VY7523-102: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study in Participants with Early Alzheimer's Disease

Inclusion Criteria:

1. Clinical diagnosis of early AD, defined as:

2. Meet the NIA-AA core clinical criteria for MCI due to AD or mild AD.

3. Mini Mental State Examination (MMSE) score between 18 and 30, inclusive, atScreening (Cohort 1 and 2) and score between 22 and 30, inclusive, at Screening (Cohort 3).

4. Report a history of subjective memory decline with gradual onset and slowprogression over at least the last 6 months before Screening; must becorroborated by an informant/caregiver.

5. CDR Memory Box score ≥0.5 CDR global score of 0.5 for MCI due to AD or 0.5 or 1for mild AD.

6. Evidence of pathology consistent with AD diagnosis:

7. For Cohort 1 and Cohort 2 only, by documented historical amyloid PET showingimaging agent uptake into the brain conducted within 24 months before screeningOR elevated plasma pTau217/np-Tau217 ratio within the Screening Period.

8. For Cohort 3 only, evidence of pathology consistent with AD diagnosis by both:

• Evidence of Tau PET imaging agent uptake into the brain by central readAND
• Evidence of positive brain amyloid pathology as indicated by one of thefollowing:

1. Documented historical amyloid PET showing imaging agent uptake into the brainconducted within 24 months before screening OR

2. CSF beta amyloid and tau levels consistent with AD diagnosis within theScreening Period.

3. Body mass index (BMI) ≥18 and ≤35 kg/m2 at Screening.

4. Apart from the clinical diagnosis of early AD, participant must be in good health,based on medical history and screening assessments.

5. If participant is receiving an approved symptomatic AD treatment such as but notlimited to acetylcholinesterase inhibitor (AChEIs), memantine, rivastigmine,galantamine and tacrine for AD, participant must be on a stable dose for at least 8weeks prior to Screening.

6. Treatment-naive participants for AD can be entered into the study.

7. Unless otherwise stated, participants must have been on stable doses of allother (non-AD-related) permitted concomitant medications for at least 4 weeksprior to Screening.

8. Participants currently on β amyloid therapies may not be enrolled.

9. Must have an identified reliable informant/caregiver (defined as a person able tosupport the participant for the duration of the study e.g., spouse, sibling, closefriend, who spends at least 10 hours per week with the participant) who assented to:

10. Accompany the participant to clinic visits.

11. Provide information to study Investigator/staff about functioning, cognitiveabilities and AEs.

12. Support participants returning for per-protocol follow-up visits andprocedures.

Exclusion Criteria:

1. Any medical or neurological/neurodegenerative or psychiatric condition (other thanAD) that, in the opinion of the Investigator, may be contributing cause to cognitiveimpairment or could confound interpretation of drug effect, affect studyassessments, or affect participant's ability to participate and complete the studyor lead to safety concerns.

2. History of transient ischemic attack or stroke or any unexplained loss ofconsciousness within 1 year prior to Screening.

3. History of seizures within 10 years prior to screening or history of epilepticsyndrome (except for history of febrile seizures in childhood)

4. Lifetime history of a major psychiatric disorder including schizophrenia or bipolardisorder. History of major depressive disorder that has resulted in 2 or morehospitalizations in a lifetime.

5. Presence of a clinically significant uncontrolled medical disorder involving one ormore of these major organ systems: cardiovascular (including but not limited to aQTcF of >470 ms for women and >450 ms for men and uncontrolled hypertension),respiratory, renal, gastrointestinal, immunologic, hematologic including bleedingdisorder, hepatic, or endocrine.

6. Contraindications to lumbar puncture, including but not limited to coagulation orbleeding disorders, unsafe suspension of anticoagulant, infections at the injectionsite, spinal deformities or previous spinal surgeries that may affect safe LPperformance, or conditions associated with increased intracranial pressure.

7. Contraindications to MRI scanning, including but not limited to cardiacpacemaker/defibrillator, ferromagnetic metal implants (devices other than thoseapproved as safe for use in MRI scanners).

8. History of a malignant disease (cancer) except for resected cutaneous squamous cellcarcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, in situprostate cancer with a normal posttreatment prostate-specific antigen within thelast five years or other cancers in remission for at least 5 years

9. Any immunological disease which is not adequately controlled, or which requirestreatment with immunoglobulins, systemic mAbs (or derivatives of mAbs), systemicimmunosuppressants, or plasmapheresis during the study.

10. History of severe allergies, or history of an anaphylactic reaction (nonactive hayfever is acceptable).

11. Participation in a clinical drug trial or device within 30 days (or 5 half-lives,whichever is longer and 3 months for a biologic) of screening, unless the studyblind has been broken and the participant was known to be on placebo.

12. Last administration of B-secretase and gamma-secretase inhibitors in a study within 3 months or 5 half-lives (whichever is longer) prior to screening, unless it can bedocumented that the participant only received placebo.

13. Current use of an approved AD disease modifying or anti-amyloid therapy (includingbut not limited to any mAb therapies).

14. Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding thatis not managed optimally and could place a participant at an increased risk forintraoperative or postoperative bleeding.