Development of next-generation IS-Ab drugs

While  our  lead  IS-Abs  for  CD40,  OX40  and  4-1BB  represent  the  current  state  of  the  art  for  clinical molecules, we have strong indications that further development can result in more advanced IS-Ab designs with superior therapeutic index. Abs consist of two major functional domains: the antigen- binding Fab-domain that contains hyper-variable regions determining antigen-specificity, and the relatively constant Fc-domain that constitutes the framework of the molecule and mediates binding to immune cells through Fc-receptors, as well as to other immune molecules (e.g. complement). Our program intends to develop a second generation of agonist IS Abs with superior therapeutic index through modification of the Fab and Fc-domains by means of four distinct, innovative approaches:

 

  modification of the primary sequence of the Fc-domain (University of Southampton)
modification of the glycosylation of the mAb, in particular the Fc-domain (SME-partner Glycotope)
generation of dual-specific mAbs capable of targeting two complementary immune pathways (SME-partner BioInvent)
generation of trimeric IS-Abs with enhanced agonist function (SME-partner Leadartis)