Xencor Provides Data Updates on XmAb Bispecific Antibody Programs

Xencor, Inc. (NASDAQ: XNCR), aclinical-stage biopharmaceutical company developing engineered monoclonalantibodies for the treatment of autoimmune diseases, asthma and allergicdiseases, and cancer, today announced that preclinical data from threeprograms using the company's XmAb(r) bispecific Fc technology show thattargeting CD123, CD20 and CD38 antigens each activated T-cells to rapidly killtarget cells from a single dose IV bolus in cynomolgus monkeys anddemonstrated 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 AmericanSociety of Hematology (ASH) 2014 Annual Meeting in December 2014. Theabstracts were made public today on the ASH 2014 website athttp://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 andsustained reductions in targeted cells from a single IV dose in cynomolgusmonkeys," said Bassil Dahiyat, Ph.D., president and CEO of Xencor. "We believeour XmAb technology offers a potential solution to the manufacturing andcommercialization challenges that historically have limited the potential ofbispecific therapeutic antibodies."Xencor's initial bispecific programs are tumor-targeted antibodies thatcontain both a tumor antigen binding domain (CD123, CD20, or CD38) and acytotoxic T-cell binding domain (CD3). These bispecific antibodies activateT-cells for highly potent and targeted killing of malignant cells. XmAb Fcdomains confer long circulating half-lives on the antibodies, up to a week inmice, and enable fine-tuning of the potency of the T-cell killing, potentiallyimproving the tolerability of cancer immunotherapy. Dr. Dahiyat added, "Based on these data, we have selected XmAb14045, our leadanti-CD123xCD3 bispecific antibody, for IND-enabling studies and cGMP processdevelopment and manufacturing at a contract manufacturer. We look forward tobringing 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 LeukemiaChu, et al, Abstract ID# 66824, Sunday, December 7, 2014, 6:00 p.m. to 8:00p.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 daysXmAb Anti-CD20 × Anti-CD3 Bispecific Antibodies in B-cell Lymphomas andLeukemiaChu, et al, Abstract ID# 66828, Sunday, December 7, 2014 at 6:00 p.m. to 8:00p.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 daysAnti-CD38 × Anti-CD3 Bispecific Antibodies in Multiple MyelomaChuash ash , et al, Abstract ID# 66826, Monday, December 8, 2014, 6:00 p.m. to8:00 p.m. PT o Depleted circulating CD38+ cells by greater than 95% o Prolonged half-life in mice up to 8 days