News&Event
08.22
Mon 2022
NEWS

United BioPharma announces JCI publication of UB-221 mAb data demonstrating unique profiles of potent IgE neutralization, IgE synthesis reduction, and durable urticaria symptom relief

United BioPharma (UBP) announced today that the Journal of Clinical Investigation (JCI) published results featuring IgE-binding and functional characteristics of UB-221, a new class of anti-IgE mAb distinct from omalizumab and ligelizumab; and, demonstrating a potential of durable disease symptom relief in patients with chronic spontaneous urticaria (CSU)1 in a single-dose first-in-human trial [ClinicalTrials.gov: NCT03632291].

There remains an unmet medical need for a diverse array of allergic diseases, of which the combined disease prevalence has increased to affect more than 30% of the world population, which have raised the burdens to healthcare systems and global economy.2,3

Over the last two decades, omalizumab (brand name XolairÒ) is the only anti-IgE antibody approved to date for allergic asthma in 2003, chronic spontaneous urticaria (CSU) in 2014, and nasal polyps in 2020. Ligelizumab (also known as QGE031), a higher-affinity anti-IgE mAb and the only rival candidate viable in late-stage clinical trial, showed anti-CSU efficacy superior over Omalizumab in Phase-2, but it did not excel in Phase-3 trial.4

The data published in the JCI, which indicate the potential of UB-221 as an important treatment option for CSU, include the following major findings:  
■  UB-221 in free form binds IgE:CD23 complex, or in IgE-UB-221 complex form binds CD23, in an unrestricted manner; whereas ligelizumab reacts very limitedly and omalizumab stays totally inert toward CD23, which stand in good agreement that UB-221 outperforms ligelizumab and omalizumab in the CD23-mediated reduction of IgE neo-synthesis.
■  UB-221 exhibits superiority over omalizumab in IgE-binding affinity and in prevention of FcԑRI-mediated basophil activation and histamine release. UB-221 and ligelizumab neutralize with equal strength both the free IgE on FcεRI-immobilized solid phase and the high level of serum IgE in atopic dermatitis patients, while omalizumab lagged behind.
■  In studies with animal models, such as cynomolgus macaques and human IgE (ε, κ)-transgenic hIGHE (immunoglobulin heavy epsilon)-knockin mice, a single dose of UB-221 can induce a rapid, profound reduction of serum IgE.
■  UB-221, administered as intravenous infusion (0.2 to 10 mg/kg dose, n = 3/dose cohort) in a Phase-1 single-dose clinical trial with chronic spontaneous urticaria (CSU) patients has demonstrated durable relief of disease symptoms (reduction of itch and hives measured by weekly Urticaria Activity Score, UAS7) that parallels with a rapid, pronounced reduction in serum free IgE level. UB-221 is cleared from serum with a half-life of 16-22 days.
■  The prolong suppression of urticaria symptoms and reduction of serum IgE levels suggests that a single dose of >2.0 mg/kg could potentially allow UB-221 to be administered every 3 to 6 months and achieve complete response (UAS7 = 0) or well controlled stage (UAS7 ≤ 6) in the treatment of chronic CSU.

These preclinical and clinical findings also suggest additional potentials of UB-221 to treat other allergic (atopic) diseases such as food allergy, atopic dermatitis, asthma, and allergic rhinitis. These diseases could be inter-related and sometimes referred to as “Atopic March,”5-7 which may be initiated from early childhood and are largely IgE-mediated.
About IgE, FcεRI, and CD23

The immunoglobulin IgE has been known to be a source to cause allergic diseases. The functions of IgE are hinged upon interactions of its Fc region with two principal receptors: 1) FcεRI (high-affinity receptor) expressed mainly on mast cells and basophils, responsible for allergic hypersensitivity and inflammation; and 2) CD23 (low-affinity receptor), expressed mainly on B cells, involves in negative-feedback downregulation of IgE synthesis, IgE clearance and a host of other immunological functions. The non-inflammatory CD23 may serve to antagonize the allergic, inflammatory pathway.

About UB-221
UB-221 is a humanized IgG1 that targets the Cε3 domain of IgE molecule with a high binding affinity (KD) of 5.9x10-11 nM. UB-221 has been shown to be a potent IgE neutralizer and a significant inhibitor of IgE neo-synthesis. UB-221 performs superior to omalizumab (XolairÒ) over a host of IgE-neutralization study events. UB-221 in an ex vivo IgE-PBMC study system has shown to inhibit IgE production at a far greater scale than omalizumab and ligelizumab (an investigational drug). UB-221 in free form (or IgE-complex form) can interact unrestricted with IgE:CD23 complex (or CD23), a unique feature that has never been observed before for any anti-IgE monoclonal antibody (mAb), and by which UB-221 differentiated it (as a new class of anti-IgE mAb) from omalizumab and ligelizumab that do not show significant interaction with CD23. Thus, it could be of clinical benefit to target IgE toward the non-inflammatory CD23 pathway8,9. UB-221 is being developed as therapeutic biologics for treatment of allergic diseases such as chronic spontaneous urticaria, food allergy, atopic dermatitis, asthma, allergic rhinitis, etc.
 
About United BioPharma
United BioPharma (UBP) is a late clinical stage biopharmaceutical company that is dedicated to the research, development and manufacture of novel monoclonal antibodies (mAbs) for infectious and immunological diseases. UBP is headquartered in Taiwan, with subsidiary companies in Shanghai and Yangzhou China, and liaison offices in the U.S. The company has built a passionate global team, developing high-quality therapeutic mAbs and delivering affordable treatments to bring the patients better quality of life. For more information, please visit the website at: http://www.unitedbiopharma.com
 
United BioPharma Forward-Looking Statements
The information in this press release should be considered accurate only as of the date of the release. UBP has no intention of updating and specifically disclaims any duty to update the information in this press release. The press release may contain forward-looking statements involving risks and uncertainties and UBP’s actual results may differ materially from those in the forward-looking statements.

References
1.        Kuo, B-S, et al. IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms. J Clin Invest. 2022;132(15):e157765 https://doi.org/10.1172/JCI157765
2.        Pawankar R. Allergic diseases and asthma: a global public health concern and a call to action. World Allergy Organ J. 2014;7(1):12.
3.        Dierick BJH, et al. Burden and socioeconomics of asthma, allergic rhinitis, atopic dermatitis and food allergy. Expert Rev Pharmacoecon Outcomes Res. 2020;20(5):437-53.
4.        https://www.hcplive.com/view/phase-3-ligelizumab-not-superior-omalizumab
5.        Bantz SK, et al. The atopic march: Progression from atopic dermatitis to allergic rhinitis and asthma. J Clin Cell Immunol. 2014;5(2).
6.        Hill DA, and Spergel JM. The atopic march: Critical evidence and clinical relevance. Ann Allergy Asthma Immunol. 2018:120(2):131-137.
7.        Paller AS, et al. The atopic march and atopic multimorbidity: Many trajectories, many pathways. J Allergy Clin Immunol. 2019;143(1):46-55.
8.        Engeroff P, et al. CD23 provides a noninflammatory pathway for IgE-allergen complexes. J Allergy Clin Immunol. 2020.145(1):301-11 e4.
9.        Engeroff P, and Vogel M. The role of CD23 in the regulation of allergic responses. Allergy. 2021.76(7):1981-9.
 
Company contact:
Dr. Mei June Liao, Executive Vice President, Product Development
+886-3-5979288 # 6700
meijune.liao@unitedbiopharma.com
 

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