MOR106, an anti-il-17c mab, a potential new approach for treatment of moderate-tosevere atopic dermatitis: Phase 1 study

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1 , an anti-il-17c mab, a potential new approach for treatment of moderate-tosevere atopic dermatitis: Phase 1 study Diamant Thaçi 1, Maria Magdalena Constantin 2, Bernadette Rojkovich 3, Helen Timmis 4, Pia Klöpfer 5, Stefan Härtle 5, Nick Vandeghinste 4, Ingeborg Knebel 5, Juha Lindner 5, Tim Van Kaem 4, Johan Beetens 4 1 Exzellenzzentrum Entzündungsmedizin Universitätsklinikum Schleswig-Holstein Lübeck, Schleswig-Holstein, Germany 2 Arensia Exploratory Medicine, Romania 3 Polyclinic of Hospitallers Brothers of St. John, Hungary 4 Galapagos NV, Generaal De Wittelaan L11A3, 28 Mechelen, Belgium 5 MorphoSys AG, Semmelweisstraβe 7, Planegg, Germany AAD 17 Feb 218

2 Disclosures Prof Thaci Honoraria; scientific advisory board: AbbVie, Almiral, Amgen, Bioskin, Boehringer-Ingelheim, Celgene, Galapagos, GSK, Dignity, Dermira, Janssen, Leo, Maruho, Morphosys, Lilly, Novartis, Pfizer, Regeneron/Sanofi, Sandoz-Hexal, Sun-Pharma, UCB and Xenoport Speaker: AbbVie, Almiral, Celgene, Janssen, Leo, Maruho, Medac, Lilly, Novartis, Pfizer, Regeneron/Sanofi, Sandoz-Hexal, Sun-Pharma, UCB Research grants: AbbVie, Celgene and Novartis Dr Constantin Honoraria; consultancy: Pfizer, AbbVie Dr Rojkovich None 2

3 Introduction fully human recombinant IgG1 monoclonal antibody first-in-class mab against IL-17C in clinical development in atopic dermatitis Mode of action specific and potent blockade of IL-17C with high affinity blockade of IL-17C suppresses multiple cytokine pathways and reduces (skin) inflammation in different animal models Rationale for AD IL-17C produced mainly in epithelial cell lining (e.g. keratinocytes); acts locally and amplifies other inflammatory mediators IL-17C increased in atopic dermatitis skin 3

4 Study design Phase 1 study, multiple ascending doses in atopic dermatitis 3 cohorts (N = 25) 1mg/kg, 4mg/kg, 1mg/kg vs placebo Objectives and endpoints primary and secondary: safety and PK exploratory: efficacy including EASI and SCORAD Weekly IV infusion over 4 weeks (4 infusions in total) 1 week follow up period 4

5 Key inclusion /exclusion criteria Inclusion: adult patients with atopic dermatitis for at least 6 months EASI 16 (on -72 scale) IGA score 3 (on -4 IGA scale) 1% BSA of AD involvement willingness to continue stable use of an additive free, basic, bland emollient twice daily for at least 7 days before baseline visit Exclusion: any concomitant treatment for atopic dermatitis was prohibited wash-out period of at least 2 (topical) or 4 (systemic) weeks before baseline 5

6 Baseline disease characteristics Baseline Characteristics 1mg/kg N=6 4mg/kg N=6 1mg/kg N=6 Placebo N=7 Age* (years) AD duration* (years) EASI* IGA: 3/4 (n) 4/2 1/5 1/5 2/5 SCORAD* BSA* (%) DLQI *: median 6

7 Pharmacokinetics Serum conc. [ng/ml] 1 Cohort 1 mg/kg1 (1 mg/kg) Cohort 4 mg/kg2 (4 mg/kg) 1 Cohort 1 mg/kg 3 (1 mg/kg) Time [h] mean ± SD exposure increased approximately dose proportional Serum levels in AD patients in range with healthy volunteers Terminal half-lives ranging from 13 to 17 days 7

8 % change from baseline EASI, % change from baseline Pooled subjects (median) Weeks after start of treatment Infusion Placebo 8

9 % of subjects EASI-5 score % of patients with 5% EASI improvement baseline Placebo 1mg/kg 4mg/kg 1mg/kg Weeks since start of treatment N = 7 N = 6 N = 6 N = 6 Infusion 9

10 % change from baseline SCORAD, % change from baseline Pooled subjects (median) Weeks after start of treatment Infusion Placebo 1

11 Safety 1mg/kg n(%) 4mg/kg n (%) 11 1mg/kg n (%) Placebo n (%) TEAE 5 (83.3) 5 (83.3) 3 (5.) 2 (28.6) Serious Death Worst TEAE intensity Mild Moderate Severe 2 (33.3) 3 (5.) 2 (33.3) 3 (5.) 1 (16.7) 2 (33.3) 2 (28.6) Treatment related 2 (33.3) 1 (16.7) 1 (16.7) Permanently stopped 1 (16.7) 1 (14.3) All AEs mild or moderate, transient and not dose dependent No infusion related reactions, no clinically significant findings in ECG and vital signs One patient with -specific ADA formation detected in follow-up period, no impact on safety of subject

12 Conclusion, a first-in-class mab, is a potential new therapy for inflammatory skin disorders Promising results in AD skin efficacy parameters up to 83 % of patients achieved EASI 5 by week 4 in high dose group fast onset of response response maintained after stopping treatment (> 2 months) PK properties as anticipated for mabs dose-proportional, half life days Well tolerated with no safety concerns 12