BiOrion’s core technology is based on proprietary PDGF-ß-receptor medium-affinity binding bicyclic peptides, derived from the amino acid binding sequence of its natural ligand PDGF-BB. 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. PDGF-ß receptors are specifically expressed in high density on myofibroblasts from different sources, including pericytes, as they are present in all fibrotic organs and tissues. The medium-affinity binding of the bicyclic peptides in combination with the cell-specific overexpression of PDGF-ß-receptors, allow cell specific targeting platform to myofibroblasts.
BiOrion’s bicyclic peptides can be conjugated to functional groups such as radionuclides, for imaging diagnostics, or (existing) antifibrotic drugs, for antifibrotic therapy. These bicyclic peptide-drug conjugates bind with medium-affinity to PDGF-ß-receptors without interfering in the PDGF signaling cascade. Side effects and off-target effects are therefore excluded. After binding to PDGF-ß-receptors on myofibroblasts, the bicyclic peptide-drug conjugates are internalized and have their intended intracellular effect. The PDGF-ß-receptor is therefore used as a Trojan horse: only binding to the receptor to get internalized and accumulated into the myofibroblast, without any effect on PDGF signaling.
BiOrion has developed a library of potential PDGF-ß-receptor targeted drug candidates, including cytokines, cytotoxic drugs, adenovirus vectors, whether or not encapsulated in liposomal nanoparticles.