PowerPoint Presentation 0 20 40 60 80 100 0 1 2 4 6 8 12 M C ID in D LQ I, % p at ie nt s† Synopsis • IL-17A and IL-17F are pro-inflammatory cytokines that share ~50% structural homology and overlapping biological function.1–3 Both IL-17A and IL-17F are expressed at sites of inflammation4,5 and independently co-operate with other cytokines to mediate inflammation4 (Figure 1) • Dual neutralization of IL-17A and IL-17F in disease-relevant human cellular systems resulted in lower expression of inflammation-linked genes and pro-inflammatory cytokines as well as greater suppression of immune cell migration when compared with IL-17A blockade alone4 • Bimekizumab, a monoclonal IgG1 antibody, potently and selectively neutralizes the biological function of both IL-17A and IL-17F4,6,7 References 1Yang et al, J Exp Med 2008;1063–1075; 2Hymowitz et al, EMBO 2001;20:5332–5341; 3Chu, Targeting the IL-17 Pathway in Inflammatory Disorders 2017, ADIS; 4Glatt et al, Ann Rhem Dis 2018;77:523–532; 5Van Baarsen et al. Arthritis Res & Ther 2014;16:426; 6Glatt et al, Br J Clin Pharm 2017;83:991–1001; 7Papp et al, JAAD 2018;doi: 10.1016/j.jaad.2018.03.037 Disclosures, funding, and acknowledgements This study was funded by UCB Pharma KA Papp has received consultant fees from Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, CanFite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Janssen, Kyowa Hakko Kirin, LEO Pharma, Meiji, Seika Pharma, MSD, Merck Serono, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi/Genzyme, Takeda, UCB, and Valeant; investigator fees from Astellas, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GSK, Janssen, Kyowa Hakko Kirin, LEO Pharma, MedImmune, MSD, Merck-Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi/Genzyme, Takeda, UCB, and Valeant; speaker fees from Astellas, Celgene, Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, MSD, Novartis, Pfizer, and Valeant; has participated in advisory boards for Astellas, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Galderma, Janssen, MSD, Novartis, Pfizer, Regeneron, Sanofi/Genzyme, UCB, and Valeant; is a steering committee member for Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Kyowa Hakko Kirin, MSD, Merck-Serono, Novartis, Pfizer, Regeneron, Sanofi/Genzyme, and Valeant; and is a scientific officer for Kyowa Hakko Kirin. JF Merola has received honoraria from AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Samumed and UCB. AB Gottlieb has received consultant fees, advisory board fees or speaker bureau fees from Janssen Inc.; Celgene Corp., Bristol Myers Squibb Co., Beiersdorf, Inc., Abbvie, UCB, Novartis, Incyte, Lilly, Reddy Labs, Valeant, Dermira, Allergan, Sun Pharmaceutical Industries; and research grants from Janssen, Incyte, Lilly, Novartis, Allergan, LEO. CEM Griffiths has received grants and personal fees from AbbVie, Celgene, LEO, Lilly, Janssen, Novartis, Pfizer, and UCB Pharma; grants from Sandoz; personal fees from Almirall and Galderma. CG has received research grants from AbbVie, Celgene, Novartis, Eli Lilly, Janssen, Sandoz, Pfizer, LEO, and UCB. KK Harris, N Cross, L Peterson and C Cioffi are employees of UCB. L Peterson and C Cioffi hold UCB stock or stock options. A Blauvelt has received consultant fees from Eli Lilly and Company, Janssen, Regeneron, and Sanofi Genzyme; and a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Inc., Eli Lilly and Company, Genentech/Roche, GlaxoSmithKline, Janssen, Leo, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, Valeant, and Vidac. The authors would like to acknowledge Alexandra Webster, MSc, of iMed Comms, an Ashfield Company, for medical writing support that was funded by UCB Pharma in accordance with Good Publication Practice (GPP3) guidelines. Dual neutralization of IL-17A and IL-17F with bimekizumab improves quality of life in patients with moderate-to-severe plaque psoriasis: results from a Phase 2b study and correlation with clinical response Kim A. Papp1, Joseph F. Merola2, Alice B. Gottlieb3, Christopher E.M. Griffiths4, Kristina K. Harris5, Nancy Cross6, Luke Peterson6, Christopher Cioffi7, Andrew Blauvelt8 1Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada; 2Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA; 3New York Medical College, Metropolitan Hospital, New York, NY, USA; 4Dermatology Centre, University of Manchester, Manchester, UK; 5UCB Pharma, Hong Kong, China; 6UCB Biosciences Inc., Raleigh, NC, USA; 7UCB Pharma, Brussels, Belgium; 8Oregon Medical Research Center, Portland, OR, USA 37th FCD Conference 18–21 October 2018 Las Vegas, NV, USA Conclusion • Dual neutralization of IL-17A and IL-17F with bimekizumab in patients with moderate-to-severe plaque psoriasis was associated with rapid onset of clinically meaningful efficacy, with no unexpected safety findings • Bimekizumab treatment also resulted in rapid improvements in disease-specific quality of life measures in the majority of patients, which correlated with clinical response • These data support achievement of high levels of skin clearance (absolute PASI ≤2) being associated with superior improvements in disease-specific HRQoL Weeks Figure 4A. MCID, 3x MCID and 4x MCID in DLQI at Week 12; Figure 4B. MCID in DLQI by visit in patients with baseline DLQI ≥4, full analysis set (observed values); *percentages calculated based on total numbers of evaluable patients at Week 12; †percentages calculated based on total numbers of evaluable patients at each visit Figure 5A. DLQI of 0 or 1 by absolute PASI at Week 12; Figure 5B. DLQI of 0 or 1 by BSA affected by psoriasis at Week 12; combined bimekizumab dose group, full analysis set (observed values); *percentages calculated based on total numbers of evaluable patients at Week 12 In the pooled bimekizumab group, patients with lower absolute PASI (≤2) more frequently achieved DLQI of 0 or 1 versus those with higher absolute PASI at Week 12 (Figure 5A); similar results were observed at Week 12 in patients with lower BSA versus higher BSA involvement (Figure 5B) Figure 1. Dual neutralization of IL-17A and IL-17F in immune-mediated inflammatory diseases Results At the individual patient level, rapid improvements were observed in absolute PASI over time for those receiving bimekizumab. By Week 12, in the three highest bimekizumab dose groups almost all patients had an absolute PASI <2 with the majority of patients at or near zero (Figure 3); PASI improvements were correlated with reductions in DLQI, with the majority of patients achieving a DLQI of 0 or 1 (no impact of psoriasis on disease-specific HRQoL) at Week 12 (Figure 3) All or nearly all patients with baseline DLQI ≥4 achieved MCID in DLQI at Week 12 in the top three bimekizumab dose groups; 3x MCID and 4x MCID were also achieved by a substantially greater percentage of bimekizumab patients with baseline DLQI ≥12 and ≥16, respectively, compared with placebo (Figure 4A). MCID in DLQI was achieved rapidly and differentiated from placebo after first dose across all bimekizumab groups (Figure 4B) BKZ 64 mg; n=33 BKZ 160 mg; n=37 BKZ 320 mg; n=37 BKZ 160 mg (320 mg LD); n=34 BKZ 480 mg; n=31 A) B) 79.6 53.6 64.3 52.5 0 20 40 60 80 100 ≤1 >1 – ≤3 >3 – ≤5 >5 DLQI of 0 or 1, % patients* B S A a ff ec te d by p so ri as is B) n=40 n=14 n=28 n=108 77.7 73.9 51.7 29.4 0 20 40 60 80 100 ≤1 >1 – ≤2 >2 – ≤5 >5 DLQI of 0 or 1, % patients* A bs ol ut e PA S I Absolute PASI in bimekizumab-treated patients BSA affected by psoriasis in bimekizumab-treated patients A) n=17 n=29 n=23 n=121 0 20 40 60 80 100 0 2 4 6 8 10 12 PA S I1 00 r es po ns e, % ( S E ) of p at ie nt s 28.2%** 27.9%*** 48.8%*** 60.0%*** 55.8%*** 0% Weeks BE ABLE 1: summary of key results • In this Phase 2b, double-blind, placebo-controlled study (NCT02905006), patients with moderate-to-severe plaque psoriasis were randomized (1:1:1:1:1:1) to receive bimekizumab 64 mg, 160 mg, 160 mg with 320 mg loading dose, 320 mg, 480 mg, or placebo every 4 weeks for 12 weeks; the primary objective was to evaluate the dose response of bimekizumab7 • There was a significant dose response for Psoriasis Area Severity Index (PASI)90 (P<0.0001) at Week 12. The primary endpoint, PASI90 at Week 12, was achieved by significantly more patients receiving each bimekizumab dose compared with placebo (Figure 2A)7 • Up to 60.0% of bimekizumab-treated patients achieved complete skin clearance (PASI100) at Week 12 (Figure 2B)7 • The safety profile of bimekizumab was consistent with previous studies4,5 with no unexpected safety findings7 Figure 2A. PASI90 response over time7; Figure 2B. PASI100 response over time7, full analysis set (non- responder imputation); **p<0.001, ***p<0.0001 versus placebo (Fisher’s exact test); note: no patients receiving placebo achieved PASI90 or PASI100 at any time point; SE, standard error Methods • Patients completed the Dermatology Life Quality Index (DLQI) questionnaire at baseline, Week 1, Week 2, Week 4, Week 8 and Week 12 • DLQI of 0 or 1 was used to indicate no impact of psoriasis on disease-specific HRQoL; minimal clinically important difference (MCID) was defined as 4-point reduction in DLQI from baseline • Patients were grouped by absolute PASI (≤1, >1–≤2, >2–≤5, >5) and BSA affected by psoriasis (≤1%; >1–≤3%, >3–≤5%, >5%) to evaluate a possible correlation between clinical response and achievement of DLQI 0 or 1 • Patient demographics and baseline disease characteristics were balanced across treatment groups (mean [SD] DLQI total: 10.7 [6.9]; PASI: 19.1 [6.5]; percentage BSA involvement: 25.1 [13.3])7 0 20 40 60 80 100 0 2 4 6 8 10 12 Weeks 0% 46.2%*** 67.4%*** 72.1%*** 75.0%*** 79.1%*** P A S I9 0 re sp on se , % ( S E ) of p at ie nt s PASI90 response PASI100 response 27.3 81.3 90.9 100 97.1 96.4 10.5 66.7 76.5 78.6 53.3 85.7 7.7 53.8 37.5 80.0 57.1 62.5 0 20 40 60 80 100 Placebo BKZ 64 mg BKZ 160 mg BKZ 160 mg (320 mg LD) BKZ 320 mg BKZ 480 mg A) B) 3x MCID n=19 4x MCID n=13 MCID n=33 3x MCID n=21 4x MCID n=13 MCID n=32 3x MCID n=17 4x MCID n=8 MCID n=33 3x MCID n=14 4x MCID n=10 MCID n=29 3x MCID n=15 4x MCID n=7 MCID n=35 3x MCID n=14 4x MCID n=8 MCID n=28 Placebo; n=36 M C ID in D LQ I, % p at ie nt s* Objective To evaluate disease-specific health-related qualify of life (HRQoL) data from the Phase 2b study7 and its correlation with the absolute PASI and Body Surface Area (BSA) affected Figure 3. Absolute PASI and DLQI over time (patient-level data); x missing data imputed as last observation carried forward; box plots are first quartile, median and third quartile. Whiskers extend to ±1.5 times the interquartile range. Where the whisker value exceeded the data range, the maximum or minimum value was used, as appropriate Placebo; n=42 BKZ 64 mg; n=39 BKZ 160 mg; n=43 BKZ 320 mg; n=43 BKZ 160 mg (320 mg LD at baseline); n=40 BKZ 480 mg; n=43 PASI Placebo; (n = 42) BKZ 480 mg; (n = 43) BKZ 320 mg; (n = 43) BKZ 160 mg; (n = 43) BKZ 64 mg; (n = 39) BKZ 160 mg; (320 mg LD; n = 40) 0 5 10 15 20 25 30 35 40 45 50 P A S I Baseline Week 4 Week 8 Week 12 PASI=2 Slide Number 1