Xencor (Monrovia, Calif.), a company developing protein and antibody therapeutics, announced that it raised $45 million in a private financing led by MedImmune Ventures, Inc, and including new investors Novo Nordisk and HealthCare Ventures, as well as existing investor Zen Investments. To date, Xencor has raised $130 million in financing. The new financing will be used in part to advance the clinical development of a first-in-class protein therapeutic, XPro 1595, developed using the company's Protein Design Automation® (PDA®) technologies licensed from the California Institute of Technology (Caltech).

PDA technology combines high performance computing with proprietary molecular biology processes and assays to create very broad protein diversity to optimize key protein physico-chemical properties, such as binding affinity, selectivity, stability, solubility, shelf life, pharmacokinetics, and expression level, which are targeted to yield therapeutic proteins with enhanced safety and efficacy. In addition, the application of PDA technology has created an expanding portfolio of over 2000 antibody Fc domain variants that can be used to optimize a variety of valuable antibody properties (eg, potency, targeting capacity, and half-life) and has attracted collaboration partners such as Genentech, Roche, Centocor, and MedImmune.

Xencor expects to advance XPro 1595, its lead protein therapeutic drug candidate, into clinical development by the end of 2006 for treatment of rheumatoid arthritis and other inflammatory conditions. XPro 1595, a variant of TNF-α, is a highly selective, dominant-negative inhibitor (which abrogates the function of its natural counterparts) of TNF-α. The variant possesses a greatly increased half-life by modification via PEGylation and is able to form a homotrimeric complex with native TNF-α proteins, but with the final complex being unable to bind the TNF receptor. The end result prevents the signaling of TNF-mediated inflammatory responses. The company intends to administer XPro 1595 as a subcutaneous injection.

Xencor has engineered dominant-negative inhibitors of other members of the TNF structural superfamily such as RANKL for the treatment of osteoporosis and metastatic bone disease, and BLyS/BAFF for systemic lupus erythematosus and other autoimmune disorders.

—A. Techman