NP001, Alzheimer's Disease, and Blood Markers of Inflammation

Abnormal inflammatory monocytes/macrophages, systemically and locally in the central nervous
system (CNS), are implicated in the neuro-inflammatory process seen in Alzheimer's disease.
NP001 is a novel immune regulator of inflammatory monocytes/macrophages.

Given the key role inflammatory monocytes/macrophages may play in the pathogenesis of AD,
this study will assess the changes in inflammatory monocyte-associated biomarkers, including
CD16 and HLA-DR, pre- and post- NP001.

This is a Phase 1 single-site, randomized, double-blind, placebo-controlled pilot biomarker
study of a single dose of NP001 in individuals with mild-to-moderate Alzheimer's disease.
Fourteen individuals will be enrolled and randomized 1:1 to NP001 and placebo. Drug or
placebo will be given intravenously. Biomarkers will be measured at baseline and 1 and 7 days
following infusion.

Inclusion Criteria:

1. Male or female, 55 years of age or older,

2. Diagnosis of probable Alzheimer's disease using the National Institute of Neurological
and Communicative Disorders and Stroke and the Alzheimer's disease and Related
Disorders Association criteria by Principal Investigator,

3. Score 14 to 24 (inclusive) on the Mini-Mental Status Examination,

4. Global Clinical Dementia Rating (CDR) Scale ≥ 0.5 or greater with CDR memory ≥ 0.5 or
greater,

5. Score ≤ 4 or lower on the Hachinski Ischemic Scale,

6. Score ≤ 5 on the Geriatric Depression Scale (GDS),

7. Current (stable dose for 4 weeks or longer) or past treatment with
acetylcholinesterase inhibitors, memantine, or cognitive enhancers are allowed,

8. Females must not be of childbearing potential (i.e., must be post-menopausal with
cessation of menses for ≥ 12 months or have been surgically sterilized which includes
hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or tubal ligation),

9. Males must agree not to engage in sexual relations with a woman of childbearing
potential without effective means of birth control during the study and for 30 days
after study drug administration. Must also agree to refrain from sperm donation from
receipt of study drug and for 90 days thereafter.

10. Be capable of providing written informed consent using a form that has been approved
by the IRB.

11. Have veins suitable for intravenous administration of study drug or alternatively,
have a venous access device.

Exclusion Criteria:

1. Diagnosis of another neurologic disorder which can mimic Alzheimer's disease including
dementia with Lewy Bodies, frontotemporal dementia and normal pressure hydrocephalus,

2. Diagnosis of other neurologic disorders which can also impair cognition including
stroke, MS, seizures, CNS tumors,

3. Uncontrolled major psychiatric disorder,

4. History of unstable medical illness in the 3 months prior to screening including
emergent hospitalizations,

5. Diagnosis of any of the following disorders: systemic sclerosis/scleroderma,
inflammatory bowel disease, systemic lupus erythematosus (SLE), rheumatoid arthritis,
mixed connective tissue disease, polymyalgia rheumatica, giant cell arteritis,
polymyositis, dermatomyositis, and psoriasis,

6. Active pulmonary disease under treatment including uncontrolled asthma, chronic
obstructive pulmonary disease, pulmonary fibrosis, pulmonary infection in the last 3
months, or history of aspiration,

7. History of unexplained jaundice by subject report,

8. History of Hepatitis A, B, or C or HIV by subject report,

9. History of stem cell therapy,

10. History of immune modulator therapy (e.g., corticosteroids, IV immunoglobulin,
immunosuppressive chemotherapeutic agents, plasma exchange, GM-CSF, MCSF, interferons,
infliximab, natalizumab, fingolimod [GILENYA], masitinib, ibudilast, tofacitinib
citrate [XELJANZ], or any other approved drugs intended to affect the immune system)
within 12 weeks of Screening Visit. Locally-acting corticosteroids (inhaled,
intranasal, and topical) are permitted,

11. Participation in an experimental drug trial (of agents other than immune modulators)
within 12 weeks prior to Screening Visit. Observational trials with no intervention
are acceptable provided permission from the other study sponsor is obtained in
writing,

12. Systolic blood pressure < 100 mm Hg or > 160 mm Hg, diastolic blood pressure > 98 mm
Hg. Patients on stable treatment for at least 3 months for hypertension are allowed as
long as they meet entry criteria,

13. Hematocrit < 33%, platelet count < lower limit of normal, or neutrophil count <
1,500/mm3,

14. Estimated creatinine clearance (eCCr) < 50 mL/minute by Cockcroft-Gault Formula,

15. Elevated aspartate aminotransferase (AST) or alanine aminotransferance (ALT) greater
than 3 times the upper limit of normal,

16. Pregnant or lactating females,

17. Have any condition which, in the opinion of the investigator, would put the subject at
risk by participating in this study.