Safety, Tolerability, and Pharmacokinetics Study of NDX-1017

NDX-1017 is being developed for the treatment of Alzheimer's disease (AD).

This Phase 1 randomized, placebo-controlled, double-blinded, first-in-human study will
evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of
NDX-1017 in healthy young and elderly subjects, and elderly subjects with mild AD. The study
contains the following two parts:

Part A:

A single-ascending dose (SAD) study conducted in an inpatient setting for 3 days in healthy
young male and healthy elderly male and female volunteers evaluated in up to 7 dose cohorts
to identify the maximum tolerated dose (MTD) within the single dose range studied. Up to 56
subjects (aged 18 to 45 years for young and 60 to 85 years for elderly) may be enrolled in
Part A.

Part B:

A multiple ascending dose (MAD) study conducted in an inpatient setting for 10 days in male
or female healthy elderly volunteers (aged 60 to 85 years) or subjects with amnestic mild
cognitive impairment (MCI), Alzheimer's disease (mild, mild-to-moderate, or moderate), or
mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or moderate)
(aged 40 to 85 years) in up to 6 dose cohorts that were proven tolerable in the SAD part of
the study to identify the MTD within the multiple dose range studied. Up to 44 subjects (aged
40 to 85 years) may be enrolled in Part B.

Subjects will be screened for eligibility within 28 days (or 90 days for amnestic MCI,
Alzheimer's Disease, or mixed dementia with Alzheimer's and vascular components) prior to
enrollment. Those eligible will be admitted to an inpatient facility for investigational
product administration, safety monitoring, and collection of blood or urine for
pharmacokinetic evaluations.

INCLUSION CRITERIA:

- Generally in good health

- Body mass index (BMI) of ≥ 18.0 and ≤ 30.0 kg/m2 at Screening, with minimum weight of
60 kg. (No BMI upper limit for mild AD and amnestic MCI subjects)

- Male subjects and their partners must be willing to comply with the contraceptive
requirements of the study. Only female subjects of non-childbearing potential are
eligible for participation.

- [Young subjects] Male subjects must be aged 18 to 45 years (inclusive) at the time of
Screening.

- [Healthy elder subjects only] Male and female subjects must be aged 60 to 85 years at
the time of screening

- [Amnestic MCI and Alzheimer's Subjects] 9. Patients with Alzheimer's disease, with
confirmed diagnosis of amnestic mild cognitive impairment, Alzheimer's disease (mild,
mild-to-moderate, or moderate), or mixed dementia with Alzheimer's and vascular
components (mild, mild-to-moderate, or moderate).

1. Either newly diagnosed treatment naïve patients, OR,

2. Patients who are currently on standard Alzheimer's Disease treatment may be
considered for participation if they are not tolerating treatment and/or they are
willing and clinically able to tolerate a discontinuation, 14 days for dose
titration + 5x half-lives for washout, or 4 weeks (whichever is longer) prior to
randomization. For these patients, the screening window will be allowed for up to
90 days prior to randomization to evaluate discontinuation of symptomatic
treatment for Alzheimer's disease.

EXCLUSION CRITERIA:

- Any medical condition that requires chronic medication use.

- History of drug and/or alcohol abuse within 12 months prior to Screening.

- History of having taken another investigational drug within 30 days prior to Admission
(Day -1).

- Donation of blood or plasma within 30 days prior to dosing.

- Major surgery within 90 days prior to Admission (Day -1) or anticipated surgery during
the study.

- Smokers

- [Healthy elderly subjects] Reported changes in cognition and reported history of
declines in everyday life in the last year.