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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SOURCE Xencor, Inc.