The following changes were made: • Section 6.5.7 (Monitoring Subjects for AEs of Special Interest) and Section 7.12 (Stopping Rules) were revised, and Section 7.12.1 (Suspension of Study) was added to be consistent with the Food and Drug Administration (FDA) industry guidance on drug-induced liver injury. • The liver function test exclusion was reduced to 1.5 x the upper limit of normal. • The new Lycera facsimile number was added to the cover page. • Minor revisions/clarifications were made throughout.

The following changes were made: • Exploratory efficacy endpoint referencing “mucosal healing” changed throughout to “endoscopic improvement” as histologic evaluation of mucosa to validate healing was not performed. • Secondary efficacy endpoint Week 8 TMS clinical remission definition revised to include rectal bleeding score of 0. • Section 4.4.1: Inclusion criteria 4 revised to require women of childbearing potential to use 2 highly effective forms of birth control. • Section 4.4.2: Elevated serum creatinine added to Exclusion criteria 6 to exclude patients with renal impairment. • Section 6.4.1 definition of left-sided disease added to clarify which subjects could have flexible sigmoidoscopy at week 8 based on demarcation of inflammation observed in Screening colonoscopy. • Section 6.4.1 clarified that endoscopy video recording was to be provided for central reading and central readers had study specific training, including that a Mayo endoscopic score of 0 or 1 could not include any degree of “friability” as this was inconsistent with remission. • Section 6.4.1 clarified that stool frequency and rectal bleeding data for Mayo scoring was obtained from the diary completed by the subjects. Also clarified that average stool frequency and rectal bleeding score calculated from the individual 3 consecutive days was used for the Mayo score. • Section 6.5.7 revised to state that study drug was to be withheld in subjects who exhibited any of the listed laboratory elevations in liver biochemical parameters and lactate. • Section 7.5 revised to add SAE reporting information including time frame for reporting SAEs to US FDA. • Section 6.6.1.2 clarified serial pharmacokinetic sub-study blood sample collection. • Section 7.10: sponsor medical monitor name and contact information added. • Section 7.12: individual stopping criteria added based on abnormal ECG findings of prolonged QT/QTc interval. • Section 11.1 removed statement that subjects were identified

The following changes were made: • Throughout protocol: revised all references to “anti-tumour necrosis factor” therapy to state “biologic” therapy • Section 1.0 revised to add countries participating in study and the estimated last subject last visit; • Sections 1.0 - 2.5 updated and reorganized • Section 4.1 revised language related to open-label extension protocol • Section 4.4.1 Inclusion criteria #2 revised to add clarity to histological evaluation if done at Screening • Section 4.4.1 Inclusion criteria #4 revised to add clarity to effective birth control • Section 4.4.1 Inclusion criteria #5 revised to add clarity • Section 4.4.1 Inclusion criteria #6 revised to add clarity • Section 4.4.2 Exclusion criteria #3 revised for clarity regarding bleeding disorders • Section 4.4.2 Exclusion criteria #10 revised to define history of uveitis • Section 4.4.2 Exclusion criteria #12 revised to define type of colon polyp being referenced • Section 4.4.2 Exclusion criteria #19 revised to remove reference to use of “topical” 5-ASA and steroids • Section 5.5.2-5.5.3 revised to add clarity related to IWRS and compliance • Section 5.6 revised to be consistent with other sections of protocol and to specify that corticosteroid taper was not allowed during the study • Section 6.2.1 revised wording related to timing for Screening procedures when a subject was already scheduled for a colonoscopy • Section 6.5.4 revised to clarify calculation of QTcF will not be done by sites • Section 6.5.7 revised to specify that Baseline abdominal pain and vomiting was to be carefully assessed • Section 7.4 revised to include the CTCAE criteria for assessment of AE severity • Section 7.12.1 study suspension criteria revised to state that if 50% of subjects experienced clinically important drug-related AEs (instead of TESAEs) with severity of CTCAE Grade 2 • Appendix B revised: hepatitis blood sample removed.

The following changes were made: • Section 4.4.1 Inclusion criteria #5 revised to allow inclusion of subjects on concomitant thiopurine UC treatment and to allow subjects on no UC treatment. • Section 4.4.1 Inclusion criteria #6 revised to include thiopurine. • Section 4.4.2 Exclusion criteria #7 revised to remove reference to thiopurines and to reduce the washout of other immunomodulatory medications to 4 weeks prior to the Screening endoscopy. • Section 4.4.2 Exclusion criteria #10 removed (history of uveitis). • Section 4.4.2 Exclusion criteria #12 revised to allow subjects with a history of cancer that was in remission for ≥ 5 years and exclude subjects with cancer diagnosed within the past 5 years unless approved by the study medical monitor. • Section 4.4.2 Exclusion criteria #17 biologic washout period determination revised and Appendix D added. • Section 4.4.2 Exclusion criteria #19 revised to allow use of rectal 5-ASA medications. • Section 5.6 revised to allow concomitant use of a stable dose of thiopurines. • Section 6.2.6 revised to specify that the Visit 6 date was the date of study completion. • Section 6.6.1.1, Table 3 footnote and Appendix B revised to specify that up to 20 subjects were planned to participate in the safety PK sub-study. • Section 6.6.1.2, Table 3 footnote and Appendix B revised to specify that up to 12 subjects were planned to participate in the serial PK sub-study. • Section 7.12 revised to specify that a repeat ECG was to be performed if QT/QTc prolongation stopping criteria were noted for confirmation.