Based on the Peptabody technology platform, MDP01 binds the extracellular part of Epidermal Growth Factor Receptor (EGFR) specifically and with a high avidity. EGFR targeting is accomplished by the ligand part: a full Epidermal Growth Factor (EGF) which has been combined with a monomer of the generic hCOMP backbone. The pentamerization and the resulting avidity of the molecule are assured through the hCOMP backbone.
We took advantage of the peptabody concept to specifically target cancer cells overexpressing EGFR. For efficient EGFR binding and subsequent activation of its cell signalling pathway, a high density of receptor molecules is required. This ensures an efficient targeting of cancer cells overexpressing EGFR and therefore limits effects on cells expressing normal physiological levels of the receptor.
MDP01 is a fully human version of a peptabody developed at Med Discovery and it is currently in pre-clinical development.
Rapid clearance of MDP01 from blood pool
Pharmacokinetic studies of radio-labeled MDP01 in mice showed rapid clearance from blood circulation. Furthermore, a high level of tissue penetration was observed with rapid subsequent clearance. This kinetic profile is in contrast with typical half-life of antibodies which show prolonged retention in circulation. The combination of strong binding and rapid clearance should reduce the risk of side effect on normal cells expressing a low level of EGFR.
EGFR Targeting in a Mouse Tumor Model
In vivo targeting of EGFR expressing tumors was evaluated in a mouse xenograft model for bladder cancer showing overexpression of EGF receptor. A targeting of EGF receptor expressing tumors was observed.
Such pharmacokinetic behavior is favorable for the generation of a high degree of contrast between target-bound and free molecules in imaging applications.
Ligand: the full length human Epidermal Growth Factor EGF (EGFR ligand)