A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease

The study uses a randomized, double-blind, placebo-controlled, parallel group, adaptive
design with variable treatment duration in approximately 2000 cognitively unimpaired
participants aged 60 to 75 years, with at least one APOE4 allele (Homozygotes or
Heterozygotes) and, if Heterozygotes, with evidence of elevated brain amyloid.

The screening period is expected to last about 12 weeks. Participants will receive disclosure
of their individual test results for APOE genotyping and brain amyloid status.

Treatment duration is variable (event driven trial) for at least 60 months, and up to an
expected maximum of 84 months.

Participants will return to the study site every three months for drug dispensing and every
six months for safety and efficacy assessments, including neuropsychological scales with
input from the study partner. Brain MRI scans will be conducted at month 6 and month 12, and
on a yearly basis thereafter.

The Follow-up visit will be scheduled 12 weeks after the end of the Treatment Epoch. An
additional CSF and / or PET AD biomarker assessments will be conducted on a voluntary basis
at year 2 and 5.

The study (also known as the Generation Study 2) is conducted as part of the Alzheimer's
Prevention Initiative (API) program.

Inclusion Criteria:

- consent to receive disclosure of their risk estimates to develop clinical symptoms of
AD based on their APOE genotype and, if Heterozygotes, evidence of elevated brain
amyloid.

- Male or female, age 60 to 75 years inclusive. Females must be considered
post-menopausal and not of child bearing potential

- Cognitively unimpaired as evaluated by memory tests performed at screening.

- Participant's willingness to have a study partner.

- Carrier of at least one APOE4 gene if Heterozygotes, elevated brain amyloid (as
measured by CSF Abeta or amyloid PET imaging).

Exclusion Criteria:

- Any disability that may prevent the participants from completing all study
requirements. -

- Current medical or neurological condition that might impact cognition or performance
on cognitive assessments.

- Advanced, severe progressive or unstable disease that may interfere with the safety,
tolerability and study assessments, or put the participant at special risk.

- History of malignancy of any organ system, treated or untreated, within the past 60
months.

- Indication for, or current treatment with ChEIs and/or another AD treatment (e.g.
memantine).

- Contraindication or intolerance to MRI.

- Brain MRI results showing findings unrelated to AD that, in the opinion of the
Investigator might be a leading cause to future cognitive decline, might pose a risk
to the participant, or might prevent a satisfactory MRI assessment for safety
monitoring.

- Suicidal Ideation in the past six months, or Suicidal Behavior in the past two years.

- A positive drug screen at Screening, if, in the Investigator's opinion, this is due to
drug abuse.

- Significantly abnormal laboratory results at Screening, not as a result of a temporary
condition.

- Current clinically significant ECG findings.

- Clinically relevant depigmenting or hypopigmenting conditions (e.g. albinism,
vitiligo) or active / history of chronic urticaria in the past year.