With "our crown jewel back in our hands and the opportunity to bring it all the way to the market," Symphogen A/S found cause to celebrate, said CEO Kirsten Drejer, as the firm makes plans to finish the phase IIb trial begun by Merck KGaA with Sym004 and move the cancer antibody product forward.

"This is very good news," Drejer told BioWorld Today about the news from Merck, which is giving back rights to Sym004 not because of any safety or efficacy signals in experiments so far, but because the Darmstadt, Germany-based pharma giant is reprioritizing its pipeline.

Symphogen, of Copenhagen, Denmark, entered the potential €500 million (then US$631.6 million) deal with Merck in September 2012, collecting €20 million up front, with €225 million to come as clinical and regulatory milestones are reached, followed by a further €250 million for hitting sales targets. Merck agreed to fully fund all development and commercialization work on the first-in-class Sym004, a mixture of two recombinant antibodies targeted against epithelial growth factor receptors on the surface of cancer cells. (See BioWorld Today, Sept. 7, 2012.)

"They already had Erbitux [cetuximab], but they could see that this product could do something" even more exciting, Drejer said. In February 2004, Erbitux – partnered with Indianapolis-based Eli Lilly and Co. and Bristol-Myers Squibb Co., of New York – became the first monoclonal antibody to be approved by the FDA for metastatic colorectal cancer (mCRC). The compound, a recombinant chimeric IgG1 monoclonal antibody that, like Sym004, works in the EGFR pathway, was developed by Imclone Systems Inc., also of New York, acquired by Lilly in 2008. (See BioWorld Today, Feb. 13, 2004, and Oct. 7, 2008.)

"In contrast to monoclonals that have a blocking effect, in our case we get removal of the receptors that are responsible for the growth of the cancer cells, so we are hopeful it will work not only in resistant patient populations but also in earlier-stage patients, so you might avoid development of resistance," Drejer said. The removal effect was reported a couple of years ago in research, and "we've biopsied the patients and we can confirm this is also what's happening in the clinical setting," she said.

Merck had started three clinical trials. A phase Ib in Japan in esophageal cancer will be finished and Symphogen will "have a look at the data and see whether we're going to pursue" the indication, Drejer said. A phase Ib combination trial with chemotherapy in non-small-cell lung cancer is "too large for Symphogen to take over, so Merck will wind that down." The phase IIb in mCRC will complete at "the end of 2016 and maybe 2017," she said. "It will take some time because the clinical endpoint is overall survival."

Symphogen has €70 million (US$79.2 million) in cash, "sufficient for the next two years, running the program in mCRC, [and we can] file the investigational new drug application [IND] for pan-HER and bring it into phase I and extension studies" and more, Drejer said. The pan-HER-targeting therapy, Sym013, is a mix of six humanized full-length monoclonal antibodies targeting EGFR, HER2 and HER3. Also in the works is preclinical Sym015, a multitargeting monoclonal antibody mixture program against cMET, and the company likely can file the IND and get phase I trials with extension studies under way with the resources on hand, Drejer said.

Symphogen is opening a clinical development unit in New Jersey under the watch of its chief medical and scientific officer, Ivan Horak. Joining the company as chief technology officer is Esper Boel, formerly in the biotechnology research unit of Bagsvaerd, Denmark-based Novo Nordisk A/S.

Merck, for its part, has hardly given up oncology, moving ahead with the programmed death ligand 1 inhibitor MSB0010718C under a global deal two months ago with New York-based Pfizer Inc., worth $850 million up front and about $2 billion more in payments based on reaching regulatory and commercial milestones.

Also on board with Merck is TH-302, a hypoxia-activated prodrug consisting of a 2-nitroimidazole phosphoramidate conjugate, licensed from South San Francisco-based Threshold Pharmaceuticals Inc. in 2012. The pharma firm forked over $25 million up front to Threshold, and promised potentially $280 million more as regulatory and development milestones are achieved, plus as much as $245 million in sales-based milestone payments. (See BioWorld Today, Feb. 6, 2012, and Nov. 18, 2014.)