Slide 1: Dupilumab Monotherapy in Adults with Moderate-to-Severe Atopic Dermatitis
Exhibit 99.1 Dupilumab Monotherapy in Adults with Moderate-to-Severe Atopic Dermatitis: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Study Thomas Bieber,1 Diamant Thaçi,2 Neil Graham,3 Gianluca Pirozzi,4 Ariel Teper, 4 Haobo Ren,3 Neil Stahl,3 George Yancopoulos, 3 Allen Radin 3 1Departme
Slide 2: Disclosures
Disclosures • D Thaçi is a consultant for Astellas, Novartis, Regeneron, Celgene, Abbott, Pfizer, Janssen-Cilag, MSD, Leo-Pharma • T Bieber is a consultant for Regeneron, Basilea, L’Oréal, Oxagen, Bioalliance, Stern Biologics and a speaker for Astellas • N Graham, H Ren, N Stahl, G Yancopoulos, and
Slide 3: Introduction
Introduction • Moderate-to-severe atopic dermatitis (AD) is characterized by eczematous dermatitis with intractable pruritus associated with sleep disturbance and lower quality-of-life • For many patients, current therapies are inadequate and can be associated with unwanted side effects • IL-4 and I
Slide 4: Introduction
Introduction • Dupilumab is a fully human monoclonal antibody targeting the IL-4 receptor alpha subunit (IL-4R ), thus blocking the intracellular signaling of both IL-4 and IL-13 • Earlier clinical trials indicated that dupilumab monotherapy had an acceptable safety profile and was efficacious in pa
Slide 5: Dupilumab (anti-IL-4R) blocks the IL-4/IL-13 receptor/ligand system
Dupilumab (anti-IL-4R ) blocks the IL-4/IL-13 receptor/ligand system IL-4 IL-13 IL-4R c IL-4R IL-13R 1 Type I Receptor Type II Receptor B cells, T cells, Monocytes, Epithelial cells, Smooth muscle Eosinophils, Fibroblasts cells, Fibroblasts, Monocytes, Activated B cells 5
Slide 6: Phase 2a Study Design (NCT01548404)
Dupilumab Monotherapy in Adults with Moderate-to-Severe Atopic Dermatitis: A European 12-Week, Randomized, Double-Blind, Placebo-Controlled Phase 2a Study (NCT01548404) Screening (adult patients Study treatment Safety follow-up with moderate-to- severe AD) (weekly SC injection for 12 wks) (16 wks) D
Slide 7: Key inclusion/exclusion criteria
Key inclusion/exclusion criteria Inclusion Exclusion • Male or female 18 yrs • Prior treatment with dupilumab • Chronic AD 3 yrs • Acute or chronic infections • EASI 16 • Recent treatment with topical corticosteroids, calcineurin • IGA 3 inhibitors, immunosuppressive/ • 10% BSA of AD immunomodulatin
Slide 8: Baseline demographics and disease characteristics
Baseline demographics and disease characteristics* Dupilumab Placebo 300 mg (n=54) (n=55) Age, yrs 39.4 (12.3) 33.7 (10.4) Caucasian, n (%) 54 (100) 55 (100) Men, n (%) 27 (50.0) 31 (56.4) BMI, kg/m2 24.51 (4.64) 25.89 (4.84) AD diagnosis age, yrs 14.4 (18.35) 6.6 (10.52) EASI score (0-72) 30.8 (13.
Slide 9: Percent change in EASI and SCORAD scores over 12 weeks
Percent change in EASI and SCORAD scores over 12 weeks 10 10 10 20 30 40 50 60 70 80 90 10 20 30 40 50 60 70 80 90 0 0 -10 -10 -14.3% Placebo -20 -23.3% -20 Placebo -30 -30 *p<0.001, **P<0.0001 -40 -40 † p<0.002, **P<0.0001 -50 -50 -53.6% -60 -60 300 mg dupilumab -70 -70 -74.0% -80 -80 300 mg dupilu
Slide 10: Proportion of patients who achieve EASI-50 and EASI-75 over 12 weeks
Proportion of patients who achieve EASI-50 and EASI-75 over 12 weeks 100 100 90 ** ** ** ** ** ** ** ** 85.5% 90 80 80 ** 300 mg dupilumab ** 70 ** ** 70 ** * 61.8% 60 60 ** ** † p<0.01, *p<0.001, **P<0.0001 300 mg dupilumab 50 ** 50 40 40 * † p<0.01, *p<0.001, **P<0.0001 35.2% 30 30 Placebo 20 20 1
Slide 11: Percent patients achieving IGA 0-1 and mean BSA at day 85
Percent patients achieving IGA 0-1 and mean BSA(%) at day 85 Placebo 300 mg dupilumab 50.8 ** 46.8 40.0 41.8 ** 19.4 7.4 Placebo 300 mg Baseline Day 85 dupilumab ** p<0.0001; LOCF 11
Slide 12: Percent change in NRS and 5-D pruritus scores over 12 weeks
Percent change in NRS and 5-D pruritus scores over 12 weeks 0 10 20 30 40 50 60 70 80 90 10 0 10 20 30 40 50 60 70 80 90 -5 0 -10 -9.9% -10 -15.1% -15 Placebo -20 Placebo -20 -30 ** -25 **P<0.0001 ** **P<0.0001 -40 -30 ** ** -35 -50 ** -40 ** -39.7% ** -55.7% -60 ** ** ** ** ** ** ** -45 300 mg dupi
Slide 13: Treatment emergent adverse events over 28 weeks
Treatment emergent adverse events over 28 weeks Placebo Dupilumab 300 mg (n = 54) (n = 55) Total number of AEs 159 163 Total number of AEs related to study drug 45 49 Total number of serious AEs 11 1 Deaths 0 0 Number (%) of patients discontinued from study Due to AE 3 (5.6) 1 (1.8) Due to Lack of E
Slide 14: Skin infections were less frequent with dupilumab compared to placebo
Skin infections were less frequent with dupilumab treatment compared to placebo Placebo Dupilumab 300 mg (n = 54) (n = 55) Total number of patients (%) 13 (24.1%) 3 (5.5%) with skin infections Total number of skin infections* 14 3 Impetigo 3 1 Skin bacterial infection 3** 0 Eczema herpeticum 2** 0 S
Slide 15: Serious Adverse Events
Serious Adverse Events Placebo Dupilumab 300 mg (n = 54) (n = 55) Number of SAEs 11 1 Patients with SAE*, n (%) 7 (13.0%) 1 (1.8%) Facial bones fracture [traumatic] 0 1 (1.8%) Angina pectoris 1 (1.9%) 0 Cellulitis 1 (1.9%) 0 Eczema herpeticum 1 (1.9%) 0 Skin bacterial infection 1 (1.9%) 0 Renal fail
Slide 16: Summary
Summary • In this Phase 2a study of 109 European adults with moderate-to- severe AD, dupilumab (anti-IL-4R ) 300 mg SC weekly was associated with rapid and marked sustained improvement in EASI, SCORAD, IGA, and BSA%, and pruritus • At 12 weeks, the dupilumab group achieved statistically superior cli
Slide 17: Acknowledgements
Acknowledgements All participating patients Investigators Olga Filipovska Thomas Bieber Jens Ulrich Lajos Kemeny Romana Machackova Regina Foelster-Holst Thomas Werfel Marcin Ambroziak Petr Trestik Martin Kaatz Margitta Worm Dorota Bystrzanowska Catherine Goujon Knut Schaekel Klara Bajor Maris Czubek
Slide 18: BACK-UP
BACK-UP 18
Slide 19: The 5-D itch scale: a new measure of pruritus
The 5-D itch scale: a new measure of pruritus • 5-D Pruritus Scale: Duration, Degree, Direction, Disability, Distribution – Single-item domain scores (duration, degree and direction) are equal to the value of the response choice – The disability domain includes four items that assess the impact of i