Science Overview

SuppreMol´s core competence is around the function and modulation of Fcy Receptors (FcgRs). FcgRs play a pivotal role in mounting and controlling the antibody-mediated immune response, as this receptor is virtually omnipresent on all immunologically active cells, except T cells. The receptor is responsible for the uptake of immune complexes and their subsequent presentation to T cells, the induction of antibody dependent cellular cytotoxicity (ADCC) or the release of immune stimulants.

Three classes of FcγRs exist in humans: the high affinity receptor FcγRI and the low affinity receptors FcγRII and FcγRIII. FcγRII exists in two isoforms, FcγRIIA and FcγRIIB, which differ in the extracellular region only by 6% of the amino acid residues but possess distinct cytoplasmic regions that mediate either an activating or an inhibitory signal to the expressing cell. The activating FcγRIIA is the key receptor for mediating phagocytosis of immune complexes and the induction of ADCC, while FcγRIIB represents the sole inhibitory FcγR among the family of FcγRs. Its main function is to inhibit activating signals, which is generally achieved through co-crosslinking of FcγRIIB with other membrane proteins. Specifically such proteins are, for example, activating FcγRs or the B cell receptor (BCR). In consequence, on B cells where FcgRIIB represents the only FcgR the co-crosslinking of FcγRIIB and the BCR by immune complexes (ICs) down-regulates B cell proliferation and antibody production.

The most advanced clinical product in SuppreMols pipeline, SM101, is a soluble FcγRIIB (sFcγRIIB), which competes with FcγRs expressed on immune cells for pathogenic immune complexes that are formed during autoimmune diseases.

The Company is also developing a framework of monoclonal antibodies directed against human FcγRIIB. The respective products, SM201, SM211 and SM301 directly recruit the inhibitory FcγRIIB for a down regulation of the immune system.