ASLAN Pharmaceuticals announced the late-breaking poster presentation of translational data from head-to-head studies of eblasakimab and dupilumab in human healthy and COPD-derived lung tissue models at the American Thoracic Society (ATS) International Conference 2024 in San Diego, California. ATS 2024 International Conference presentation details: Late-breaker poster presentation Eblasakimab Significantly Alleviates IL-4 and IL-13 Induced Bronchial Airway Constriction in COPD-Derived Lung Slices (Poster ID 13753) Type 2 inflammation is observed in 30-40% of COPD patients and during exacerbations, characterized by impaired airflow, obstruction, and dyspnea. Interleukin-4 (IL-4) and interleukin-13 (IL-13) are central mediators of Type 2 inflammation and are implicated in various mechanisms of airway obstruction in asthma, suggesting they may play an essential role in COPD.

Blocking dual IL-4 and IL-13 signaling may have the potential to prevent bronchoconstriction. This was tested using the precision cut-lung slices (PCLS) model of COPD by treatment with dupilumab and eblasakimab which target different receptor subunits of the IL-4 and IL-13 signaling pathway. PCLS from a 66-year-old male with no known history of lung diseases (healthy PCLS) and a 67-year-old female with COPD (COPD PCLS) were used to test constriction and dilation responses to different treatment conditions including IL-4, IL-13, methacholine (bronchoconstrictor), formoterol (dilatory agent), and a range of concentrations of dupilumab and eblasakimab.

In both healthy and COPD-derived lung tissues, eblasakimab significantly reduced IL-4- and IL-13-induced bronchial airway constriction. In IL-4 and IL-13 pre-treated healthy lung tissues, eblasakimab further restored formoterol-induced airway dilation, significantly better than dupilumab at the lower concentration, and improved methacholine-induced constriction. The results suggest eblasakimab may provide a therapeutic benefit in reducing IL-4- and IL-13-induced airway hyperresponsiveness and that eblasakimab may provide relief in situations of acute airway constriction.

In COPD PCLS, eblasakimab showed significant improvement across all measured bronchial outcomes whereas dupilumab, tested at the same concentrations, did not achieve statistical significance relative to placebo for all measures. This suggests that eblasakimab may potentially provide stronger relief against bronchoconstriction as well as improved dilatory function in COPD compared to dupilumab. The results support further investigation of eblasakimab as a therapeutic option for COPD with potentially more effective blockade of Type-2 mediated effects in lung tissue and improvement in bronchoconstriction.