Health authority (US Food and Drug Administration (FDA)) feedback regarding the inclusion of a responder analysis for the Hammersmith Functional Motor Scale Expanded (HFMSE) as part of the secondary efficacy objective was addressed. The data analysis and statistical methods section were revised to include the following two secondary endpoints: • Achievement of at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the overall study population • Achievement of at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the 2 to <5 years age group The schedule of sensory nerve action potential (SNAP) assessments were modified in view of ethical consideration and clinical best practice to ensure evaluation and monitoring of potential neurotoxicity SNAPs were evaluated in all patients at screening as described in the previous protocol version. However SNAP evaluation at five post-treatment visits was adjusted. The neurological examination, which was already incorporated in the protocol at every post-treatment visit, was used to primarily evaluate potential sensory abnormalities in patients. Upon detection of a potential sensory abnormality, a SNAP assessment would then be performed as a secondary evaluation.

The Central Treatment Site (hybrid model) was removed, which had not been utilized and was therefore not applicable for study execution. Adaptations were made to clarify that the threshold used for anti-AAV9 antibody titer is one that was reported to be elevated. Due to the nature of the immunoassay used to evaluate anti-AAV9 antibody titer, the reported titer value as elevated may be different. In addition, further adaptations were made for clarity, including mirroring exclusion criteria in Treatment Period 2 from Treatment Period 1 for safety considerations, and updating the section discussing OAV101 risks. The risks of inaccurate anti-AAV9 antibody testing results were added because the test was being used to assess eligibility had not been approved by regulatory authorities for this purpose. The visit schedule for troponin I collection was modified to better align with timepoints for electrocardiogram and echocardiogram assessments. The revised visit schedule for troponin I now aligns with ECG and ECHO, as well as with other ongoing OAV101 studies. Sensory nerve action potential (SNAP) evaluation on asymptomatic participants was no longer applicable and therefore was removed for clarity. All patients underwent a neurological exam and SNAP at screening, and those with clinically significant sensory abnormalities in the neurological examination or those who were unable to obtain SNAP, were not eligible. Post-treatment, SNAP was ONLY performed if there were sensory abnormalities in the neurological examination. Therefore, there were no cases of asymptomatic participants for SNAP evaluation. Editorial changes were made throughout for clarity.

Several exclusion criteria were revised so that they are now anchored to the Day 1 visit (day of OAV101 administration or the sham procedure). The number of participants listed in the five strata has been removed. Based on experience gained thus far, it is not considered feasible to have an equal balance of patients across strata, as originally planned. Finally, a theoretical risk of tumorigenicity due to vector DNA integration has been added to the OAV101 risks section. The risk language has been revised to include the theoretical risk of tumorigenicity due to the very low potential incorporation of AAV vector DNA into chromosomal DNA that has been noted based on published literature for AAV-based therapies.

Text updated to enhance consultation between the Principal Investigator and Sponsors for patients retesting of abnormal laboratory and other clinical parameters, to clarify interpretation of total score, and to ensure compliance with expedited reporting of potential Hy’s Law cases based on health authority guidance