The following changes were made: • CHOP-INTEND and Ability Captured Through Interactive Video Evaluation – mini (ACTIVE-mini) assessed at additional time points • Urine, saliva, and feces sample collections added for future research of viral shedding • Blood sample collected at Day 60 to assess serum antibody, T-cell response (ELISpot), and for future research • Treat patients with positive T-cell immune response with prednisolone (1 to 2 mg/kg once daily) and close monitoring of T-cell immune reaction

The following changes were made: • Safety laboratory assessments collected at additional time points • Direct bilirubin and albumin added to safety laboratory analyses • Immunology (anti-AAV9/SMN antibody and T-cells), research blood, and urinalysis collected at additional time points • Added vaccination recommendations • Prednisolone treatment changed to approximately 1 mg/kg once per day starting prophylactically 1 day prior to AVXS-101 infusion with a tapering protocol based on immune response to AVXS-101 o Dose could have been increased to approximately 2 mg/kg once per day, depending on T-cell response measured by ELISpot assay • Administer AVXS-101 within 8 hours of preparation

The following changes were made: • Intermediate dose of 2.0 X 10^14 vg/kg Cohort 2 (n=3) added • High dose of 3.3 X 10^14 vg/kg moved to Cohort 3 (n=3)

The following changes were made: • Secondary objective of study revised to the time from birth until death or time to ≥16-hour respiratory assistance continuously for ≥2 weeks in the absence of an acute reversible illness • Maintain prophylactic prednisolone treatment for ≤30 days • Revised prednisolone tapering schedule to be based on interferon-gamma T-cell response and aspartate aminotransferase/alanine aminotransferase values • Request permission for autopsy at time of death

The following changes were made: • Primary objective of study revised to determination of safety based on the development of unacceptable toxicity: defined as the occurrence of any one Grade 3 or higher, unanticipated, treatment-related toxicity • Cohort 2 to include ≥3 and ≤6 patients and Cohort 3 to include up to 3 patients • Prednisolone did not need to be maintained for ≤30 days and revised tapering schedule • Research urine, saliva, and stool assessed at additional time points • Replace AE severity classifications with Common Terminology Criteria for Adverse Events (CTCAE) v4.03 classifications (Grades 1 to 5) • Severity of liver toxicity assessed using NIH Guideline for Severity Grading in Drug Induced Liver Injury (Grades 1 to 5), including assessments of association or relatedness to AVXS-101 • Required dose level toxicities to be unanticipated • Saliva, urine, and stool research samples collected at additional time points

The following changes were made: • Bayley Scales added to exploratory outcome measures with fine and gross motor subtests administered to patients who achieved CHOP-INTEND scores ≥60 • Research urine assessed at additional time point • Removed severity of liver toxicity grading added in Protocol v11.0 • Stopping criteria required Grade 3 or higher AE toxicity, clinical symptoms, and medical treatment

The following changes were made: • Removed Cohort 3 and Cohort 2 renamed Cohort 2A • Extended enrollment to 6 additional patients (intermediate dose) following gene transfer of first 9 patients • Addendum 2, v1.0 (24Jun2015) o Expand sample size with Cohort 2B (2.0E14 vg/kg) and added Cohort 3 (3.3E14 vg/kg), each consisting of 3 patients o The age of patients on the day of AVXS-101 infusion was decreased to 6 months of age or younger for Cohort 2B and Cohort 3

The following changes were made: • Added secondary objective of change from baseline in CHOP-INTEND score, and improvement of motor function and muscle strength as determined by achievement of significant development milestones including but not limited to the ability to sit alone and roll over unassisted o Additionally, AveXis could provide videos of the physical exams, CHOP-INTEND assessments, and/or Bayley Scales assessments to an independent, blinded reviewer for confirmation of the development milestones • Added objective of compelling, demonstrable, documented evidence of efficacy as determined by changes in functional abilities as captured during videotaping sessions during site visits and/or captured by patient/parent/legal guardian at home • Added primary analysis for efficacy assessed when all patients reach 13.6 months of age, and follow-up safety analysis completed when the last patient reaches 24 months post-dose • Initial genetic testing and diagnosis could be completed by a different institution/laboratory and could be confirmed by AveXis through a third-party laboratory using an additional blood sample • Updates and clarifications to CHOP-INTEND requirements • Bayley Scales fine motor, gross motor, and cognition subtests administered for CHOP-INTEND scores ≥60 • During the first year, Bayley Scales gross and fine motor subtests assessed monthly, and cognition subtest assessed every 3 months. During the second year, all Bayley Scales subtests assessed every 3 months, except for patients being seen monthly for CHOP-INTEND assessments. For these patients, the first year assessment schedule was followed. • Assess the age at which significant motor milestones achieved using the Motor Milestone Development Survey and Gross Motor Skills Checklist.

The following change was made: • This Institutional Review Board-approved amended protocol, which added a co-primary endpoint and secondary endpoints, was rescinded 23Jan2017, in response to feedback received from the FDA suggesting the objectives and endpoints set forth in Protocol dated 21Apr2016 be maintained due to the open-label nature of the study

The following change was made: • Quarterly instead of monthly visits during the second year