Symphogen Publishes Pre-Clinical Data Demonstrating Encouraging Results for Sym004
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“Sym004 specifically targets EGFR on cancer cells, which is a proven and attractive therapeutic target and represents a potential multi-billion dollar market opportunity.”
Sym004 is a therapeutic composed of two anti-epidermal growth factor receptor (EGFR) monoclonal antibodies against different nonoverlapping EGFR epitopes. Like other anti-EGFR antibodies, Sym004 inhibits cancer cells by blocking ligand binding, receptor activation/phosphorylation, and downstream signaling. However, Sym004 also showed an ability to induce removal of the EGFR receptors from the cancer cell surface by inducing EGFR internalization and degradation.
The Company demonstrated that the two IgG1 antibodies, 992 and 1024, mixed 1:1 in Sym004 can bind simultaneously to the extracellular domain of EGFR.
Sym004 synergistically inhibited cancer cell growth in vitro. 11 of the 19 different cancer cell lines tested were inhibited by Sym004, whereas only 7 cell lines were inhibited by the individual 992 and 1024 monoclonal antibodies.
Sym004 induced efficient internalization of EGFR on cancer cells. Sym004-treated cells had a significantly higher number of antibody-containing vesicles (two to three times) in all concentrations tested, compared to cetuximab (ERBITUX®).
Sym004-induced internalization of EGFR was followed by receptor degradation. The level of EGFR decreased drastically in all four Sym004-treated cell lines, whereas only a small decrease in EGFR levels was seen in cells treated with marketed antibodies.
Sym004 was a potent inhibitor of tumor growth in a range of cancer xenograft models as compared to both cetuximab and panitumumab (Vectibix®).
Sym004 caused complete removal of the EGF Receptor in vivo. Sym004-treated tumors did not contain any EGFR, whereas cetuximab-treated tumors contained significant levels of EGFR (although still lower than control-treated tumors).
Sym004 treatment was less sensitive to ligand-dependent resistance. Sym004 inhibited proliferation of cell line models of anti-EGFR antibody resistance.
Sym004-induced downregulation of EGFR inhibits ligand-induced phosphorylation of downstream signaling molecules.