The original protocol CF102-201HCC was approved on 07 January 2014. Subsequently, the protocol was amended a first time on 16 June 2014: • Addressed comments and requests for information from FDA in correspondence dated 15 May 2014. • Clearly described rules for dose interruption due to toxicity and criteria for dose modification. • Revised eligibility to require prior treatment with sorafenib. • Required collection of data documenting the reasons for sorafenib intolerance and the duration of prior sorafenib treatment. • Added collection of sparse pharmacokinetic samples to allow for exploratory analyses of exposure-response relationships for CF102. • Added collection of additional ECGs at the anticipated maximal CF102 concentrations at steady state.

The original protocol CF102-201HCC was approved on 07 January 2014. Subsequently, the protocol was amended a second time on 03 October 2014: • The Sponsor had recently completed the in-life portion of 90-day toxicology studies in monkeys and rats. In a 90-day monkey study (30, 100, 300 mg/kg/day), preliminary data indicated that there was a dose-related increase in incidence and severity of microscopic thyroid follicular atrophy/degeneration with or without a concurrent neutrophil infiltrate. Thyroid follicular change was noted as minimal in severity in 1 of 6 animals at the low dose, minimal-to-mild severity in 2 of 6 animals at the mid dose, and mild-to-moderate severity in 4 of 6 animals at the high dose. Recovery was not evaluated in this study. The highest non-severely toxic dose in this study was 30 mg/kg. This information was added to the protocol.

The original protocol CF102-201HCC was approved on 07 January 2014. Subsequently, the protocol was amended a third time on 21 October 2015: • Changed the assay methodology for A3AR expression determination. • Revised information which was previously clarified, corrected or changed as per the following: o Global Note to File GLO_P_Am. 01_16Jun2014 dated 11 August 2014 o Global Note to File GLO_P_PBMC_08Oct2014 dated 01 April 2015 o Global Note to File GLO_P_WBC_08Oct2014 dated 02 June 2015 The protocol was modified to reflect the new procedure and correct already existing information.

The original protocol CF102-201HCC was approved on 07 January 2014. Subsequently, the protocol was amended a fourth time on 21 September 2018: • Eliminated the requirement for 75 deaths prior to the end of the post-accrual period • Terminated the double-blind period of the study prior to the occurrence of 75 deaths • Deleted the MITT population • Added the PP population • Efficacy analyses were to be performed on the ITT population • Tumor response was to be analyzed using the PP population • Subjects who remained on blinded drug were offered the opportunity to continue dosing with open-label CF102 25 mg BID indefinitely, following the protocol-specified schedule of events.

The original protocol CF102-201HCC was approved on 07 January 2014. Subsequently, the protocol was amended a fifth time on 06 November 2018: • Added Table 1-2: Schedule of Events for Open Label (OL) Treatment. • Amendment 5 implemented the transition to open-label (OL) dosing for patients who were surviving and remaining on drug at the time of analysis; and established the assessments and schedule of visits for the OL dosing aspect of the trial. This included defining the OL eligibility criteria; detailing the visit and assessment schedule; and specifying that the only patients still on treatment in this trial at the time of this amendment were in Romania. • Required a separate signed ICF prior to subject’s continuation on OL treatment. • Provided for self-administration of CF102 or placebo BID in continuous 28-day cycles beginning on Day 1 of Cycle 1. • Provided for collection of information regarding the occurrence of adverse events during the OL period, up 28 days following the last dose of study drug (OL Follow-Up Visit). Any data for AEs related to study drug that were ongoing at the OL Follow-Up Visit would be collected until the AE resolved or stabilized. • Provided for PE, laboratory testing, ECG, liver chemistry, INR, and measuring of viral load during the OL period and OL Follow-Up.