A Study to Evaluate ART101 in Adult Participants With Hypertension

Inclusion Criteria:

1. Male or female (excluding women of child bearing potential [WOCBP]) aged 18 to 65years (inclusive at the time of informed consent).

2. Hypertensive but otherwise in good general health, with no clinically significantmedical history, and have no clinically significant abnormalities on physicalexamination at Screening and/or before the first administration of study drug at thediscretion of the PI.

3. Either of the following:

4. Drug Naïve.

5. Has previously received monotherapy or dual therapy for hypertension but hasceased medication(s) under the supervision of the participant's medicalprofessional eg, General Practitioner or Specialist. Note: Where applicable, a participant must have ceased administering therapy forhypertension from ≥ 3 weeks prior to Screening.

6. Mean sitting SBP > 130 mmHg and ≤ 159 mmHg per USA guidelines at Screening (byoscillometric AOBP measurement). Note: If the PI (or designee) considers that the Screening oscillometric AOBPmeasurement is spuriously elevated, oscillometric AOBP may be retested once duringScreening.

7. Mean SBP > 130 mmHg and ≤ 159 mmHg from the daytime BP measurements and a night-timemean SBP ≥ 110mg Hg at Baseline per USA guidelines (assessed by 24-hour ABPM duringthe Screening Period) without hypertensive medication. Note: Where the PI (or designee) is informed that the 24-hour ABPM has failedquality check, the 24-hour ABPM may be repeated once during the Screening Period.

8. BMI between ≥ 18.0 and ≤ 35.0 kg/m2 at Screening and weight ≥ 50 kg at Screening.

9. Nonsmoker and must not have used any nicotine-containing products within 6 monthsprior to Screening.

10. ECG findings at Screening within normal range, unless deemed not clinicallysignificant by the PI or designee.

11. Males must be surgically sterile vasectomized since at least 6 months prior to firststudy drug administration, OR if not surgically sterile AND will engage in sexualrelations with a WOCBP, his female partner must meet 1 of the following criteria:

12. Surgically sterile (eg, bilateral tubal occlusion, hysterectomy, bilateralsalpingectomy, bilateral oophorectomy, bilateral tubal ligation) orpostmenopausal.

13. Agree to use acceptable, highly effective, double barrier contraception fromScreening until study completion, including the Follow-up Period. Acceptable,highly effective, double barrier contraception is defined as meeting 1 of thefollowing criteria: i. Simultaneous use of hormonal contraceptives (implant, injection, pills, vaginalrings and skin patches) and must agree to use the same hormonal contraceptivethroughout the study, and condom for the male participant. ii. Simultaneous use of Intrauterine Device (IUD) or Intrauterine System (IUS) (Mirena or Kyleena) and condom for the male participant. iii. Simultaneous use of diaphragm or cervical cap and male condom for the maleparticipant. Note: Males with same-sex partners (abstinence from penile-vaginal intercourse) orare abstinent from heterosexual intercourse are not required to use contraceptionwhen this is their preferred and usual lifestyle. Note: Males must be willing not todonate sperm from the first dose of study drug until at least 90 days after studycompletion.

14. Able and willing to comply with study procedures, study restrictions, and visits tothe study site.

15. Able and willing to provide written informed consent after the nature of the studyhas been explained and prior to the commencement of any study procedures.

Exclusion Criteria:

1. WOCBP or female who is pregnant, breastfeeding, or planning to become pregnantduring the study.

2. Mean sitting DBP > 110 mmHg at Screening (by oscillometric AOBP measurement) withouthypertensive medication.

3. History of secondary hypertension including, but not limited to, any of thefollowing:

4. Renovascular hypertension (unilateral or bilateral renal artery stenosis).

5. Coarctation of the aorta.

6. Primary hyperaldosteronism.

7. Cushing's disease, pheochromocytoma.

8. Polycystic kidney disease.

9. Drug induced hypertension.

10. Any of the following:

11. Postural tachycardia (ie, > 30 bpm upon standing).

12. Orthostatic hypotension (ie, a fall in SBP of ≥ 20 mmHg or DBP of ≥ 10 mmHgwithin 1 minute of standing up from a supine position).

13. History of hypotension.

14. Arm circumference does not align with any blood pressure cuff size. Note: Whereapplicable, a participant must have ceased administering monotherapy or dualtherapy for hypertension from ≥ 3 weeks prior to Screening. Note: The relevant Australian Product Information should be reviewed by the PI ordesignee to determine the appropriate washout period for a prescription medication. Note: Cessation of prescription medication (eg, monotherapy or dual therapy forhypertension) by participant must occur with the approval of the participant'smedical professional eg, General Practitioner or Specialist.

15. Diagnosed with diabetes mellitus.

16. Is participating in a concurrent experimental therapy study with a study drug ormedical device.

17. Any of the following:

18. Has received experimental therapy with a small molecule within 30 days of thefirst administration of study drug or 5 half-lives of the small moleculeexperimental therapy (whichever is the longer). Note: Experimental therapy witha small molecule refers to any small molecule compound (eg, Lipitor, Benadryl)under investigation in a clinical trial.

19. Has received experimental therapy with a large molecule within 90 days of thefirst administration of study drug or 5 half-lives of the large moleculeexperimental therapy (whichever is the longer).Note: Experimental therapy with a large molecule refers to a large molecule (eg, monoclonal antibodies, peptides) under investigation in a clinical trial.

20. Has received experimental therapy with antisense oligonucleotides or siRNAwithin 12 months of the first administration of study drug or 5 half-lives (whichever is longer).

21. Has participated in more than 4 experimental therapy studies with anexperimental therapy or medical device within 1 year prior to firstadministration of study drug.

22. Has received any immune suppressing drug (including experimental therapies aspart of a clinical study) within 4 months of the first administration of studydrug or 5half-lives, whichever is longer.

23. Evidence or history of any clinically significant immunologic, hematologic, renal,endocrine, pulmonary, gastrointestinal, cardiovascular, musculoskeletal, hepatic,psychiatric, neurologic, allergic disease (including clinically significant ormultiple drug allergies), surgical conditions, or any condition that, in the opinionof the PI, that would jeopardize the safety of the participant, prevent completeparticipation in the study, or compromise interpretation of study data.

24. History of allergic reaction to an oligonucleotide, GalNAc-containing medication, orthe study drug or its constituents.

25. History or presence of a condition associated with significant immunosuppression.

26. History of life-threatening infection (eg, meningitis).

27. History of malignancy, except for the following:

28. Basal or squamous cell carcinoma of the skin excised more than 2 years prior toScreening.

29. Cancer that has been resolved or has been in remission for more than 5 yearsprior to Screening.

30. History of porphyria, myopathy, cardiac valve repair, cardiac device implantation oran active liver disease (including steatotic hepatitis and fibrosis).

31. Has undergone surgical procedures within 4 weeks of Day -1, or is planning electivesurgery until the angiotensinogen level has returned to >50% predose Baseline levelor until at least Day 365 whichever comes first.

32. Unstable / underlying cardiovascular disease defined as:

33. Any history of congestive heart failure (New York Heart Association [NYHA]Class III-IV).

34. Any history of previous myocardial infarction, coronary revascularization,unstable or stable angina pectoris ˂ 6 months prior to Screening.

35. Any hemodynamically unstable atrial or ventricular arrhythmias.

36. Significant uncorrected valvular heart disease.

37. History of stroke or transient ischemic attack < 6 months prior to Screening.

38. A cardiac valve repair, cardiac device implantation, and/or a hospitalization forheart failure within 3 months of Screening.

39. Any of the following:

40. A personal or family history of long QT syndrome, Torsades de Pointes, or othercomplex ventricular arrhythmias, or family history of sudden death.

41. History of, or current, clinically significant arrhythmias as judged by the PI,including ventricular tachycardia, ventricular fibrillation, atrialfibrillation, sinus node dysfunction, or clinically significant heart block.Participants with minor forms of ectopy (eg, premature atrial contractions) arenot necessarily excluded.

42. Abnormal ECG findings at Screening that are considered by the PI or designee tobe clinically significant.

43. Any of the following:

44. Evidence of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) infection at Screening. During the study, a participant with aninfection may continue the study at the discretion of the PI.

45. Oral temperature > 38 °C on Day-1.

46. Has experienced fever (body temperature > 38°C) or symptomatic viral orbacterial infection within 2 weeks prior to Screening.

47. Has experienced any illness within 4 weeks of Day -1 deemed by the PI to beclinically significant. Has experienced infection within 3 months prior to Screening that requiredparenteral antibiotics.

48. Vaccination with a live vaccine (eg, MMR, rotavirus) within 4 weeks prior to thefirst administration of study drug. Note: Other exclusions pertaining to vaccination will be per PI discretion, inconsultation with the Sponsor.

49. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase,gamma-glutamyl transferase, and/or bilirubin (total, direct, indirect) values > 1.5 × upper limit of normal at Screening. Bilirubin levels above > 1.5 x upper limit ofnormal will be acceptable, if they are consistent with Gilbert's syndrome, accordingto PI discretion. Repeat testing at Screening is acceptable for out-of-range valuesfollowing approval by the PI or designee.

50. Positive test for HIV antibody, hepatitis C virus antibody, hepatitis B surfaceantigen.

51. Any clinically significant laboratory values (based on laboratory normal range) inthe opinion of the Investigator. Repeat testing at Screening is acceptable forout-of-range values following approval by the PI or designee.

52. Estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73m2 (using the MDRDformula).

53. Blood donation > 500 mL, significant blood loss (ie, > 500 mL) within 3 months priorto the first study drug administration, and /or receipt of a blood transfusionwithin 1 year of first study drug administration.

54. Plasma donation within 7 days prior to the first administration of study drug.

55. Any of the following:

56. OTC medication, herbal remedies, supplements, vitamins, or other substancesfrom 7 days prior to first administration of study drug and during course ofstudy without prior approval of the PI and CRO Medical monitor (with theexception of paracetamol use [maximum 2 g daily] for treatment of analgesia,ibuprofen use from Day 29, and nasal decongestant use from Day 29 [eg,phenylephrine hydrochloride, pseudoephedrine, naphazoline hydrochloride]).

57. Unwilling to refrain from prohibited medication for study duration.

58. Use of ß-blockers within 30 days prior to first administration of study drug, oranticipated use of ß-blocker medication during the study period.

59. Anticipated use of sildenafil (Viagra®), tadalafil (Cialis®), or vardenafil (Levitra®) during the study period.

60. Anticipated using organic nitrate preparations (eg, nitroglycerin, isosorbidemononitrate, isosorbide dinitrate, pentaerythritol) during the study period.

61. Positive urine drugs screen or alcohol breath test at Screening or Day -1.

62. History of substance abuse or dependency or history of illicit drug use over thelast 1 year (by self-declaration).

63. Any of the following:

64. Regular alcohol consumption defined as > 14 standard units per week for femalesand > 21 standard units per week for males (where 1 standard unit = 360 mL ofbeer, 30 mL of 40% spirit or a 150 mL glass of wine) or > 4 standard units onany single day.

65. Unwilling to abstain from alcohol beginning 48 hours prior to the firstadministration of study drug until participant check-out from the CRU.

66. Any of the following:

67. Unwilling to abstain from caffeine (eg, coffee, tea, caffeine-containing sodasand colas) beginning 48 hours prior to the administration of the study drug andat anytime while domiciled at the CRU.

68. Unwilling to limit the intake of caffeine beverages to < 5 cups/day from timeof CRU discharge until the angiotensinogen level has returned to > 50% predoseBaseline level or until at least Day 365 whichever comes first.

69. Unwilling to abstain from xanthine-containing products (eg, chocolate) at anytime while domiciled at the CRU.

70. Unwilling to refrain from strenuous exercise (including weightlifting) for 96 hoursprior to each blood collection for clinical laboratory tests.

71. Employed (or is intending to be employed) as a shift worker from Screening until theangiotensinogen level has returned to > 50% predose Baseline level or until at leastDay 365 whichever comes first. A shift worker is defined as a person who is employedat times falling within one of the following periods (Australian Government FairWork Ombudsman):

72. A night shift (commencing at or after 3 pm and before 11 pm).

73. An early morning shift (commencing at or after 11 pm and before 4.30 am).

74. A morning shift (commencing at or after 4.30 am and before 6.30 am).

75. Tattoos, scarring or birthmarks on the abdomen, upper arms or upper thighs thatwould affect the assessment of injection site reactions in the opinion of PI (ordesignee).

76. Anything that the PI considers that would jeopardize the safety of the participant,prevent complete participation in the study, or compromise interpretation of studydata.