Safety and Efficacy of TRx0237 in Subjects With Early Alzheimer's Disease

Inclusion Criteria:

- Diagnosis of early Alzheimer's Disease (AD), encompassing probable AD and mild
cognitive impairment due to AD (MCI-AD) based on the 2011 National Institute on Aging
and Alzheimer's Association (NIA/AA) criteria

- Documented PET scan that is positive for amyloid

- Mini-Mental State Examination (MMSE) score of 20-27 (inclusive)

- Global Clinical Dementia Rating (CDR) of 0.5 (including a score of >0 in one of the
functional domains: Community Affairs, Home and Hobbies, or Personal Care)

- Age <90 years

- Females must be surgically sterile, have undergone bilateral tubal occlusion /
ligation, be post-menopausal, or use adequate contraception

- Subject, consistent with national law, is able to read, understand, and provide
written informed consent in the designated language of the study site

- Has one or more identified adult study partner who either lives with the subject or
has sufficient contact to provide assessment of changes in subject behavior and
function over time and information on safety and tolerability; is willing to provide
written informed consent for his/her own participation; is able to read, understand,
and speak the designated language at the study site; agrees to accompany the subject
to each study visit; and is able to verify daily compliance with study drug

- Must not be taking an acetylcholinesterase inhibitor and/or memantine for at least 60
days at the time of the Baseline 18F-FDG-PET

- Able to comply with the study procedures in the view of the investigator

Exclusion Criteria:

- Significant central nervous system disorder other than probable AD or MCI-AD

- Significant intracranial focal or vascular pathology seen on brain MRI scan that would
lead to a diagnosis other than probable AD or MCI-AD

- Clinical evidence or history of cerebrovascular accident; transient ischemic attack;
significant head injury with associated loss of consciousness, skull fracture or
persisting cognitive impairment; other unexplained or recurrent loss of consciousness
for ≥15 minutes

- Epilepsy

- Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria
met for major depressive disorder; schizophrenia; other psychotic disorders, bipolar
disorder; substance (including alcohol) related disorders

- Metal implants in the head, pacemaker, cochlear implants, or any other non-removable
items that are contraindications to MRI

- Resides in hospital or moderate to high dependency continuous care facility

- Any physical disability that would prevent completion of study procedures or
assessments

- History of swallowing difficulties

- Pregnant or breastfeeding

- Glucose-6-phosphate dehydrogenase (G6PD) deficiency

- History of significant hematological abnormality or current acute or chronic
clinically significant abnormality

- Abnormal serum chemistry laboratory value at Screening deemed to be clinically
relevant by the investigator

- Clinically significant cardiovascular disease or abnormal assessments

- Pre-existing or current signs or symptoms of respiratory failure

- Concurrent acute or chronic clinically significant immunologic, hepatobiliary, or
endocrine disease and/or other unstable or major disease other than probable AD or
MCI-AD

- Diagnosis of cancer within the past 2 years prior to Baseline, unless treatment has
resulted in complete freedom from disease for at least 2 years

- Prior intolerance or hypersensitivity to methylthioninium (MT)-containing drug or
methemoglobinemia induced by MT-containing drug, similar organic dyes, or any of the
excipients

- Treatment currently or within 90 days before Baseline with Souvenaid®, clozapine,
carbamazepine, primidone, valproate, or drugs for which there is a warning or
precaution in the labeling about methemoglobinemia at approved doses

- Current or prior participation in any clinical trial of TRx0237; a clinical trial of a
product for cognition prior to Baseline in which the last dose was received within 90
days prior to Baseline unless confirmed to have been randomized to control; or a
clinical trial of a drug, biologic, device, or medical food in which the last dose was
received within 28 days prior to Baseline