PDGF / PDGFR axis

BiOrion’s core technology of its 2 lead programs is based on proprietary PDGFRB binding bicyclic peptides and binding single domain antibodies.

All the PDGF sub-types are growth factors that regulate recruitment and growth of cells, and, together with TGF-ß, are the main drivers of fibroblast proliferation, trans-differentiation and activation during fibrosis. PDGFRB are specifically overexpressed on myofibroblasts from different sources, including pericytes, as they are present in all fibrotic organs and tissues.

The binding of the bicyclic peptides and single domain antibodies in combination with the cell-specific overexpression of PDGFRB, allow cell specific targeting to myofibroblasts.

BiOrion’s bicyclic peptides and single domain antibodies can be conjugated to functional groups such as NOTA, allowing chelation of radionuclides for PET-imaging diagnostics and targeted radiotherapy, but also (existing) antifibrotic drugs, for antifibrotic therapy. The bicyclic peptide-drug conjugates and single domain antibody-drug conjugates bind to PDGFRB without interfering in the PDGF signaling cascade. Adverse side effects and off-target effects have not be seen and are therefore unlikely. After binding to PDGFRB on myofibroblasts, the bicyclic peptide-drug conjugates and single domain antibody-drug conjugates are internalized and have their intended effect. The PDGFRB is therefore used as a Trojan horse: solely binding to the receptor to get internalized and accumulated into the myofibroblast, without any effect on PDGF signaling.