Clinical Study of Neflamapimod in Patients With Primary Progressive Aphasia

Inclusion Criteria:

• Men and women aged 40-85 years at Screening.

• Participant or participant's legally authorized representative (where applicable) iswilling and able to provide written informed consent.

• Clinical diagnosis of nfvPPA by consensus criteria [Gorno-Tempini et al, 2011].

• At least one of the following core features must be present:

1. Agrammatism in language production
2. Effortful, halting speech with inconsistent speech sound errors anddistortions (apraxia of speech)

• At least 2 of 3 of the following other features must be present:

1. Impaired comprehension of syntactically complex sentences
2. Spared single-word comprehension
3. Spared object knowledge

• Global CDR® plus National Alzheimer's Coordinating Center Frontotemporal LobarDegeneration (NACC FTLD) score of 0.5 or 1 during Screening.

• CDR® plus NACC FTLD language domain score of 0.5, 1 or 2 during Screening.

• Normal or corrected eyesight and auditory abilities, sufficient to perform allaspects of the study scales and assessments.

• Fluent in English, per Investigator judgement.

• Must have reliable study partner that is able to attend all study visits withparticipant. Study partner must be able to read, write, and understand the Englishlanguage.

Exclusion Criteria:

• Brain Magnetic Resonance Image (MRI) incompatible with a diagnosis of nfvPPA.

• History or evidence of a central nervous system (CNS) condition other than nfvPPAwhich may cause symptoms of aphasia or dementia, including but not limited toAlzheimer's disease (AD), Dementia with Lewy Bodies (DLB),inflammatory/demyelinating CNS conditions, Creutzfeldt Jakob disease, vasculardementia, post-stroke dementia, etc.

• Features or Parkinsonism, corticobasal syndrome or progressive supranuclear palsythat are as or more prominent than the language features of nfvPPA, and/or motorfeatures which are sufficiently severe that they could significantly impactperformance on any of the clinical or neuropsychological measures.

• Plasma pTau217 result with a high likelihood of the presence of amyloid pathology atScreening or documented evidence of positive biomarkers associated with Alzheimer'sdisease pathology (e.g., abnormal plasma Aβ42/40 ratio, abnormal CSFphospo-tau/amyloid ratio, or presence of amyloid tracer update on brain amyloidpositron emission tomography [PET] imaging).

• Known progranulin (GRN) mutations.

• 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.

• Metabolic or toxic encephalopathy or dementia due to a general medical condition.

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

• 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.

• Clinically relevant intellectual impairment that may interfere with the ability tocomplete the study scales and assessments, at the discretion of the Investigator.

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

• Poorly controlled clinically significant medical illness, such as hypertension;myocardial infarction within 6 months; uncompensated congestive heart failure orother significant cardiovascular, pulmonary, renal, liver, infectious disease,immune disorder, or metabolic/endocrine disorders or other disease that wouldinterfere with assessment of drug safety.

• 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 participant has a documented history of Gilbert's syndrome, criterion oftotal bilirubin >1.5 x ULN is not applicable.

• If participant is taking anticoagulants (e.g., warfarin), and has no knownliver issues, INR >3.

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

• Participated in a study of an investigational drug or transcranial direct currentstimulation less than 6 weeks or 5 half-lives of an investigational drug, whicheveris longer, before enrollment in this study.

• Male with female partner(s) of childbearing potential, unwilling or unable to adhereto contraception requirements specified in the protocol.

• Female of childbearing potential (see Section 5.10), with a positive pregnancy testresult during Screening and are unwilling or unable to adhere to contraceptionrequirements specified in the protocol.

• Weight less than 50 kg at Screening.

The following additional exclusion criteria applies for participants undergoing (18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography) 18F-FDG PET-CT (18F-FDG PET-CT scans are optional):

• Blood glucose levels >200 mg/dL.

• Contraindications to having a PET scan.