Sym004 was the first product candidate from Symphogen's oncology pipeline to enter the clinic. Sym004 targets the human cancer antigen EGFR (epidermal growth factor receptor).
The Sym004 product is a mixture of two synergistic full-length anti-EGFR antibodies, which bind to two separate non-overlapping epitopes on EGFR.
The combination has a unique mechanism of action, which leads to sustained growth inhibition of cancer cells. Sym004 has proven to be superior to available monoclonal antibodies in several established animal models and has shown promising results in early human clinical trials.
Preclinical studies with Sym004 conducted in a series of in vitro and in vivo xenograft models have demonstrated its superior efficacy in a variety of EGFR-expressing solid tumors. Symphogen believes that the unique mechanism of action and differentiated profile of Sym004 may enable the drug to compete effectively against both antibody and small molecule competitors in a variety of tumor types and across multiple clinical applications.
Symphogen initiated a clinical phase 2a trial in patients with KRAS wild-type metastatic colorectal cancer (mCRC) in the first quarter of 2011 and a clinical phase 2a trial in patients with squamous cell carcinoma of the head and neck (SCCHN) in July 2011. Initial safety and efficacy data from both trials have been presented at ASCO Annual Meetings in 2013 and 2014. At these meetings, Phase 2 proof-of-concept data were reported for Sym004 in SCCHN and in mCRC that signaled clinical activity and were supportive of the proposed mechanism of action, respectively.
Sym004 is not only designed to block ligand binding, receptor activation and downstream signaling but also elicits effective removal of the EGFR receptors from the cancer cell surface by inducing EGFR internalization and degradation.
Both Sym004 antibodies, called 992 and 1024, are mandatory in order to cross-link EGFR receptors on the cell surface, which leads to very effective receptor elimination and induction of secondary effector functions. Such extensive crosslinking of the receptors cannot be achieved with a single monoclonal antibody.