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AMT-101: an oral human IL-10 fusion protein

Presented By
Dr R. Mrsny, Applied Molecular Transport, USA
ECCO 2020
A newly designed chimaera of human IL-10 genetically fused to a non-toxic and poorly immunogenic fragment of the cholix exotoxin, termed AMT-101, demonstrated efficacy in preclinical models of colitis and has advanced to the clinic. Its gastro-intestinal selectivity should lead to improved safety. IL-10 is a central anti-inflammatory cytokine that can modulate many pro-inflammatory signals, but clinical application has been limited by dose-limiting systemic side effects. This led to the development of a new chimaera of human IL-10 termed AMT-101. In mice, the oral gavage of AMT-101 blocked histological changes of colonic tissue associated with oxazolone-induced colitis [1]. AMT-101 curbed increases in serum levels of pro-inflammatory cytokines IL-1β, IL-6, and IL-17A, as well as IL-10 (see Figure). Cynomolgus monkeys dosed orally with AMT-101 showed much lower serum levels than after intravenous injection of AMT-101 [1]. First author Dr Randall Mrsn...

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