Event was defined as the first confirmed diagnosis of MCI due to Alzheimer's disease (AD) or dementia due to AD (whichever occurred first) after adjudication by the progression adjudication committee (PAC) as triggered either by an investigator diagnosis or an increase in the Clinical Dementia Rating (CDR) global score. An event had to be confirmed by the PAC at two consecutive visits. In case no confirmed event was observed for a participant, the observation was censored, and the censoring date was defined as the last date where the diagnostic classification was assessed. The Study was terminated and only confirmed events collected up to the data cut-off point were counted. Due to the early termination of the study only a small number of events were observed and time-to-event could not be analyzed. Kaplan-Meyer (KM) estimates were provided to estimate probability that a subject would have an event prior to the specified visit.

n=number of participants at risk to experience an event at the time-point

APCC is a composite score derived from the specific scores from the Repeatable Battery for the Assessment of Neurological Status (RBANS), Mini-Mental State Examination (MMSE) and the Raven's Progressive Matrices. The APCC score is a weighted score with ranges from from 0 to 100 where higher scores correspond to better cognitive performance.

Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.

The CDR was obtained through semi-structured interviews of participants and informants, and cognitive functioning was rated on a 5-point scale of functioning in six domains: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. The CDR global score ranged from zero to three, while the CDR-SOB was the sum of the ratings from the six domains, ranging from 0 to 18 with a minimum increment of 0.5. Higher scores indicated greater disease severity.

Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.

Repeatable Battery for the Assessment of Neurological Status (RBANS) is a clinical tool designed to detect and characterize the earliest neurocognitive changes associated with dementia. The RBANS generates age-adjusted index scores for five neurocognitive domains: Immediate Memory, Visuospatial/Constructional, Language, Attention and Delayed Memory, which are used to calculate a Total Scale Index score. Index scores and total score range from 40 to 160 and a higher score indicates better cognitive functioning.

Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.

Repeatable Battery for the Assessment of Neurological Status (RBANS) is a clinical tool designed to detect and characterize the earliest neurocognitive changes associated with dementia. The RBANS generates age-adjusted index scores for five neurocognitive domains: Immediate Memory, Visuospatial/Constructional, Language, Attention and Delayed Memory, which are used to calculate a Total Scale Index score. Index scores and total score range from 40 to 160 and a higher score indicates better cognitive functioning.

Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.

Everyday Cognition Scale (ECog) measures cognitively-relevant everyday abilities comprised of 39 items covering 6 cognitively-relevant domains: Everyday Memory, Everyday Language, Everyday Visuospatial Abilities, Everyday Planning, Everyday Organization, and Everyday Divided Attention. The questionnaire is a self-reported measure completed by both participant and study partner (informant). The total score for the 39 items ranges from 39 to 195, with greater scores indicating worse daily function.

Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.

Everyday Cognition Scale (ECog) measures cognitively-relevant everyday abilities comprised of 39 items covering 6 cognitively-relevant domains: Everyday Memory, Everyday Language, Everyday Visuospatial Abilities, Everyday Planning, Everyday Organization, and Everyday Divided Attention. The questionnaire is a self-reported measure completed by both participant and study partner (informant). The total score for the 39 items ranges from 39 to 195, with greater scores indicating worse daily function. Cohort I=C I and Cohort II=C II.

Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.

Safety MRI included sequences necessary for ascertainment of possible ARIA-E (Amyloid Related Imaging Abnormality-Edema), ARIA-H (Amyloid Related Imaging Abnormality- Hemorrhage, including superficial siderosis and microhemorrhages), assessment of recent infarcts and white matter integrity examination (White matter disease worsening since baseline) and a general assessment of brain abnormalities. Assessment of cerebral amyloid angiopathy (CAA) is included in the overall safety MRI findings results.

Safety analysis set - only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.

Annualized % change from baseline in volume of specific brain regions of interest (ROIs): whole brain (WB), hippocampus (Hip), and lateral ventricles (LV). Annualized percentage change was calculated as (percentage per participant / time interval (in days)) x 365.25. Time interval (in days) was derived as date of current MRI assessment on study drug - date of baseline MRI assessment + 1.

Safety analysis set - only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.

Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): Amyloid Beta 40 (Aβ40)

No lumbar punctures for CSF collection were performed due to early termination of trial

Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): Amyloid Beta 42 (Aβ42)

No lumbar punctures for CSF collection were performed due to early termination of trial

Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): total tau protein and phosphorylated tau protein levels

No lumbar punctures for CSF collection were performed due to early termination of trial

To demonstrate the effects of CNP520 vs placebo on tau pathology in the brain

No post baseline data collected

To demonstrate the effects of CAD106 vs placebo on Alzheimer's Disease-related biomarkers

Only available for Cohort I. For Cohort II, no post-baseline (year 2) amyloid PET scans could be obtained due to the early trial termination

Alzheimer's Disease-related biomarkers analyzed in blood serum: light chain neurofilaments (NfL)

Only participants with a value at both Baseline and that visit are included. CI last post-baseline assessment. CII Last on-treatment is the last assessment before or at last day on study drug + 31 days.

Prospective suicidality assessment was performed with the use of Columbia-Suicide Severity Rating Scale (C-SSRS), a questionnaire using a detailed branched logic algorithm evaluating participant's suicidality ideation and behavior. Answer "yes" on item 4 or 5 of the Suicidal Ideation section or "yes" on any item of the Suicidal Behavior section was considered positive.

Safety analysis set which includes only participants with events

No analysis performed due to early termination, no month 60 data

Cmax is the maximum Titer Concentration of any post-baseline 'on treatment' visit. A visit is considered as 'on treatment' if visit date is within {last injection + 180 days}.

- Geometric mean and CI's are back-transformed from the estimates for Log mean and CI's.

Safety population

AUC is calculated based on 'on treatment' visit only.(missing values for peak visits were linearly interpolated for calculation; missing values for trough visits were imputed by average of non-missing trough values.).

Safety population