DIRECTOR, RESEARCH AND DISCOVERY

Dr. Simone Oostindie is Director, Research and Discovery at Gyes B.V., a biotechnology company that focuses on creating a pioneering Multispecific Antibody Platform (MAP) to discover and develop differentiated antibody therapeutics. Before Joining Gyes B.V. in 2023, Dr. Oostindie was a Sr. Scientist in the Translational Research department at Genmab, where she led the translational research and biomarker strategy for Genmab’s (pre)clinical therapeutic antibody candidates.

During her career at Genmab, she was involved in the discovery and development of novel antibody technology platforms including DuoHexaBody® and HexElect® and in the preclinical development of multiple therapeutic antibody candidates currently progressing in the clinic.

Dr. Oostindie received her PhD in immunology from Leiden University, with a focus on avidity engineering as a rational design principle for potentiated antibody therapeutics.

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.