A Double-blind Dual Study Assessing Safety and Efficacy of Buntanetap in Participants With Early AD

Inclusion Criteria:

1. Diagnosis of AD according to the 2024 National Institute on Aging and Alzheimer'sAssociation criteria.

2. Male or female, aged 55 - 85 years.

3. MMSE 20-28 at screening and baseline.

4. CDR global score=0.5 or 1, with memory box score at least 0.5 at screening andbaseline.

5. Positive for amyloid beta as defined by plasma p-tau217 level at screening.

6. Neuroimaging (MRI) consistent with the clinical diagnosis of AD and without findingsof significant exclusionary abnormalities (see exclusion criteria # 4). A historicalMRI, up to 1 year prior to screening, may be used as long as there have been nointerval clinical neurologic events that may suggest a change in the MRI scan.

7. Have a study partner who will provide written informed consent to participate, is infrequent contact with the participant (defined as at least 10 hours per week) andwill accompany the participant on study visits at designated times.

8. Female participants of childbearing potential* must have a negative urine pregnancytest at screening, must be non-lactating and must agree to use a highly effectivemethod of contraception (i.e., a method resulting in a failure rate of less than 1%per year when used consistently and correctly) during the trial and for one monthafter the last dose of trial treatment, such as:

• Oral, intravaginal, or transdermal combined (estrogen plus progestogen)hormonal contraception associated with inhibition of ovulation,

• Oral, injectable, or implantable progestogen-only hormonal contraceptionassociated with inhibition of ovulation,

• Intrauterine device (IUD),

• Intrauterine hormone-releasing system (IUS),

• Bilateral tubal occlusion,

• Vasectomized partner (a vasectomized partner is a highly effectivecontraception method provided that the partner is the sole male sexual partnerof the participant. If not, an additional highly effective method ofcontraception should be used),

• Sexual abstinence (sexual abstinence is considered a highly effective methodonly if defined as refraining from heterosexual intercourse during the entireperiod of risk associated with the study treatment. The reliability of sexualabstinence needs to be evaluated in relation to the duration of the study andthe preferred and usual lifestyle of the participant).

• Non-childbearing potential includes surgically sterilized orpostmenopausal with no menstrual bleeding for at least one year prior tostudy start.

9. Male participants must be sterile or sexually inactive or agree not to father achild during the study and one month after the last dose of study medication andmust agree to use a barrier method for contraception. Female partners of maleparticipants must adopt a highly effective method of contraception with a failurerate of less than 1% per year when used consistently and correctly such as:

• Oral, intravaginal, or transdermal combined (estrogen plus progestogen)hormonal contraception associated with inhibition of ovulation,

• Oral, injectable, or implantable progestogen-only hormonal contraceptionassociated with inhibition of ovulation,

• IUD,

• IUS,

• Bilateral tubal occlusion.

10. General cognition and functional performance sufficiently preserved that the subjectcan provide written informed consent. At re-consent, a legally authorizedrepresentative may co-sign if participants do not meet the general cognition andfunctional performance needed in the opinion of the investigator.

11. No evidence of current suicidal ideation or previous suicide attempt in the pastmonth as evaluated in the Columbia Suicide Severity Rating Scale.

12. Stability of permitted medications for at least 4 weeks prior to screening. Refer toConcomitant Medications section for details on prohibited and permitted medications.

• Cholinesterase inhibitors and/or memantine medication,

• Anticonvulsant medications used for epilepsy or mood stabilization, orneuropathic pain indications, and have not had a breakthrough seizure in 3years prior to screening

• Mood-stabilizing psychotropic agents including, but not limited to, lithium.

13. Adequate visual and hearing ability (physical ability to perform all the studyassessments).

14. Participants previously exposed to buntanetap can still be included in the studyafter a 28-day wash out period.

Exclusion Criteria:

1. Has a history of psychiatric disorder such as schizophrenia, bipolar disorder, ormajor depression according to the criteria of the most current version of theDiagnostic and Statistical Manual of Mental Disorders (DSM), unless they are stableon treatment or no longer need treatment. Mild depression or history of depressionthat is stable on treatment with selective serotonin reuptake inhibitors (SSRI),serotonin and norepinephrine reuptake inhibitors (SNRI) or other anti-depressionmedication (e.g. Wellbutrin) at a stable dose is acceptable. Refer to ConcomitantMedications section above for details on prohibited and permitted medications.

2. Has non-AD dementia, such as vascular dementia, Lewy body dementia, frontotemporaldisease, PD dementia, B12 and thyroid deficiency caused dementia.

3. History of a seizure disorder, if stable on medication is acceptable. Refer toConcomitant Medications section above for details on prohibited and permittedmedications.

4. Screening MRI (or historical MRI, if applicable) of the brain indicative ofsignificant abnormality, including, but not limited to, prior hemorrhage (>5) orinfarct > 1 cm3, > 3 lacunar infarcts, cerebral contusion, encephalomalacia,aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupyinglesion (e.g., abscess or brain tumor such as meningioma unless they are documentedand stable).

5. Has a history or current evidence of long QT syndrome, Fridericia's formulacorrected QT (QTcF) interval ≥ 450 ms for men and ≥ 460 ms for women ((in theabsence of a bundle branch block), or torsades de pointes.

6. Has bradycardia (<50 bpm) or tachycardia (>100 bpm) on the ECG at screening anddeemed medically significant by the PI.

7. Has uncontrolled Type-1 or Type-2 diabetes. A participant with hemoglobin subunitalpha 1c (HbA1c) levels up to 7.5% can be enrolled if the PI believes theparticipant's diabetes is under control.

8. Has clinically significant renal (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) <50 mL/min/BSA (body surface area) or hepatic impairment (alkalinephosphatase (ALP) > 2.0 ULN and/or total bilirubin > 2.0 ULN).

9. Has any clinically significant abnormal laboratory values. Participants with liverfunction tests (aspartate aminotransferase (AST) or alanine aminotransferase (ALT))greater than twice the upper limit of normal will be excluded.

10. Is at imminent risk of self-harm, based on clinical interview and responses on theC- SSRS, or of harm to others in the opinion of the PI. Participants must beexcluded if they report suicidal ideation with intent, with or without a plan ormethod (e.g., positive response to items 4 or 5 in assessment of suicidal ideationon the C-SSRS) in the past 2 months, or suicidal behavior in the past 6 months.

11. Has cancer or has had a malignant tumor within the past year, except participantswho underwent potentially curative therapy with no evidence of recurrence (participants with stable untreated cancer are not excluded).

12. Alcohol / Substance use disorder, moderate to severe, in the last 5 years accordingto the most current version DSM.

13. Participation in another clinical trial with an investigational agent and have takenat least one dose of study medication, unless unblinded on placebo, within 4 weeksprior to the start of screening, or five half-lives of the investigational drug,whichever is greater. The end of a previous investigational trial is the date thelast dose of an investigational agent was taken.

14. Participants with learning disability or developmental delay.

15. Participants whom the PI deems to be otherwise ineligible.

16. Participants with a known allergy to the investigational drug or any of itscomponents. Inactive ingredients of the investigational medicinal product:

• Silicified Microcrystalline Cellulose

• Dibasic Calcium Phosphate Dihydrate

• Mannitol

• Stearic Acid

• Hypromellosee (capsule shells structure)

• Titanium dioxide (opacifier of the capsule shells)

17. Participant is currently pregnant, breast-feeding, and/or lactating.

18. Participant is currently taking strong and moderate CYP3A4 inhibitors and/orinducers. Refer to Concomitant Medications section below for details on prohibitedand permitted medications.

19. Participants with uncontrolled hypertension (systolic >160mm Hg and/or diastolic >95mm Hg) or hypotension (systolic <90mm Hg and/or diastolic <60 mm Hg) and deemedmedically significant by the PI.