Amgen and Xencor, Inc., a clinical-stage biopharmaceutical company, have formed a research and license agreement to develop and commercialize therapeutics in the areas of cancer immunotherapy and inflammation in a deal valued up to $1.745 billion. The research collaboration brings together Amgen’s capabilities in target discovery and protein therapeutics with Xencor’s XmAb bispecific technology platform. Bispecific technologies seek to engineer monoclonal antibodies to bind two unique drug targets as opposed to traditional antibodies that are designed to bind to a single antigen target.

The collaboration includes molecular engineering by Xencor and the preclinical development of bispecific molecules for five programs proposed by Amgen, leveraging 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 agreement, Xencor will receive a $45 million upfront payment and up to $1.7 billion in clinical, regulatory, and sales milestone payments in total for the six programs. Xencor is eligible to receive mid to high single-digit royalties for candidates directed against Amgen’s targets, and high single to low double-digit royalties for Xencor’s CD38 bispecific T cell engager.

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.

As opposed to traditional monoclonal antibodies that target and bind to a single antigen, bispecific antibodies are designed to elicit multiple biological effects that require simultaneous binding to two different antigen targets. Xencor’s XmAb bispecific Fc domain technology is designed to maintain full-length antibody properties in a bispecific antibody, potentially enabling favorable in vivo half-life and simplified manufacturing, according to information from Amgen Efforts at bispecific antibody design are typically frustrated by poor molecular stability, difficulties in production, and short in vivo half-life, according to information from Amgen. Xencor has engineered a series of Fc domain variants that spontaneously form stable, heterodimeric bispecific antibodies and that can be made and purified with standard antibody production methods. These bispecific Fc domains are used to generate candidates in a range of molecule formats.

Xencor’s initial bispecific programs are tumor-targeted antibodies that contain both a tumor antigen binding domain and a cytotoxic T-cell binding domain (CD3 binding domain). These bispecific antibodies activate T cells at the site of the tumor for highly potent killing of malignant cells. The XmAb Fc domain format allows Xencor to tune the potency of the T-cell killing, potentially improving the tolerability of the tumor immunotherapy. Xencor plans to begin clinical testing for two internal programs, XmAb14045 and XmAb13676, in 2016.

Xencor has also partnerships with Merck, Janssen R&D LLC, Alexion, Novo Nordisk, and Boehringer Ingelheim.

Source: Amgen