simufilam

The change from baseline to Week 52 in the ADAS-Cog12, a psychometrician-administered battery comprised of several cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Scores range from 0 (best) to 80 (worst).

The change from baseline to Week 52 in the ADCS-ADL, a 23-item study partner questionnaire that covers both basic activities of daily living (ADL) and more complex ADL or instrumental ADL. Scores range from 0 to 78, with a lower score indicating greater severity of functional loss.

Blood draws will be done to evaluate levels of PTI-125 in the plasma using non-compartmental methods in WinNonlin.

Levels of PTI-125 will be assessed to determine how long it takes to reach the Cmax

Levels of PTI-125 will be assessed to determine the last time point where PTI-125 can be detected.

Levels of PTI-125 will be assessed to determine the elapsed time to where PTI-125 can last be detected in the plasma.

AUC for PTI-125 plasma concentration from time zero to the last quantifiable plasma concentration.

Assessment of the half-life in plasma of PTI-125

Alzheimer's Disease Assessment Scale-Cognitive Subscale 11-item: Change from baseline in cognition over the course of 24 months Possible range in score: 0-70; Subscales are summed; Higher values represent a more cognitively impaired participant Decrease in mean value represents improvement in cognition from one timepoint to the next.

Alzheimer's Disease Assessment Scale-Cognitive Subscale 11-item: Change from baseline in cognition Starting at month 12 through month 24; Possible range in score: 0-70; Higher values represent a more cognitively impaired participant; Decrease in mean value represents improvement in cognition from one timepoint to the next.

The most frequently reported Treatment Emergent Adverse Events indicative of abnormal vital signs (hypertension/worsening of hypertension and blood pressure increase) of simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)

The most frequently reported Treatment Emergent Adverse Event indicative of abnormal vital signs (hypotension) of simufilam (PTI-125) or placebo during the randomized withdraw portion of the study : Month 12 to Month 18

The number of subjects that had Treatment Emergent Adverse Events indicative of abnormal Electrocardiogram results while on simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)

The number of subjects that had Treatment Emergent Adverse Events indicative of abnormal Electrocardiogram results while on simufilam (PTI-125) or placebo during the randomized withdraw portion of the study: Month 12 to Month 18

The most frequently reported Treatment Emergent Adverse Events indicative of abnormal physical examination (weight increase or weight decrease) while administered simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)

The number of subjects that had Treatment Emergent Adverse Events of indicative of abnormal physical examination while on simufilam (PTI-125) or placebo during the randomized withdraw portion of the study: Month 12 to Month 18

Treatment Emergent Adverse Events when three or more subjects reported abnormal clinical laboratory results while on simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)

Treatment Emergent Adverse Events when two or more subjects reported abnormal clinical laboratory results while on simufilam (PTI-125) or placebo during the randomized withdraw portion of the study: Month 12 to Month 18

Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid levels of Amyloid beta42

Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid total tau.

Change from Baseline (screening) to Day 28 in cerebrospinal fluid P-tau181

Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurogranin

Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurofilament light chain

Change from Baseline (screening) in cerebrospinal fluid YKL-40

The time to peak drug concentration will be obtained directly from the data without interpolation

The elimination rate constant (λz) will be calculated.

The terminal elimination half-life (T1/2) will be calculated.

The AUC from time zero to the time of the last quantifiable concentration (AUClast) will be calculated.

The AUC from time zero extrapolated to infinity (AUCinf) will be calculate.

The percentage of AUCinf based on extrapolation (AUCextrap\[%\]).

The apparent oral clearance will be calculated.

Vz/F, apparent volume of distribution will be calculated.

Area Under the Curve of simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately)

Maximum simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately)

Time to maximum simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately)

Half-life of simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately)

Elimination rate constant of simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately)

Area Under the Curve for each total radioactivity, parent drug and metabolite(s) in plasma.

Maximum concentration for each total radioactivity, parent drug and metabolite(s) in plasma.

Time to maximum concentration for each total radioactivity, parent drug and metabolite(s) in plasma.

Half-life for each total reactivity, parent drug and metabolite(s) in plasma.

Elimination rate constant for each total reactivity, parent drug and metabolite(s) in plasma.