PowerPoint Presentation Winter Clinical Miami • Feb. 17 – 20th, 2023 Introduction • Atopic dermatitis (AD) is a chronic, heterogeneous, relapsing-remitting disease characterized by intense itch and eczematous lesions. • Two advanced systemic therapies are approved in adolescents with moderate-to-severe AD. • This study describes demographic characteristics, clinical and patient-reported outcomes in adolescents with moderate-to-severe AD in the TARGET-DERM AD registry stratified by advanced systemic therapy (AST) treatment status. 1 Northwestern University Feinberg School of Medicine, Chicago, IL 2 Target RWE, Durham, North Carolina, 3 LEO Pharmaceuticals, Madison, New Jersey, 4 Rady Children’s Hospital, San Diego, CA 5 University of California San Diego, San Diego, CA Unmet Needs of Adolescents with Moderate to Severe Atopic Dermatitis in the TARGET-DERM Registry Paller A1, Knapp K2, Munoz B2, Kalam A2, Claxton A3, Balu S3, Schneider S3, Eichenfield L4,5 aa Conclusions • In adolescents with moderate-to-severe AD, nearly one-third did not progress to AST despite being eligible based on clinical and disease characteristics. • Evaluation of prospective AST-treated showed more than 40% were not improved or had worsened at 12 weeks, on measures with n>=14. • Although physician-reported outcomes with n>=14 were largely improved by 52 weeks, patient-reported quality of life (CDLQI), depression, and anxiety were unchanged or worsened in >50% of prospectively treated AST. • These real-world data suggest there is an unmet need to understand the reasons behind treatment inadequacies and potentially advancing more adolescents with moderate-to- severe AD who meet criteria to AST, and that more treatment options are needed for this population. Inclusion/Exclusion Criteria • Adolescent (12-17 years) at enrollment • Moderate/severe AD defined by a score of 3 or 4 on validated Investigator Global Assessment (vIGA-AD) • At least one follow-up visit post-enrollment • Clinical trial patients excluded AST-treatment groups • AST-naïve (never AST-treated) • AST-treated: • Retrospective (initiated AST prior to enrolling in TARGET- DERM AD) • Prospective (initiated AST after enrolling in TARGET-DERM AD) • Failed, stopped an AST and had either: a vIGA-AD increase or an AST-related adverse event Methods • TARGET-DERM AD, launched in 2019, is an ongoing, longitudinal, observational study of patients managed in clinical practice at 48 community (n=23) or academic (n=25) sites in the United States; first enrolled patients Jan. 25th, 2019, and the data herein spans the registry start date to November 11, 2022. • Enrollment demographic, site, and clinical characteristics are analyzed descriptively • Categorical variables are presented as numbers and percentages. Continuous variables are shown as means with standard deviation, medians, minimum and maximum • ASTs considered in this study: dupilumab and upadacitinib • Outcomes are only reported at each timepoint (enrollment, 12, 24, 36 and 52 weeks) if there were at least 14 patients with data on any given measure, at each timepoint Longitudinal outcomes Compared to enrollment, prospectively AST-treated patients were unimproved or worsened at 12 weeks on outcomes with n>=14, except where noted: • Disease severity measures: vIGA-AD (43.9%), BSA (43.9%), vIGA x BSA (53.6%) • PROs: PROMIS depression (66.7%) and PROMIS anxiety (60.0%) Several PRO measures persisted as unimproved or worse vs enrollment to 24, 36, 52 weeks, respectively • CDLQI (57.1%, 63.3%, and 55.0%) • PROMIS Depression (69.5%, 66.7%, and 66.7%) • PROMIS Anxiety (65.2, 66.6, and 63.0%) Acknowledgements and Disclosures: Target RWE communities are collaborations among academic & community investigators, the pharmaceutical industry, and patient community advocates. Target RWE communities are sponsored by TARGET PharmaSolutions Inc (d.b.a., Target RWE). The authors would like to thank all the investigators, participants, and research staff associated with TARGET-DERM AD. ClinicalTrials.gov Identifier: NCT03661866. AP has been an investigator with: AbbVie, AnaptysBio, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, Regeneron, UCB; consultant with honorarium with: Abbvie, Acrotech, Almirall, Amgen, Amryt, Arcutis, Arena, Azitra, BioCryst, BiomX, Boeringer Ingelheim, Botanix, Bridgebio, Castle Biosciences, Catawba, Eli Lilly, Exicure, Gilead, Incyte, Janssen, Kamari, Leo, Novartis, Pfizer, Pierre Fabre, RAPT, Regeneron, Sanofi/Genzyme, Seanergy, UCB, Union; on a Data Safety Monitoring Board with: AbbVie, Abeona, Bausch, Bristol Myers Squibb, Galderma, Inmed, Novan; KK, BM, and AK are TARGET RWE employees and may hold options. AC, SB, and SS are LEO Pharmaceutical employees and may hold options. EG is an employee of Mount Sinai and has received research grants research Grants paid to her institution: Boehringer Ingelheim, Leo Pharma, Pfizer, Cara Therapeutics, UCB, Kyowa Kirin, RAPT, Amgen, GSK, Incyte, Sanofi, Bristol Meyers Squibb, Aslan, Regeneron, Anaptysbio, Concert, Janssen and has been a consultant with: Abbvie, Almirall, Amgen, Aslan Pharmaceuticals, AstraZeneca, Biolojic Design, Boerhinger-Ingelhiem, Bristol Meyers Squibb, Cara Therapeutics, Connect, Pharma, DBV Technologies, Eli Lilly, EMD Serono, Evidera, Galderma, Gate Bio, Genentech, Incyte, Inmagene, Janssen Biotech, Kyowa Kirin, Leo Pharma, Merck, Pfizer, Q32 Bio, RAPT, Regeneron, Sanofi, SATO, Siolta, Target, UCB, Ventyx TARGET-DERM AD All patients N=2930 Age 12-17 (N=364) Study population N=128 • AST-naïve (n=40) • AST-treated (N=88)) AST-treated N=88 • Moderate N=57 • Severe N=31 ___________________________ • Prospective N=50 • Retrospective N=34 • Failed N=4 AST-naïve N=40 • Moderate N=28 • Severe N=12 Had 1+ follow-up visits (N=128) Moderate or severe AD: vIGA-AD of 3 or 4 (N=196) Figure 1. Patient Disposition Results AST-usage • Of 128 adolescents who met study criteria, 40 (31.3%) were AST-naïve, 34 (26.6%) were retrospectively-treated, 50 (39.1%) were prospectively-treated, and 4 (3.1%) were AST- failed • All AST treatment was dupilumab, no upadacitinib usage reported. Median days of dupilumab treatment was 500, 613, and 141 (retrospective, prospective and failed; p=0.01) • Of 35 physicians, 25 (71%) were dermatologists and 7 (29%) allergists in this analysis. A dermatologist was the treating physician for AST-naïve (85%), AST-retrospective (94.1%), AST-prospective (96.0%) and AST-failed (100%). The remainder were treated by an allergist. Differences were not significant (p=0.14) Enrollment outcomes • At enrollment, there were no significant differences among treatment groups on demographic variables, physician specialty/site, vIGA-AD, and all PROs. • Significant enrollment differences were observed for median BSA (15% naïve, 18% retrospective, 40% prospective, 36% failed; p<0.01) and median vIGA-AD x BSA (45 naïve, 49 retrospective, 113 prospective, 124 failed; p<0.01) Demographic/concomitant treatment variables • Patient demographics • Site and physician type • Prior and concomitant topical AD therapy (any, calcineurin inhibitor, corticosteroid, phosphodiesterase) Disease severity measures: • vIGA-AD (scores 0-4) • Body Surface Area (BSA) (score %) • vIGA-AD x BSA (score 0-400) Table 1. Change Over Time Definitions 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 80.0% 90.0% 100.0% F e m a le ( % ) H is p a n ic /L a ti n o N H W h it e N H B la ck A si a n O th e r/ N o t re p o rt e d M o d e ra te S e ve re N o n e a t a ll S m a ll M o d e ra te V e ry l a rg e E xt re m e ly l a rg e A ll e rg is t D e rm a to lo g is t M e d ic a id P ri va te U n in su re d A ca d e m ic C o m m u n it y Sex Race/Ethnicity vIGA Children's DLQI Specialty Insurance Site Type P e rc e n ta g e AST-Naïve AST-Retrospective AST-Prospective 0 20 40 60 80 100 120 A g e ( y e a rs ) T B S A v IG A -A D s co re x B S A P O -S C O R A D P O E M P R O M IS I tc h - M o o d /S le e p P R O M IS D e p re ss io n (T -S co re ) P R O M IS A n xi e ty (T -S co re ) M e d ia n S co re AST-Naïve AST-Retrospective AST-Prospective AST-failed not included due to small n Figure 2. Patient Characteristics at Enrollment by AST-status Figure 3. Disease Severity and Patient-Reported Outcomes at Enrollment Figure 4. Duration of Dupilumab Therapy Figure 5. Percentage of Prospectively AST-treated Unchanged or Worsening at 24, 36, 52 Weeks* with n>=14 0 10 20 30 40 50 60 70 80 90 100 vIGA-AD N=41 BSA N=41 VxBSA N=41 CDLQI N=14 POEM N=16 PROMIS Depression N=23 PROMIS Anxiety N=23 P e rc e n ta g e 24 Weeks 36 Weeks 52 Weeks *12-week data not shown due to small n Patient reported outcomes: • CDLQI: Children’s Dermatology Life Quality Index (scores 0-30) • POEM: Patient-Oriented Eczema Measure (scores 0-28) • PO-SCORAD: Patient-Oriented Scoring Atopic Dermatitis (scores 0-103) • Patient-Reported Outcomes Measurement Information System (PROMIS) Depression (scores 41.0-79.4) and PROMIS Anxiety (scores 40.9-85.2) AST-failed not included due to small n 0 500 613 0 100 200 300 400 500 600 700 D a ys AST-Naïve AST-Retrospective AST-Prospective P=0.0007 P=0.0013 ________________P=0.0005_________________