A Clinical Study of Neflamapimod in Patients with Dementia with Lewy Bodies

Inclusion Criteria:

1. Men and women aged ≥55 years.

2. Subject is willing and able to provide written informed consent.

3. Probable DLB by consensus criteria (McKeith et al, 2017; McKeith et al, 2020).

4. MoCA score ≥18 during Screening.

5. If the patient is currently receiving cholinesterase inhibitor and/or memantinetherapy, the patient must have received such therapy for greater than 3 months andon a stable dose for at least 6 weeks at the time of enrollment. Except for reducingthe dose for tolerability reasons, the dose of cholinesterase inhibitor may not bemodified during the study. If the patient is not currently receiving such therapy,but received such therapy previously, that therapy must have been discontinued atleast 3 months prior to enrollment.

6. Normal or corrected eyesight and auditory abilities, sufficient to perform allaspects of the cognitive and functional assessments.

7. No history of learning difficulties that may interfere with their ability tocomplete the cognitive tests.

8. Received vaccination for SARS-CoV-19 unless medical contraindications prevent beingvaccinated or has a history of natural infection.

9. Must have reliable informant or caregiver.

Exclusion Criteria:

1. Diagnosis of any other ongoing central nervous system (CNS) condition other thanDLB, including, but not limited to, post-stroke dementia, vascular dementia,Alzheimer's disease (AD), Frontotemporal dementia (FTD), or Parkinson's disease (PD).

2. Ongoing major and active psychiatric disorder and/or other concurrent medicalcondition that, in the opinion of the Investigator, might compromise safety and/orcompliance with study requirements.

3. Suicidality, defined as active suicidal thoughts within 6 months before Screening orat Baseline, defined as answering yes to items 4 or 5 on the Columbia-SuicideSeverity Rating Scale (C-SSRS), or history of suicide attempt in previous 2 years,or, in the Investigator's opinion, at serious risk of suicide.

4. Diagnosis of alcohol or drug abuse within the previous 2 years.

5. Poorly controlled clinically significant medical illness, such as hypertension (blood pressure >180 mmHg systolic or 100 mmHg diastolic); myocardial infarctionwithin 6 months; uncompensated congestive heart failure or other significantcardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, ormetabolic/endocrine disorders or other disease that would interfere with assessmentof drug safety.

6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × the upperlimit of normal (ULN), total bilirubin >1.5 × ULN, and/or International NormalizedRatio (INR) >1.5. If patient is taking blood thinners (e.g., warfarin), and has noknown liver issues, INR >3.

7. Positive screen for human immunodeficiency virus, hepatitis B surface antigen (HbsAg), antibody (anti-HbS), hepatitis C virus (HCV) antibody or evidence of latentor active tuberculosis, active opportunistic or life-threatening infections.

8. Participated in a study of an investigational drug less than 6 weeks or 5 half-livesof an investigational drug, whichever is longer, before enrollment in this study.

9. Receipt of a live vaccine, with the exception of influenza, within 4 weeks beforestarting study drug treatment.

10. History of previous neurosurgery to the brain within the past five years.

11. If male with female partner(s) of child-bearing potential, unwilling or unable toadhere to contraception requirements specified in the protocol.

12. If female who has not has not reached menopause >1 year previously or has not had ahysterectomy or bilateral oophorectomy/salpingo-oophorectomy, has a positivepregnancy test result during Screening and/or is unwilling or unable to adhere tothe contraception requirements specified in the protocol.

13. If female, currently pregnant or breastfeeding.