Proof-of-Concept Study of a Selective p38 MAPK Alpha Inhibitor, Neflamapimod, in Subjects With Mild Alzheimer's Disease

Inclusion Criteria

• Men and women age 55 to 85 years, inclusive.
• Willing and able to provide informed consent.
• Must have mild cognitive impairment (MCI) or mild AD with evidence of progression ("Mild-AD"), as defined by the following:
• CDR-Global Score of 0.5 or 1.0, with CDR memory subscore of at least 0.5.
• MMSE score ranging from 20 to 28, inclusive.
• Positive biomarker for AD, as defined by a CSF Aβ1-42R below the threshold and phospho-tau above the threshold for the assay utilized in the study and assessed by the central laboratory.
• Computed tomography (CT) or magnetic resonance imaging (MRI) findings within 2 years of Screening that are compatible with AD and no other pathologic processes that might potentially account for the subject's cognitive impairment.
• If the subject is taking a single drug for AD (e.g., donepezil or other cholinesterase inhibitors or memantine; dual therapy is excluded), he/she has been on a stable dose for at least 2 months prior to baseline, and the dose must remain unchanged during the study unless required for management of adverse events (AEs).
• Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments.
• Must have reliable informant or caregiver.

Exclusion Criteria

• Evidence that the primary basis for cognitive impairment is neurodegenerative disease other than AD, including, but not limited to, vascular dementia, dementia with Lewy bodies, and Parkinson's disease.
• Suicidality, defined as active suicidal thoughts within 6 months before Screening or at Baseline, defined as answering yes to items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS), or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
• History of major and active psychiatric disorder, moderate to severe depressive symptoms, and or other concurrent medical condition that, EIP-VX17-745-304, Version 1.0, 17 November, 2017 Page 7 of 46 EIP Pharma, LLC Confidential in the opinion of the Investigator, might compromise safety and/or compliance with study requirements.
• Diagnosis of alcohol or drug abuse within the previous 2 years.
• History of cancer within the last 5 years, except basal cell carcinoma, squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years.
• Poorly controlled clinically significant medical illness.
• History of serum B12 abnormality, anemia with hemoglobin ≤10 g/dL, thyroid function abnormality, electrolyte abnormality, or positive syphilis serology that have not been corrected and/or otherwise addressed.
• History of epilepsy or unexplained seizure within the past 5 years.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × the upper limit of normal (ULN), total bilirubin >2 × ULN, and/or International Normalized Ratio (INR) >1.5
• Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
• Subject participated in a study of an investigational drug less than 3 months or 5 half-lives of the investigation drug, whichever is longer, before enrollment in this study.