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Efficacy of anti-inflammatory SI g As after topical treatment in inflammatory bowel disease

Efficacy of anti-inflammatory SI g As after topical treatment in inflammatory bowel disease. DISCLOSURE R. Arends 1, , R. Ubink 1 , M. van der Lee 1 , G. de Roo 2 , L. Dickey 3 , G. Rouwendal 4 , G. Ariaans 4 , W. Dokter 1 1 Preclinical Department, 2 Bio DSP, 3 LEX Platform

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Efficacy of anti-inflammatory SI g As after topical treatment in inflammatory bowel disease

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  1. Efficacy of anti-inflammatory SIgAs after topical treatment in inflammatory bowel disease • DISCLOSURE • R. 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. Neurath • Department of Gastroenterology, Pneumology and Endocrinology of the MedizinischeKlinik 1, Erlangen, Germany • B. Corthésy • Centre HospitalierUniversitaireVaudois, R & D Laboratory of the Division of Immunology and Allergy, Lausanne, Switzerland

  2. Introduction SECRETORY-iga (SIgA) SIgA produced in Lemna minor effectively binds human and mouse TNFα (Patent application WO2013/087912 ) 2

  3. uptake of SIgA in polarized Caco-2 cells Cy5 labeled SIgA in green ZonaOccludens (ZO-1) in red, Nuclei (DAPI) in blue Apical uptake of SIgA by polarized Caco-2 cells 3

  4. BIO-IMAGING OF ORALLY ADMINISTERED SIgA SIgA molecule ends up in gut, 24h after oral treatment 4

  5. Localization of sIgA in distal colon after topical administration Lumen SC-20656 ULEX-1DAPI Lumen SC-20656 EpCAMDAPI Sc-20656 (human secretory chain) in red, DAPI (Nuclei) in blue LEFT ULEX-1 (Lectin) in green RIGHTEpCAM (Epithelial cell adhesion molecule) in green SIgA localized in epithelial cells in distal colon after oral and rectal administration 5

  6. Biodistribution (Qwba) SIgA iV and PO Intravenous Oral SIgA rapidly cleared from circulation after IV administration t1/2 ~2h Very low systemic exposure after oral administration 6

  7. SIgA in TNBS-INDUCED IBD model in mice SIgA inhibits TNBS-induced IBD after Oral and Rectal administration

  8. 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.

  9. SIgAs the future for topical IBD treatment!

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