Seattle Genetics, Inc. and Agensys, Inc., an affiliate of Tokyo-based Astellas Pharma Inc. announced that Seattle Genetics has exercised an option to co-develop a second antibody-drug conjugate (ADC) under the companies' existing ADC collaboration agreement. The ADC, known as ASG-22ME (formerly AGS-22M6E), targets the Nectin-4 antigen, which is expressed on multiple solid tumours. During the first quarter of 2011, Agensys submitted an investigational new drug (IND) application to the US Food and Drug Administration (FDA) for a phase I trial of ASG-22ME. Seattle Genetics and Agensys are also co-developing another ADC known as ASG-5ME, which is currently in phase I clinical trials for pancreatic and prostate cancer.

"ASG-22ME is the second ADC we are co-developing under our collaboration with Agensys/Astellas, and the fifteenth ADC using Seattle Genetics' technology in clinical development across both our internal pipeline and collaborator programs," said Eric L. Dobmeier, chief business officer of Seattle Genetics. "The progress we and Agensys/Astellas are making demonstrates the synergy of combining Seattle Genetics' innovative, industry-leading ADC technology with Agensys' proprietary cancer targets and antibodies to develop potential new treatments for patients with cancer."

"These two co-development programs with Seattle Genetics, coupled with other internal programs such as our AGS-16M8F ADC that is in a phase I trial for renal cell carcinoma, demonstrate our commitment to ADCs and the strength of our growing oncology pipeline," said Sef Kurstjens, M.D., Ph.D., president and chief executive officer of Agensys. "We look forward to continuing our productive and strong collaboration with Seattle Genetics."

The single-agent phase I trial will evaluate the safety, tolerability, pharmacokinetic profile and antitumour activity of escalating doses of ASG-22ME. The study is designed to enrol up to 50 patients at multiple centres in the United States.

ASG-22ME is an ADC composed of a fully human antibody directed to Nectin-4, an antigen expressed in multiple cancers including bladder, breast, lung and pancreatic cancers. Preclinically, ASG-22ME has demonstrated potent antitumour activity, including regressions in models of established breast, bladder and lung cancer. The antibody is attached to a potent, synthetic cytotoxic agent, monomethyl auristatin E (MMAE), via an enzyme-cleavable linker using Seattle Genetics' proprietary technology. The ADC is designed to be stable in the bloodstream, but to release MMAE upon internalization into Nectin-4-expressing tumour cells, resulting in targeted cell-killing.

Seattle Genetics and Agensys entered into the ADC collaboration in January 2007, and expanded it in November 2009. Under the collaboration, Agensys has the right to obtain exclusive ADC licenses for multiple cancer targets. The companies are co-developing and will globally co-commercialize and share profits on a 50:50 basis for ASG-5ME and ASG-22ME. Seattle Genetics also has an option for 50:50 cost and profit-sharing of a third ADC programme at the time of IND submission. Any ADC programs to which Seattle Genetics does not opt-in will be developed and commercialized exclusively by Agensys, and Seattle Genetics is entitled to progress-dependent fees, milestone payments and mid-single digit royalties on worldwide net sales of such products.

Agensys utilizes its portfolio of novel cancer targets to generate high affinity fully human, proprietary antibodies, and combines selected antibodies with Seattle Genetics' ADC technology to produce new cancer therapies. ADCs utilize the targeting ability of monoclonal antibodies to deliver potent, cell-killing payloads to specific cells. Seattle Genetics' technology employs synthetic, potent drugs attached to antibodies through proprietary linker systems. The linkers are designed to be stable in the bloodstream but to release the cell-killing payload under specific conditions once inside target cells. This approach is intended to spare non-targeted cells and thus may help minimize the potential toxic effects of traditional chemotherapy while allowing for the selective targeting of cancer cells, thus potentially enhancing the antitumour activity.

Seattle Genetics is a clinical-stage biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer and autoimmune disease.

Agensys, Inc., an affiliate of Astellas Pharma Inc., is developing a pipeline of therapeutic fully human monoclonal antibodies (MAbs) to treat cancer.

Astellas Pharma Inc., located in Tokyo, Japan, is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products.