The following updates were made: • Addition of cardiac enzyme (CK-MB) monitoring • Added exclusion criterion for patients < 35 weeks gestational age at the time of birth • Updated Phase 1 study results added • Clarified wording related to autopsy and post-mortem tissue/organ collection • Updated until dose terminology based upon improved analytical method (ddPCR) with AveXis GMP product • Revised timepoints for laboratory assessments to allow for blood volume required for CK-MB monitoring • Added length of time for which mother should discontinue breastfeeding in instance of positive antibody titers. • Updated section on saliva, urine, and stool collection to reflect most recent viral shedding data • Minor clarifications and corrections were made to the overall document

The following updates were made: • An administrative change to correct a discrepancy in capillary blood gas timepoint.

The following updates were made: • Included recent Good Laboratory Practice (GLP) toxicology data • Added benefit/risk language from the Investigator Brochure • Updated onasemnogene abeparvovec-xioi infusion time to 60 minutes from 30-60 minutes. • Added language to allow for prednisolone equivalent • Deleted option for dilution of onasemnogene abeparvovec-xioi with normal saline • Updated schedule and timing of 12-Lead ECGs and echocardiograms • Added 24-hour Holter monitoring • Added Troponin I assessment • Updated immunology testing to remove ELISpot • Adjusted amount of blood volume required for laboratory assessments • Clarified collection of CK-MB and Troponin I relevant to enrollment • Added Pharmacovigilance reporting • Included an additional reference

•Information on, and changes throughout the document as a result of, the acute liver failure case reported in the US Managed Access Program, including: - Update to the prophylactic administration of prednisolone regimen to dampen the immune response to AVXS 101 administration - Risk language updated to include description of recent adverse events and recommendations for liver safety, prolonged monitoring and detailed guidance on tapering of steroid use according to the language from the IB - Participant Exclusion Criterion 12 language updated to include more stringent criteria for liver function tests •Exploratory Objective and Exploratory Endpoint added to provide clarification on evaluation of independent sitting. •Participant Withdrawal Criteria updated to clarify that participants will be offered to continue on the long-term follow-up study. •Clarification provided regarding requirements for reporting elevated liver enzymes and reporting in the Clinical Trial Report. •To include Day 44 and Day 72 visits for blood chemistry, specifically LFTs

•Removed exploratory objective and endpoint of ability to sit with support, in order to eliminate Bayley III item 19 which is not a defined milestone for this study •Clarified that 30 eligible participants were planned to be enrolled, but that patients who were already in screening at the time this enrollment target was met who met eligibility criteria could enroll upon approval of AveXis; this was so as to acknowledge that the number of participants may slightly exceed the enrollment target in this competitive enrolment trial •Added statement that patients who discontinue this trial prematurely will be invited to participate in the long-term follow up study •Updated description of the timing of post-treatment visits to be relative to date of gene therapy until the patient is 14 months of age (14 month of age visit), after which visits are to be relative to the patient’s date of birth •Head circumference measurement was added to Physical Examination in order to align with the physical examination case report form •Removed statement that biological mothers who test positive for antibodies to AAV9 will be asked to refrain from breast feeding until at least 1 month after AVXS-101 dose

The following updates were made: • Removal of Safety Objective to determine the safety of onasemnogene abeparvovec-xioi based on the development of unacceptable toxicity • Amended description of the role of the DSMB/DMC, timing and schedule of reviews, and recommendations and notification to regulatory authorities, as described in the DSMB/DMC Charter • Revised safety endpoints and analysis description • Risk language updated to include description of non-human primate (NHP) intrathecal study findings and the potential risk of neuronal toxicity following IT administration of onasemnogene abeparvovec-xioi • Detailed and age appropriate sensory testing added to be performed at each visit and any clinically significant abnormal finding recorded as an adverse event • Non-invasive ventilatory support usage recorded in the electronic Case Report Form (eCRF) to assist with identification of survival endpoints • All adverse events that occur after signing the informed consent through to the last trial visit collected and recorded in the eCRF • All SAEs (related and unrelated) recorded after signing of the consent form through 30 days after the last study visit • Trial enrolment not interrupted should any patient experience an unanticipated Grade 3 or higher related adverse event, pending DSMB/DMC review • Unanticipated Grade 3 or higher related adverse events will not be reported within 24 hours, unless they are adverse events of special interest (AESIs) or serious adverse events (SAEs) • AESIs, such as hepatotoxicity, thrombocytopenia, cardiac adverse events and sensory abnormalities potentially due to dorsal root ganglia inflammation are included/defined and the reporting requirements clarified • Elective procedures or minor surgeries where hospitalisation is required, should not be reported as SAE • Updated schedule of assessments and references.

The following updates were made: • Insertion of new language to address the impact of COVID-19 on trial conduct • Key Contact Information and additional study contact information updated as part of administrative changes • Addition of abbreviations and definitions of terms • Application of consistent definition of primary endpoint and exploratory endpoints • Clarification of the collection and central review of videos of efficacy parameters • Insertion of specific safety reporting requirements of the French Competent Authority • Insertion of Hy’s Law Criteria • Clarification and correction of statistical analysis definitions