Merck has signed an exclusive worldwide license agreement with Denmark based Symphogen A/S, for Sym004, an investigational antibody mixture targeting the epidermal growth factor receptor (EGFR).

Sym004 is currently being evaluated in a phase I/II trial for the treatment of patients with advanced KRAS wild-type metastatic colorectal cancer (mCRC) who have previously progressed on treatment with standard chemotherapy and a marketed anti-EGFR monoclonal antibody.

In addition, a singlearm, open-label phase II trial in patients with squamous cell carcinoma of the head and neck (SCCHN) who have failed anti-EGFR–based therapy is currently ongoing.

“Sym004 further strengthens our early development pipeline by adding a product that is thought to act via a proposed synergistic mechanism of action not previously studied, but more specifically, it has the potential to become a key asset complementing our already highly successful Erbitux franchise,” commented Dr Susan Jane Herbert, head of Global Business Development and Strategy for the Merck Serono division. Herbert further added, “This collaboration once again reflects our strong commitment to fighting cancer and to providing new treatment options to patients.”

Under the agreement, Merck will gain exclusive worldwide rights to develop and commercialize Sym004. In exchange, Symphogen will receive from Merck an upfront payment of €20 million as well as payments for clinical development, regulatory and sales performance milestones. Symphogen will also be eligible for potential royalties on net worldwide sales.

Sym004 is comprised of two antibodies that are not only designed to block ligand binding, receptor activation and downstream signaling but are also thought to elicit removal of the EGFR receptors from the cancer cell surface by inducing EGFR internalization and degradation.

“We believe that Merck is uniquely well positioned to develop Sym004 based on its deep knowledge of the EGFR area," said Kirsten Drejer, chief executive officer of Symphogen. “This transaction further validates the antibody mixture approach as a highly attractive option.”

As of July 2012, 88 patients have been treated with Sym004 in clinical trials. The adverse events from preliminary clinical data include diarrhea, skin rash, mucosal inflammation, nausea, infusion-related reaction and hypomagnesemia. Exposure data from the patients, after weekly repeated infusions, do not indicate an anti-drug antibody response.

Symphogen is developing antibody therapeutics (monoclonal, monoclonal mixtures and polyclonal) to help people with serious diseases and significant unmet medical needs.