UB-221

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

United BioPharma (UBP) announced today that the Phase 2 clinical trial of a novel anti-IgE monoclonal antibody UB-221 has been approved by Taiwan FDA to proceed. Patients with chronic spontaneous urticaria (CSU) who failed the 1st and 2nd-line treatment will receive two intravenous infusions of UB-221 at an interval of 3 months (long-acting usage) to evaluate the pharmacokinetics, pharmacodynamics, safety and efficacy of UB-221. In the phase 1 clinical trial with participants of moderate to severe CSU who were followed up to 99 days after a single dose of UB-221 (6 or 10 mg/kg) as an add-on therapy, the participants’ serum IgE levels diminished quickly and maintained at undetectable level till the end of the study. Also, the scores for itch and hives (UAS7) decreased significantly in the first week after UB-221 administration. The therapeutic effect reached to 99 days or longer, implying that, a single dose of UB-221 could significantly or completely relieve the symptoms of the disease for more than three months. The forthcoming Phase 2 clinical trial (double-blind, placebo-controlled) aims to evaluate the safety and efficacy of UB-221 as a long-acting add-on therapy. This trial is planned to enroll 25 of moderate to severe CSU patients and randomly divide the participants into two treatment groups (5 and 10 mg/kg) and one placebo group at a ratio of 2:2:1 with two intravenous infusions at an interval of 12 weeks (three months). It is expected that this trial is able to provide the evidence showing the therapeutic potential of two high-dose UB-221 treatments over a 6-month period or longer. About UB-221 UB-221 is a humanized IgG1 that targets the Cε3 domain of IgE antibody. UB-221 is not only able to neutralize free/soluble IgE, but also to inhibit the IgE synthesis by binding to FcεRII (CD23) receptor on B cells surface. According to preclinical studies, UB-221 is superior to currently marketed therapeutic antibody targeting IgE (Xolair® ; Omalizumab) by 8-folds in terms of pharmacological effects. UB-221 shows 2 to 5-folds inhibition of IgE synthesis than Xolair® in the in vitro study. UB-221 only takes a 1/10 dose to achieve the same effect of Xolair® in huIGHE-knock-in mice model. A PK study in cynomolgus monkeys demonstrated UB-221 has a longer serum half-life (~11 days with SC administration) than Xolair®. According to the results of phase 1 clinical trial, CSU patients treated with a single dose of UB-221 responded quickly and their free IgE in the serum were suppressed for weeks to months. UB-221 effectively relieved the symptoms of chronic spontaneous urticaria (CSU) in all trial participants. In In vitro studies, UB-221 is able to inhibit the production of new IgE by binding to the IgE already bound on the low-affinity receptor CD23 (FcεRII). This is a unique IgE binding property not shared by Xolair®, the only anti-IgE mAb approved for clinical use. Since UB-221 can curb the synthesis of IgE, the speed of IgE rebound will be slower than that of Xolair® after the treatment is discontinued. The highest dose of UB-221 administered intravenously in phase 1 clinical trial has a long half-life up to 22 days. Potential indications of UB-221 include IgE-mediated allergies, such as chronic spontaneous urticaria, allergic asthma, allergic rhinitis, food allergies, and atopic dermatitis. UB-221 is with a great potential for application. About Chronic Spontaneous Urticaria (CSU) Spontaneous urticaria is categorized into acute (less than six weeks) and chronic (more than six weeks) spontaneous urticaria. Chronic spontaneous urticaria (CSU) is also formerly known as chronic idiopathic urticaria (CIU) and chronic urticaria (CU). With the incidence rate of 0.5–1%, patients are suffered from the disease at any time. Although all age groups can be affected, peak incidence has been observed between 20 and 40 years of age. CSU brings tremendous detrimental effects on quality of life, such as sleep deprivation and psychiatric comorbidity. CSU also has a large impact on the economy in terms of direct and indirect health care costs as well as reduced performance at work. In the majority of CSU patients, an underlying cause cannot be identified, making a causal and/or curative treatment difficult. Nonsedating H1‐antihistamines are the mainstay of symptomatic therapy, however treatment with licensed doses relieves symptoms effectively in <50% of patients. Although guideline‐recommended updosing up to fourfold increases symptom control in many patients, a substantial number of patients only benefit a little from H1‐anti-histamine medication. Hence, there is still a great need for new therapeutic strategies. (Reference: Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in chronic spontaneous urticaria. A GALEN task force report. Allergy. 2011;66 (3):317-330). 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 diseases, cancer and immune disorders. UBP is headquartered in Taiwan, with subsidiary companies in Shanghai and Yangzhou China, and liaison offices in the U.S. The company has a highly passionate global team, developing first-in-class, best-in-class therapeutic mAbs and delivering high-quality, affordable treatments to bring a better quality of life to patients. 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. Company contact: Dr. Mei June Liao, Executive Vice President, Product Development +886-3-5979288 # 6700 meijune.liao@unitedbiopharma.com