Rademikibart data at ATS25

Connect Biopharma announced clinical and preclinical data supporting rademikibart, the Company’s next-generation, potentially best-in-class anti-interleukin-4-receptor alpha (IL-4Rα) antibody, which was presented at the American Thoracic Society (ATS) 2025 International Conference, taking place from May 18-21 in San Francisco.

Title: Rapid Improvement in Lung Function Observed with Rademikibart in Patients with Moderate-to-Severe Uncontrolled Asthma

• At-home spirometry readings from Connect’s Phase II b trial of rademikibart for moderate-to-severe uncontrolled asthma were evaluated in a post-hoc analysis to assess rademikibart’s ability to rapidly improve lung function.
• Rademikibart rapidly improved lung function (FEV₁) during the initial week of treatment, and most FEV₁ increase was observed within 24 hours.
• Improvements in self-assessed prebronchodilator FEV₁ were greatest in patients with elevated eosinophil counts (≥300 cells/µL) with or without elevated exhaled nitric oxide (FeNO ≥25 ppb), markers of type 2 inflammation, as compared with the overall population.
• Patients with type 2 inflammatory asthma in this study also showed a significant reduction in acute exacerbations.
• Findings support rademikibart’s potential as an effective therapy for patients with asthma or COPD experiencing an acute exacerbation, providing both fast-acting and sustained improvements in lung function.
  
  

Title: Efficacy of Rademikibart in COPD-like Patients: Sub-analyses From the Phase IIb Trial in Patients with Moderate-to-Severe Asthma

• Results from the Company’s Phase IIb trial of rademikibart in moderate-to-severe asthma were assessed in a post-hoc analysis to determine rademikibart’s efficacy in subgroup of COPD-like patients, defined as asthma onset after 40 years of age and post−bronchodilator FEV₁/FVC ratio <0.7.
• Rademikibart significantly improved prebronchodilator FEV₁ from first assessment and was sustained during 24 weeks of treatment, with greatest improvements in patients with elevated baseline eosinophil counts (≥150 cells/µL and ≥300 cells/µL).
• These results suggest that rademikibart has the potential to improve outcomes for patients with COPD, particularly in patients with eosinophilic-driven COPD.
  
  

Title: Effect of Rademikibart on Blood Eosinophil Counts in Patients with Asthma: Is There an IL-4Rα Class Effect?

• In a post-hoc analysis, eosinophil data from the Company’s Phase IIb trial of rademikibart and from the Phase III VENTURE and QUEST trials of dupilumab were indirectly compared to determine whether hypereosinophilia is an IL-4Rα inhibitor class effect following published cases of dupilumab-associated hypereosinophilia.
• Rademikibart treatment groups were associated with substantially lower proportions of patients experiencing high post-baseline eosinophil counts than with dupilumab treatment groups. Proportions of patients with high post-baseline eosinophil counts were comparable in the placebo groups, indicating that differences in the active treatment groups are due to drug effect.
• In the rademikibart treatment groups mean eosinophil counts decreased by approximately 30% at Week 24, compared to a mean eosinophil increase between 50% and 120% for dupilumab during 52 weeks of treatment.
• Based on this analysis, the lack of an increase in eosinophils with rademikibart suggests that increased eosinophil counts observed in published data for dupilumab is unlikely to be an IL-4Rα inhibitor class effect, further differentiating rademikibart’s safety profile as a potentially best-in-class IL-4Rα inhibitor.
  
  

Title: Optimized Second-generation IL-4Rα Inhibition: Structural and Molecular Dynamics Properties of Rademikibart Fab-IL-4Rα Complex

• Rademikibart is an optimized next-generation human monoclonal antibody targeting IL-4Rα.
• In this study, Connect evaluated the atomic-resolution 3D structures of rademikibart and dupilumab, that may lead to an understanding of the differences in efficacy and safety between the two drugs.
• The x-ray crystal structure of rademikibart Fab-IL-4Rα complex revealed an ~60° rotation of rademikibart on IL-4Rα compared to dupilumab, optimizing interference with the natural IL-4/IL-13 epitope, while dupilumab binds to IL-4Rα via only domain 1, thereby incompletely engaging the natural IL-4/IL-13 epitope on IL-4Rα.
• Compared to dupilumab, molecular dynamics studies showed rademikibart forms a very strong and stable interaction with IL-4Rα, confirmed structurally by lower B-factors (less motion) and more hydrogen bonds (stronger binding) than dupilumab.
• These results further support previously published data showing that rademikibart demonstrated better inhibition of STAT6 intracellular signaling, provided similar potency in prohibiting both IL-4-induced TARC release and IL-4-induced B cell activation and has more than 2-fold higher binding affinity to IL-4Rα compared to dupilumab.
• These data support the underlying molecular and structural rationale for enhanced IL-4Rα inhibition by rademikibart compared to dupilumab.
• “We are pleased to share new clinical and preclinical data highlighting rademikibart’s potential as a best-in-class treatment for patients with asthma or COPD experiencing an acute exacerbation,” said Dr. Barry Quart,  CEO and Director of Connect Biopharma. “The new analyses from our previously completed Phase 2b study not only demonstrate rademikibart’s rapid onset of action and significant improvement in lung function, but also further differentiate its safety profile, overcoming limitations of existing IL-4Rα inhibitors on the market. Taken together, these data reinforce our confidence in our clinical development plan and provide strong commercial rationale for rademikibart as a potentially superior next-generation IL-4Rα inhibitor.”