Orally administered Nanofitins® active in the GI tract
Treating locally diseases of the gastrointestinal tract, such as inflammatory bowel diseases (IBD), thanks to oral administration of targeted therapies shall enable a better targeting of the inflammation site, decreasing systemic exposure and as such the risk of systemic-related adverse events, while increasing patient comfort and compliance to treatment. TNFα is a cytokine considered a key regulator of immune cells and a clinically validated target in IBD. Anti-TNFα Nanofitins® demonstrated their capacity to be delivered orally without any gastric-resistant formulation and to achieve TNFα blockade in vivo. Healing of the mucosal inflammatory lesions in murine IBD models was consistent with the biology of the Nanofitins ® and their ability at localizing within the mucosal ulceration sites. The SADEL project was partially sponsored from January 2012 to December 2016 by a grant from the European Commission under FP7 framework (https://cordis.europa.eu/project/id/278042 ).
The mucosal inflammatory response in IBD is complex and IBD pathogenesis can involved overlapping or offsetting signaling pathways, which results in a significant proportion of the IBD patients (~30%) not responding to induction anti-TNFα treatment. Moreover, within the responder population, another 50% develop resistance within 1 year of treatment. Affilogic is actually developing a orally available bi-specific Nanofitin® construct targeting both TNFα and Oncostatin M (OSM), a biomarker of primary anti-TNFα therapy resistance, clinically validated. The Nanomodule project already validated the successful construction of multifunctional Nanofitin® -based therapeutics using straightforward molecular approaches, while preserving the original pharmacologic and stability properties of the parent proteins.
Thanks to its discovery process, Affilogic can help its partners design a single Nanofitin® or a multispecific Nanofitin®-based biotherapy for a local effect in the gastrointestinal tract, such as targeting several inflammatory pathways in auto-immune diseases, targeting several pathogens in infectiology, targeting gut microbiota…