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

Exclusion Criteria

• •1. Any medical or neurological/neurodegenerative or psychiatric condition (other than AD) that, in the opinion of the Investigator, may be contributing cause to cognitive impairment or could confound interpretation of drug effect, affect study assessments, or affect participant's ability to participate and complete the study or lead to safety concerns.
• •2. History of transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening.
• •3. History of seizures within 10 years prior to screening or history of epileptic syndrome (except for history of febrile seizures in childhood)
• •4. Lifetime history of a major psychiatric disorder including schizophrenia or bipolar disorder. History of major depressive disorder that has resulted in 2 or more hospitalizations in a lifetime.
• •5. Presence of a clinically significant uncontrolled medical disorder involving one or more of these major organ systems: cardiovascular (including but not limited to a QTcF of \>470 ms for women and \>450 ms for men and uncontrolled hypertension), respiratory, renal, gastrointestinal, immunologic, hematologic including bleeding disorder, hepatic, or endocrine.
• •6. Contraindications to lumbar puncture, including but not limited to coagulation or bleeding disorders, unsafe suspension of anticoagulant, infections at the injection site, spinal deformities or previous spinal surgeries that may affect safe LP performance, or conditions associated with increased intracranial pressure.
• •7. Contraindications to MRI scanning, including but not limited to cardiac pacemaker/defibrillator, ferromagnetic metal implants (devices other than those approved as safe for use in MRI scanners).
• •8. History of a malignant disease (cancer) except for resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, in situ prostate cancer with a normal posttreatment prostate-specific antigen within the last five years or other cancers in remission for at least 5 years
• •9. Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic mAbs (or derivatives of mAbs), systemic immunosuppressants, or plasmapheresis during the study.
• •10. History of severe allergies, or history of an anaphylactic reaction (nonactive hay fever 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 study blind 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 be documented that the participant only received placebo.
• •13. Current use of an approved AD disease modifying or anti-amyloid therapy (including but not limited to any mAb therapies).
• •14. Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and could place a participant at an increased risk for intraoperative or postoperative bleeding.