![Page 1: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/1.jpg)
Drug development @ LIED
Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED)
University of Lübeck, Germany
![Page 2: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/2.jpg)
High medical need for new treatments of inflammatory skin diseases
Psoriasis • Comorbidity • Unresponsive to biologicals • High treatment cost • Mortality still increased
![Page 3: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/3.jpg)
High medical need for new treatments of inflammatory skin diseases
Psoriasis • Comorbidity • Unresponsive to biologicals • High treatment cost • Mortality still increased
Pemphigus and Pemphigoid (AIBD) • Increasing incidence • Immunosuppression required to maintain
clinical remission • Treatment-associated adverse events • Mortality 2-3-fold increased
![Page 4: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/4.jpg)
Pemphigus- and Pemphigoid diseases
Pemphigus (Bulous) Pemphigoid
Clin
ics
His
tolo
gy
![Page 5: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/5.jpg)
Pemphigus- and Pemphigoid diseases
Pemphigus (Bullous) Pemphigoid
Clin
ics
Dire
ct IF
![Page 6: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/6.jpg)
Treatment of AIBD
Pemphigus vulgaris Bullous pemphigoid
First line - High-dose systemic corticosteroids
- Combination with other immunusup..
First line - topical corticosteroids
- Combination with dapson, doxicylin
Second line / alternatives - anti-CD20 (Rituximab) - IVIG - Immunoadsorbtion / plasmapheresis - Cyclophosphamide - Combinations
![Page 7: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/7.jpg)
Pathogenesis of AIBD
![Page 8: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/8.jpg)
Pathways to new treatments pursued at LIED
In vitro validation
In vivo validation
Pre-clinical models
Clinical trials
Hypotheses Omics Screening Computation LIED & partners from academia and industry
![Page 9: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/9.jpg)
Pathways to new treatments pursued at LIED
In vitro validation
In vivo validation
Pre-clinical models
Clinical trials
Hypotheses Omics Screening Computation LIED & partners from academia and industry
![Page 10: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/10.jpg)
Use of dimethylfumarate in bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA)
In vitro validation
In vivo validation
Pre-clinical models
Clinical trials
Hypotheses • Dimethylfumarate (DMF) established treatment of psoriasis
• DMF recently licenced for multiple sclerosis
• DMF has manifold immune-modulatory fuctions
• DMF is an effective treatment for BP / EBA
![Page 11: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/11.jpg)
DMF impairs neutrophil activation
In vitro validation
In vivo validation
Pre-clinical models
Clinical trials
Hypotheses
Normal human serum EBA serum
![Page 12: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/12.jpg)
DMF impairs neutrophil activation
In vitro validation
In vivo validation
Pre-clinical models
Clinical trials
Hypotheses neg pos
DMF 15 µg/ml
![Page 13: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/13.jpg)
Use of dimethylfumarate in bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA)
In vitro validation
In vivo validation
Pre-clinical models
Clinical trials
Hypotheses
![Page 14: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/14.jpg)
DMF treatment improves already Established EBA
Immunization
Weeks
0 3 9
Clinical assessment Randomization to treatment
1. Solvent 2. DMF
In vitro validation
In vivo validation
Pre-clinical models
Clinical trials
Hypotheses
![Page 15: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/15.jpg)
DMF treatment improves already Established EBA
In vitro validation
In vivo validation
Pre-clinical models
Clinical trials
Hypotheses
* * * *
![Page 16: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/16.jpg)
Individual treatment of BP patients with DMF
In vitro validation
In vivo validation
Pre-clinical models
Clinical trials
Hypotheses
2xtgl Clobetasol* + Fumaderm®
Inclusion 4 months 16 months
Fumaderm® End of study
Endpoint: Observation
![Page 17: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/17.jpg)
Pathways to new treatments pursued at LIED
In vitro validation
In vivo validation
Pre-clinical models
Clinical trials
Hypotheses Omics Screening Computation LIED & partners from academia and industry
![Page 18: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/18.jpg)
High-throughput screening identifies novel neutrophil-inhibitory compounds
In vitro validation
In vivo validation
Screening
ongoing
![Page 19: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/19.jpg)
High-throughput screening identifies novel neutrophil-inhibitory compounds
In vitro validation
In vivo validation
Screening
ongoing RO
S re
leas
e (r
el)
Inhibitory compounds #1-33 / 1.200
![Page 20: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/20.jpg)
High-throughput screening identifies novel neutrophil-inhibitory compounds
In vitro validation
In vivo validation
Screening
ongoing
���������������
�����
�������
������
�����
�������
������
�����
�������
������
�����
��
�
����
����
����
����
����
��� ��� ������ ��� ������������������������������������������������ ���� ��� ������������� ��
Activatory compound Control Inhibitory compound
![Page 21: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/21.jpg)
In vivo validation of 4 compounds
In vitro validation
In vivo validation
Screening
ongoing
DMSOMPM2
4 80 1612
5
10
0
15
* *** §
Affe
cted
bod
y s
urfa
ce a
rea
(%)
Days
DMSO M2
![Page 22: Drug development @ LIED · Drug development @ LIED Ralf Ludwig Lübeck Institute of Experimental Dermatology (LIED) University of Lübeck, Germany . High medical need for new treatments](https://reader034.vdocuments.net/reader034/viewer/2022042622/5f94376f3621625b5041c6af/html5/thumbnails/22.jpg)
Summary
1. Comprehensive drug development programm for inflammatory diseases
2. Identification of DMF as potential drug candidate for BP
3. Drug-repurposing for neutrophil-inhibitory compounds