Amendment v1.1 with following changes to original protocol: - Optional adjustments in dose, dosing frequency (weekly or every other week), and route of administration (IV or SC) was added - Option for dose administration and assessments at home after demonstration of sufficient safety, to reduce burden on subjects and parents/caregivers was added - Adjustment of blood sampling schedules and key PK/PD sample timepoints to accommodate every other week dosing - Alignment of neurocognitive/developmental/quality of life (QoL) instruments with Phase 3 program based on expert review - Adjustment of frequency of neurocognitive/developmental/QoL and neurological/neuromotor assessments to reflect timeframes considered more likely to show changes in this population - Optional food effect substudy was added

Protocol v2.0 (US, Canada, Portugal) with following changes to v1.1 (incorporated on 08-May-2029 in Protocol v2.1 for UK): - Dosing was changed to requiring 24-week IV dosing before a change to an SC route, the option for every other week dosing was removed and the following dosing schedule was recommended: IV administration once weekly for Weeks 1 through 24; SC administration once weekly for Weeks 25 through 48; as clinically indicated thereafter for Years 2 and 3 - Replacement of "AEB1102" by the generic drug name "pegzilarginase" - Defined that initial mg/kg SC dose was to match the last IV dose the subject received - Subsequent SC doses can be administered outside of the CRU by appropriately trained home health care professionals if considered safe and appropriate by investigator and sponsor - List of examples for hypersensitivity reactions was updated and recommendations for their management and severity classification were included - Noted that the benefits and risks of corticosteroid treatment should be carefully considered, as it may cause hyperammonemia in this patient population

Protocol v3.0 with following change to v2.0: - PK sampling during SC administration and the PK parameters to be evaluated were added

Protocol v4.0 with the following changes to v3.0: - Optional food effect substudy was removed, as no subjects consented to participate - Short-Form 36 evaluation was removed due to no assessment in CAEB1102-101A; no Short-Form 36 data were collected in the trial prior to this protocol amendment - Frequency of assessments were adjusted to reduce subject's burden

Protocol v5.0 with following changes to v4.0: - Extension of pegzilarginase treatment for up to 4 years if pegzilarginase was not commercially available or otherwise available, e.g. as part of an extended access protocol - Guidance on the COVID-19 pandemic was added

Protocol v6.0 with following changes to v5.0: - Continuation of treatment with pegzilarginase for subjects who completed Year 4 was allowed, post assessments after Week 192 were added and the study period changed from "up to 4 years (192 weeks of dosing)" to "until available through other means" - Height and clinical growth assessment was added to Week 168 and physical examination to Week 168 and Week 192 to be consistent with assessments being conducted every 24 weeks - Follow-up visit was changed from 4 weeks to 2 weeks post last dose - Identity of study drug was updated to include newest vial presentation: 10-mL single use glass vials with a green cap, containing 5 mL of formulated drug product at a concentration of 5 mg/mL for SC administration - Storage temperature of study drug was changed from "at or below 65°C" to "at or below 60°C" based on stability data - PD samples were updated to include "PD analyses may also be conducted via dried blood spot by fingerstick or via alternate methods as outlined in the lab manual once they are available and will be sent to a designated central laboratory"