TAVOTEK BIOTHERAPEUTICS, CSO

Mark is the Chief Scientific Officer at Tavotek Biotherapeutics. He has nearly 35 years of experience in new drug discovery for AbbVie/Abbott Laboratories and Janssen. Prior to joining Tavotek, Dr. Chiu was the Head of the Process Analytical Sciences at Biotherapeutics Development and Head of Antibody Engineering in the Biologics Research Department at Janssen, the pharmaceutical branch of Johnson & Johnson (JNJ). His leadership resulted in more than 15 New Molecular Entities with 6 projects transitioning from Phase 1 to Phase 3 trials with 4 approved drugs.

Dr. Chiu received his A.B. in Biophysics from University of California at Berkeley; Ph.D. degree from the University of Illinois at Urbana-Champaign, and then completed postdoctoral training at the Laboratory of Physical Chemistry at the Federal Institute of Technology at Zurich, Switzerland and the Department of Microbiology at the University of Basel Biocentre.

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.