Xencor Inks Oncology Partnership with MD Anderson

Xencor Inks Oncology Partnership with MD Anderson
Illustration of a dendritic cell (centre) presenting an antigen to T-lymphocytes. Both cells are components of the bodys immune system. Dendritic cells are antigen-presenting cells (APCs), that is, they present pathogens or foreign molecules (antigens) to other cells of the immune system to be eliminated. T-cells are activated by dendritic cells to effect an immune response.

The University of Texas MD Anderson Cancer Center and Xencor Inc. have announced a strategic research collaboration and commercialization agreement to develop novel CD3 bispecific antibodies for the oncology market. The collaboration pairs Xencor’s XmAb technology and protein engineering expertise with MD Anderson’s expertise in discovery of novel therapeutic antibodies, including the Cancer Center’s Oncology Research for Biologics and Immunotherapy Translation (ORBIT) platform.

“Xencor’s modular antibody engineering platform enables the rapid generation of XmAb bispecific antibodies, and our research collaboration with MD Anderson will further expand the use of our technology to explore novel therapeutic targets, which could result in the creation of new therapies for patients with cancer,” said John Desjarlais, Ph.D., senior vice president and chief scientific officer at Xencor.

T cell-engaging bispecific antibodies are designed to recognize and bind to an antigen on tumor cells as well as an activating receptor on T cells, such as CD3, in order to directly recruit and activate T cells against tumor cells.

Xencor’s modular scaffold for engineering bispecific antibodies is the XmAb bispecific Fc domain, which enables the rapid creation of stable antibodies with novel anti-tumor mechanisms of action. The company’s four primary XmAb Fc domains are designed to enhance immune regulation, cytotoxic potency, or circulating half-life by creating stable bispecific antibody structures that are also long-acting and readily produced. The company says “The plug-and-play nature of each domain has enabled the rapid discovery of a portfolio of differentiated drug candidates with a diversity of mechanisms, targets and potential disease indications.”

“There is an urgent need to discover new therapeutic targets and to develop antibody-based strategies to trigger an immune response against the tumors that express them,” said Dongxing Zha, Ph.D., institute head of the ORBIT platform at MD Anderson. “Xencor’s multi-format-capable CD3 bispecific antibody platform enables us to rapidly develop and investigate therapies against intriguing tumor targets, and we look forward to evaluating the first candidates to be engineered as part of this collaboration.”

Over the last thirty plus years the market for mAbs has evolved into one of the largest classes of new drugs, and features many of the best-selling drugs in the world.  The FDA has approved almost 80 therapeutic mAbs to date.  The global market for these products is estimated at over $115 billion and expected to more than double by 2025.

While Xencor has products in development in a range of therapeutic areas, cancer is one of the most active of these areas, and it has at least 10 bispecific mAbs already in development for various cancers.  Several of these products are being developed in partnership with big pharmas.

Xencor’s current oncology partners include Amgen, Novartis, and Astellas. There have been some bumps along the way. AMG 424 was picked up by Amgen back in 2015 as part of a deal worth potentially $1.7 billion and involving six bispecific antibodies. Amgen kicked AMG 424 back to Xencor in July of 2020.

In 2019 Novartis shed the rights to a bispecific antibody it had licensed from Xencor as part of a 2016 deal potentially worth $2.41 billion. Also in 2019, the FDA placed a partial clinical hold on another product from that deal, XmAb14045, which was in phase I for AML and other CD123-expressing blood cancers. But that hold was lifted in April of that year.

In April 219, Xencor inked a cancer deal with Astellas and the companies have two bispecific antibodies in development against solid tumors: XmAb2314 and XmAb22841. The value of that deal was not announced, but Xencor receives an upfront payment, as well as development regulatory and sales milestone payments, and high single digit to low-double digit percentage royalties on net sales.