PDGF/PDGFR

BiOrion’s core technology of its 2 lead programs is based on proprietary PDGFRB medium-affinity binding bicyclic peptides and PDGFRB high affinity binding single domain antibodies (sdAbs, VHHs, nanobodies).

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 overexpressed 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 to myofibroblasts.

BiOrion’s bicyclic peptides and single domain antibodies can be conjugated to functional groups such as radionuclides for PET-imaging diagnostics and targeted radiotherapy, or (existing) antifibrotic drugs, for antifibrotic therapy. The bicyclic peptide-drug conjugates and single domain antibody-drug conjugates bind to PDGF-ß-receptors without interfering in the PDGF signaling cascade. Adverse side effects and off-target effects are therefore unlikely. After binding to PDGF-ß-receptors on myofibroblasts, the bicyclic peptide-drug conjugates and single domain antibody-drug conjugates are internalized and have their intended effect. The PDGF-ß-receptor 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.

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.

The receptor-binding bicyclic peptide or single domain antibody can be labeled with a PET radionuclide, here Gallium-68, for PET imaging diagnostic purposes. When labeled with a radio-toxic radionuclide, here Lutetium-177, the receptor-bearing cells will be damaged from radiation and eliminated. In both applications, the receptor binding peptide or antibody is identical, only the radionuclide needs to be changed. This combined use of only 1 product is called a theranostic.