Phase 3, Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy and Safety of AR1001 in Participants With Early Alzheimer's Disease (Polaris-AD)

Inclusion Criteria:

1. Male or female participants aged 55 to 90 years of age inclusive at the time ofsigning the informed consent form

2. Mild cognitive impairment or mild dementia consistent with AD defined by stages 3 to 4 according to the National Institute on Aging and Alzheimer's Association (NIA-AA)at Screening

3. Participants with a history of subjective cognitive and memory decline with onsetwithin 5 years before Screening, confirmed by study partner.

4. Participants who have a MMSE score greater than or equal to 20

5. Participants with a CDR global rating of 0.5 or 1

6. Participants with a RBANS score based on the Delayed Memory Index (DMI) score lessthan or equal to 85

7. If an historic magnetic resonance imaging (MRI) is available, findings must excludeother causes of dementia.

8. Positive biomarker for brain amyloid pathology as indicated by assessment of atleast one of the following:

9. Current or historical CSF assessment with FDA-cleared assays, includingLumipulse® beta-amyloid ratio [1-42/1-40] ≤ 0.072, Elecsys® pTau 181/Aβ[1-42]greater than 0.023, Elecsys® tTau /Aβ[1-42] greater than 0.28, or other assaysor cut-offs as they become FDA-cleared.

10. Historical amyloid positron emission tomography (PET) assessment confirmed bythe Sponsor or Designee.

11. Participants (or participant's legally authorized representative) and caregiver (s)who can sign an informed consent to participate in the study.

12. Participants who have one (or more) identified adult study partners (s) who, in theopinion of the Investigator, has sufficient contact with and knowledge about theparticipant as to be able to report knowledgably about the participant's cognition,function, behavior, and safety, and compliance with the protocol. The informant/carepartner must be available by phone to provide information to the Investigator andstudy staff about the participant as well as agree to attend in-person clinic visitsthat require partner input for scale completion. The informant/care partner must beliterate and provide informed consent and should be available for the duration ofthe study. The same informant/care partner is required to be consistent across allstudy visits except under rare, unavoidable circumstances (e.g., unexpectedinformant health crisis) that are approved by the Investigator and Sponsor.

Exclusion Criteria:

1. Participants who are female and are either pregnant, nursing, or of childbearingpotential and not practicing effective contraception

2. Participants who have signs of significant delirium which, in the opinion of theInvestigator, would interfere with this study

3. Participants who have any diagnosis of dementia or cognitive decline other than thatrelated to AD, including, but not limited to concomitant history of significant headtrauma, alcohol abuse, frontotemporal dementia, Huntington Disease, Parkinsonism (e.g., Parkinson's disease, Dementia with Lewy Bodies, etc.), significantcerebrovascular disease, and/or significant seizure disorder

4. Participants with any current psychiatric diagnosis if, in the judgment of theInvestigator, the psychiatric disorder (e.g., schizophrenia) or symptom is likely toconfound interpretation of drug effect, affect cognitive assessments, or affect theparticipant's ability to complete the study

5. Participants with a history of vascular dementia

6. Participants with evidence of other neurological conditions thought to interferewith the evaluations in this study

7. Participants with a history of myocardial infarction, unstable angina, coronaryartery disease, and/or New York Heart Association (NYHA) class III or IV heartfailure within the last 12 months

8. Participants with uncontrolled hypertension (systolic blood pressure (BP) >160 mmHgor diastolic BP > 95 mmHg) or hypotension (systolic BP <90 mmHg or diastolic BP <50mmHg). Participants may undergo repeated testing to ensure that accurate BP readingsare obtained

9. Participants with a body mass index (BMI) > 35 kg/m2

10. Participants with any of the following:

11. elevation (>2.5x upper limit of normal [ULN]) of AST (aspartateaminotransferase, ALT (alanine transaminase, or total bilirubin (unless knownprior history of Gilbert's syndrome)

12. deficiency (< lower limit of normal [LLN]) of Vitamin B12

13. known history of HIV (human immunodeficiency virus) positivity or positive testfor HIV 1/2 at screening

14. known history of Hepatitis C virus (HCV) or positive test for HCV antibody (HCVAb) at screening (unless negative on confirmatory PCR test)'

15. positive test for Hepatitis B surface antigen (HBsAg)

16. known history of neurosyphilis or positive test for RPR at screening

17. Participants who have history of cancer or malignant tumor within 5 years prior toscreening with the exception of:

18. Basal or squamous cell carcinoma of the skin or cervical dysplasia, which hasbeen adequately treated

19. In situ Grade 1 cervical cancer, fully treated at least 2 years prior toscreening, and without recurrence.

20. Prostate cancer, confined to the prostate gland, which has been adequatelytreated (e.g., surgery and/or radiation or watchful waiting) with normal or lowand stable prostate-specific antigen (PSA) levels for 2 years prior toScreening

21. Adequately treated non-metastatic breast cancer

22. Participants who in the opinion of the Investigator have an inadequately treatedthyroid disorder

23. Participants with inherited degenerative retinal disease

24. Participants who have an undiagnosed or uncontrolled seizure disorder (and/or anepileptic syndrome), which has or could lead to cognitive impairment either fromrepeated seizures or the medications used to control the seizure disorder

25. Participants who are being treated, or likely to require treatment during the study,with any medications prohibited by the study protocol

26. Participants who have participated in any investigational drug or device trialwithin the previous 30 days or five half-lives of an investigational drug atScreening, whichever is longer

27. Participants taking an oral cholinesterase inhibitor and/or memantine not on astable dose for at least 3 months prior to screening. Treatment and dosing shouldremain stable, with no changes throughout the trial.

28. Participants who have been and/or are currently being treated with anti-amyloid,anti-tau, or any other investigational therapies for AD

29. Participants who currently take any other PDE-5 Inhibitors (e.g., sildenafil)

30. Participants who are currently receiving (or unable to stop use for at least 14 days [2 weeks] prior to receiving the first dose of the AR1001 and throughout the study)prescription or nonprescription medications or other products known to be potentinhibitors of cytochrome P450 isozyme 3A4 (CYP3A4)

31. Alcohol or substance use disorder within the past 5 years according to Diagnosticand Statistical Manual of Mental Disorders (DSM-5)

32. Participants who have previously participated in a clinical trial with AR1001

33. Participants, in the opinion of the Investigator, who are unsuitable to participatein the trial

34. Participants who in the opinion of the Investigator are at significant risk ofsuicide.

35. GDS-15 score greater than equal to 8 at Screening

36. Participants, in the opinion of the Investigator, who have any who have anycontraindications to undergoing LP. Participants receiving ongoing anticoagulanttherapy or antiplatelet therapy (other than aspirin and non-steroidalanti-inflammatory drugs [NSAIDs]) should also be excluded if it is considered unsafeto temporarily discontinue the therapy