Confidential Do not use externally | Company Confidential © 2019 Efficacy and safety of upadacitinib induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from the phase 3 U-ACHIEVE study Silvio Danese,1 Séverine Vermeire,2 Wen Zhou,3 Aileen Pangan,3 Jesse Siffledeen,4 Xavier Hébuterne,5 Hiroshi Nakase,6 Peter D.R. Higgins,7 Min-Hu Chen,8 Yuri Sanchez Gonzalez,3 Bidan Huang,3 Wangang Xie,3 John Liu,3 Michael A. Weinreich,3 Remo Panaccione9 Confidential Do not use externally | Company Confidential © 2019 1Humanitas University and Humanitas Research Hospital, IRCCS, Milan, Italy; 2Department of Gastroenterology & Hepatology, University Hospital Leuven, KU Leuven, Leuven, Belgium; 3AbbVie Inc., North Chicago, IL, USA; 4University of Alberta, Edmonton, Canada; 5Université Côte d’Azur, CHU de Nice, Nice, France; 6Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan; 7Department of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA; 8Division of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; 9Division of Gastroenterology, University of Calgary, Calgary, Alberta American College of Gastroenterology (ACG), October 22-27, 2021, Hybrid Conference P19

Background and aim • Despite availability of multiple treatment options, many patients with ulcerative colitis (UC) do not achieve disease remission with current therapies and unmet therapeutic need remains, especially in patients with moderate to severe disease.1,2 • Upadacitinib (UPA) is a selective and reversible JAK inhibitor in development for the treatment of moderately-to-severely active UC. • U-ACHIEVE is one of two phase 3 induction trials that evaluates the safety and efficacy of UPA 45 mg once daily (QD) in adults with moderately-to-severely active UC. 1. Singh S, et al. Clinical Gastroenterology and Hepatology 2020;18(10): 2179-2191.e 2. Tripathi, K. and Feuerstein, J.D. Drugs Context. 2019;8:212572

U-ACHIEVE study design DB, double-blind; OL, open-label, QD, once daily; UPA, upadacitinib

Endpoints • The primary endpoint was proportion of patients achieving clinical remission at week 8 • Per adapted Mayo Score (stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ≤1) • Ranked secondary endpoints included: • Endoscopic improvement at week 8 (Mayo endoscopic subscore ≤1) • Endoscopic remission at week 8 (Mayo endoscopic subscore = 0) • Clinical response per adapted Mayo Score at week 8 (decrease in adapted Mayo score ≥2 points and ≥30% from baseline and a decrease in rectal bleeding subscore ≥1 or an absolute rectal bleeding score ≤1) • Clinical response per partial adapted Mayo Score at week 2 (decrease in partial adapted Mayo score ≥1 points and ≥30% from baseline and a decrease in rectal bleeding subscore ≥1 or an absolute rectal bleeding score ≤1) • Histologic-endoscopic mucosal improvement at week 8 (endoscopic subscore of 0 or 1 and Geboes score ≤3.1) • Safety was assessed through week 8 (reported as occurrence of adverse events [AE])

Induction study: Patient disposition ITT population N=473 PBO n=154a UPA 45 mg QD n=319 Discontinued study drug: 19 (12.3%) • Adverse event: 7 (4.5%) • Withdrew consent: 2 (1.3%) • Lack of efficacy: 9 (5.8%) • Other: 1 (0.6) Discontinued study drug: 12 (3.8%) • Adverse event: 7 (2.2%) • Withdrew consent: 1 (0.3%) • Lack of efficacy: 2 (0.6%) • Lost to follow-up: 1 (0.3%) • Other: 1 (0.3%) Completed n=135 (87.7%) Completed n=307 (96.2%) ITT, intent-to-treat population, consisting of all randomized patients who received at least one dose of study drug. aOne subject treated with placebo was excluded from the efficacy analysis due to significant non-compliance issue at the site. This patient was included in safety analysis.

Baseline characteristics and demographics Variable PBO (n=154)a UPA 45 mg QD (n=319) Female, n (%) 57 (37.0) 121 (37.9) Race, white, n (%) 100 (64.9) 206 (64.6) Age, median (range), y 44.5 (18–76) 43.0 (19–76) Disease duration, mean (SD), y 9.1 (8.8) 8.6 (7.2) Weight, mean (SD), kg 74.0 (19.2) 71.3 (17.4) Disease extent Left-sided 74 (48.1) 158 (49.5) Extensive/pancolitis 80 (51.9) 161 (50.5) Fecal calprotectin, median (range), mg/kg 1902 (30–28,800) 1780 (30–28,800) hsCRP, median (range), mg/L 4.7 (0.2–179) 4.1 (0.2–105) Baseline aminosalicylates use, n (%) 102 (66.2) 220 (69.0) Baseline corticosteroid useb,c, n (%) 61 (39.6) 124 (38.9) Biologic-IR, n (%) 78 (50.6) 168 (52.7) Number of prior biologics, ≤1 21 (26.9) 55 (32.7) Number of prior biologics, >1 57 (73.1) 113 (67.3) Non−biologic-IR, n (%) 76 (49.4) 151 (47.3) Prior anti-TNF use, n (%) 73 (47.4) 163 (51.1) Prior vedolizumab use, n (%) 47 (30.5) 91 (28.5) Baseline Full Mayo Score, n (%) ≤9 79 (51.3) 162 (50.9) >9 75 (48.7) 156 (49.1) Baseline adapted Mayo score, b n (%) ≤7 94 (61.0) 195 (61.3) >7 60 (39.0) 123 (38.7) hsCRP, high-sensitivity C reactive protein; IR, inadequate responder; PBO, placebo; QD, once daily; UPA, upadacitinib. aOne PBO patient was excluded from efficacy analyses because of site non-compliance; this patient was included in the safety analysis. bStratification factors for randomization. cThe highest allowed prednisolone dose at baseline was 30 mg

Clinical remission (primary endpoint) and clinical response (ranked secondary endpoint) at week 8 Primary endpoint per adapted Mayo score (defined as stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ≤1) at week 8. Clinical response at week 8 based on adapted Mayo score (defined as decrease in adapted Mayo score ≥2 points and ≥30% from baseline and a decrease in rectal bleeding subscore ≥1 or an absolute rectal bleeding score ≤1). Adjusted treatment difference and 95% CI were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for randomization stratification factors. aOne PBO patient was excluded from efficacy analyses because of site non-compliance. 131/308 Clinical Remission at Week 8 (Primary Endpoint) Clinical Response at Week 8

Clinical response (per partial adapted Mayo Score) over time Clinical response based on partial adapted Mayo score (defined as decrease in partial adapted Mayo score ≥1 points and ≥30% from baseline and a decrease in rectal bleeding subscore ≥1 or an absolute rectal bleeding score ≤1); nominal P values except week 2. aOne PBO patient was excluded from efficacy analyses because of site non-compliance. Clinical response at week 2 is one of the ranked secondary endpoints

Ranked secondary endpoints at week 8 Endoscopic improvement (defined as Mayo endoscopic subscore ≤1). Endoscopic remission defined as Mayo endoscopic subscore 0. Histologic-endoscopic mucosal improvement (HEMI) defined as endoscopic subscore of 0 or 1 and Geboes score ≤3.1. Adjusted treatment difference and 95% CI were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for randomization stratification factors. aOne PBO patient was excluded from efficacy analyses because of site non-compliance.

Change from baseline in inflammatory markers at week 8 C-reactive protein (mg/L) Fecal calprotectin (mg/kg) MMRM (mixed effect model repeat measurement) with baseline, treatment, visit, treatment by visit interaction and stratification factors in the model. Nominal P values.

Safety overview AEs, n (%) Placebo (n=155) UPA 45 mg QD (n=319) Any AE 93 (60.0) 180 (56.4) AE possibly related to study drug 36 (23.2) 87 (27.3) Severe AE 14 (9.0) 9 (2.8) Serious AE 9 (5.8) 8 (2.5) Serious AE possibly related to study drug 3 (1.9) 4 (1.3) AE leading to discontinuation of study drug 14 (9.0) 6 (1.9) Deatha 0 0 AE, adverse event aIncludes both treatment-emergent and non-treatment-emergent death.

Most frequently reported AEs, reported by ≥4% of patients in any treatment group, n (%) Placebo (n=155) UPA 45 mg QD (n=319) Acne 1 (0.6) 15 (4.7) Blood creatine phosphokinase increased 3 (1.9) 15 (4.7) Nasopharyngitis 6 (3.9) 15 (4.7) Headache 4 (2.6) 13 (4.1) Anaemia 9 (5.8) 7 (2.2) Worsening of ulcerative colitis 21 (13.5) 3 (0.9) AEs of special interest , n (%) Serious infection 2 (1.3) 5 (1.6) Hepatic disorder 6 (3.9) 9 (2.8) Anaemia 14 (9.0) 9 (2.8) Neutropenia 1 (0.6) 16 (5.0) Lymphopenia 1 (0.6) 10 (3.1) Creatine phosphokinase elevation 3 (1.9) 15 (4.7) Opportunistic infection (excluding TB and herpes zoster) 0 1 (0.3) Herpes zoster 0 1 (0.3) AE, adverse event, TB, tuberculosis.

Conclusions • In U-ACHIEVE, UPA 45 mg QD was superior to PBO in improvement of clinical, endoscopic, and histologic endpoints in patients with moderately-to-severely active UC over 8 weeks • UPA 45 mg QD as induction therapy was well-tolerated and safety was comparable with the known safety profile of UPA, and no new safety signals were identified • The results are consistent with the second phase 3 UPA 45 mg QD induction study (U-ACCOMPLISH; ECCO presentation #OP231) • Both induction studies met primary and all ranked secondary endpoints 13 1. Vermeire S. et al. OP23 Efficacy and safety of upadacitinib as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from phase 3 U-ACCOMPLISH study. European Crohn’s and Colitis Organisation, 16th Congress of ECCO, July 2-3 & 8-10, 2021.

Backup data on Bio- experienced vs naive Bio-IR (inadequate response to biologic) Patients are more difficult to treat, and generally have lower levels of response and remission to both drug and placebo Comparing response and remission for Bio-experienced (Bio-IR) vs. bio-naïve participants

* Bio-IR status: Experienced previous biologic failure (inadequate response, loss of response, or intolerance to biologic therapies). Non-Bio-IR: Status of previous failure, inadequate response, loss of response or are intolerance to conventional therapy. Non-responder imputation incorporating multiple imputation and 95% CI for response rate based on Student's t-distribution from PROC MIANALYZE procedure was used if data was missing data due to COVID-19. Bio-IR Non-Bio-IR Primary endpoint Secondary endpoints 0.4% 18% 17% 54% 13% 64% Δ 18% Δ 38% Δ 52% 0 20 40 60 80 100 Percentage of Patients Clinical remission (8 wk) Clinical response (2 wk) Clinical response (8 wk) PBO UPA 45 mg QD N= 76 151 76 151 76 151 9.2% 35% 38% 42% 82% Δ 29% Δ 40% Δ 26% 67% U-ACHIEVE Induction Trial: UPA 45 mg QD was Superior Compared to PBO for Clinical Remission and Clinical Response Regardless of Previous Treatment Failure 0 20 40 60 80 100 Percentage of Patients Clinical remission (8 wk) Clinical response (2 wk) Clinical response (8 wk) PBO UPA 45 mg QD 0 20 40 60 80 100 Percentage of Patients Clinical remission (8 wk) Clinical response (2 wk) Clinical response (8 wk) PBO UPA 45 mg QD N= 78 168 78 168 78 168 Clinical remission (wk 8) Clinical response (wk 2) Clinical response (wk 8) Clinical remission (wk 8) Clinical response (wk 2) Clinical response (wk 8)

* * Bio-IR status: Experienced previous biologic failure (inadequate response, loss of response, or intolerance to biologic therapies). Non-Bio-IR: Status of previous failure, inadequate response, loss of response or are intolerance to conventional therapy. Non-responder imputation incorporating multiple imputation and 95% CI for response rate based on Student's t-distribution from PROC MIANALYZE procedure was used if data was missing due to COVID-19. Bio-IR Non-Bio-IR Primary endpoint Secondary endpoints 0 20 40 60 80 100 Percentage of Patients PBO UPA 45 mg QD Clinical remission (8 wk) Clinical response (2 wk) Clinical response (8 wk) N= 89 173 89 173 89 173 2.4% 30% 19% 69% 20% 62% Δ 27% Δ 50% Δ 42% 0 20 40 60 80 100 Percentage of Patients Clinical remission (8 wk) Clinical response (2 wk) Clinical response (8 wk) PBO UPA 45 mg QD N= 85 168 85 168 85 168 38% 64% 32% 80% 32% 5.9% Δ 33% Δ 48% Δ 32% U-ACCOMPLISH Trial: UPA 45 mg QD was Superior Compared to PBO for Clinical Remission and Clinical Response Regardless of Previous Treatment Failure 0 20 40 60 80 100 Percentage of Patients Clinical remission (8 wk) Clinical response (2 wk) Clinical response (8 wk) PBO UPA 45 mg QD

0 20 40 60 80 100 Percentage of Patients HEMI Endoscopic improvement Endoscopic remission PBO UPA 45 m N= 76 151 76 151 76 151 12% 38% Δ 26% Δ 16% 2.6% 19% 13% Δ 34% 47% Bio-IR Non-Bio-IR Bio-IR status: Experienced previous biologic failure (inadequate response, loss of response, or intolerance to biologic therapies). Non-Bio-IR: Status of previous failure, inadequate response, loss of response or are intolerance to conventional therapy. Non-responder imputation incorporating multiple imputation and 95% CI for response rate based on Student's t-distribution from PROC MIANALYZE procedure was used if data was missing due to COVID-19. 0 20 40 60 80 100 Percentage of Patients HEMI Endoscopic improvement Endoscopic remission PBO UPA 45 mg QD 78 168 78 168 N= 78 168 8.9% 1.4% 23% 0 1.7% 27% Δ 21% Δ 8.9% Δ 25% U-ACHIEVE Induction Trial: UPA 45 mg QD was Greater Compared to PBO at Week 8 for Endoscopic and Histologic Endpoints Regardless of Previous Treatment Failure

0 20 40 60 80 100 Percentage of Patients HEMI Endoscopic improvement Endoscopic remission N= 85 168 85 168 85 168 2.4% 12% 51% 7.2% 43% 24% Δ 22% Δ 36% Δ 39% Bio-IR Non-Bio-IR Bio-IR status: Experienced previous biologic failure (inadequate response, loss of response, or intolerance to biologic therapies). Non-Bio-IR: Status of previous failure, inadequate response, loss of response or are intolerance to conventional therapy. Non-responder imputation incorporating multiple imputation and 95% CI for response rate based on Student's t-distribution from PROC MIANALYZE procedure was used if data was missing data due to COVID-19. 0 20 40 60 80 100 Percentage of Patients HEMI Endoscopic improvement Endoscopic remission N= 89 173 89 173 89 173 13% 1.2% 4.8% 37% 4.6% 31% Δ 12% Δ 32% Δ 26% U-ACCOMPLISH Trial: UPA 45 mg QD was Greater Compared to PBO at Week 8 for Endoscopic and Histologic Endpoints Regardless of Previous Treatment Failure