T cells in the tumor microenvironment require engagement of both their T cell receptor (TCR) and their co-stimulatory receptors, like CD28, to achieve full activation. The CD28 signal is diminished in cancer because tumor cells do not typically express CD28 ligands (i.e., CD80 and CD86), which leads to potentially compromised activity of CD3 T cell engagers or anti-PD1 checkpoint inhibitors.

Xencor has developed a modular XmAb^® bispecific antibody platform that allows for the rapid generation of drug candidates that co-stimulate CD28 only in the presence of tumor cells and TCR engagement. Xencor’s XmAb bispecific Fc domain serves as a scaffold for a non-superagonist anti-CD28 binding domain and any tumor-associated antigen of interest. Xencor’s Xtend™ Fc technology further enhances circulating half-life of the antibody.

“Xencor has rapidly generated multiple CD28 co-stimulatory bispecific antibodies with potential broad applicability across a range of solid tumors, and each of these programs has demonstrated compelling activity,” said John Desjarlais, Ph.D., executive vice president and chief scientific officer at Xencor. “We are leveraging the plug-and-play nature of our XmAb bispecific antibody platforms to generate and explore additional CD28 drug candidates against a broader universe of solid tumor targets.”

The poster will be archived under “Events & Presentations” in the Investors section of the Company’s website located at www.xencor.com.

About XmAb808 (B7-H3 x CD28)

Xencor is conducting a Phase 1 study of XmAb808 in patients with advanced solid tumors. XmAb808 is a tumor-selective, co-stimulatory XmAb 2+1 bispecific antibody designed to bind to the broadly expressed tumor antigen B7-H3 and selectively to the CD28 T-cell co-receptor only when bound to tumor cells, which was demonstrated in in vitro studies. Strong potentiation of checkpoint and CD3 cytotoxic activity was also observed in vivo. XmAb808 is a wholly owned Xencor program.

About Xencor

Xencor is a clinical-stage biopharmaceutical company developing engineered antibodies and cytokines for the treatment of patients with cancer and autoimmune diseases. More than 20 candidates engineered with Xencor’s XmAb^® technology are in clinical development, and three XmAb medicines are marketed by partners. Xencor’s XmAb engineering technology enables small changes to a proteins structure that result in new mechanisms of therapeutic action. For more information, please visit www.xencor.com.

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