Xencor presents data on anti-CD19 and anti-CD40 antibodies

Dec 10 2008

Xencor, Inc. presented results Sunday at the 50th Annual Meeting of the American Society of Hematology from pre-clinical studies evaluating XmAb 5574, a monoclonal antibody engineered using Xencor's XmAb Fc technologies that targets the antigen CD19.

In the studies, treatment with XmAb5574 achieved near complete elimination of B cells in cynomolgus monkeys, complementing previous data showing strong antitumor potency and anti-proliferative apoptotic activity similar to that of rituximab.

During the poster presentation titled "XmAb 5574, an Fc Engineered Humanized Anti-CD19 Monoclonal Antibody, has Potent In Vitro and In Vivo Activities, and has the Potential for Treating B Cell Malignancies," (poster: II-715, abstract: 2621) Xencor presented new data from its anti-CD19 antibody program showing that XmAb5574 was well tolerated in cynomolgus monkeys at various single dose levels (0, 0.3, 1.0, 3.0, and 10.0 mg/kg, intravenous infusion) and elicited immediate and sustained B cell depletion in a dose-dependent manner. At a 3mg/kg dose, XmAb5574 achieved near complete B cell depletion while the non Fc-engineered analog did not cause any depletion.

"These results demonstrate the effectiveness of Fc engineering in increasing antibody potency and validate the compound's potential as a promising next-generation immunotherapeutic for leukemias and lymphomas," said John Desjarlais, Ph.D., Vice President of Research at Xencor.

"We are continuing to grow our antibody pipeline with highly active candidates such as XmAb5574 that are generated from the company's proprietary Fc engineering capabilities," added Bassil Dahiyat, Ph.D., CEO of Xencor. "The pipeline also includes XmAb2513 for Hodgkin lymphoma and T cell lymphomas, which is making steady progress in Phase I studies, pre-clinical candidate, XmAb5485, and several early stage compounds designed to prolong half-life."

Anti-CD40 Antibody Program Data

In an oral presentation today at 7:15 AM PST (abstract: 881) titled "Fc-Engineered Humanized Anti-CD40 Monoclonal Antibody, XmAb5485, Exhibits Potent Activity In Vitro and In Vivo Against Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia and Multiple Myeloma," Xencor presented data showing that XmAb5485 eliminated detectable tumors in 80 percent of the mice and displayed statistically significant superiority compared to anti-CD40 IgG1 analog. In contrast, detectable tumors were eliminated in only seven percent of animals that received rituximab.

XmAb5485 is characterized by increased affinity for Fc gamma receptors (FcãR), improved effector function and increased antitumor potency. Antibody-dependent cell-mediated cytoxicity (ADCC) increased 150-fold relative to the non Fc-engineered version and was found to be superior to that of rituximab. Antibody-dependant cellular phagocytosis (ADCP) displayed increased potency and efficacy relative to rituximab (15- and 1.6-fold) and the non-Fc engineered anti-CD40 1gG1 analog.