BiOrion’s core technology is based on proprietary PDGF-ß-receptor medium-affinity binding bicyclic peptides and PDGF-ß-receptor high affinity binding single domain antibodies (VHH).
These bicyclic peptides and single domain antibodies are conjugated to a NOTA chelator allowing capturing radionuclides, such as 68-Gallium and 177-Lutetium.
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 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 intracellular 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.
Figure: General principle of BiOrion’s technology.
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 approaches, the receptor binding peptide or antibody can be identical. Only the radionuclide needs to be changed.