A Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study With an Open-Label Extension Phase to Confirm Safety and Efficacy of BAN2401 in Subjects With Early Alzheimer’s Disease

Diagnosis: Mild Cognitive Impairment (MCI) due to Alzheimer’s disease – intermediate
likelihood:

– Meet the National Institute of Aging – Alzheimer’s Association (NIA-AA) core clinical
criteria for MCI due to Alzheimer’s disease – intermediate likelihood

– Have a global Clinical Dementia Rating (CDR) score of 0.5 and CDR Memory Box score of
0.5 or greater at Screening and Baseline

– Report a history of subjective memory decline with gradual onset and slow progression
over the last 1 year before Screening; must be corroborated by an informant

Mild Alzheimer’s disease dementia:

– Meet the NIA-AA core clinical criteria for probable Alzheimer’s disease dementia

– Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of 0.5 or greater at
Screening and Baseline

Key Inclusion Criteria that must be met by all participants:

– Objective impairment in episodic memory as indicated by at least 1 standard deviation
below age-adjusted mean in the Wechsler Memory Scale IV-Logical Memory (subscale) II
(WMS-IV LMII)

– Positive biomarker for brain amyloid pathology

– Male or female participants aged greater than or equal to (>=) 50 and less than or
equal to (<=) 90 years, at the time of informed consent - Mini mental state examination (MMSE) score >=22 at Screening and Baseline and <=30 at Screening and Baseline - Body mass index (BMI) greater than (>)17 and less than (<) 35 at Screening - If receiving an approved Alzheimer's disease treatment such as acetylcholinesterase inhibitor (AChEIs) or memantine or both for Alzheimer's disease, must be on a stable dose for at least 12 weeks prior to Baseline. Treatment-naive participants for Alzheimer's disease can be entered into the study. Unless otherwise stated, participants must have been on stable doses of all other (that is, non-Alzheimer's disease-related) permitted concomitant medications for at least 4 weeks prior to Baseline. Use of memantine will not be allowed for Japanese participants - Have an identified study partner (defined as a person able to support the participant for the duration of the study and who spends at least 8 hours per week with the participant) - Provide written informed consent. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study (example, Germany and Spain), they will not be enrolled Extension Phase: Inclusion Criteria: - Participants who have completed the Core Study - Have a BMI >17 and <35 - Must continue to have a study partner who is willing and able to provide follow-up information on the participant throughout the course of the Extension Phase - Provide written informed consent for the Extension Phase. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required and in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study (example, Germany and Spain), they will not be enrolled Exclusion Criteria - Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's Alzheimer's disease - History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of Screening - Any psychiatric diagnosis or symptoms (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant - Geriatric Depression Scale (GDS) score >=8 at Screening

– Contraindications to MRI scanning, including cardiac pacemaker/defibrillator,
ferromagnetic metal implants (example in skull and cardiac devices other than those
approved as safe for use in MRI scanners)

– Evidence of other clinically significant lesions on brain MRI at Screening that could
indicate a dementia diagnosis other than Alzheimer’s disease

– Other significant pathological findings on brain MRI at screening, including but not
limited to: more than 4 microhemorrhages (defined as 10 millimeter [mm] or less at the
greatest diameter); a single macrohemorrhage >10 mm at greatest diameter; an area of
superficial siderosis; evidence of vasogenic edema; evidence of cerebral contusion,
encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of
multiple lacunar infarcts or stroke involving a major vascular territory, severe small
vessel, or white matter disease; space occupying lesions; or brain tumors (however,
lesions diagnosed as meningiomas or arachnoid cysts and <1 centimeter [cm] at their greatest diameter need not be exclusionary) - Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study - Participants with a bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] >1.5 for participants
who are not on anticoagulant treatment, example, warfarin). Participants who are on
anticoagulant therapy should have their anticoagulant status optimized and be on a
stable dose for 4 weeks before Screening

– Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal
disease) which are not stably and adequately controlled, or which in the opinion of
the investigator(s) could affect the participant’s safety or interfere with the study
assessments

– Participation in a clinical study involving any therapeutic monoclonal antibody,
protein derived from a monoclonal antibody, immunoglobulin therapy, or vaccine within
6 months before screening unless it can be documented that the participant was
randomized to placebo

– Participation in a clinical study involving any anti-amyloid therapies (including any
monoclonal antibody therapies and any β-site amyloid precursor protein cleaving enzyme
[BACE] inhibitor therapies) unless it can be documented that the participant only
received placebo

– Participants who have any known prior exposure to BAN2401

– Participants who were dosed in a clinical study involving any new chemical entities
for Alzheimer’s disease (AD) within 6 months prior to screening unless it can be
documented that the participant was in a placebo treatment arm

Extension Phase: Exclusion Criteria

– Participants who discontinued early from the Core Study

– Participants who develop the following conditions from the time of Screening for the
Core Study to the start of the Extension Phase

– TIA, stroke, or seizures

– Any neurological condition that may be contributing to cognitive impairment above
and beyond that caused by the participant’s AD

– Any psychiatric diagnosis or symptoms, (example, hallucinations, major
depression, or delusions) that could interfere with study procedures in the
participant

– Contraindications to MRI scanning, including cardiac pacemaker/defibrillator,
ferromagnetic metal implants (example, in skull and cardiac devices other than
those approved as safe for use in MRI scanners)

– Other significant pathological findings on brain MRI during the Core Study
including but not limited to: cerebral contusion, encephalomalacia, aneurysms,
vascular malformations, or infective lesions; evidence of multiple lacunar
infarcts or stroke involving a major vascular territory, severe small vessel, or
white matter disease; space occupying lesions; or brain tumors (however, lesions
diagnosed as meningiomas or arachnoid cysts and <1 cm at their greatest diameter need not be exclusionary - Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study - Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments