XmAb®7195 is a monoclonal antibody in late preclinical development as a potential treatment for allergic asthma and other atopic diseases. XmAb7195 targets IgE with its variable domain, and uses our XmAb immune inhibitor Fc domain to target FcγRIIb, resulting in three distinct mechanism 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, we have 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 in circulation. The only FDA-approved antibody for severe asthma, the anti-IgE omalizumab, does not clear IgE from the circulation or prevent IgE production.
As demonstrated by omalizumab, IgE inhibition is a validated strategy to result in reduced asthma symptoms and disability, but omalizumab only reaches a fraction of its market potential due to suboptimal potency. Because of our XmAb immune inhibitor Fc domain, XmAb7195 achieved unprecedented low levels of serum IgE in preclinical animal studies and offers the potential for superior IgE control and superior clinical efficacy.