ARGENX, CO-FOUNDER

Hans de Haard is a serial pioneer of antibody platforms and has been active in the antibody engineering field since 1989, initially at AKZO Nobel. Subsequently, at the University of Maastricht, he created a large non-immune human Fab library that subsequently became a core asset of Dyax, yielding multiple therapeutic antibodies including ImClone products IMC-A12, IMC-1F8 and the recently approved anti-VEGFR2 antibody ramucirumab (formerly called IMC-1121B). From 1998 to 2002 he was responsible for the discovery of llama VHH-based products at Unilever.

From 2002 until he joined argenx, Prof. de Haard worked at Ablynx NV as Director Technology Development, and latterly as Senior Director Discovery Research. He was responsible for setting up the Nanobody® discovery engine and introduced VHH formatting, which turned out to be a major advantage of this platform. He was centrally involved in the development of the Nanoclone® methodology based on B cell selection.

During his career, Prof. de Haard has discovered numerous therapeutic antibody leads, seven of which are now progressing in the clinic. He holds a Master of Science in Biochemistry and a PhD in Molecular Immunology from the University of Maastricht. He is a Professor of Immunology at University of Franche Comté (Besançon, France).

The central role of FcRn in regulating immunoglobulin G (IgG) persistence and transport provides opportunities for targeting this receptor in multiple different diagnostic and therapeutic situations. The engineering of IgGs with higher affinity for FcRn can be used to produce antibodies with longer in vivo half-lives, but only if the low affinity of the IgG-FcRninteraction at near neutral pH is retained. Conversely, an engineered IgG or Fc fragmentwith increased affinity for FcRn at both acidic and near neutral pH acts as a potent inhibitor of FcRn. Consequently, such an antibody (‘Abdeg’, for antibody that enhancesIgG degradation) can lower the levels of endogenous IgG and has led to the FcRn antagonist, efgartigimod, that has been developed by argenx and recently approved for the treatment of myasthenia gravis. Our recent work has also resulted in the generation of engineered Fc-fusions that selectively clear antigen-specific antibodies (‘Seldegs’, for selective degradation). Developments related to the modulation of the dynamic behavior of IgG in the bodywill be presented.