- Novel mechanism of action resulted in superior anticancer effects vs ERBITUX® and Vectibix®
- Sym004 advancing into the clinic
- Results further validate Symphogen’s proprietary discovery platforms to identify potential antibody therapeutics for serious diseases
COPENHAGEN, Denmark and PRINCETON, New Jersey – Symphogen A/S today announced the publication of encouraging data for Sym004 in the on-line edition of Cancer Research (January 15, 2010; 70(2)). The data showed that Sym004 provided synergistic inhibitory effects against cancer cell lines of different tissue origin in vitro and in vivo.
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 a unique ability to induce rapid and efficient removal of the EGFR receptors from the cancer cell surface by inducing EGFR internalization and degradation.
“We believe that Sym004’s novel mechanism of action resulted in these impressive results demonstrating antitumor activity in EGFR-expressing tumors and that the combination of these two antibodies to form Sym004 led to the powerful synergistic effects demonstrated in this study,”
stated Kirsten Drejer, M.Sc. and Ph.D., Chief Executive Officer of Symphogen.
“We are hopeful that Sym004 proves to be a safe and efficacious agent for patients and we look forward to advancing Sym004 into Phase 1 clinical trials soon.”
”Even with the two approved anti-EGFR antibody therapies on the market, cetuximab and panitumumab, there remains a strong unmet need for more efficacious treatments for patients with EGFR-resistant tumors,”
stated Josep Tabernero, M.D., Head of Gastrointestinal Tumors and Phase I Unit at Vall d’Hebron University Hospital in Barcelona, Spain.
“The preclinical results indicate that Sym004 appears to exhibit anti-cancer effects on EGFR-resistant tumors. We look forward to reviewing ongoing clinical data from Sym004 as the compound progresses through development.”
Data Reported in Cancer Research
- 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.
“Sym004 specifically targets EGFR on cancer cells, which is a proven and attractive therapeutic target and represents a potential multi-billion dollar market opportunity,”
continued Dr. Drejer.
“This data validates the ability of our proprietary antibody discovery and screening platforms to identify and select potent monoclonal antibody combinations that more effectively address the multi-mechanistic nature of cancer. We believe our approach should translate to other ligand-dependent cancers as well as other serious diseases with complex target antigens, including many autoimmune and infectious diseases.”
Symphogen is developing superior antibody therapeutics (monoclonal, biclonal and polyclonal) to help people with serious diseases and significant unmet medical needs. With its proprietary, unique Symplex™ discovery and Sympress™ manufacturing platforms, the company captures the diversity and specificity of the natural immune response in rationally designed recombinant antibody compositions. Symphogen is maturing a diversified pipeline of internal and partnered products across multiple indications including cancer, autoimmune and infectious disease. Symphogen is a private biopharmaceutical company headquartered in Copenhagen, Denmark, with a US subsidiary in Princeton, New Jersey.