MOR106, an anti-IL-17C mAb, potential new approach for treatment of moderate to severe atopic dermatitis: Phase 1 study

Background:
IL-17C induces expression of cytokines, proinflammatory mediators and antimicrobial peptides in epidermal keratinocytes. MOR106 is a fully human monoclonal antibody binding with high affinity to human Il-17C, thereby neutralizing its biological activity. MOR106 showed to be effective in animal models of atopic dermatitis and psoriasis and could be a potential new treatment target in these diseases.


Methods:
Phase I study evaluating single ascending doses (SAD) in healthy volunteers (HV), and multiple ascending doses (MAD) in patients with moderate-to-severe atopic dermatitis (AD).
In the SAD part, 56 subjects received a single i.v. infusion up to 20 mg/kg. In the MAD part, 25 AD patients received weekly i.v. infusions over 4 weeks with a 10 week follow up period. End points included safety and tolerability, pharmacokinetic profile, including IL-17C antibody complex in serum and assessment of immunogenicity. Key exploratory effiacy endpoints in the MAD part included percent change of Eczema Area Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD) and number of patients with a 50 % reduction in EASI (EASI-50) at week 4 compared to baseline.

Results:
MOR106 was well tolerated with no serious or severe adverse events (AE) reported. A dose-proportional increase in drug exposure was observed; comparable between healthy volunteers and patients. Estimated half-life ranged between 13 and 17 days. A linear relationship between dose and MOR106 concentrations in skin could be demonstrated in HV as measured 96 hours after administration. IL-17C, complexed to MOR106 and accumulated in the serum at day 8, was 2-3 fold higher in AD patients compared to HV. There was higher variability in AD patients than in HV. Although not statistically powered to show differences in efficacy between treatment groups, at the highest dose level (10 mg/kg) of MOR106, in 83% of patients (5 out of 6), an improvement of at least 50% in signs and symptoms of atopic dermatitis measured by EASI score was recorded at week 4. The onset of activity was rapid, occurred within a few weeks and was maintained for over 2 months after the last treatment. These results were corroborated by the SCORAD scores.


Conclusion:
MOR106 was well tolerated and reported adverse events were not dose -limiting. The study supports IL-17C as a potential target in atopic dermatitis."

Authors

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)

Organisations

Exzellenzzentrum Entzündungsmedizin Universitätsklinikum Schleswig-Holstein Lübeck, Schleswig-Holstein, Germany (1)
Arensia Exploratory Medicine, Romania (2)
Polyclinic of Hospitallers Brothers of St. John, Hungary (3)
Galapagos NV, Generaal De Wittelaan L11A3, 2800 Mechelen, Belgium (4)
MorphoSys AG, Semmelweisstra╬▓e 7, 82152 Planegg, Germany (5

Presenting author

Johan Beetens, Development Project Leader, Sr Director, Galapagos NV
johan.beetens@glpg.com
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