Background  Certolizumab pegol is a pegylated humanised Fab’ fragment of a monoclonal antibody with high specificity for human TNF α  Phase II studies have demonstrated the efficacy and tolerability of sc certolizumab pegol 400mg 4-weekly (Q4W) in patients with moderate to severe Crohn’s disease (CD)  PRECiSE 1 and 2 are large well controlled studies demonstrating the safety and efficacy of certolizumab pegol in inducing and maintaining response and remission in patients with moderate to severe CD

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Crohn’s disease  Chronic inflammatory disease of the gastrointestinal tract  considerable unmet need  Prevalence:  over 1 million patients worldwide  Only around 15% and around 8% of Crohn’s patients are currently treated with anti-TNFs in US and Europe respectively  Remicade ® (infliximab), administered by infusion, the only anti- TNF biologic currently approved

Certolizumab Pegol (CIMZIA TM ), a humanised anti-TNF PEGylated Fab' fragment, is safe and effective in the maintenance of response and remission following induction in active Crohn’s disease: a Phase III study (PRECiSE 2) Stefan Schreiber, 1 Munaa Khaliq-Kareemi, 2 Ian Lawrance, 3 Stephen Hanauer, 4 Juliet McColm, 5 Ralph Bloomfield, 5 William Sandborn 6 1 Christian-Albrechts-Univ., Kiel, Germany; 2 Dalhousie Univ., Halifax, Canada; 3 Univ. of Western Australia, Fremantle Hosp, Australia; 4 Univ. of Chicago Medical Center, Chicago, USA; 5 UCB, Slough, UK; 6 Mayo Clinic, Rochester, USA

Background  Certolizumab pegol is a pegylated humanised Fab’ fragment of a monoclonal antibody with high specificity for human TNF α  Phase II studies have demonstrated the efficacy and tolerability of sc certolizumab pegol 400mg 4-weekly (Q4W) in patients with moderate to severe Crohn’s disease (CD)  PRECiSE 1 and 2 are large well controlled studies demonstrating the safety and efficacy of certolizumab pegol in inducing and maintaining response and remission in patients with moderate to severe CD

Aim  Determine the efficacy and safety of certolizumab pegol maintenance treatment compared to three doses of certolizumab followed by placebo in patients with moderate to severe Crohn’s disease

PRECiSE 2 study design CDAI score 220–450 points inclusive Stratified for: – CRP <10 mg/L or ≥10 mg/L – baseline steroids and immunosuppressants Responders a Nonresponders Discontinue Certolizumab Q4W Placebo Q4W Primary endpoint a Defined as patients with ≥100-point fall from Week 0 CDAI score Doses Weeks Identify Responders, a Randomise 1:1 Randomised, double-blind maintenance phase Certolizumab open-label induction phase

Efficacy Measures  Primary efficacy:  Clinical Response (≥ 100 point decrease from Baseline CDAI) at Week 26 in patients with baseline CRP  10 mg/L  Secondary efficacy (selected):  Clinical Response (≥100 points) irrespective of baseline CRP  Clinical Remission (CDAI≤150 points) in overall population and in patients with CRP ≥ 10 mg/L  Patients with change in IBDQ ≥ 16 points

Patient Disposition Responders Randomized N=428 Placebo n=212 (102,110) Certolizumab n=216 (113,103) ITT n=215 (112,103) ITT n=210 (101,109) Completed 26 weeks n=109 (51.9%) (46 ;45.5%, 63; 57.8%) Completed 26 weeks n=150 (69.8%) (77; 68.8%, 73; 70.9%) Entered Induction N=668 “n” for CRP ≥ 10 /< 10

Demographic & Baseline Characteristics (ITT) 3 inj. + Placebo (N=210) Certolizumab (N=215) Age (years)Mean (SD)37.6 (12.07)37.5 (11.21) Range GenderMale109 (51.9%)92 (42.8%) Female101 (48.1%)123 (57.2%) Duration of DiseaseMean (years)Median Range<1-43<1-33 Resection Performed Previous Infliximab Yes 73 (34.8%) 51 (24.3%) 64 (29.8%) 52 (24.2%)

Concurrent Use of Crohn’s Treatment at Baseline* (ITT) 3 inj. + Placebo (N=210) Certolizumab (N=215) Corticosteroids (CS)78 (37.1%)75 (34.9%) Mesalazine82 (39.0%)86 (40.0%) Sulfasalazine35 (16.7%)32 (14.9%) Immunosuppressants (IS)86 (41.0%)87 (40.5%) AZA62 (29.5%)73 (34.0%) MTX9 (4.3%)9 (4.2%) 6-MP16 (7.6%)6 (2.8%) CS and IS34 (16.2%)28 (13.0%) * Patients could be on multiple therapies

Clinical Response at Week 6, Open Label (All Patients, N=668)

Clinical Response at Week 26 (ITT) N=210N=215n=101n=112 p < 0.001

Clinical Response over Time CRP  10 (ITT) p < † Non overlapping confidence interval † † †

Clinical Response over Time All (ITT) p < † Non overlapping confidence interval † † † †

Clinical Remission at Week 26 (ITT) N=210N=215n=101n=112 p<0.01

Clinical Remission over Time CRP  10 (ITT) p < 0.01 † Non overlapping confidence interval †

Clinical Remission over Time All (ITT) p < † Non overlapping confidence interval † †

Clinical Response at Week 26 by Use of Immunosuppressants (CRP≥10 mg/L, ITT) n= 41 n=45 n=60 n=67 p = 0.002p = 0.014

Clinical Response at Week 26 by prior Anti-TNF Use All (ITT) n=159n=163n=51n=52 *

Patients with Increase in IBDQ ≥16 Points at Week 26 (ITT) p<0.05p<0.001 N=210N=214n=101n=112

Safety Profile – Open Label Any AE Intensity Mild Moderate Severe Related SAE AE leading to withdrawal AE leading to death Certolizumab (N=668) 1094 (392, 58.7%) 675 (290, 43.4%) 348 (193, 28.9%) 71 (54, 8.1%) 336 (161, 24.1%) 56 (47, 7.0%) 65 (51, 7.6%) 1 (1, 0.1%) Number of AEs (number of patients, % of patients)

Safety Any AE Intensity Mild Moderate Severe Related SAE AE leading to withdrawal Certolizumab (N=216) 411 (140, 64.8%) 254 (105, 48.6%) 135 (70, 32.4%) 22 (16, 7.4%) 87 (49, 22.7%) 19 (12, 5.6%) 25 (18, 8.3%) Number of AEs (number of patients, % of patients) 3 inj. + Placebo (N=212) 394 (143, 67.5%) 211 (97, 45.8%) 154 (84, 39.6%) 29 (19, 9.0%) 120 (58, 27.4%) 19 (14, 6.6%) 34 (28, 13.2%)  Greater incidence of injections site reactions with placebo  1 case of TB  Low incidence of antibodies to certolizumab (8%)

Conclusions  Treatment with certolizumab pegol 400 mg Q4W was superior in maintaining response and remission in patients with CD compared to three injections of certolizumab followed by placebo (p<0.001)  Efficacy (Response & Remission) statistically significantly different between maintenance with certolizumab and three injections of certolizumab followed by placebo, irrespective of baseline CRP  Significant difference achieved in patients previously exposed to infliximab  Certolizumab pegol was well tolerated and its safety profile did not identify any signals of concern