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)

Inclusion criteria:

1. Has a reliable study partner, that is, a parent, sibling, or caregiver ≥ 21 years ofage, who has known the participant for > 6 months (i.e., a reliable and competentindividual with a close relationship with the participant) and is capable ofproviding accurate information about the participant's history, can attend allscheduled study visits and provide feedback regarding the participant's symptoms andperformance as described in the protocol, and can comply with all study requirementsand 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 neurologicalexamination, and with no diagnosis of dementia or mild cognitive impairment.

Exclusion criteria:

1. Has unstable psychiatric illness, including psychosis, or untreated major depressionwithin 90 days before Screening, as determined by the Investigator.

2. Has any unstable medical condition likely to hamper the evaluation of safety and/orefficacy of the Study Drug (e.g., moderate or severe untreated obstructive sleepapnea, medical history of clinically significant B12 or folate deficiency that iscurrently 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 anycontraindications to having a brain MRI (e.g., MRI-incompatible pacemaker, aneurysmclips, artificial heart valves, or other metal foreign body; claustrophobia thatcannot be medically managed without requiring general anesthesia).

Note: Other protocol defined inclusion/exclusion criteria may apply.