RewinD-LB - Clinical Study of Neflamapimod in Patients with Dementia with Lewy Bodies

Inclusion Criteria:

1. Men and women aged ≥55 years.

2. Subject or subject's legally authorized representative is willing and able toprovide written informed consent.

4. Probable DLB by consensus criteria (McKeith et al, 2017), including a positiveDaTscan™. Specifically, the subject must have the presence of dementia inassociation with:

• At least two (2) core clinical features (fluctuating cognition, visualhallucinations, REM sleep disorder, and/or parkinsonism); or

• One (1) core clinical feature plus an abnormal DaTscan™. Historicalpolysomnography (PSG)-verified REM sleep behavioral disorder (RBD), FDG-PETimaging, or MIBG myocardial scintigraphy can take the place of an abnormalDaTscan™ in a patient with only one core clinical feature.

4. CDR Global Score 0.5 (very mild dementia) or 1.0 (mild dementia) during Screening

5. Background dementia therapy:

• Not currently receiving cholinesterase inhibitor therapy. If the patientreceived such therapy previously, that therapy must have been discontinued atleast 3 months prior to randomization.

• Receiving cholinesterase inhibitor therapy alone. If the patient is currentlyreceiving cholinesterase inhibitor therapy, the patient must have received suchtherapy for greater than 3 months and on a stable dose for at least 6 weeks atthe time of randomization. Except for reducing the dose for tolerabilityreasons, the dose of cholinesterase inhibitor may not be modified during thestudy.

• Memantine therapy is allowed, if it had been started at least 3 months prior torandomization and the patient is also receiving cholinesterase inhibitortherapy. If the patient has never been on cholinesterase inhibitor therapy (naïve), then memantine monotherapy is allowed.

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), or Parkinson's disease (PD).

2. Plasma ptau181 result above the threshold that indicates evidence of pathologyassociated with Alzheimer's disease at Screening.

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 C-SSRS, or history ofsuicide attempt in previous 2 years, or, in the Investigator's opinion, at seriousrisk of suicide.

4. 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.

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

6. 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.

7. 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.

8. Known human immunodeficiency virus, hepatitis B, or active hepatitis C virusinfection.

9. Participated in a study of an investigational drug less than six weeks or 5half-lives of an investigational drug, whichever is longer, before enrollment inthis study.

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. Weight less than 50kg.

All participants who complete the initial 16-week period of the study will be able to continue in the study and receive neflamapimod for an additional 32 weeks (8 months) regardless of whether they received neflamapimod of placebo during the the first 16 weeks.