In summary, the main changes included the following: • Further details on the pharmacokinetics of mangoral • Clarification to the text of the secondary objectives • Additional assessment of pregnancy testing for participant safety • Corrections made to the text describing variables and method for visualization of focal liver lesions • Clarification on the text for brain MRI procedures • Addition of an Independent Data Safety Monitoring Board • Clarification that the inter-reader agreement was to be evaluated by the intraclass correlation coefficient for the 2 co-primary efficacy variables based on the participant level.

In summary, the main changes included the following: • Additional objectives included to ensure consistency with the variables analyzed • Revised some of the ranges of MRI parameters in Protocol Table 6 based on feedback received during the site initiation visits and discussions with the investigators • Clarification that the brain MRI is not a mandatory procedure • Additional exclusion criterion to exclude participants with simple liver cysts only • Revision of exclusion criterion 24 so as to allow patients with iron deficiency anemia or participants on iron therapy to enter the study as discussions with the investigators revealed that neither iron therapy nor iron deficiency anemia would jeopardize the analysis of the variables • Exclusion of participants with conditions that could interfere with excretion of mangoral • Revised details of prohibited concomitant medications specifically dietary iron supplementation • Additional detail to the primary objective to only include lesions identified on unenhanced images in analysis of co-primary efficacy variables • Addition of a fourth reader who was not included in the efficacy reads to track and match detected lesions on unenhanced MRI, mangoral-enhanced MRI, and combined MRI as per Food and Drug Administration recommendations • Clarification of analysis populations • Revision of the primary efficacy analysis to use mean scores instead of sum scores and to include an analysis of comparison between unenhanced MRI and mangoral-enhanced MRI alone in the same way as the primary analysis • Addition of both inter-reader and intra-reader agreement analysis.

In summary, the main changes included the following: • Increase in the number of sites • Correction of IMP shelf life.

In summary, the main changes included the following: • Clarification of inclusion criteria defining chronic kidney disease according to clinical practice and guidelines • Clarification of inclusion criteria to achieve approximately a 20% hepatic carcinoma cap • Clarification to the primary objective to align with exclusion criterion 1 (participants with simple liver lesions only) • Revision to MRI parameters to fit with sites’ clinical practices and MRI machine settings • Clarification that new or worsening events should be reported as an adverse event (irrespective of clinical significance) if observed after IMP administration compared to previous predose assessments • Revision to assessment of serious adverse event to include seizure, stroke, cerebral venous thrombosis, and QTcF or QTcB >480 msec or QTcF or QTcB increase of 60 msec over baseline as important medical events.

In summary, the main changes included the following: • Revision to the inclusion criteria so participants requiring dialysis are allowed at all sites • Added a section on permitted oral intake to include glucose or juice intake during the fasting period to treat hypoglycemia or diabetes mellitus type I and type II • Revision to exclusion criteria to remove the restriction of moderate hepatic impairment (Child-Pugh score B) • Removal of the exclusion criteria for patients on dialysis (excluding patients in the pharmacokinetic [PK] subgroup) • Changed follow up 1 (Visit 4) and follow up 2 (Visit 5) to optional remote visits (excluding patients from the PK subgroup).