STUDY 303 A Phase III, Randomized, Multi-Center, Open-Label, 12 to 14 Month Extension Study to Evaluate the Safety and Tolerability of Mesalamine Given Once Daily Vs. Twice Daily for the Maintenance of Ulcerative Colitis in Remission

Study 303: Objectives  Study design  Patient disposition  Definitions  Safety of 8-week acute extension  Efficacy of 8-week acute extension  Safety of 12-month long-term extension  Efficacy of 12-month long-term extension  Summary

Study Design of 303  Open-label, multicenter, phase III study 12–14-month extension of the Lichtenstein et al. and Kamm et al. studies (parent studies)  Two phases 8-week acute extension phase  Patients not in remission at the end of the parent studies  Mesalamine 4.8 g/day (given b.i.d.) 12-month long-term extension phase  Patients in remission at the end of the parent studies or the end of the 8-week acute extension phase  Mesalamine 2.4 g/day (given q.d. or 1.2 g b.i.d.) Adapted from Kamm et al. Gut 2008;57(7):

Study 303 End Points 1  Primary objective: to assess the long term safety and tolerability of Mesalamine 2.4 g/day over 12 months Efficacy was not a primary endpoint of Study 303  Secondary objectives included: Safety in acute extension phase Time to relapse in long-term extension phase Patients in remission at 12 months Patient satisfaction Adapted from Kamm et al. Poster presented at BSG

Mild (Score = 1) Moderate (Score = 2) Severe (Score = 3) Rectal bleeding  Streaks of blood  Obvious blood  Mostly blood Stool frequency  1-2/day > normal  3-4/day > normal  > 4/day > normal Mucosal appearance  Erythema  Decreased vascular pattern  Minimal granularity  Friability *  Marked erythema  Friability *  Granularity  Absent vascular pattern  Bleeding minimal trauma  No ulcerations  Ulceration  Spontaneous bleeding PGA (Physician’s Global Assessment)  Mild  Moderate  Severe * Friability moved from Score of 1 to 2 Adapted from Kamm et al. Gastroenterology 2007;132:66–75. Modified* Ulcerative Colitis-Disease Activity Index

End Point Definitions  Relapse: Withdrawal from the study due to a requirement for alternative treatment (including a dose increase or surgery) for an exacerbation of UC  Remission: Modified UC-DAI score  1, calculated as a score of 0 for rectal bleeding and for stool frequency, a combined Physician’s Global Assessment (PGA) and sigmoidoscopy score of  1, no mucosal friability, and a sigmoidoscopy score reduction of 1 point or more from baseline Adapted from Kamm et al. 2008;57(7):

623 (Parent Studies) 558 (89.6%) (Rolled over into 303) 312 (56%) (Acute Extension Phase) 246 (44%) (Long-term Extension Phase) (q.d. Group) 234 (b.i.d. Group) 459 (Safety population) (Long-term Extension Phase) (68%) Adapted from: 1 Kamm et al. Poster presented at BSG Kamm et al. Gut 2008;57(7): Patient Disposition 1,2

Efficacy Results: 8-Week Acute Extension Phase

8-Week Acute Extension Phase: Efficacy Results  Remission 59.5% of patients in the efficacy population (n=304) achieved remission  Modified UC-DAI score Mean reduction of 3.9 ± 2.8 points from week 0* to end point Mean reduction of 5.0 ± 2.7 from parent study baseline to end point  Symptom improvement 65.1% of patients had a score of 0 for stool frequency at end point compared to 7.9% at week % of patients had a score of 0 for rectal bleeding at end point compared to 27.3% at week 0 *Week 0=First study visit of the acute extension phase Adapted from Lichtenstein GR, et al. Poster presented at ACG, 2007.

(n = 107) (n = 78) (n = 41) Prior treatment Up to 8 weeks’ active treatment Up to 16 weeks’ active treatment Patients in Remission After Eight Weeks’ Extension Therapy

Number of patients (%) Adapted from Lichtenstein et al. Poster presented at ACG *Week 0=First study visit of the acute extension phase 8-Week Acute Extension Phase: Sigmoidoscopy Scores

STUDY 303 Acute Extension Phase Conclusions 1,2  Mesalamine 4.8 g/day (2.4 g dosed b.i.d.) was well- tolerated in the 8-week acute extension phase Safety profile similar to that of the parent studies (Lichtenstein et al. and Kamm et al.)  Mesalamine 4.8 g/day for up to 4 months was well- tolerated  Approximately 60% of patients achieved remission, using stringent clinical and endoscopic criteria Adapted from: 1 Lichtenstein et al. Poster presented at APhA Lichtenstein et al. Poster presented at ACG 2007.