Cancer-fighting deal easy as ADC

Millennium pays $4 million to Seattle Genetics in antibody-drug conjugate collaboration

Lori Lesko
BOTHELL, Wash.—Amidst the fierce pharma competition to discover, develop and commercialize cancer-fighting drugs, the recently announced collaboration between Millennium's Takeda Oncology Co. and clinical stage biotech Seattle Genetics Inc. was a deal neither could refuse.

Under the terms of a worldwide agreement announced April 6, Cambridge, Mass.-based Millennium will pay a $4 million upfront fee to Washington-based Seattle Genetics for the development of antibody-drug conjugates (ADCs), crucial to alleviating the toxic effects of chemotherapy, thus making this traditional cancer treatment more bearable.

Millennium's initial payment bought an exclusive ADC license to an initial antigen expressed on solid tumors. The firm will be able to exercise options for exclusive licenses to two other antigens upon payment of additional fees to Seattle Genetics, says Eric L. Dobmeier, chief business officer of Seattle Genetics.

In turn, Millennium, which focuses on creating drugs that target disease pathways for a variety of cancers, will provide for research, product development, manufacturing and commercialization of all ADC products, according to the terms of the collaboration.

ADCs are empowered monoclonal antibodies that carry potent, cell-killing drugs, Dobmeier explains. Seattle Genetics has developed proprietary technology employing synthetic, highly potent drugs that can be attached to antibodies through stable linker systems.

"The linkers are designed to be stable in the bloodstream and release the drugs under specific conditions once inside targeted cell," Dobmeier says. "This approach is intended to spare non-targeted cells, and thus reduce many of the toxic effects of traditional chemotherapy. "By using the ADC technology, a cytotoxic drug is attached to an antibody that targets certain cells, binds selectively to the surface of the targeted cells, is then internalized and kills the targeted cells. There are an increasing number of ADCs utilizing Seattle Genetics' technology in clinical trials."

In fact, Seattle Genetics is advancing its own proprietary pipeline of ADC programs, including SGN-35, which is in a pivotal trial for Hodgkin lymphoma, and a planned Phase II trial for systemic anaplastic large cell lymphoma (ALCL), Dobmeier says.

"SGN-35 has shown strong, objective anti-tumor activity at well-tolerated doses in patients and a planned Phase II trial," Dobmeier reports. "In a Phase I dose-escalation trial, at doses of 1.2 mg/kg and higher, SGN-35 achieved a 54 percent objective response rate. Of that, 32 percent of patients had a complete response to treatment."

Working together as a team makes both companies more effective, he says.

"Entering into ADC collaborations with world-class oncology companies such as Millennium is part of our strategy to leverage our proprietary technology to enhance our product portfolio and bring non-dilutive capital into the company," Dobmeier says. "To date, we have generated more than $75 million through ADC collaborations with leading biotechnology and pharmaceutical companies."

Each company brings its own expertise and resources to the table, says Dan Curran, Millennium's vice president of corporate development.

"Millennium brings industry-leading discovery and preclinical development capabilities that pairs well with the unique technological expertise in ADCs and a great platform from Seattle Genetics," Curran says. "We will be working to generate a new drug candidate to enter the clinic. Currently, this program is in pre-clinical development, and we cannot speculate when, or if, it will enter into clinical development."

The agreement also makes Seattle Genetics eligible for progress-dependent milestone payments and mid-single-digit royalties from Millennium on worldwide net sales of any ADC products. Seattle Genetics also will receive material supply and annual maintenance fees, as well as research support payments, for the help it will provide to Millennium.

Dr. Deborah Dunsire, president and CEO of Millennium, says the collaboration takes the medical community closer to targeting the cancer, rather than the whole patient.

Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Genentech, Bayer, CuraGen, Progenics, Daiichi Sankyo and MedImmune, a subsidiary of AstraZeneca, as well as an ADC co-development agreement with Agensys, a subsidiary of Astellas Pharma.

Seattle Genetics is also developing a number of preclinical ADC programs, including SGN-75, which the company is advancing towards a planned 2009 investigational new drug submission for CD70-positive malignancies.
 

Lori Lesko

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