![]() ![]() TPP1820 was effective in preventing experimental MG in rats in both prophylactic and therapeutic dosing regimens. We found the mAbs were human, cynomolgus monkey and/or rat cross-reactive and each had a distinct, novel mechanism of C7 inhibition. ![]() We investigated C7 as a target and assessed the in vitro function, binding epitopes and mechanism of action of three mAbs against C7. Secondly, given the known heterogenous mechanisms of action of autoantibodies in MG, effective patient stratification in the REGAIN trial may have provided more favorable efficacy readouts. Firstly, further C5 inhibitors are in clinical development, but other terminal pathway proteins, such as C7, have been relatively understudied as therapeutic targets, despite the potential for lower and less frequent dosing. It is an expensive drug and was approved despite missing the primary efficacy endpoint in the Phase 3 REGAIN study. Eculizumab, a C5-inhibitor, is the only approved treatment for MG that mechanistically addresses complement-mediated loss of nicotinic acetylcholine receptors. Myasthenia Gravis (MG) is mediated by autoantibodies against acetylcholine receptors that cause loss of the receptors in the neuromuscular junction. 5Medicines, Science and Technology, Protein Cellular and Structural Sciences (PCSS) Protein and Cellular Sciences, GlaxoSmithKline Research & Development (GSK R&D), Stevenage, United Kingdom.4Medicines, Science and Technology, Protein Cellular and Structural Sciences (PCSS) Structural and Biophysical Sciences, GlaxoSmithKline Research & Development (GSK R&D), Stevenage, United Kingdom.3Medicinal Science and Technology, Biopharm Discovery, GlaxoSmithKline Research & Development (GSK R&D), Stevenage, United Kingdom.2Division of Infection and Immunity and Dementia Research Institute, Systems Immunity Research Institute, School of Medicine, Cardiff University, Wales, United Kingdom.1Immunology Research Unit, GlaxoSmithKline Research & Development (GSK R&D), Stevenage, United Kingdom.Kitchen 1 Maria Feeney 1 Susannah Davis 3 B. Burden 3 Richard Priest 3 Trevor Wattam 3 Semra J. Wear 1 Sebastien Petit-Frere 1 Michael N. Osuch 1 Elen John-Morris 1 Lasse Stach 3 Darren Gormley 1 Andrew Sanderson 5 Angela Bridges 5 Elizabeth R. Zelek 2 David Gower 3 Claus Spitzfaden 4 Isabelle H. ![]()
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