Company: CNTB
Filing Date: 2025-03-31
Form Type: 10-K
Source: 0001835268-25-000014
Chunk: 46

Company: Connect Biopharma Holdings Ltd
Filing Date: 2025-03-31
Form: 10-K
Item: Item 1
Chunk 46
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 return for emergency care. To address this unmet need, during the first half of 2025, we plan to initiate two Phase 2 trials of rademikibart for the treatment of acute exacerbations of chronic respiratory disease, including asthma and COPD. The Phase 2 acute asthma trial, Seabreeze ASTHMA STAT, and the acute COPD trial, Seabreeze COPD STAT will evaluate rademikibart plus SoC compared to SoC plus placebo in patients with asthma and COPD and Type 2 inflammation who are having an acute exacerbation. The primary endpoint of these two trials is treatment failure over 28 days after randomization. Treatment failure includes: death (any cause), (re)admission to the hospital, an urgent visit to an outpatient or emergency department provider for symptoms that are worsening, or the necessity to intensify pharmacologic treatment. The key secondary efficacy endpoints of these trials are the rate of new exacerbations, the time to the first new exacerbation, change in symptoms, and change in lung function in the 28 days after randomization. Exploratory endpoints of these trials include time-to-discharge in hospitalized patients, and disease-specific patient-reported outcomes.

We have also undertaken a study to determine differences in the atomic-resolution three dimensional (“3D”) structures of rademikibart and dupilumab, that may potentially lead to an understanding of the differences in efficacy and safety between the two drugs. X-ray crystallography was used to determine the atomic resolution 3D structure of rademikibart fragment antigen binding bound to IL-4Rα. Three loops of the IL4Rα at the interface are involved in the binding interactions with antibodies. The major differences between the equilibrated structures of dupilumab-IL4Rα and rademikibart-IL4Rα complexes is at the third interface loop (residue 148 to 152). The average B factor of the third loop is 133.22 for dupilumab complex and 53.42 for rademikibart complex. The third loop of IL4Rα in dupilumab complex has larger B factors and stays further away from the antibody, while all three loops in the rademikibart complex show low B factors and bind closely to the antibody. It indicates that the antibody-antigen binding is more stable for the rademikibart than the dupilumab. Hydrogen (H) bond interactions