Shanghai Shen Lian Biomedical Corporation (688098.SH) has announced that its controlled subsidiary, Yangzhou Shizhiyuan Biotechnology Co., Ltd., achieved the primary endpoint in a Phase II clinical study of its proprietary Class 1 biologic drug UB-221 injection for treating chronic spontaneous urticaria (CSU), with positive topline results.

The trial, 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," successfully met its main objective.

UB-221 is a subcutaneously administered humanized monoclonal antibody targeting IgE, developed as a next-generation product by Professor Zhang Ziwen, the inventor of anti-IgE therapy and omalizumab. It is designed to treat IgE-mediated allergic diseases. The drug works by binding to IgE, neutralizing free IgE molecules in the bloodstream, and blocking their interaction with receptors on mast cells and basophils, thereby suppressing the release of inflammatory mediators like histamine. Additionally, CD23, also known as FcεRII, a low-affinity IgE receptor on B cells, plays a role in the negative feedback regulation of IgE production. Notably, UB-221 does not interfere with IgE's binding to CD23, which may partially reduce IgE synthesis, suggesting a potentially differentiated mechanism of action.

Earlier, the Phase I trial results of UB-221 for CSU were published in the internationally recognized journal The Journal of Clinical Investigation. The Phase II study, a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, enrolled 145 subjects with moderate-to-severe CSU. Participants were randomized in a 2:2:2:1:1 ratio into five treatment arms: 4 mg/kg UB-221, 2 mg/kg UB-221, 1 mg/kg UB-221, 300 mg omalizumab, or placebo.

Results demonstrated that UB-221 exhibited positive efficacy and a favorable safety profile in CSU patients. For the primary efficacy endpoint of HSS7=0, indicating complete wheal resolution at week 12, a dose-response relationship was observed. Response rates were 54%, 53%, and 43% for the 4 mg/kg, 2 mg/kg, and 1 mg/kg UB-221 groups, respectively, all significantly higher than the placebo group's 11% (p<0.005, <0.005, and <0.05, respectively), while the omalizumab 300 mg group achieved 41%.

The key secondary endpoint, UAS7=0, reflecting complete resolution of both wheals and pruritus at week 12, also showed a dose-response trend, with response rates of 46%, 39%, and 38% across the UB-221 doses. The 4 mg/kg group reached statistical significance versus placebo (p<0.05), compared to 29% for the omalizumab group. Efficacy continued to improve beyond week 12; the 4 mg/kg group's HSS7=0 response rate rose to 69% at week 22, six weeks after the last dose, and remained at 60% at week 28, twelve weeks post-treatment. In contrast, the omalizumab group's rate was 24% at the same time point, a 36-percentage-point difference, indicating that UB-221 offers robust and durable clinical benefits, supporting its potential differentiated profile.

In terms of safety, UB-221 was generally well-tolerated. The incidence of treatment-related adverse events was similar across all groups, with no treatment-related serious adverse events or hypersensitivity reactions, including anaphylactic shock. Injection site reactions were infrequent and did not lead to treatment discontinuation. Based on these Phase II findings, UB-221 demonstrates a clear dose-response relationship and sustained efficacy in achieving complete wheal resolution and disease control, supporting the advancement of Phase III clinical studies for chronic spontaneous urticaria.