GLP-00068950_Baseline A1C poster layout An Update on the Long-Term Safety Experience of Ixekizumab: Results from the Psoriasis Clinical Development Program with More than 3 Years of Follow-up from 12 Clinical Trials and More Than 15000 Patient-Years of Exposure to Ixekizumab April Armstrong,1 Noah Agada,2 Wen Xu,2 Gaia Gallo2 1Department of Clinical Research, Keck School of Medicine of the University of Southern California, Los Angeles, USA; 2Eli Lilly and Company, Indianapolis, USA Disclosures  A. Armstrong has served as investigator, advisor, and/or speaker for: AbbVie, Celgene, Eli Lilly and Company, Janssen, Novartis, Regeneron, Sanofi, and Valeant; N. Agada, W. Xu, and G. Gallo are current employees and shareholders of Eli Lilly and Company  This study was sponsored by Eli Lilly and Company. Medical writing assistance was provided by Cassandra Haley, PhD, CMPP, of ProScribe – part of the Envision Pharma Group, and was funded by Eli Lilly and Company Overview of Adverse Events Privacy Notice Regarding the Collection of Personal Information By scanning this QR code, you are consenting to have your IP address and, if you choose, email address temporarily retained in a secured computer system and used only for counting purposes, performing file download, and sending you an email. Your information will not be shared for any other purpose, unless required by law. You will not receive any future communications from Eli Lilly and Company based on the system-retained information. Contact information at: http://www.lilly.com/Pages/contact.aspx aInflammatory bowel disease events were defined by narrow terms Incidence Rates of Safety Topics of Special Interest Study was sponsored by Eli Lilly and Company n (IR) [95% CI] All PsO IXE (N=5871)PY=15,212.5 Serious infection 203 (1.3) [1.2, 1.5] Oral candida 144 (0.9) [0.8, 1.1] MACE 76 (0.5) [0.4, 0.6] Non-melanoma skin cancer (NMSC) 47 (0.3) [0.2, 0.4] Malignancies excluding NMSC 78 (0.5) [0.4, 0.6] Inflammatory bowel disease (IBD)a 23 (0.2) [0.1, 0.2] Crohn’s disease 6 (0.0) [0.0, 0.1] Ulcerative colitis 16 (0.1) [0.1, 0.2] IBD preferred term 1 (0.0) [0.0, 0.0] n (IR) [95% CI] All PsO IXE (N=5871)PY=15,212.5 ≥1 TEAEa 5072 (33.3) [32.4, 34.3] Mild 1389 (9.1) [8.7, 9.6] Moderate 2770 (18.2) [17.5, 18.9] Severe 912 (6.0) [5.6, 6.4] ≥1 SAE 854 (5.6) [5.2, 6.0] Deaths 32 (0.2) [0.1, 0.3] Discontinuations due to adverse event 432 (2.8) [2.6, 3.1] Patients with multiple occurrences of the same event were categorized by the highest severity aSeverity data were missing for 1 patient ■ Most common TEAEs (IR [95% confidence interval; CI] per 100 PY) were upper respiratory tract infections (viral: 9.9 [9.4, 10.4]; unspecified: 5.8 [5.5, 6.2]) and injection site-reactions (3.7 [3.5, 4.1]), which were generally mild or moderate in severity ■ Most deaths were from cardiovascular events in patients with prior risk factors, and none were due to suicide ■ In moderate-to-severe psoriasis, maintaining adequate control of disease activity generally requires long-term treatment1-4 ■ Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A5 – Has demonstrated significant efficacy in the treatment of moderate- to-severe psoriasis6-9 – Is approved for treating moderate-to-severe plaque psoriasis – Safety profile is aligned with IL-17A inhibition and similar to that of etanercept in the short-term (UNCOVER-2 and -3)8,9 BACKGROUND ■ To summarize integrated safety data based on more than 15,000 patient-years (PY) of ixekizumab exposure during 12 clinical trials in patients with psoriasis OBJECTIVE References 1. Jacobs A, et al. Br J Dermatol. 2015;173:910-921. 2. Mease PJ, et al. Drugs. 2014;74:423-441. 3. Mrowietz U, et al. J Eur Acad Dermatol Venereol. 2012;26(Suppl.2):12-20. 4. Sandoval LF, et al. Am J Clin Dermatol. 2014;15:165-180. 5. Liu L, et al. J Inflamm Res. 2016;9:39-50. 6. Leonardi C, et al. N Eng J Med. 2012;366:1190-1199. 7. Gordon KB, et al. J Am Acad Dermatol. 2014;71:1176-1182. 8. Griffiths CE, et al. Lancet. 2015;386:541-551. 9. Gordon KB, et al. N Eng J Med. 2016;375:345-356. Treatment-emergent adverse event (TEAE) data were integrated from 12 controlled and uncontrolled ixekizumab clinical trials in psoriasis, including 3 pivotal Phase 3, randomized, controlled, double-blind clinical trials (UNCOVER-1, -2, and -3) ■ Safety analysis population included all randomized patients who received ≥1 dose of study drug ■ Data cut-off date was September 22, 2017 ■ Exposure-adjusted incidence rates (IRs) of TEAEs were summarized ■ IR was expressed as the number of unique patients with a given category of TEAE per 100 PY, based on the entire duration of exposure ■ Categories included overall TEAEs, infections, injection-site reactions, allergic reactions/hypersensitivities, and malignancies ■ Summary data from the Induction Period (12 weeks) of UNCOVER-1, -2, and -3 are provided for reference ■ Data for ixekizumab doses were grouped to form the Total IXE group ■ Summary data from the 2 previous database locks (September 2015 including 7 psoriasis clinical trials and September 2016 including 11 psoriasis clinical trials) are also included for reference ■ Safety topics of special interest included serious infections, oral candida, major adverse cerebro-cardiovascular events (MACE), non-melanoma skin cancer (NMSC), malignancies excluding NMSC, and inflammatory bowel disease (including Crohn’s disease and ulcerative colitis) ■ MACE were adjudicated by an external adjudication committee METHODS Integrated Psoriasis Safety Dataset Study Design aIR per 100 PY considered exposure time as the entire time on IXE; bData for the Induction Period (0-12 Weeks) are provided for reference and display the IR for 0-12 Weeks for UNCOVER-1, -2, and -3 only; Data for Year 1 and Year 2 are also provided for reference and display IR for the 2 previous database locks (September 2015 including 7 PsO clinical trials and September 2016 including 11 PsO clinical trials) I n d u c t i o n P e r i o d b 0 - 1 2 W e e k s Y e a r 1 S e p t 2 0 1 5 Y e a r 2 S e p t 2 0 1 6 Y e a r 3 S e p t 2 0 1 7 0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 W e e k 2 4 IR P e r 1 0 0 P Y a (9 5 % C I) A ll IX E P s OT o ta l IX E I n f e c t i o n s P B O N = 7 9 1 2 3 2 8 4 2 1 3 5 6 8 9 5 8 7 1 P Y = 1 8 0 5 3 5 7 8 4 3 1 2 ,0 6 2 1 5 ,2 1 3 1 0 1 1 1 8 3 4 2 9 2 5 I n d u c t i o n P e r i o d b 0 - 1 2 W e e k s Y e a r 1 S e p t 2 0 1 5 Y e a r 2 S e p t 2 0 1 6 Y e a r 3 S e p t 2 0 1 7 0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 W e e k 2 4 IR P e r 1 0 0 P Y a (9 5 % C I) A ll IX E P s OT o ta l IX E I n j e c t i o n - s it e R e a c t io n s P B O N = 7 9 1 2 3 2 8 4 2 1 3 5 6 8 9 5 8 7 1 P Y = 1 8 0 5 3 5 7 8 4 3 1 2 ,0 6 2 1 5 ,2 1 3 1 4 6 5 9 7 6 I n d u c t i o n P e r i o d b 0 - 1 2 W e e k s Y e a r 1 S e p t 2 0 1 5 Y e a r 2 S e p t 2 0 1 6 Y e a r 3 S e p t 2 0 1 7 0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 W e e k 2 4 IR P e r 1 0 0 P Y a (9 5 % C I) A ll IX E P s OT o ta l IX E A ll e r g ic R e a c t i o n s / H y p e r s e n s i t i v i t ie s P B O N = 7 9 1 2 3 2 8 4 2 1 3 5 6 8 9 5 8 7 1 P Y = 1 8 0 5 3 5 7 8 4 3 1 2 ,0 6 2 1 5 ,2 1 3 8 1 5 7 6 6 I n d u c t i o n P e r i o d b 0 - 1 2 W e e k s Y e a r 1 S e p t 2 0 1 5 Y e a r 2 S e p t 2 0 1 6 Y e a r 3 S e p t 2 0 1 7 0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 W e e k 2 4 IR P e r 1 0 0 P Y a (9 5 % C I) A ll IX E P s OT o ta l IX E M a l i g n a n c i e s P B O N = 7 9 1 2 3 2 8 4 2 1 3 5 6 8 9 5 8 7 1 P Y = 1 8 0 5 3 5 7 8 4 3 1 2 ,0 6 2 1 5 ,2 1 3 1 1 1 11 Incidence Rates of Select TEAEs Decreased or Remained Similar Through Year 3 DatabaseKEY RESULTS Duration of Ixekizumab Exposure n (%) All PsO IXE (N=5871)PY=15,212.5 ≥1 week 5866 (99.9) ≥1 month 5806 (98.9) ≥3 months 5665 (96.5) ≥0.5 years 5455 (92.9) ≥1 year 4640 (79.0) ≥1.5 years 3357 (57.2) ≥2 years 3201 (54.5) ≥3 years 2891 (50.8) ≥4 years 1526 (26.0) ≥5 years 261 (4.4) Incidence Rates of Overall TEAEs Decreased or Remained Similar Through Year 3 Database aIR per 100 PY considered exposure time as the entire time on IXE bData for the Induction Period (0-12 Weeks) are provided for reference and display the IR for 0- 12 Weeks for UNCOVER-1, -2, and -3 only; Data for Year 1 and Year 2 are also provided for reference and display IR for the 2 previous database locks (September 2015 including 7 PsO clinical trials and September 2016 including 11 PsO clinical trials) I n d u c t i o n P e r i o d b 0 - 1 2 W e e k s Y e a r 1 S e p t 2 0 1 5 Y e a r 2 S e p t 2 0 1 6 Y e a r 3 S e p t 2 0 1 7 0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 W e e k 2 4 IR P e r 1 0 0 P Y a (9 5 % C I) A ll IX E P s OT o ta l IX EP B O N = 7 9 1 2 3 2 8 4 2 1 3 5 6 8 9 5 8 7 1 P Y = 1 8 0 5 3 5 7 8 4 3 1 2 ,0 6 2 1 5 ,2 1 3 2 0 6 2 5 6 4 6 4 0 3 3 Abbreviations AC=active comparator; CI=confidence interval; DB=double-blind; EP=optional extension period after Week 24 endpoint where patients received 80 mg IXE Q4W up to Wk 60; ETN=50 mg etanercept twice weekly; FAE=fumaric acid esters 105-mg starting dose followed by 215 mg given orally 1 to 3 times per day; IR=incidence rate; IXE=ixekizumab; IXE Q2W=80 mg ixekizumab every 2 weeks; IXE Q4W=80 mg ixekizumab every 4 weeks; IXE Q12W=80 mg ixekizumab every 12 weeks; LTE=long-term extension; MACE=major adverse cerebro-cardiovascular events; MTX=methotrexate 7.5-mg starting dose up to 30 mg given orally once a week; N=number of patients; n=number of patients who received ixekizumab and included in the September 2017 lock for integrated safety analyses; OL=open-label; PAC=placebo-controlled and active comparator; PBO=placebo; PsO=psoriasis; Pts=patients; PY=patient-years; R=randomized; SAE=serious adverse event; sPGA=static Physician’s Global Assessment; TEAE=treatment-emergent adverse event; UST=45 mg ustekinumab given as SC injection for participants ≤100 kg and 90 mg SC injection for participants >100 kg at Wk 0, 4, 16, 28, and 40; Wk=week ■ The ixekizumab psoriasis clinical safety database is large with more than 15,000 PY from 12 clinical trials and up to 5 years of study duration ■ No new safety signals were identified with longer-term ixekizumab treatment in this population of patients with moderate-to-severe plaque psoriasis ■ Ixekizumab exposure of up to greater than 3 years was not associated with an increased rate of any type or category of TEAE CONCLUSIONS aFor pts receiving IXE the starting dose was 160 mg at Wk 0 prior to receiving 80 mg IXE (Q4W or Q2W); bWithdrawal period (Wks 20-32; pts were eligible for treatment with IXE Q4W when improvement in PASI score from baseline was ≤75%); cProtocol amendment-mandated dose regimen; dPBO administered to maintain study blind; eStep-up criteria determined if dosing increased from IXE Q4W to IXE Q2W based on whether a patient achieved sPGA ≥2 at 2 consecutive visits during Wk 12 through Wk 40; fDosing increased from IXE Q4W to IXE Q2W based on investigator opinion between Wk 24 through Wk 40 Fall Clinical Dermatology Conference - 37th Anniversary (FallCDC); Las Vegas, NV, USA; October 18-21, 2018 An Update on the Long-Term Safety Experience of Ixekizumab: Results from the Psoriasis Clinical Development Program with More than 3 Years of Follow-up from 12 Clinical Trials and More Than 15000 Patient-Years of Exposure to Ixekizumab