Amendment 1: • For Part 1 and Part 2, added neurological examinations and for Part 3 and Part 4 added additional neurological examinations to safely assess possible neurological effects of USL311; • For Part 3 and Part 4, added statement about the maximum number of pre-surgical doses allowed; • For Part 3 and Part 4, clarified subjects must have fully recovered from surgery; • For all study parts, clarified subjects were monitored closely for at least 7 hours after the start of the infusion for their first dose of USL311; • For all study parts, clarified how electrocardiograms (ECGs) were collected and how continuous telemetry monitoring was performed; • For Part 1 and Part 2, clarified RANO criteria used for response assessment for all primary brain tumors; • Added exclusion criterion of subjects with lymphoma as primary cancer; • For all study parts, clarified the use of information obtained through standard-of-care procedures; • Reduced the volume of cerebrospinal fluid (CSF) collected during sample collection for all study parts due to additional information gained from analytical method development.

Amendment 2: • In Part 1, clarified weight was collected at Screening instead of the Baseline Visit (Day -1); • Changed the neurological examination at clinic discharge, for the first dosing day of USL311 for each study part, to between the 5-hour nominal time point up to clinic discharge; • Added windows for the time-matched ECG collection and safety ECG collection to allow for some flexibility in the collection at the clinical sites; • Updated Inclusion Criterion to allow for 24-hour urine collection to determine the creatinine clearance corrected for body surface area (BSA), per Investigator discretion; • Updated Inclusion Criterion to also include electrolyte values above the upper limit of normal (ULN) if considered not clinically significant per the Investigator; • Removed the Inclusion Criterion to have the surgical sterilization procedure occur 6 months prior to receiving study drug(s); • In Part 1, clarified the Baseline Visit was part of the Screening Phase because the day of dosing was the beginning of the Treatment Phase.

Amendment 3: • A study update noting observations of a potential USL311 dose-related increase in QT interval with a time-dependent profile correlating with plasma/blood USL311 concentrations was added; • An increase in infusion time was added based on the observation of prolongation of QT interval; • Clarification that bone marrow and renal/hepatic function parameters must meet entry criteria thresholds at Screening and Baseline Visits for subjects to be eligible for study treatment; • Clarification that QT changes were followed using the Fridericia correction; • Clarification that the pre-surgical dose of USL311 administered in Part 3 and Part 4 were at the defined recommended phase 2 dose (RP2D); • Added cautionary guidance on subjects avoiding unprotected sun exposure due to the unknown phototoxicity potential of USL311; • Clarification on Safety ECG thresholds for USL311 dose modification decision making.

Amendment 4: • Update clinical study findings; • Added Part 1a (oral) cohort; • Increase number of subjects; • Addition of exclusion criteria for allergy/hypersensitivity to components of USL311 and conditions that may affect USL311 absorption; • Addition of concomitant mediation and dietary restrictions; • Added oral dose and dosing information; • Removed stromal cell-derived factor 1 (SDF-1) from Part 1b and beyond; • Changes to assessments throughout.