Monrovia-Based Biotech Initiates Phase 1 Study of its Asthma Drug

Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases, and cancer, today announced that the first subject has been dosed in a Phase 1a clinical trial of XmAb7195. XmAb7195 is a monoclonal antibody engineered to suppress IgE via three distinct mechanisms of action as a potential treatment for asthma and other atopic disease.

"XmAb7195 achieved very low levels of serum IgE in preclinical studies and offers the potential for superior IgE control," saidBassil Dahiyat, Ph.D., President and CEO of Xencor. "In addition to studying safety and tolerability, the Phase 1 study allows us to observe the activity of XmAb7195 in suppressing IgE levels, which is a validated approach for treating asthma."

The Phase 1 trial will evaluate safety, pharmacokinetics and immunogenicity of a single ascending dose of XmAb7195 in a total of 64 subjects. The study will also evaluate the effect on free and total IgE levels, in addition to immune cell biomarkers, in healthy subjects and in allergic subjects with elevated levels of IgE.

In a preclinical study recently presented at the American Thoracic Society 2014 International Conference, XmAb7195 reduced free IgE to at least 10-fold lower levels than omalizumab after a single 5 mg/kg intravenous dose of XmAb7195 or omalizumab in chimpanzees.

XmAb7195 targets IgE with its variable domain, and uses Xencor's XmAb immune inhibitor Fc domain to target FcγRIIb, resulting in three distinct mechanisms of action for reducing IgE levels. First, XmAb7195 sequesters free IgE and prevents activation of mast cells and basophils, the mediators of allergic inflammation and pathology. Second, it prevents IgE production by suppressing IgE-positive B-cell activation and differentiation into IgE-secreting plasma cells. Third, Xencor has discovered a new mechanism of action whereby high FcγRIIb binding causes extremely rapid clearance of the complexes formed between XmAb7195 and IgE, resulting in rapid and marked reductions of the total IgE and free IgE in circulation.

—Xencor announcement.