Shanghai Shen Lian Biomedical Corporation (688098.SH): Phase II clinical trial of UB-221 for the treatment of chronic spontaneous urticaria meets primary endpoint

Shanghai Shen Lian Biomedical Corporation (688098.SH) announced that the Phase II clinical study of UB-221 injection, a Class 1 biologic independently developed by its controlled subsidiary Yangzhou Shizhiyuan Biotechnology Co., Ltd. ("Shizhiyuan"), for the treatment of chronic spontaneous urticaria (CSU)titled "A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of UB-221 as an Add-On Therapy in Patients with Chronic Spontaneous Urticaria (CSU)"has met its primary endpoint and achieved positive topline results. UB-221 is a subcutaneous humanized monoclonal antibody targeting IgE. It is a next-generation product developed by Professor Chang Tse-Wen, the inventor of anti-IgE therapy and omalizumab, for the treatment of IgE-mediated allergic diseases. On the one hand, UB-221 can bind to IgE, neutralize free IgE molecules in the blood, block their binding to receptors on the surface of mast cells and basophils, and inhibit the release of histamine and other inflammatory mediators. On the other hand, CD23 (also known as FcRII) is a low-affinity IgE receptor on the surface of B cells, and the binding of IgE to CD23 is involved in the negative regulatory feedback of IgE production. UB-221 does not affect the binding of IgE to the CD23 receptor on B cell surfaces; this property can reduce IgE synthesis to a certain extent, giving UB-221 a potentially differentiated mechanism of action. Previously, the Phase I clinical trial results of UB-221 for the treatment of chronic spontaneous urticaria were published in the internationally authoritative journal *The Journal of Clinical Investigation*. This Phase II clinical trial was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of subcutaneous UB-221 injection as an add-on therapy in patients with chronic spontaneous urticaria (CSU). The study enrolled a total of 145 subjects with moderate-to-severe chronic spontaneous urticaria. Patients were randomly assigned in a 2:2:2:1:1 ratio to one of five treatment groups, receiving 4 mg/kg UB-221, 2 mg/kg UB-221, 1 mg/kg UB-221, 300 mg omalizumab, or placebo. The study results showed that UB-221 injection demonstrated positive efficacy and safety in patients with chronic spontaneous urticaria. In terms of efficacy, the primary efficacy endpoint of HSS7=0 (complete resolution of wheals) at Week 12 showed a dose-response relationship. The response rates in the UB-221 4 mg/kg, 2 mg/kg, and 1 mg/kg groups were 54%, 53%, and 43%, respectively, all significantly higher than the 11% in the placebo group (p<0.005, <0.005, and <0.05, respectively), while the omalizumab 300 mg group was 41%. The key secondary efficacy endpoint of UAS7=0 (complete remission of both wheals and itch) at Week 12 also showed a dose-response relationship, with response rates of 46%, 39%, and 38% in the respective dose groups, among which the 4 mg/kg group achieved statistical significance compared with the placebo group (p<0.05), while the omalizumab 300 mg group was 29%. The efficacy of UB-221 further improved after Week 12. In the 4 mg/kg group, the HSS7=0 response rate reached 69% at Week 22 (i.e., 6 weeks after treatment discontinuation) and remained at 60% at Week 28 (i.e., 12 weeks after treatment discontinuation), compared with 24% in the omalizumab group at the same time point, a difference of 36 percentage points between the two groups. This indicates that UB-221 has overall favorable and relatively durable clinical benefits and supports its potentially differentiated characteristics of action. In terms of safety, UB-221 was generally well tolerated. The incidence of treatment-related adverse events was similar across treatment groups. No treatment-related serious adverse events or hypersensitivity reactions, including anaphylactic shock, occurred. The incidence of injection site reactions was low and did not lead to treatment discontinuation. Taken together, the Phase II study results demonstrate that UB-221 exhibits a clear dose-response relationship and sustained efficacy in terms of complete resolution of wheals and complete disease remission, supporting the subsequent advancement of Phase III clinical studies for chronic spontaneous urticaria.