant illness in the 28 days prior to the first study drug administration
11. Use of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) in the 28 days prior to the first study drug administration, that in the opinion of an Investigator would put into question the status of the participant as healthy
12. Use of over-the-counter products, including vitamins and supplements, in the 7 days prior to the first study drug administration
13. Use of St. John's wort in the 28 days prior to the first study drug administration
14. Treatment with any known drugs that are strong inhibitors of CYP2D6 (such as bupropion, fluoxetine, paroxetine, quinidine, terbinafine, and thioridazine) or substrates of CYP2D6 (such as dextromethorphan, desipramine, atomoxetine, R venlafaxine), within 30 days prior to the first dose of study drug or during the study
15. Positive test result for alcohol, cotinine, and/or drugs of abuse at Screening or prior to the first study drug administration
16. Positive screening results to HIV antigen/antibody combo, hepatitis B surface antigen, or hepatitis C virus tests
17. Any other clinically significant abnormalities in laboratory test results at Screening that would, in the opinion of an Investigator, increase the participant's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data
18. Received a dose of the study drug in a previous group for this clinical study
19. Intake of another investigational drug within 30 days or 5 half lives of the investigational drug's PK or biological activity (if known), whichever is longer, prior to the first study drug administration of this study
20. Any other condition or prior therapy that, in the Investigator's opinion, would make the participant unsuitable for the study, or unable or unwilling to comply with the study procedures
21. Donation of plasma in the 7 days prior to the first study drug administration
22. Donation of 1 unit of blood to American Red Cross or equivalent organization or donation of over 500 mL of blood in the 56 days prior to the first study drug administration
23. Involved in the planning or conduct of this study