31P-MRS Imaging to Assess the Effects of CNM-Au8 on Impaired Neuronal Redox State in Parkinson's Disease

This is a single-center open label pilot, sequential group, investigator blinded study of the
CNS metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients
who have been diagnosed with Parkinson's Disease within three years of Screening. The Sponsor
will select a starting treatment dose of CNM-Au8 for the initial treatment. Investigators and
patients will be blinded to each cohort's study dose. Upon completion of the first treatment
cohort, the Sponsor will select a single dose or two different doses for the subsequent
second cohort from a pre-specified dosing selection plan based on the evaluation of the
31P-Magnetic Resonance Spectroscopy (31P-MRS) changes versus baseline in the first cohort. Up
to a total of two treatment cohorts may be studied (n=12 patients/cohort, total n=24
patients). All patients will receive daily oral treatment over twelve consecutive weeks
during each cohort's Treatment Period.

There will be three study periods per treatment cohort:

1. A four-week screening period (Screening Period);

2. A twelve-week treatment period (Treatment Period);

3. A four-week follow-up period (End-of-Study Assessment).

The primary study outcome, CNS metabolic changes, will be assessed based upon each patient's
Week 12 study visit versus the pre-treatment baseline. The primary endpoint is the brain
metabolic effects of treatment with CNM-Au8 as assessed by an improvement of 31P-MRS
assessment of Brain Tissue Cellular Redox Potential defined by the measured tissue ratio of
NAD+:NADH concentrations following 12 weeks of once daily treatment.

Inclusion Criteria:

1. Able to understand and give written informed consent and follow study procedures.

2. Male or female, aged 30 - 80 years or age (inclusive) at the time of PD diagnosis.

3. PD subjects will be recruited in accordance with the MDS Clinical Diagnostic Criteria
for PD:

1. Parkinsonism present (bradykinesia + either rest tremor or rigidity)

2. 2 of the following 4 supportive criteria:

i. Clear and dramatic beneficial response to dopaminergic medication

ii. Presence of levodopa induced dyskinesias

iii. Rest tremor of a limb

iv. Olfactory loss or cardiac sympathetic denervation seen on prior MIBG SPECT

4. Duration of PD since diagnosis is
5. Modified Hoehn and Yahr stage
6. Treatment with dopaminergic therapy for at least 12-weeks and with no change in
current medications within the prior 6-weeks

Exclusion Criteria:

1. Atypical parkinsonism, including that due to drugs, metabolic disorders, encephalitis,
cerebrovascular disease, normal pressure hydrocephalus, or other neurodegenerative
disease.

2. The presence of any of the following:

1. Unequivocal cerebellar abnormalities

2. Downward vertical gaze limitation or slowing of downward saccades

3. Diagnosis of behavioral variant frontotemporal dementia or primary progressive
aphasia

4. Parkinsonian features restricted to the lower limbs for > 3 years

5. Treatment with dopamine blockers or depleters in a time course consistent with
drug induced parkinsonism

6. Absence of an observable response to high dose levodopa despite moderate disease
severity

7. Expert considers a diagnosis of alternative syndrome more likely than PD

8. Rapid progression of gait impairment requiring wheelchair within 5 years of onset

9. Complete absence of progression of motor symptoms over 5 years unless due to
treatment

10. Early bulbar dysfunction within the first 5 years since diagnosis

11. Inspiratory respiratory dysfunction (stridor or frequent sighs)

12. Severe autonomic failure in the first 5 years

13. Recurrent falls (>1 per year) because of impaired balance in the first 3 years

14. Disproportionate dystonic anterocollis or hand contractures of hands or feet
within 10 years

15. Absence of any of the common non-motor features of PD despite 5 years of disease

16. Otherwise unexplained pyramidal tract signs (weakness, hyperreflexia, or extensor
toe signs)

17. Bilateral symmetric parkinsonism

3. Montreal Cognitive Assessment (MoCA) score of 20 or less.

4. Patient with a history of any clinically significant or unstable medical condition
based on the Investigator's judgment.

5. History of human immunodeficiency virus (HIV), hepatitis C (HepC) virus antibody, or
hepatitis B (HepB) virus antibody.

6. Based on the investigator's judgment, patients who may have difficulty complying with
the protocol and/or study procedures.

7. Patient with clinically significant abnormalities in hematology, blood chemistry, ECG,
or physical examination not resolved by the Baseline visit which according to
Investigator may interfere with study participation.

8. Patient participating in any other investigational drug trial or using investigational
drug (within 12 weeks prior to screening and thereafter)

9. Positive screen for drugs of abuse or known history of alcohol abuse.

10. Women of child-bearing potential, or men, who are unwilling or unable to use accepted
methods of birth control for up to 6 months following study participation.

11. Women with a positive pregnancy test, are lactating, or are planning to become
pregnant during the study or within 6 months of the end of this trial.

12. Patients with implanted metal objects in their body that may be affected by an MRI
procedure.

13. Patients who are claustrophobic or otherwise unlikely to be able to complete the MRI
scanning procedures.

14. History of allergy to gold in any form.