Collaboration to Promote Development of Bispecific Antibody Therapeutics for Cancer and Inflammation

Two biomedical development companies have agreed to a joint program to promote research and commercialization of bispecific monoclonal antibodies for immunotherapy of cancer and inflammation.

A bispecific monoclonal antibody (BsMAb, BsAb) is an artificial protein that is composed of fragments of two different monoclonal antibodies and consequently binds to two different types of antigen. The most widely used application of this approach is in cancer immunotherapies, where BsMAbs are engineered that simultaneously bind to a cytotoxic cell (using a receptor like CD3) and a target such as a tumor cell to be destroyed. Cancer immunotherapy with ordinary monoclonal antibodies does not activate T-lymphocytes because this type of cell does not possess Fc receptors, so the Fc region cannot bind to them, and the Fab regions are already used for binding the tumor cells. Bispecific antibodies have a higher cytotoxic potential, as they bind to antigens that are expressed relatively weakly.

The biomedical development companies Amgen (Thousand Oaks, CA, USA) and Xencor, Inc. (Monrovia, CA, USA) have entered into a research and license agreement to develop and commercialize novel therapeutic applications for bispecific antibodies.

The partnership links Amgen's capabilities in target discovery and protein therapeutics to Xencor's XmAb bispecific technology platform. The program will focus on five programs proposed by Amgen that leverage XmAb bispecific Fc domains to make half-life extended T-cell engagers and dual targeting bispecific antibodies. The agreement also includes a preclinical bispecific T-cell engager program directed at CD38 and CD3 for multiple myeloma.

Amgen will be fully responsible for preclinical and clinical development and commercialization worldwide. Under the terms of the agreement, Xencor will receive a 45 million USD upfront payment and up to 1.7 billion USD in clinical, regulatory, and sales milestone payments in total for the six programs.

"We are pleased to be joining forces with Xencor to expand our immuno-oncology and inflammation position by leveraging Amgen's antibodies and Xencor's bispecific antibody platform," said Dr. Sean E. Harper, executive vice president of research and development at Amgen. "We are especially excited about the T-cell engaging bispecific antibody directed against CD38, which complements Amgen's BiTE platform, while growing our hematology and oncology portfolio that includes two bispecific T-cell engager antibodies, BLINCYTO (blinatumomab) and AMG 330, as well as Kyprolis (carfilzomib) for relapsed multiple myeloma."

"Amgen, which has pioneered the use of bispecific antibodies, has chosen to access our XmAb bispecific technology for its robustness, long half-life, and the plug and play ease-of-development of our platform," said Dr. Bassil Dahiyat, president and CEO of Xencor. "This opportunity expands the reach of our technology with a partner that has proven experience in bispecifics and immuno-oncology. Xencor will continue to focus on its internal programs including its immuno-oncology XmAb bispecifics, XmAb14045 in acute myeloid leukemia and XmAb13676 in B-cell malignancies, which are expected to enter clinical development in 2016."

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