Xencor Provides Data Updates on XmAb Bispecific Antibody Programs

Xencor, Inc.

, a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases, and cancer, today announced that preclinical data from three programs using the company's XmAb(r) bispecific Fc technology show that targeting CD123, CD20 and CD38 antigens each activated T-cells to rapidly kill target cells from a single dose IV bolus in cynomolgus monkeys and demonstrated prolonged half-life of approximately one week in mice. This data, and additional data on primate pharmacokinetics, efficacy and tolerability, will be presented in three poster presentations at the upcoming American Society of Hematology (ASH) 2014 Annual Meeting in December 2014. The abstracts were made public today on the ASH 2014 website at http://www.hematology.org/Annual-Meeting. "In stark contrast to bispecific platforms that do not contain an Fc domain, our candidates with XmAb bispecific Fc domains demonstrated profound and sustained reductions in targeted cells from a single IV dose in cynomolgus monkeys," said Bassil Dahiyat, Ph.D., president and CEO of Xencor. "We believe our XmAb technology offers a potential solution to the manufacturing and commercialization challenges that historically have limited the potential of bispecific therapeutic antibodies." Xencor's initial bispecific programs are tumor-targeted antibodies that contain both a tumor antigen binding domain (CD123, CD20, or CD38) and a cytotoxic T-cell binding domain (CD3). These bispecific antibodies activate T-cells for highly potent and targeted killing of malignant cells. XmAb Fc domains confer long circulating half-lives on the antibodies, up to a week in mice, and enable fine-tuning of the potency of the T-cell killing, potentially improving the tolerability of cancer immunotherapy.  Dr. Dahiyat added, "Based on these data, we have selected XmAb14045, our lead anti-CD123xCD3 bispecific antibody, for IND-enabling studies and cGMP process development and manufacturing at a contract manufacturer. We look forward to bringing this candidate into the clinic within the next 18 months." Highlights from the scheduled Xencor poster presentations are as follows: XmAb Anti-CD123 x Anti-CD3 Bispecific Antibodies in Acute Myleogenous Leukemia Chu, et al, Abstract ID# 66824, Sunday, December 7, 2014, 6:00 p.m. to 8:00 p.m. PT o Depletion of over 99% of circulating CD123+ cells in monkeys for over a week o Bone marrow CD123+ cells were depleted by over 95% at all doses in monkeys o Prolonged serum half-life in mice of 6.2 days XmAb Anti-CD20 × Anti-CD3 Bispecific Antibodies in B-cell Lymphomas and Leukemia Chu, et al, Abstract ID# 66828, Sunday, December 7, 2014 at 6:00 p.m. to 8:00 p.m. PT o Depletion of over 97% of circulating CD40+ B cells in monkeys for over a week o CD40+ B cells in the more resistant lymph nodes and bone marrow were depleted by over 90% at all doses in monkeys o Prolonged serum half-life in mice up to 6.7 days Anti-CD38 × Anti-CD3 Bispecific Antibodies in Multiple Myeloma Chuash ash , et al, Abstract ID# 66826, Monday, December 8, 2014, 6:00 p.m. to 8:00 p.m. PT o Depleted circulating CD38+ cells by greater than 95% o Prolonged half-life in mice up to 8 days