COPENHAGEN, Denmark—Private biopharmaceutical companySymphogen A/S, which focuses on the development of recombinant antibodymixtures, has announced the signing of an exclusive worldwide license agreementwith Merck KGaA for Sym004, an investigational antibody mixture that targetsthe epidermal growth factor receptor (EGFR), which has long been associatedwith lung cancer.
Per the terms of the agreement, Merck will pay Symphogen atotal of € 20 million (approximately $25.26 million) upfront, with anadditional € 225 million (approximately $284.18 million) possible in clinicaldevelopment and regulatory milestones and another € 250 million (approximately$315.76 million) possible in combined sales performance milestones. Symphogenis also eligible to receive royalties on net worldwide sales. In return, Merckis granted exclusive worldwide rights for the development and commercializationof Sym004.
"Sym004 further strengthens our early development pipelineby adding a product that is thought to act via a proposed synergistic mechanismof action not previously studied, but more specifically, it has the potentialto become a key asset complementing our already highly successful Erbituxfranchise," Dr. Susan Jane Herbert, head of Global Business Development andStrategy for Merck Serono, said in a press release about the agreement. "Thiscollaboration once again reflects our strong commitment to fighting cancer andto providing new treatment options to patients."
Sym004 is currently undergoing a Phase I/II trial inpatients with advanced KRAS wild-type metastatic colorectal cancer who havepreviously progressed on treatment with standard chemotherapy and a marketedanti-EGFR monoclonal antibody. The compound is also being evaluated in asingle-arm, open-label Phase II trial in patients suffering from squamous cellcarcinoma of the head and neck who have failed anti-EGFR-based therapy.Enrollment for the former study was completed in June of last year, and thelatter study was initiated in August of last year. The primary endpoint of thePhase II trial in squamous cell carcinoma patients is progression-free survivalat 24 week, with secondary endpoints of objective tumor response, time toprogression, biomarkers, pharmacokinetic profile and safety.
Sym004 consists of two anti-EGFR monoclonal antibodies thattarget different non-overlapping epitopes. The compound blocks ligand binding,receptor activation/phosphorylation and downstream signaling, in addition todemonstrating the ability to induce rapid removal of EGFR receptors from thesurface of cancer cells by inducing EGFR internalization and degradation.Sym004 has also shown the potential to treat tumors that present acquiredresistance to other anti-EGFR agents.
"We believe that Merck is uniquely well positioned todevelop Sym004 based on its deep knowledge of the EGFR area," KirstenDrejer, CEO of Symphogen, said in a press release. "This transaction furthervalidates the antibody mixture approach as a highly attractive option."
As of July of this year, a total of 88 patients have beentreated with Sym004 in clinical trials, and exposure data do not indicate ananti-drug antibody response. So far, adverse events in response to thecompound, according to preliminary clinical data, consist of skin rash,diarrhea, nausea, mucosal inflammation, hypomagnesemia (low levels ofmagnesium) and infusion-related reaction.
