Xencor Presents Pre-Clinical Data for Anti-CD19 Antibody at AACR.
"Pre-clinical data that we have observed to date with XmAb5574 is very encouraging and can be directly attributed to the power of our proprietary Fc engineering capabilities," said John Desjarlais, Ph.D., Vice President of Research at Xencor. "We look forward to continuing to advance development of XmAb5574 for treatment of lymphoma and leukemias such as non-Hodgkin lymphoma, and expect to initiate a Phase I clinical study in 2009."
In previously conducted pre-clinical studies, XmAb5574 demonstrated that it is highly cytotoxic against lymphoma and leukemia cell lines and that its antibody-dependent cell-mediated cytotoxicity (ADCC) and efficacy is superior to rituximab, the current standard of care for the treatment of non-Hodgkin lymphoma (NHL). Researchers at Xencor applied the company's proprietary humanization and affinity maturation technologies to decrease the immunogenicity of XmAb5574 and to increase both its affinity and stability. Xencor's XmAb[TM] technology was then applied to increase affinity for human Fcg receptors (FcgRs).
The AACR presentation included murine xenograft studies with XmAb5574 and Fc domain analogs, which demonstrated the critical role of FcgR interactions for anti-tumor activity and showed that XmAb5574 had significantly higher anti-tumor activity than an anti-CD19 with a non-engineered Fc domain (IgG1). Additionally, cynomolgus monkey pharmacology studies demonstrated that XmAb5574 caused extensive and sustained B cell depletion, consistent with its desired mechanism of action.
In addition to XmAb5574 and several other pre-clinical antibody candidates, Xencor is conducting an ongoing Phase I clinical trial with its high cytotoxicity anti-CD30 antibody, XmAb2513, for the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL).
XmAb[TM]5574 is a humanized monoclonal antibody that targets the antigen CD19 for treatment of B cell malignancies and autoimmune diseases. XmAb[TM]5574 contains a proprietary Xencor XmAb Fc domain that enhances cytotoxic potency and also downregulates B cell activation. CD19 is a pan-B cell surface receptor that is often expressed in NHL and leukemia, making it an ideal target for cancers of the lymphoid origin.
Xencor, Inc. engineers superior biotherapeutics using its proprietary Protein Design Automation([R]) technology platform and is a leader in the field of antibody Fc engineering to significantly improve antibody potency and half-life. The company is advancing XmAb[TM] antibody drug candidates optimized for activity against biologically validated targets and its XPro[TM] protein therapeutic candidate into the clinic. Xencor's product development is led by an antibody candidate, XmAb[TM]2513, in a Phase I clinical trial for the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma, and a protein therapeutic drug candidate, XPro[TM]1595 DN-TNF, for the treatment of inflammatory disease. With multiple partners, such as industry leaders Genentech, Boehringer Ingelheim, Centocor, MedImmune and Human Genome Sciences, Xencor is applying its suite of XmAb antibody Fc domains to improve antibody drug candidates for traits such as potency and sustained half-life. For more information, please visit www.xencor.com.
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|Date:||Apr 15, 2008|
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