MONROVIA, Calif., April 18, 2018 /PRNewswire/ -- Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases and cancer, announced preclinical data on XmAb24306, an IL15/IL15-receptor alpha complex fused to a bispecific XmAb Fc domain (IL15/IL15Rα-Fc) for the treatment of multiple oncology indications. Data show that the engineered complex enhanced the duration and magnitude of T and NK cell proliferation in vitro and in vivo. XmAb24306 is designed for reduced potency and extended half-life, and exhibited a steady, tolerable and sustained increase in T-cells in primates.
Key findings from the study presented today at the American Association for Cancer Research (AACR) 2018 Annual Meeting include:
- Fusing IL15/IL15Rα with Xencor's highly stable heterodimer Fc platform and Xtend Fc domain creates a long-acting CD122 agonist, without targeting CD25
- Potency reduction of the complex promotes improved exposure and sustained pharmacodynamics
- Preserves native CD122/CD132 signaling despite potency reduction
- Marked and sustained peripheral NK and T cell expansion at well-tolerated doses
"The plug and play nature of our XmAb technology provides tremendous opportunity to build a suite of tumor microenvironment activators with tunable potency and sustained activity, which have the potential for improved performance over current approaches," said Bassil Dahiyat, president and chief executive officer of Xencor. "With the IL15/IL15Rα-Fc platform, we have an engine to develop these candidates quickly, and are on track to file an IND for XmAb24306 in 2019."
XmAb24306 is the first of a suite of tumor microenvironment activators using the IL15 bispecific platform. Additional IL15 bispecific candidates, which target specific sub-populations of T cells, in preclinical development include:
- A PD1 targeted IL15/IL15Rα (PD1 x IL15) candidate to promote selective expansion and activation of exhausted T cells
- Additional targeted IL15/IL15Rα candidates
About XmAb® IL15 Bispecific Platform
Xencor's XmAb® IL15 bispecific antibody platform provides a more druggable version of IL15 with reduced potency to improve tolerability, slow receptor-mediated clearance, and prolong half-life. IL15 is an extremely potent cytokine that stimulates the proliferation of lymphocytes, however its potential as a therapeutic has been limited by low tolerability and very fast clearance that limits therapeutic window. IL15 naturally targets CD122 without targeting CD25. Xencor has engineered the IL15/IL15Rα-Fc complex to create lead candidate XmAb24306 and to provide a basis for rapid generation of targeted T-cell activators. These Fc-fusions have been tuned for enhanced in vivo lymphocyte proliferation as a result of more sustained exposure.
About Xencor, Inc.
Xencor is a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases and cancer. Currently, 11 candidates engineered with Xencor's XmAb® technology are in clinical development internally and with partners. Xencor's internal programs include: XmAb®5871 in Phase 2 development for the treatment of IgG4-Related Disease, and also for the treatment of Systemic Lupus Erythematosus; XmAb®7195 in Phase 1 development for the treatment of asthma and allergic diseases; XmAb®14045 in Phase 1 development for acute myeloid leukemia; XmAb®13676 in Phase 1 development for B-cell malignancies; XmAb®18087 in Phase 1 development for the treatment of neuroendocrine tumors and gastrointestinal stromal tumors; and XmAb®20717, XmAb®22841, XmAb®23104 and XmAb®24306 in pre-clinical development for the treatment of multiple cancers. Xencor's XmAb antibody engineering technology enables small changes to the structure of monoclonal antibodies resulting in new mechanisms of therapeutic action. Xencor partners include Novartis, Amgen, MorphoSys, CSL/Janssen, Alexion and Boehringer Ingelheim. For more information, please visit www.xencor.com.
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