Protocol amendment 1 Version 1.0 US (Sequential dosing): Removed Part 2

Protocol amendment 1 Version 1.1 (Parallel dosing): Removed Part 2

Protocol amendment 2 Version 1.0 (Sequential dosing): Corrected IND number. Investigational Plan: clarifications. Revised Inclusion Criteria: 2. Revised serum ALP concentration. Clarified and specified the criteria by which Investigators can determine suspected hepatic fibrosis. Revised platelet count. Revised exclusion criteria: Clarified worsening of liver disease. Description of Treatments: Added: Description and rationale for study doses and placebo (40, 80, and 160 mg) and study design for Part 2 Clarification that Part 2 will be randomly assigned (3:1) in parallel treatment cohorts. Selection and Timing of Dose for Each Participant: added language to provide guidance in the even a participant misses a dose of study drug. Allowed Medications: Revised prednisone doses. Disallowed Medications: Added: New contraception language for male and female participants of childbearing potential. Study Procedures: Retesting of a screening laboratory test(s) and/or ultrasound-based transient elastography (FibroScan®) may be permitted once. Liver Imaging (optional): Clarification. Electrocardiograms: Added language regarding triplicate ECG. Definition of SAEs: Added clarification as to which events would not be defined as SAEs. Early Discontinuation of Study or Individual Participants clarification. Retention for the study data for 25 years if per local requirements. Schedule of Assessments, appendix 1: Added or revised assessments to align with revised study procedures

Protocol amendment 2 Version 1.1 (Parallel dosing): Corrected IND number. Investigational Plan: clarifications. Revised Inclusion Criteria: 2. Revised serum ALP concentration. Clarified and specified the criteria by which Investigators can determine suspected hepatic fibrosis. Revised platelet count. Revised exclusion criteria: Clarified worsening of liver disease. Description of Treatments: Added: Description and rationale for study doses and placebo (40, 80, and 160 mg) and study design for Part 2 Clarification that Part 2 will be randomly assigned (3:1) in parallel treatment cohorts. Selection and Timing of Dose for Each Participant: added language to provide guidance in the even a participant misses a dose of study drug. Allowed Medications: Revised prednisone doses. Disallowed Medications: Added: New contraception language for male and female participants of childbearing potential. Study Procedures: Retesting of a screening laboratory test(s) and/or ultrasound-based transient elastography (FibroScan®) may be permitted once. Liver Imaging (optional): Clarification. Electrocardiograms: Added language regarding triplicate ECG. Definition of SAEs: Added clarification as to which events would not be defined as SAEs. Early Discontinuation of Study or Individual Participants clarification. Retention for the study data for 25 years if per local requirements. Schedule of Assessments, appendix 1: Added or revised assessments to align with revised study procedures

Protocol amendment 3 Version 1.0 (Sequential dosing): Added background information on bexotegrast Updated to include new information for ongoing and completed studies. Investigational Plan: Added: Description and rationale for 320 mg QD dose for Part 3 following DSMB to evaluate the current 80 and 160 mg dose from Part 2. Data are reviewed by the DSMB; removed option for review by Competent Authorities (if applicable). Revised Inclusion Criterion 7. Revised Exclusion Criterion 18. Revised Exclusion Criterion 21. New formulation (phosphate salt formulation of bexotegrast) to be used in Part 3 (supplied as 80-mg immediate-release tablets). Revised storage conditions. Blinding: Added clarification that contacting the Sponsor’s Study Director before unblinding. Added additional data from medication-medication interaction studies between bexotegrast and fluconazole and digoxin. Revised definition of postmenopausal state. Removed option for use of liver MRI within 3 months of Screening as an alternative to baseline MRI. Clarified that targeted physical examination will be performed based on prior findings in the general exam. List of Laboratory tests: Added prothrombin time (coagulation) and CA-19-9 (screening test). Clarified that pharmacogenomics sampling is optional. Causal Relationship of an Adverse Event: Corrected to Yes (related). Definition of SAEs: Clarified timing of pregnancy reporting. Added language to provide direction as to how AEs and serious adverse events are to be reported. Revision of process for reporting SAEs from utilizing EDC to pharmacovigilance vendor (CTI) Interim Analysis: Updated Section to include description of additional interim analyses. Appendix 2 Schedule of Assessments: Part 3: Added assessments and visits for Part 3.

Protocol amendment 3 Version 1.1 (Parallel dosing): Added background information on bexotegrast Updated to include new information for ongoing and completed studies. Investigational Plan: Added: Description and rationale for 320 mg QD dose for Part 3 following DSMB to evaluate the current 80 and 160 mg dose from Part 2. Data are reviewed by the DSMB; removed option for review by Competent Authorities (if applicable). Revised Inclusion Criterion 7. Revised Exclusion Criterion 18. Revised Exclusion Criterion 21. New formulation (phosphate salt formulation of bexotegrast) to be used in Part 3 (supplied as 80-mg immediate-release tablets). Revised storage conditions. Blinding: Added clarification that contacting the Sponsor’s Study Director before unblinding. Added additional data from medication-medication interaction studies between bexotegrast and fluconazole and digoxin. Revised definition of postmenopausal state. Removed option for use of liver MRI within 3 months of Screening as an alternative to baseline MRI. Clarified that targeted physical examination will be performed based on prior findings in the general exam. List of Laboratory tests: Added prothrombin time (coagulation) and CA-19-9 (screening test). Clarified that pharmacogenomics sampling is optional. Causal Relationship of an Adverse Event: Corrected to Yes (related). Definition of SAEs: Clarified timing of pregnancy reporting. Added language to provide direction as to how AEs and serious adverse events are to be reported. Revision of process for reporting SAEs from utilizing EDC to pharmacovigilance vendor (CTI) Interim Analysis: Updated Section to include description of additional interim analyses. Appendix 2 Schedule of Assessments: Part 3: Added assessments and visits for Part 3.

Protocol amendment 4 Version 1.1 (Parallel dosing): Changed Sponsor Study Director from Greg Cosgrove to Richard Pencek. Revised Inclusion Criterion 9. Revised Inclusion Criterion 10. Revised Inclusion Criterion 3. Revised Exclusion Criterion 11. Revised Exclusion Criterion 28. Revised last bullet to “Treatment with a disallowed medication, other investigational drug within 5 half-lives or 30 days before Screening, whichever time is longer, or the use of an investigational device within 30 days before Screening is prohibited.” Revised first sentence to “Prior use of an investigational drug within 5 half-lives or 30 days before Screening, whichever time is longer, or the use of an investigational device within 30 days before Screening is prohibited.” Moved examples of contraceptive methods with a failure rate of <1% per year under new subheading “Highly Effective Methods of Birth Control.” Revised the time between Visits 1 and 2 to be ≥2 weeks. Clarified that a plasma PK sample is not required at the EoS visit. Clarified that a plasma PK sample is not required at the EoS visit. Changes implemented for non-US sites: - Added Exclusion Criterion 29 to exclude participants who participated in an earlier part of the current study (ie, Part 1 or 2) within 6 months of dosing for a subsequent part (ie, Part 2 or 3); - Revised Exclusion Criterion 7.

Protocol amendment 4 Version 1.0 (Sequential dosing): Changed Sponsor Study Director from Greg Cosgrove to Richard Pencek. Revised Inclusion Criterion 9. Revised Inclusion Criterion 10. Revised Inclusion Criterion 3. Revised Exclusion Criterion 11. Revised Exclusion Criterion 28. Revised last bullet to “Treatment with a disallowed medication, other investigational drug within 5 half-lives or 30 days before Screening, whichever time is longer, or the use of an investigational device within 30 days before Screening is prohibited.” Revised first sentence to “Prior use of an investigational drug within 5 half-lives or 30 days before Screening, whichever time is longer, or the use of an investigational device within 30 days before Screening is prohibited.” Moved examples of contraceptive methods with a failure rate of <1% per year under new subheading “Highly Effective Methods of Birth Control.” Revised the time between Visits 1 and 2 to be ≥2 weeks. Clarified that a plasma PK sample is not required at the EoS visit. Clarified that a plasma PK sample is not required at the EoS visit. Changes implemented for non-US sites: - Added Exclusion Criterion 29 to exclude participants who participated in an earlier part of the current study (ie, Part 1 or 2) within 6 months of dosing for a subsequent part (ie, Part 2 or 3); - Revised Exclusion Criterion 7.