EFFICACY OF ANTI-INFLAMMATORY SIgAS AFTER TOPICAL TREATMENT IN INFLAMMATORY BOWEL DISEASE

DISCLOSURER. Arends1,, R. Ubink1, M. van der Lee1, G. de Roo2, L. Dickey3, G. Rouwendal4, G. Ariaans4, W. Dokter1

1Preclinical Department, 2Bio DSP, 3LEX Platform 4New Molecular Entities, Synthon Biopharmaceuticals BV, Nijmegen, The Netherlands

B. Weigmann, M. NeurathDepartment of Gastroenterology, Pneumology and Endocrinology of the Medizinische Klinik 1, Erlangen, Germany

B. CorthésyCentre Hospitalier Universitaire Vaudois, R & D Laboratory of the Division of Immunology and Allergy, Lausanne, Switzerland

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INTRODUCTION SECRETORY-IgA (SIgA)

SIgA produced in Lemna minor effectively binds human and mouse TNFα (Patent application WO2013/087912 )

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Cy5 labeled SIgA in greenZona Occludens (ZO-1) in red, Nuclei (DAPI) in blue

UPTAKE OF SIgA IN POLARIZED CACO-2 CELLS

Apical uptake of SIgA by polarized Caco-2 cells 3

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BIO-IMAGING OF ORALLY ADMINISTERED SIgA

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SIgA molecule ends up in gut, 24h after oral treatment

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LOCALIZATION OF SIgA IN DISTAL COLON AFTER TOPICAL ADMINISTRATION

SIgA localized in epithelial cells in distal colon after oral and rectal administration 5

Lumen SC-20656 ULEX-1 DAPI Lumen SC-20656 EpCAM DAPI

Sc-20656 (human secretory chain) in red, DAPI (Nuclei) in blueLEFT ULEX-1 (Lectin) in green RIGHT EpCAM (Epithelial cell adhesion molecule) in green

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BIODISTRIBUTION (QWBA) SIgA IV AND PO

SIgA rapidly cleared from circulation after IV administration t1/2 ~2hVery low systemic exposure after oral administration 6

Intravenous

Oral

Caecu

m conten

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Large i

ntestin

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testine c

ontents

Stomach conten

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Urinary

bladder:

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Bile (g

all blad

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SIgA IN TNBS-INDUCED IBD MODEL IN MICE

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SIgA inhibits TNBS-induced IBD after Oral and Rectal administration

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SUMMARY AND CONCLUSION

• We have successfully generated a monoclonal anti-TNFα secretory IgA antibody in duckweed.

• Anti-TNFα SIgA is a promising molecule for topical treatment of IBD, combining elimination of adverse effects associated with systemic exposure with the convenience of topical treatment.

SIgAs the future for topical IBD treatment!