REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome

Key Inclusion Criteria:

1. The participants caregiver(s)/ legally authorized representative must have givenwritten informed consent and any authorizations required by local law and be able tocomply with all study requirements.

2. Medically stable and can undergo sedation and/or general anesthesia withoutintubation.

3. Male or female between 2 and lesser than or equal to (≤)50 years of age, dependingon specific cohort, at the time of the in-clinic Screening visit.

4. Participant has a clinical diagnosis of Angelman syndrome (AS) with molecularconfirmation of either Ubiquitin-protein ligase E3A (UBE3A) deletion or UBE3Amutation.

5. Currently receiving stable doses of concomitant medications typically prescribed forAS, such as anti-epileptic medication, behavioral management medications, sleepmedications, gabapentin, cannabidiol, and special diets, supplements, or nutritionalsupport for at least 8 weeks prior to the Baseline visit.

6. Legally authorized representative/caregiver(s) agree(s) not to post any of theparticipant's personal medical data or information related to the study on anywebsite or social media site (e.g., Facebook, Instagram, X (formerly Twitter),YouTube, TikTok, etc.) from the time of enrollment until they are notified that thestudy is completed.

Key Exclusion Criteria:

1. Must not have any clinically significant abnormalities in medical history (e.g.,major surgery within 3 months of screening), or on physical examination for whichtreatment with an antisense oligonucleotide (ASO) would be contraindicated or which,in the opinion of the Principal Investigator (PI), could confound the results ofthis study.

2. Known brain or spinal disease that would interfere with the lumbar puncture (LP)procedure, cerebrospinal fluid (CSF) circulation, or presence of other factors wouldaffect the safety of the LP procedure.

3. Must not have any other conditions, which, in the opinion of the Investigator, wouldmake the participant unsuitable for inclusion or could interfere with theparticipant participating in or completing the study.

4. Must not have any laboratory abnormalities or any other clinically significantabnormalities that would, as assessed by the Investigator, at screening or Baseline,render a participant unsuitable for inclusion.

5. Previous treatment with an oligonucleotide (including small interfering ribonucleicacid (RNA) [siRNA], ASOs) gene therapy or gene editing. This exclusion criteriondoes not apply to approved nucleic acid-based vaccines, including mRNA vaccines,which are allowed.

6. Has molecular confirmation of AS due to paternal uniparental disomy, imprintingcenter defect, or mosaic findings.

Other inclusion/exclusion criteria may apply.