A Study to Evaluate the Safety and Efficacy of CT1812 in Subjects With Mild to Moderate Alzheimer's Disease.

This is a multi-center, randomized, double-blind, placebo-controlled, parallel group 36 week
multicenter Phase 2 study of two doses of CT1812 in adults with mild to moderate Alzheimer's
Disease (AD).

This Phase 2 study is designed to evaluate the safety of two doses of CT1812 administered
once daily for 6 months in adults aged 50 to 85 who have been diagnosed with mild to moderate
Alzheimer's disease (the targeted clinical indication for CT1812). Randomized participants
will receive 100 mg of CT1812, 300 mg of CT1812, or placebo once daily for 182 days.
Exploratory endpoints that evaluate the effect of CT1812 on biomarkers are also included.

1. Men, and women of non-childbearing potential, 50-85 years of age inclusively, with a
diagnosis of mild to moderate Alzheimer's disease according to the 2011 NIA-AA
criteria and at least a 6 month decline in cognitive function documented in the
medical record.

i) Non-childbearing potential for women is defined as postmenopausal (last natural
menses greater than 24 months) or undergone a documented bilateral tubal ligation or
hysterectomy. If last natural menses less than 24 months, a serum FSH value confirming
post-menopausal status can be employed.

ii) Male participants who are sexually active with a woman of child-bearing potential
must agree to use condoms during the trial and for 3 months after last dose unless the
woman is using an acceptable means of birth control. Acceptable forms of birth control
include abstinence, birth control pills, or any double combination of: intrauterine
device (IUD), male or female condom, diaphragm, sponge, and cervical cap.

2. Diagnostic confirmation by amyloid PET with florbetaben or another approved amyloid
PET ligand. Previous amyloid imaging study with a positive result will be accepted. If
none is available, then amyloid PET will be conducted during screening. Diagnostic
confirmation by a CSF sample collected at the screening visit lumbar puncture in place
of amyloid PET will also be acceptable

3. Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of
Alzheimer's disease and without findings of significant exclusionary abnormalities
(see exclusion criteria, number 4). An historical MRI, up to 1 year prior to
screening, may be used as long as there is no history of intervening neurologic
disease or clinical events (such as a stroke, head trauma etc.) and the subject is
without clinical symptoms or signs suggestive of such intervening events.).

4. MMSE 18-26 inclusive.

5. No active depression and a GDS ≤6 (see exclusion criteria number 6).

6. Modified Hachinski ≤ 4.

7. Formal education of eight or more years.

8. Subjects must have a caregiver/ study partner who in the opinion of the site principal
investigator, has contact with the study subject for a sufficient number of hours per
week to provide informative responses on the protocol assessments, oversee the
administration of study drug, and is willing and able to participate in all clinic
visits and some study assessments. The caregiver/ study partner must provide written
informed consent to participate in the study.

9. Subjects living at home or in the community (assisted living acceptable).

10. Ability to swallow CT1812 capsules.

11. Stable pharmacological treatment of any other chronic conditions for at least 30 days
prior to screening.

12. Subjects must be capable of providing written informed consent to the study procedures
and for use of protected health information [Health Insurance Portability and
Accountability Act (HIPAA), if applicable]. Written informed consent also shall be
obtained from the responsible caregiver. All consent processes must be undertaken in
the presence of a witness and prior to any study procedures.

13. Must consent to apolipoprotein E (ApoE) genotyping for data analysis stratification.

14. Subjects shall be generally healthy with mobility (ambulatory or ambulatory-aided,
i.e., walker or cane), vision and hearing (hearing aid permissible) sufficient for
compliance with testing procedures.

15. Must be able to complete all screening evaluations.

EXCLUSION CRITERIA:

Participants will be excluded from the study if any of the following conditions apply:

1. Hospitalization (except for planned procedures) or change of chronic concomitant
medication within one month prior to screening.

2. Subjects living in a continuous care nursing facility.

3. Contraindication to the MRI examination for any reason.

4. Screening MRI (or historical MRI, if applicable) of the brain indicative of
significant abnormality, including, but not limited to, prior hemorrhage or infarct >1
cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular
malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess
or brain tumor such as meningioma). If a small incidental meningioma is observed, the
medical monitor may be contacted to discuss eligibility..

5. Clinical or laboratory findings consistent with:

1. Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal
dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.).

2. Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral
sclerosis, etc.).

3. Seizure disorder.

4. Other infectious, metabolic or systemic diseases affecting the central nervous
system (syphilis, present hypothyroidism, present vitamin B12 or folate
deficiency, other laboratory values etc.).

6. A current DSM-V diagnosis of active major depression, schizophrenia or bipolar
disorder. Subjects with depressive symptoms successfully managed by a stable dose of
an antidepressant are allowed entry.

7. Clinically significant, advanced or unstable disease that may interfere with outcome
evaluations, such as:

1. Chronic liver disease, liver function test abnormalities or other signs of
hepatic insufficiency (ALT, AST, alkaline phosphatase > 1.5 ULN, lactate
dehydrogenase (LDH) > 1.5 x ULN).

2. Respiratory insufficiency.

3. Renal insufficiency eGFR < 50 mL/min based on the CKD‐EPI formula,
https://www.mdcalc.com/ckd-epi-equations-glomerular-filtration-rate-gfr

4. Heart disease (myocardial infarction, unstable angina, heart failure,
cardiomyopathy within six months before screening).

5. Bradycardia (<50/min.) or tachycardia (>100/min.).

6. Poorly managed hypertension (systolic >160 mm Hg and/or diastolic >95 mm Hg) or
hypotension (systolic <90 mm Hg and/or diastolic <60 mm Hg).

7. Uncontrolled diabetes defined by HbA1c >7.5.

8. History of cancer within 3 years of screening with the exception of fully excised
non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for
at least 6 months.

9. Seropositive for human immunodeficiency virus (HIV).

10. History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive
for hepatitis B surface antigen [HbsAg] or anti-hepatitis C [HCV] antibody).

11. Clinically significant abnormalities in screening laboratory tests, including:

a. Hematocrit less than 35% for males and less than 32% for females, absolute
neutrophil cell count of 1500/uL (with the exception of a documented history of a
chronic benign neutropenia), or platelet cell count of < 120,000/uL; INR >1.4 or other
coagulopathy, confirmed by repeat assessment of: i. Hematocrit ii. Neutrophil count
iii. Platelet count

12. Disability that may prevent the subject from completing all study requirements (e.g.
blindness, deafness, severe language difficulty, etc.).

13. Within 4 weeks of screening visit or during the course of the study, concurrent
treatment with antipsychotic agents, antiepileptics, centrally active
anti-hypertensive drugs (e.g., clonidine, l-methyl dopa, guanidine, guanfacine, etc.),
sedatives, opioids, mood stabilizers (e.g., valproate, lithium); or benzodiazepines,
with the following exception:

a. Low dose lorazepam may be used for sedation prior to MRI scan for those subjects
requiring sedation. At the discretion of the investigator, 0.5 to 1 mg may be given
orally prior to scan with a single repeat dose given if the first dose is ineffective.
No more than a total of 2 mg lorazepam may be used for the MRI scan.

14. Any disorder that could interfere with the absorption, distribution, metabolism or
excretion of drugs (e.g. small bowel disease, Crohn's disease, celiac disease, or
liver disease).

15. Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and memantine.

16. Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g alcohol
(approximately 1 liter of beer or 0.5 liter of wine) per day indicated by elevated MCV
significantly above normal value at screening.

17. Suspected or known allergy to any components of the study treatments.

18. Enrollment in another investigational study or intake of investigational drug within
the previous 30 days or five half lives of the investigational drug, whichever is
longer.

19. Intake of drugs or substances potentially involved in clinically significant induction
or inhibition of CYP3A4 or P-gp mediated drug interactions with CT1812, within 4 weeks
or five half-lives of the interacting drug prior to administration of CT1812 and
throughout the course of the study. Grapefruit juice should be avoided in the two
weeks prior to dosing and throughout the course of the study. See Appendix A for a
complete list of prohibited substances.

20. Exposure to immunomodulators, anti Aβ vaccines, passive immunotherapies for AD (e.g.
monoclonal antibodies) within the past 180 days and/or exposure to BACE inhibitors
within the past 30 days.

21. Anticipated use of nonsteroidal anti-inflammatory drugs (NSAIDs) on more than 14 days
during the period from Baseline to Day 182.

22. Contraindication to undergoing an LP including, but not limited to: inability to
tolerate an appropriately flexed position for the time necessary to perform an LP;
international normalized ratio (INR) > 1.4 or other coagulopathy; platelet count of <
120,000/μL; infection at the desired lumbar puncture site; taking anti-coagulant
medication within 90 days of screening (Note: low dose aspirin is permitted);
degenerative arthritis of the lumbar spine; suspected non-communicating hydrocephalus
or intracranial mass; prior history of spinal mass or trauma.

23. Any condition, which in the opinion of the investigator or the sponsor makes the
subject unsuitable for inclusion.