2. Academic Validation
  3. IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms

IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms

  • J Clin Invest. 2022 Aug 1;132(15):e157765. doi: 10.1172/JCI157765.
Be-Sheng Kuo 1 2 3,  Chao-Hung Li 1,  Jiun-Bo Chen 2,  Yu-Yu Shiung 2,  Chia-Yu Chu 4,  Chih-Hung Lee 5,  Yaw-Jen Liu 1,  Je-Hung Kuo 1,  Cindy Hsu 1,  Hsiao-Wen Su 1,  Ywan-Feng Li 1,  Annie Lai 1,  Yueh-Feng Ho 1,  Yi-Ning Cheng 1,  Hong-Xuan Huang 1,  Meng-Chung Lung 1,  Ming-Syue Wu 1,  Fu-Hung Yang 1,  Chen-Han Lin 1,  William Tseng 1,  Jasper Yang 1,  Chia-Yin Lin 1,  Pei-Hua Tsai 2,  Heng-Kwei Chang 2,  Yi-Jen Wang 1,  Techeng Chen 1,  Shugene Lynn 1,  Mei-June Liao 1,  Chang Yi Wang 1 2 3
Affiliations

Affiliations

  • 1 United BioPharma, Inc., Hsinchu, Taiwan.
  • 2 UBI Asia, Hsinchu, Taiwan.
  • 3 United Biomedical, Inc., Hauppauge, New York, USA.
  • 4 Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
  • 5 Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
PMID: 35912861 DOI: 10.1172/JCI157765
Abstract

Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)-knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.

Keywords

Allergy; Immunology.

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