SuppreMol´s core competence is around the function and modulation of Fcy Receptors (FcγRs). In autoimmune diseases, the FcγR plays a pivotal role in mounting and controlling the antibody-elicited inflammation, 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 is primarily responsible for mediating phagocytosis of immune complexes and exists in two isoforms, FcγRIIA and FcγRIIB, which differ in the extracellular region only by 6% of the amino acid residues. FcγRIIA is the key receptor for the induction of ADCC, while the inhibitory FcγRIIB represents the sole FcγR, which is expressed on B cells. The Fc gamma receptor IIB (FcγRIIB) is the only inhibitory receptor among the family of FcγRs expressed on immune cells. Its main function is to inhibit activating signals, which is generally achieved through co-crosslinking of FcγRIIB with membrane proteins that possess an activating motif in their cytoplasmatic region. Specifically such proteins are, for example, activating FcγRs or the B cell receptor (BCR). In consequence, this co-crosslinking of FcγRIIB and the BCR by immune complexes (ICs) down regulates antigen-specific B cell responses. In several autoimmune diseases it has been observed that the patients exhibit a lower FcγRIIB expression compared to that of the activating FcγRs.
The most advanced clinical product in SuppreMols pipeline, SM101, is a soluble Fc gamma receptor IIB (sFcγRIIB), which competes with FcγRs expressed on immune cells for pathogenic immune complexes.
The Company is also developing a framework of monoclonal antibodies directed against human FcγRIIB. These products, SM201, SM211 and SM301 modulate the immune system directly via targeting the inhibitory FcγRIIB on cells.