Senior Director of Biotherapeutics at Xencor Will Present at GTCbio’s 2nd Protein Therapeutics Discovery & Development Conference

David Szymkowski, Senior Director of Biotherapeutics at Xencor will Present at GTCbio’s 2nd Protein Therapeutics Discovery & Development Conference on September 8-9, 2008 in San Diego, CA

Monrovia, CA, June 13, 2008 --( Dr. David Szymkowski, Senior Director of Biotherapeutics at Xencor will be speaking at GTCbio’s 2nd Protein Therapeutics Discovery & Development conference on September 8-9, 2008 in San Diego, CA. Dr. Szymkowski will give a presentation entitled Coengagement of B cell Receptor and FcgRIIb Inhibitory Receptor via an Fc-Engineered Antibody: A New Strategy to Suppress B Cell Function in Autoimmune Diseases.

B cell activation can be inhibited by coengagement of B cell receptor (BCR) and inhibitory receptor FcγRIIb, which occurs physiologically via binding of immune complexes of IgGs and their cognate antigens. To mimic the inhibitory effect of immune complexes, Xencor engineered a novel therapeutic antibody that coengages BCR and FcγRIIb with high affinity. The Fc domain of a humanized anti-CD19 antibody was engineered to have over 400-fold increased binding affinity for FcγRIIb, with decreased binding to activating Fcγ receptors. Such "IIb enhanced" (IIbE) variants stimulated the SHIP-mediated FcγRIIb signaling cascade, and strongly inhibited BCR-induced calcium mobilization and ex vivo proliferation of activated human primary B cells. Preliminary studies also suggest that XmAb™5871, Xencor’s clinical candidate IIbE antibody, blocks B cell-mediated immune responses in huPBL-SCID mouse models. The new therapeutic strategy described here inhibits B cell function by mimicking the physiological negative feedback mechanism induced by immune complex coengaging FcγRIIb and BCR. XmAb™5871 represents an alternative therapeutic antibody to the clinically validated B cell depletion strategy, and raises the possibility of suppressing autoimmunity without compromising long-term host immunity.

Dr. Szymkowski will introduce a novel therapeutic approach that is grounded in well-established biology (e.g., the phenomenon of B cell negative regulation has been accepted for over one hundred years) as well as describe the cutting-edge antibody Fc engineering which was essential to success. (Antibodies with native Fc domains, including other therapeutic antibodies, do not stimulate this regulatory pathway). He will also discuss how the B cell is now a clinically validated target in oncology and in autoimmune disease, yet "IIbE" represents a fresh approach with a completely different mechanism than conventional B cell depleting therapeutics and last of all present a case study of early R&D through to candidate selection of XmAb™5871, a humanized and high-affinity (Fv and Fc) antibody with a novel mechanism of action.

GTCbio’s 2nd Annual Protein Therapeutics Discovery and Development Conference will explore the therapeutic applications of proteins, with a look at discovery and design of therapeutics, overcoming challenges associated with protein based drugs, and new tools and strategies in process development. Finally, attendees will get an update on novel developments in protein therapeutics. The keynote presentation will be given by Dr. Michael Hanley, Vice President of Discovery Research & CSO of Amylin Pharmaceuticals.

GTCbio organizes conferences specifically for the biomedical and biopharmaceutical industries. Our goal is to facilitate the exchange of biopharmaceutical and biomedical intelligence between industry leaders, academic and government organizations, and the financial community.

GTCbio is a subsidiary of Global Technology Community, LLC, a privately held company founded in 2002.

Contact: GTCbio (626) 256-6405, (626) 256-6460 fax

Rania Hafez