Hero: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics (PK) and Pharmacodynamics (PD) of ION269 in Participants With Down Syndrome (DS) at Risk for Alzheimer's Disease (AD)

Eligibility Criteria

• 1. Has a reliable study partner, that is, a parent, sibling, or caregiver ≥ 21 years of age, who has known the participant for \> 6 months (i.e., a reliable and competent individual with a close relationship with the participant) and is capable of providing accurate information about the participant's history, can attend all scheduled study visits and provide feedback regarding the participant's symptoms and performance as described in the protocol, and can comply with all study requirements and activities.
• 2. Has a diagnosis of Down syndrome and has an intelligence quotient (IQ) ≥ 45.
• 3. Has evidence of amyloid pathology on amyloid-positron emission tomography (PET) scan.
• 4. Is assessed as being cognitively stable.
• 5. Is in good health as evidenced by medical history, physical, and neurological examination, and with no diagnosis of dementia or mild cognitive impairment.
• 1. Has unstable psychiatric illness, including psychosis, or untreated major depression within 90 days before Screening, as determined by the Investigator.
• 2. Has any unstable medical condition likely to hamper the evaluation of safety and/or efficacy of the Study Drug (e.g., moderate or severe untreated obstructive sleep apnea, medical history of clinically significant B12 or folate deficiency that is currently uncontrolled, clinically significant abnormalities of thyroid function, stroke, or other cerebrovascular conditions), as per Investigator's judgment.
• 3. Is unable to complete MRI and amyloid/tau-PET procedures or has any contraindications to having a brain MRI (e.g., MRI-incompatible pacemaker, aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia that cannot be medically managed without requiring general anesthesia).