Conclusions High levels of skin clearance were observed with bimekizumab after one dose and at Week 16, compared with placebo. Clinical responses were durable through 56 weeks, regardless of bimekizumab dosing schedule. Bimekizumab was well-tolerated and the safety profile was consistent with previous studies.4–7 Objectives To compare the efficacy and safety of bimekizumab with placebo over 16 weeks in patients with plaque psoriasis, and evaluate the effect of randomized treatment withdrawal, compared with continued treatment, in Week 16 responders. Background Bimekizumab is a monoclonal IgG1 antibody that has been rationally designed to selectively inhibit IL-17F in addition to IL-17A.1,2 Both of these interleukins are implicated in the immunopathogenesis of plaque psoriasis (PSO).3 Bimekizumab led to substantial clinical improvements in patients with moderate to severe PSO in the phase 2 BE ABLE study (NCT02905006, NCT03010527), with no unexpected safety findings.4,5 Methods Adult patients with moderate to severe PSO were enrolled in the pivotal phase 3 BE READY study (NCT03410992), which incorporated a 16-week randomized, double-blinded, placebo-controlled period followed by a 40-week randomized withdrawal period (Figure 1). • The co-primary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) and an Investigator’s Global Assessment score of 0 or 1 (IGA 0/1) at Week 16. Secondary endpoints included PASI 100 at Week 16 and PASI 75 at Week 4. Other endpoints included PASI 75, PASI 90, and PASI 100 at other timepoints. • Missing data were imputed with non-responder imputation (NRI). • Treatment emergent adverse events (TEAEs) were classified using MedDRA version 19.0. Results Patient Population • Baseline characteristics are shown in Table 1. Efficacy • Co-primary endpoints of PASI 90 and IGA 0/1 at Week 16 were achieved by 90.8% and 92.6% of bimekizumab-treated patients, respectively, compared with 1.2% and 1.2% in the placebo group, respectively (p<0.001 for both). • Response was rapid, with over 75% of bimekizumab-treated patients achieving PASI 75 at Week 4, after just one dose (Figure 2). • PASI 90 response was well-maintained in patients re-randomized to bimekizumab, regardless of dosing schedule (Figure 3). • Among patients re-randomized to placebo, loss of response was slow; median time to relapse (loss of PASI 75 response following re-randomization was ~28 weeks (~32 weeks from last bimekizumab dose). Safety • Overall, bimekizumab was well-tolerated; discontinuation due to TEAEs was low, and there were no deaths in the study (Table 2). • All cases of oral candidiasis were localized, mild, or moderate superficial infections, and no cases led to discontinuation (Table 2). The most common TEAEs with bimekizumab were nasopharyngitis, oral candidiasis, and upper respiratory tract infection. K. Gordon,1 P. Foley,2 J.G. Krueger,3 A. Pinter,4 K. Reich,5 R. Vender,6 V. Vanvoorden,7 C. Madden,8 L. Peterson,8 A. Blauvelt9 Figure 1 Study design Author Affiliations: 1Medical College of Wisconsin, Milwaukee, WI, USA; 2Skin Health Institute, Carlton, Victoria, Australia; 3The Rockefeller University, New York, NY, USA; 4University Hospital Frankfurt am Main, Department of Dermatology, Frankfurt am Main, Germany; 5Center for Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf and Skinflammation® Center, Hamburg, Germany; 6Division of Dermatology, McMaster University, Hamilton, Ontario, Canada; 7UCB Pharma, Brussels, Belgium; 8UCB Pharma, Raleigh, NC, USA; 9Oregon Medical Research Center, Portland, OR, USA. Presented at Fall Clinical Dermatology Conference 2020 | October 29–November 1 | Las Vegas, NV Efficacy and Safety of Bimekizumab in Patients with Moderate to Severe Plaque Psoriasis: Results from BE READY, a 56-Week Phase 3, Randomized, Double-Blinded, Placebo-Controlled Study with Randomized Withdrawal References: 1Durham L. Curr Rheumatol Reports 2015;17:55; 2Fujishima S. Arch Dermatol Res 2010;302:499–505; 3Johnston A. et al. J Immunol 2013;190:2252–62; 4Papp K. et al. JAAD 2018;79(2):277–286, NCT02905006; 5Blauvelt A. et al. AAD 2019 (OP11180), NCT03010527; 6Glatt S. et al. Br J Clin Pharm 2017;83(5):991i1001; 7Glatt S. et al. Ann Rheum Dis 2018;77:523–32. Author Contributions: Substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: KG, PF, JGK, AP, KR, RV, VV, CM, LP, AB; Drafting of the publication, or revising it critically for important intellectual content: KG, PF, JGK, AP, KR, RV, VV, CM, LP, AB; Final approval of the publication: KG, PF, JGK, AP, KR, RV, VV, CM, LP, AB. Author Disclosures: KG: Honoraria and/or research support from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira Inc., Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma. PF: Received grant support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sun Pharma, and Sanofi; served as an Investigator for AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Botanix, Celgene, Celtaxsys, CSL, Cutanea, Dermira Inc., Eli Lilly, Galderma, Genentech, Geneseq, GSK, Hexima, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., Reistone, Roche, Sanofi, Sun Pharma, UCB Pharma, and Valeant; served on the advisory board of AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Mayne Pharma, Merck, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Valeant; served as a consultant for Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, UCB Pharma, and Wintermute; received travel grants from AbbVie, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, and Sanofi; served as a speaker for or received honoraria from AbbVie, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer, and Roche. JGK: Grants paid to institution from AbbVie, Akros, Allergan, Amgen, Avillion, Biogen MA, Boehringer Ingelheim, Botanix, Bristol-Myers Squibb, Celgene, Eli Lilly, Exicure, Incyte, Innovaderm, Janssen, LEO Pharma, Novan, Novartis, Paraxel, Pfizer, Regeneron, Sienna, UCB Pharma, and Vitae; personal fees from AbbVie, Allergan, Almirall, Amgen, Arena, Aristea, Asana, Aurigne, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Escalier, LEO Pharma, Nimbus, Novartis, Menlo, Sanofi, Sienna, Sun Pharma, Pfizer, UCB Pharma, and Valeant. AP: Worked as an investigator and/or speaker and/or advisor for AbbVie, Almirall Hermal, Amgen, Biogen, Boehringer Ingelheim, Celgene, GSK, Eli Lilly, Galderma, Hexal, Janssen, LEO Pharma, MC2, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Schering-Plough, and UCB Pharma. KR: Served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Affibody, Almirall, Amgen, Avillion, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Covagen, Dermira Inc., Eli Lilly, Forward Pharma, Fresenius Medical Care, Galapagos, GSK, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Medac, Merck Sharp & Dohme, Miltenyi Biotec, Novartis, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Sun Pharma, Takeda, UCB Pharma, Valeant, and Xenoport. RV: Consultant, and/or scientific advisor, and/or investigator, and/or speaker for Amgen, AbbVie, Astellas, Bausch Health/Valeant, Bristol- Myers Squibb, Boehringer Ingelheim, Celgene, Dermira Inc., Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Merck, Sharp & Dohme, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, and UCB Pharma. VV, CM, LP: Employees of UCB Pharma. AB: Served as a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Allergan, Almirall, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira Inc., Eli Lilly, Forte, Galderma, Janssen, LEO Pharma, Novartis, Ortho, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma; paid speaker for AbbVie. Acknowledgements: This study was funded by UCB Pharma. We thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. The authors acknowledge Susanne Wiegratz, MSc, UCB Pharma, Monheim am Rhein, Germany and Eva Cullen, PhD, UCB Pharma, Brussels, Belgium for publication coordination and critical review, Joe Dixon, PhD, Costello Medical, Cambridge, UK, for medical writing and editorial assistance, and the Costello Medical Design Team for design support. All costs associated with development of this poster were funded by UCB Pharma in accordance with the Good Publication Practice (GPP3) guidelines. aOne placebo-randomized patient achieved PASI 90 at Week 16 and continued to receive placebo treatment to Week 56. Synopsis Patients were randomized 4:1 to receive bimekizumab every four weeks or placebo for an initial 16 weeks of treatment Methods To compare the efficacy and safety of bimekizumab with placebo in patients with moderate to severe plaque psoriasis Objective BE READY met both of its co-primary endpoints at Week 16, with significantly higher PASI 90 and IGA 0/1 responder rates vs placebo Results PASI 90 High levels of skin clearance were observed with bimekizumab at Week 16 Bimekizumab was well-tolerated and the safety profile was consistent with previous studies Conclusion IGA 0/1 Table 1 Baseline characteristics Figure 2 PASI 75, PASI 90, and PASI 100 over 16 weeks (ITT, NRI) Figure 3 PASI 90 in maintenance and withdrawal arms (Week 16 PASI 90 responders, NRI) Table 2 Safety Placebo n=86 Bimekizumab 320 mg Q4W n=349 All patients N=435 Age (years), mean ± SD 43.5 ± 13.1 44.5 ± 12.9 44.3 ± 12.9 Male, n (%) 58 (67.4) 255 (73.1) 313 (72.0) Caucasian, n (%) 79 (91.9) 324 (92.8) 403 (92.6) Weight (kg), mean ± SD 91.7 ± 22.2 88.7 ± 20.6 89.3 ± 20.9 Duration of PSO (years), mean ± SD 19.1 ± 12.8 19.6 ± 13.3 19.5 ± 13.2 PASI, mean ± SD 20.1 ± 7.6 20.4 ± 7.6 20.3 ± 7.6 BSA (%), mean ± SD 24.4 ± 16.0 24.6 ± 15.2 24.5 ± 15.4 IGA, n (%) 3: moderate 62 (72.1) 242 (69.3) 304 (69.9) 4: severe 24 (27.9) 107 (30.7) 131 (30.1) DLQI total, mean ± SD 11.3 ± 6.9 10.4 ± 6.3 10.6 ± 6.4 Any prior systemic therapy, n (%) 71 (82.6) 276 (79.1) 347 (79.8) Prior biologic therapy, n (%) 37 (43.0) 154 (44.1) 191 (43.9) anti-TNF 12 (14.0) 62 (17.8) 74 (17.0) anti-IL-17 18 (20.9) 85 (24.4) 103 (23.7) anti-IL-23 5 (5.8) 28 (8.0) 33 (7.6) anti-IL-12/23 11 (12.8) 40 (11.5) 51 (11.7) BSA: body surface area; DLQI: Dermatology Life Quality Index; IGA: Investigator’s Global Assessment; IL: interleukin; ITT: intent-to-treat; LFT: liver function test; MACE: major adverse cardiovascular event; NEC: not elsewhere classified; NRI: non-responder imputation; PASI 75/90/100: ≥75/90/100% improvement from baseline in Psoriasis Area and Severity Index; PSO: psoriasis; Q4W: every 4 weeks; Q8W: every 8 weeks; SD: standard deviation; SIB: suicidal-ideation behavior ; TEAE: treatment emergent adverse event; TNF: tumor necrosis factor. Initial period (Weeks 0–16) Randomized withdrawal period (Weeks 16–56) Bimekizumab 320 mg Q4W Placebo (n=86) n (%) Bimekizumab 320 mg Q4W (n=349) n (%) Placebo (n=105) n (%) Bimekizumab 320 mg Q8W (n=100) n (%) Bimekizumab 320 mg Q4W (n=106) n (%) Incidence of TEAEs Any TEAE 35 (40.7) 213 (61.0) 72 (68.6) 77 (77.0) 78 (73.6) Serious TEAEs 2 (2.3) 6 (1.7) 4 (3.8) 3 (3.0) 5 (4.7) Discontinuation due to TEAEs 1 (1.2) 4 (1.1) 3 (2.9) 2 (2.0) 0 Drug-related TEAEs 7 (8.1) 65 (18.6) 23 (21.9) 23 (23.0) 28 (26.4) Severe TEAEs 1 (1.2) 3 (0.9) 4 (3.8) 1 (1.0) 4 (3.8) Deaths 0 0 0 0 0 Common TEAEs (>5% of Patients) Nasopharyngitis 4 (4.7) 23 (6.6) 20 (19.0) 23 (23.0) 11 (10.4) Oral candidiasis 0 21 (6.0) 6 (5.7) 9 (9.0) 12 (11.3) Upper respiratory tract infection 7 (8.1) 14 (4.0) 5 (4.8) 8 (8.0) 12 (11.3) TEAEs of Interest Inflammatory bowel disease 0 0 0 0 0 Adjudicated SIB 0 0 0 0 0 Malignancies 0 1 (0.3)a 1 (1.0)b 0 0 Neutropenia 0 3 (0.9) 0 1 (1.0) 0 Hypersensitivity reactionsc 1 (1.2) 12 (3.4) 3 (2.9) 2 (2.0) 3 (2.8) Adjudicated MACE 0 0 0 1 (1.0)d 0 Hepatic events 1 (1.2) 10 (2.9) 0 3 (3.0) 8 (7.5) Liver function analysese 1 (1.2) 9 (2.6) 0 2 (2.0) 8 (7.5) Fungal infectionsf,g 2 (2.3) 40 (11.5) 7 (6.7) 14 (14.0) 22 (20.8) Candida infections 0 27 (7.7) 6 (5.7) 10 (10.0) 16 (15.1) Tinea infections 0 9 (2.6) 0 1 (1.0) 4 (3.8) aOne case of basal cell carcinoma; bOne case of prostate cancer; cHypersensitivity reactions were predominantly cutaneous, with no cases of acute anaphylaxis in any treatment group; dA non-fatal myocardial infarction in a 53-year old male with 6 pre-existing cardiovascular risk factors, which was not attributed to the study drug; eIn the initial treatment period, incidence of LFT elevations with bimekizumab was generally low and comparable to placebo; majority of LFT elevations were transient and resolved by end of study; fAll fungal infections not classified as Candida or Tinea were classified as fungal infections NEC; gIn addition, all opportunistic infections were localized mucocutaneous fungal infections defined as opportunistic by convention; there were no systemic opportunistic infections or cases of active tuberculosis reported. *p<0.001 versus placebo. For PASI 75 at Week 4, and PASI 90/PASI 100 at Week 16, p values for the comparison of treatment groups were based on the Cochran–Mantel–Haenszel test from the general association; for other comparisons, p values for a general association were based on a stratified Cochran–Mantel–Haenszel test, where region and prior biologic exposure were used as stratification variables, are considered nominal, and were not controlled for multiplicity. Placebo responder rates at Week 4: PASI 75=1.2%, PASI 90=0%, PASI 100=0%; Placebo responder rates at Week 16: PASI 75=2.3%, PASI 90=1.2%, PASI 100=1.2%. *nominal p<0.001 versus placebo. p values for the comparison of treatment groups were based on stratified Cochran–Mantel–Haenszel test, where region and prior biologic exposure were used as stratification variables. Patients randomized to bimekizumab 320 mg Q4W who achieved PASI 90 at Week 16 were re-randomized for maintenance treatment; for patients re-randomized to placebo, the last dose of bimekizumab was at Week 12. n=349 n=86 n=100 n=106 n=105 Week 16Baseline Week 56 20 weeks after last dose for patients not enrolling in extension study: safety follow-up 2–5 weeks Bimekizumab 320 mg Q4W Bimekizumab 320 mg Q4W 12-week escape arm: bimekizumab 320 mg Q4W Bimekizumab 320 mg Q8W Placeboa Placeboa