Ozureprubart, a next-gen anti-IgE antibody, inhibits IgE binding to FcαRI, dissociates FcαRI-bound IgE, and reduces FcαRI expression on basophils 2258455

Abstract

Abstract Introduction Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic inflammatory diseases. Omalizumab, the only FDA-approved anti-IgE therapy currently available to patients, has been shown to be effective in treating moderate-to-severe persistent asthma, chronic spontaneous urticaria (CSU), chronic rhinosinusitis with nasal polyps (CRSwNP), and in reducing allergic reactions to accidental exposure to IgE allergens in food-allergic individuals, including anaphylaxis. Methods Ozureprubart (also known as JYB1904 and RPT904) is a next-generation, half-life extended, anti-IgE monoclonal antibody designed to target the same epitope as omalizumab that uses the YTE mutation (M252Y/S254T/T256E) to significantly increase half-life. Additional modifications resulted in increased binding avidity to IgE, improvement of antibody stability, and reduction of the potential for immunogenicity. Results We report here that ozureprubart shows a 2-to-3-fold increase in ability to block IgE binding to FcαRI compared with omalizumab. Additionally, ozureprubart, like omalizumab, dissociates IgE bound to FcαRI and reduces levels of receptor-bound IgE and FcαRI on basophils. Conclusion These data show that ozureprubart shares many of the mechanisms of action of omalizumab. In combination with its extended half-life, these properties give ozureprubart the potential to be an improved anti-IgE therapy. Ozureprubart is currently in Phase 2 clinical development for the treatment of food allergy*, asthma**, and CSU**. *Study sponsored by RAPT Therapeutics, Inc. **Studies sponsored by Shanghai Jeyou Pharmaceutical Co., Ltd. in China Funding Source n/a Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)