PowerPoint Presentation 0 20 40 60 80 10 0 5657 60 5556 63 404042 R e s p o n d e rs , % Worst Weekly Pruritus NRS ≤3 0 20 40 60 80 10 0 7172 75 70 73 81 5657 61 R e s p o n d e rs , % DLQI ≤5 Materials and Methods Patients and treatment • In ECZTEND, patients who completed PT of tralokinumab received open-label tralokinumab 300 mg every two weeks (Q2W, home use) after a 600 mg loading dose plus optional topical corticosteroids (US class ≥4 or Europe class ≤3) or topical calcineurin inhibitor, with visits every 8 weeks o All patients who completed PT at sites with ECZTEND were eligible to enroll in ECZTEND, regardless of prior treatment or response o For key inclusion and exclusion criteria, please see Blauvelt et al3 • Adult patients included in this post hoc analysis completed 56 weeks of open-label tralokinumab treatment in ECZTEND by the data cutoff (April 30, 2021) (Figure 1A) • Patients self-reported race at baseline of ECZTEND (Figure 1B) • Proportion of patients achieving EASI-75/90, IGA 0/1, EASI≤7, Worst Weekly Pruritus NRS≤ 3, and DLQI ≤ 5 were assessed. EASI-75/90 determined relative to PT baseline • Data are presented as observed. Intermittent missing data are presented using last observation carried forward (LOCF). Modified non-responder imputation (mNRI) sets discontinuation from ECZTEND due to adverse event(s) or lack of efficacy as non-response and uses LOCF for other missing data • To account for potential baseline confounders with racial subgroup, logistic regression analysis adjusting for country, weight, EASI, ethnicity and age (all at ECZTEND baseline) in addition to racial subgroup were conducted. Estimated proportions from these analyses were expressed relative to US non-Hispanic patients • Data were used as per Food and Drug Administration (FDA) label and United States Prescribing Information (USPI) Analyses Asian N=203 Black N=108 White N=1081 Mean age, y (SD) 37.9 (13.9) 39.6 (13.4) 39.4 (14.1) Male, n (%) 125 (61.6) 45 (41.7) 637 (58.9) Ethnicity, n (%) Hispanic or Latino Not Hispanic or Latino 2 (1.0) 201 (99.0) 5 (4.6) 103 (95.4) 79 (7.3) 1002 (92.7) Country, n (%) United States, 49 (24.1) Canada, 55 (27.1) Germany, 2 (1.0) Great Britain, 9 (4.4) Spain, 1 (0.5) France, 1 (0.5) Japan, 86 (42.4) United States, 94 (87.0) Canada, 7 (6.5) Germany, 3 (2.8) Great Britain, 3 (2.8) France, 1 (0.9) United States, 187 (17.3) Canada, 137 (12.7) Poland, 178 (16.5) Germany, 246 (22.8) Great Britain, 52 (4.8) Spain, 123 (11.4) Belgium, 62 (5.7) France, 61 (5.6) Italy, 15 (1.4) Czech Republic, 20 (1.9) Baseline scores Parent trial ECZTEND Parent trial ECZTEND Parent trial ECZTEND IGA, n (%) 3 4 89 (43.8) 114 (56.2) 51 (25.1) 14 (6.9) 73 (67.6) 35 (32.4) 22 (20.4) 7 (6.5) 575 (53.2) 506 (46.8) 308 (28.5) 63 (5.8) Mean EASI (SD) 32.5 (14.5) 9.2 (11.7) 27.9 (12.0) 6.9 (11.0) 30.7 (12.7) 8.6 (10.0) Mean SCORAD score (SD) 70.0 (13.5) 33.5 (18.5) 65.3 (12.4) 27.6 (18.6) 69.2 (12.7) 33.5 (19.1) Mean POEM (SD), n 22.6 (4.7), 199 13.2 (6.8), 197 20.4 (6.2), 99 10.6 (7.2), 106 22.3 (5.1), 1037 12.4 (7.4), 1048 Mean DLQI (SD), n 16.4 (6.9), 200 6.9 (5.8), 197 16.0 (7.7), 100 6.9 (6.4), 106 16.6 (6.9), 1041 6.7 (6.0), 1048 Mean Worst Pruritus NRS (SD), n 7.9 (1.3), 180 5.3 (2.5), 202 8.0 (1.8), 63 4.6 (2.9) 7.6 (1.5), 971 4.9 (2.7), 1080 Mean Sleep Interference NRS (SD), n 7.2 (1.9), 180 3.6 (2.8), 202 7.4 (2.2), 63 3.0 (3.1) 6.8 (2.0), 971 3.1 (2.8), 1080 Efficacy and safety of up to two years of tralokinumab treatment in adults of different racial subgroups with moderate-to-severe atopic dermatitis Tiffany Mayo1, April Armstrong2, Leon Kircik3, Jonathan I. Silverberg4, Andrew Blauvelt5, Ben Esdaile6, Shannon Schneider7, Thomas Mark8, Melinda Gooderham9, Andrew F. Alexis10 1University of Alabama at Birmingham, Birmingham, AL, USA; 2Keck School of Medicine of University of Southern California, Los Angeles, CA, USA;3Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4The George Washington School of Medicine and Health Sciences, Washington, DC, USA; 5Oregon Medical Research Center, Portland, OR, USA; 6Whittington Health National Health Service Foundation Trust, London, UK; 7LEO Pharma Inc., Madison, NJ, USA; 8LEO Pharma A/S, Ballerup, Denmark; 9SKiN Centre for Dermatology, Peterborough, ON, Canada; 10Weill Cornell Medicine, New York, NY, USA Table 1. Baseline demographic and disease characteristics of patients by racial subgroup Table 2. Summary of AEs in ECZTEND by racial subgroup aIn PTs, worst pruritus NRS was assessed daily; in ECZTEND, worst pruritus NRS was assessed based on recall of the previous week before the visit. Conclusions • Improvements in disease severity, itch, and quality of life were comparable across different racial subgroups following up to two years of tralokinumab treatment in adults with moderate-to-severe AD • Limitations of this analysis include the lack of a placebo arm in ECZTEND, disparate sample sizes across racial subgroups, and possible confounders not considered • The lower response rates observed for the Asian subgroup relative to other racial subgroups could be partially explained by adjusting for country Figure 1. Schematic of (A) ECZTEND interim analysis of adult patients and (B) patient disposition at parent trial completion, ECZTEND baseline, and at April 30, 2021 data cutoff Objective To evaluate the efficacy and safety of up to 2 years of tralokinumab treatment by self-identified racial subgroup (Asian, Black, White) in adults with moderate-to-severe AD Results Patients, Demographics, and Clinical Characteristics • This post hoc analysis included 1392 adult patients who had completed 56 weeks of tralokinumab in ECZTEND (up to 2 years total) at data cutoff, April 30, 2021 and self-reported their race as Asian, Black, or White (Figure 1B, Table 1) o Among patients who had completed 56 weeks of tralokinumab in ECZTEND at data cutoff, 24% had skin of color (self-reported race as Asian, Black, or Other) o Very few patients self-reported their race as other than Asian, Black, or White (N=38 patients total) and therefore were not included in this analysis • Baseline demographic and disease characteristics were largely balanced across subgroups (Table 1), although regional differences were present Figure 2. Proportion of patients by racial subgroup achieving EASI-75, EASI-90, IGA 0/1, and EASI≤7 at Week 56 of ECZTEND References 1. Weidinger S, Novak N. Lancet. 2016;387(10023):1109-1122. 2. Kaufman B, et al. Exp Dermatol 2018; 27: 340-357. 3. Blauvelt A, et al. J Am Acad Dermatol. 2022;S0190-9622(22)02345-3. Disclosures Tiffany Mayo has served as an investigator or consultant for Eli Lilly, ChemoCentryx, Pfizer, Janssen, Galderma, Bristol Myers Squibb, Acelyrin, Novartis, Leo Pharma, Arcutis, and Procter and Gamble. April Armstrong has served as a research investigator and/or scientific advisor to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, Pfizer, and Modmed. Leon Kircik has served either as an investigator, consultant, or speaker for AbbVie, Almirall, Amgen, Arcutis, Bausch Health Canada, Bristol Myers Squibb, Boehringer Ingelheim, Cellceutix, Celgene, Coherus, Dermavant, Dermira, Eli Lilly, Leo, MC2, Maruho, Novartis, Ortho Dermatologics, Pfizer, Dr Reddy's Laboratories, Sun Pharma, UCB, Taro, and Xenoport. Jonathan I Silverberg reports honoraria as a consultant/advisory board member from LEO Pharma and has acted as a consultant for and/or received grants/honoraria from AbbVie, AnaptysBio, Asana Biosciences, Galderma Research and Development, GSK, Glenmark, Kiniksa, LEO Pharma, Lilly, MedImmune, Menlo Therapeutics, Pfizer, PuriCore, Regeneron, and Sanofi. Andrew Blauvelt has served as a speaker (received honoraria) for AbbVie, Arcutis, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Regeneron, Sanofi, and UCB, served as a scientific adviser (received honoraria) for AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly and Company, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor, and has acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Almirall, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Concert, Dermavant, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma. Ben Esdaile has served either as an investigator, advisor or speaker for LEO Pharma, L’Oréal, Thornton & Ross, Bioderma, Skin + Me and AbbVie. Shannon Schneider and Thomas Mark are employees of LEO Pharma. Thomas Mark owns LEO Pharma stock. Melinda Gooderham has been an investigator, speaker and/or advisor for: AbbVie, Amgen, Akros, AnaptysBio, Aslan, Arcutis, Aristea, Bausch Health, BMS, Boehringer Ingelheim, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Incyte, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Merck, Meiji, Moonlake, Nimbus, Novartis, Pfizer, Reistone, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, and UCB. Andrew F. Alexis has received grants (funds to institution) from LEO Pharma, Novartis, Almirall, Bristol Myers Squibb, Amgen, Vyne, Galderma, Valeant (Bausch Health), Cara, Arcutis, Dermavant, Abbvie, and Castle; has served as an advisory board member or consultant for LEO Pharma, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Beiersdorf, Ortho, L’Oreal, BMS, Bausch health , UCB, Vyne , Arcutis, Janssen, Allergan, Almirall, Abbvie, Sol-Gel , Amgen, VisualDx, Eli Lilly, Swiss American, and Cutera; and a speaker for Regeneron, Sanofi-Genzyme, Pfizer, and Bristol Myers Squibb. Acknowledgements This analysis was sponsored by LEO Pharma A/S. Medical writing according and editorial support from Alphabet Health by Clair Geary, PhD was funded LEO Pharma A/S, Ballerup, Denmark, to Good Publication Practice guidelines (https://www.ismpp.org/gpp3). This poster is an encore of a previous presentation at the Fall Clinical Dermatology Conference, Oct 20 – 23, 2022. Introduction • Atopic dermatitis (AD) is a chronic skin disease which may impact patients throughout their lifespan, requiring efficacious long-term treatment options with a favorable safety profile1 • Although AD is highly prevalent in patients with skin of color, data on the efficacy of AD therapies in these patients is limited since most clinical trials enroll predominately White patients2 o Several standard measures, including EASI, can underestimate AD severity in dark skin2 • Tralokinumab, a specific, high-affinity interleukin-13 inhibitor, is approved in Europe, Canada, and the United States for the treatment of adults with moderate-to-severe AD • ECZTEND (NCT03587805) is an ongoing open-label extension trial assessing the safety and efficacy of tralokinumab over 5 years after the completion of parent trials (PT) The safety profile of up to 2 years of tralokinumab treatment was consistent across racial subgroups • Through Week 56 in ECZTEND, rates of adverse events (AEs), serious AEs, and AEs leading to drug withdrawal were comparably low across racial subgroups (Table 2) • The majority of AEs in all subgroups were mild or moderate in severity and subjects recovered from most of the AEs Figure 3. Percentage of patients achieving Worst Weekly Pruritus NRS ≤3 and DLQI ≤5 by racial subgroup at Week 56 of ECZTEND Adjusting for differences in baseline characteristics and country between subgroups impacts estimated responder proportions • Adjusted for race and country as main effects, EASI-75 was achieved in 88% of Asian patients, 90% of Black patients, and 90% of White patients (Figure 4) • Similar patterns of estimated response were observed for IGA 0/1 (Figure 4) and when adjusting for region as main effect or the interaction between region and race Figure 4. Percentage of patients achieving EASI-75 and IGA 0/1 by racial subgroup before and after adjusting for baseline differences Asian (n=203; PYE=386.2) Black (n=108; PYE=169.7) White (n=1081; PYE=1808.0) n (%) Rate (nE/100 PYE) n (%) Rate (nE/100 PYE) n (%) Rate (nE/100 PYE) All AEs 162 (79.8) 167.8 71 (65.7) 142.6 850 (78.6) 208.2 Severity Mild 143 (70.4) 130.2 57 (52.8) 101.9 717 (66.3) 134.1 Moderate 67 (33.0) 34.7 35 (32.4) 35.3 503 (46.5) 66.8 Severe 10 (4.9) 2.8 7 (6.5) 5.3 80 (7.4) 7.4 Serious AEs 12 (5.9) 3.4 7 (6.5) 4.7 81 (7.5) 5.4 Leading to withdrawal from trial 2 (1.0) 0.5 2 (1.9) 1.2 30 (2.8) 1.7 Outcome Not recovered/ not resolved 68 (33.5) 28.0 23 (21.3) 24.2 269 (24.9) 23.7 Recovering/resolving 18 (8.9) 5.4 12 (11.1) 10.0 153 (14.2) 12.2 Recovered/resolved 151 (74.4) 133.1 65 (57.4) 106.0 799 (73.9) 169.2 Recovered/resolved with sequelae 1 (0.5) 0.3 3 (2.8) 1.8 16 (1.5) 1.0 Unknown 3 (1.5) 1.0 1 (1.0) 0.6 28 (2.6) 1.9 Scan to download a copy of this poster Copies of this poster and its content, obtained through this QR code, are for personal use only and may not be reproduced without written permission from the authors Abbreviations adj., adjusted; AE, adverse event; AD, atopic dermatitis; DLQI, dermatology life quality index; E, number of adverse events; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; LOCF, last observation carried forward; mNRI, modified non-responder imputation; n, number of patients achieving the indicated metric, or with ≥1 event; nE, number of events; N, number of patients with recorded observation; NRS, numerical rating scale; PYE, patient-years of exposure; PT, parent trial; Q2W, every 2 weeks; SD, standard deviation Comparable efficacy across racial subgroups with up to two years of tralokinumab treatment o Worst weekly pruritus NRS ≤3 was achieved in 42% (71/169) of Asian patients, 63% (48/76) of Black patients, and 60% (458/765) of White patients, as observed (Figure 3) o Similar patterns of response were observed for EASI-90, EASI ≤7, IGA 0/1, and DLQI ≤5, and when using LOCF or mNRI to account for missing data (Figures 2 and 3) • At Week 56 in ECZTEND o EASI-75 was achieved in 78% (130/167) of Asian patients, 88% (66/75) of Black patients and 83% (186/347) of White patients, as observed (Figure 2) n 169 202 202 76 108 108 765 941 941 n 164 201 201 73 108 108 700 939 939 0 20 40 60 80 10 0 49 57 60 44 56 63 35 4042 R e s p o n d e rs , % Worst Weekly Pruritus NRS ≤3 0 20 40 60 80 10 0 56 72 75 55 73 81 50 57 61 R e s p o n d e rs , % DLQI ≤5 Asian mNRI Asian LOCF Asian AO Black AO Black LOCF Black mNRI White AO White LOCF White mNRI 0 20 40 60 80 10 0 7879 838283 88 7374 78 7879 838283 88 7374 78 R e s p o n d e rs , % EASI-75 0 20 40 60 80 10 0 5859 646566 72 4647 51 R e s p o n d e rs , % EASI-90 0 20 40 60 80 10 0 4950 53 6464 69 353537 R e s p o n d e rs , % IGA 0/1 0 20 40 60 80 10 0 7677 818283 87 7071 74 R e s p o n d e rs , % EASI ≤7 https://www.ismpp.org/gpp3 Slide 1: Efficacy and safety of up to two years of tralokinumab treatment in adults of different racial subgroups with moderate-to-severe atopic dermatitis