Translational data presented during a late-breaker poster session from a head-to-head study of eblasakimab and dupilumab in a human tissue model of COPD indicates that eblasakimab performed better than dupilumab in improving airway function and enhancing bronchodilation at the same concentrations
Results support further investigation of eblasakimab as a potential therapeutic option for COPD with potentially more effective blockade of Type-2 mediated inflammatory effects in lung tissue
SAN MATEO, Calif. and SINGAPORE, May 21, 2024 (GLOBE NEWSWIRE) -- ASLAN Pharmaceuticals (Nasdaq: ASLN), a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients, today 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.
"We are pleased to present the translational data that we have generated on eblasakimab in COPD at this prestigious conference. Eblasakimab showed significant improvement across all measured bronchial outcomes, a result we believe may be attributed to the potential of eblasakimab to inhibit the Type 2 receptor complex more efficiently than approved biologics, resulting in greater reduction in Th2 cytokine activity. Since airway hyperresponsiveness is clinically shared across asthma, COPD, and other lung disorders, these data support the further investigation of eblasakimab in a range of Type 2-driven lung conditions," said Dr Carl Firth, Chief Executive Officer, ASLAN Pharmaceuticals.
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 patients1 and during exacerbations, characterized by impaired airflow, obstruction, and dyspnea2. Interleukin-4 (IL-4) and interleukin-13 (IL-13) are central mediators of Type 2 inflammation3 and are implicated in various mechanisms of airway obstruction in asthma4, suggesting they may play an essential role in COPD4. 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.
A copy of the poster is available to view online in the Publications section of ASLAN's website.
Singh et al (2014) Eur Resp Journal 44: 1697-1700
Celli BR, et al (2023) Am J Respir Crit Care Med 207(9):1134-1144
Bao K & Reinhardt RL (2015) Cytokine 75(1):25-37
Oishi K et al (2020) J Clin Med 9(8):2670
加利福尼亞州聖馬特奧和新加坡，2024年5月21日（GLOBE NEWSWIRE）——亞斯蘭製藥（納斯達克股票代碼：ASLN）是一家臨床階段、專注於免疫學的生物製藥公司，該公司正在開發創新療法，以改變患者生活。該公司今天宣佈發佈最新海報，介紹依拉薩基單抗和杜普利單抗在人類健康和慢性阻塞性肺組織模型中正面交鋒研究的轉化數據在加利福尼亞州聖地亞哥舉行的2024年美國胸科學會（ATS）國際會議上。
“我們很高興在這次享有盛譽的會議上介紹我們在慢性阻塞性肺病中依布拉薩基單抗生成的轉化數據。Eblasakimab在所有測得的支氣管結局中均顯示出顯著改善，我們認爲這一結果可能歸因於依拉沙基單抗有可能比批准的生物製劑更有效地抑制2型受體複合物，從而進一步降低Th2細胞因子活性。由於哮喘、慢性阻塞性肺病和其他肺部疾病在臨床上都存在氣道過度反應，因此這些數據支持對依布拉薩基單抗在一系列2型驅動的肺部疾病中的進一步研究。” 亞斯蘭製藥首席執行官卡爾·菲斯博士說。
ATS 2024 國際會議演示詳情：
最新海報演示
Eblasakimab 可顯著緩解慢性阻塞性肺切片中 IL-4 和 IL-13 引起的支氣管氣道收縮（海報編號 13753）
在 30-40% 的慢性阻塞性肺病患者中觀察到 2 型炎症1 和惡化期，其特徵是氣流受損、梗阻和呼吸困難2。白介素-4（IL-4）和白介素-13（IL-13）是2型炎症的中心介質3，與哮喘的各種氣道阻塞機制有關4，這表明它們可能在 COPD4 中起着至關重要的作用。阻斷雙重 IL-4 和 IL-13 信號傳導可能有可能防止支氣管收縮。這是使用慢性阻塞性肺病的精確切肺片（PCLS）模型進行測試的，該模型是通過靶向IL-4和 IL-13 信號通路的不同受體亞單位的dupilumab和eblasakimab進行治療的。
來自一名沒有已知肺部疾病史的66歲男性（健康PCLS）和一名患有慢性阻塞性肺病（COPD PCLS）的67歲女性的PCLS用於測試對不同治療條件的收縮和擴張反應，包括白細胞介素-4、IL-13、甲膽鹼（支氣管收縮劑）、福莫特羅（擴張劑）以及一系列濃度的杜阿基魯單抗和埃布拉單抗 mab。
在健康和慢性阻塞性肺病衍生的肺組織中，依拉沙基單抗均顯著減少了IL-4和IL-13誘發的支氣管氣道收縮。在 IL-4 和 IL-13 預處理的健康肺組織中，eblasakimab 進一步恢復了福莫特羅誘導的氣道擴張，在較低濃度下明顯好於dupilumab，並且改善了甲膽鹼引起的收縮。結果表明，依布拉薩基單抗可能在降低IL-4和IL-13誘發的氣道超反應方面提供治療益處，並且依拉薩基單抗可以在急性氣道收縮的情況下緩解氣道收縮的情況。
在慢性阻塞性肺病PCLS中，eblasakimab在所有測得的支氣管結局中均顯示出顯著改善，而在相同濃度下測試的dupilumab在所有測量中均未達到與安慰劑相比的統計學意義。這表明，與dupilumab相比，依拉沙基單抗有可能更強地緩解支氣管收縮並改善慢性阻塞性肺病的擴張功能。
研究結果支持進一步研究埃布拉沙基單抗作爲慢性阻塞性肺病的治療選擇，它可能更有效地阻斷肺組織中的2型介導作用，改善支氣管收縮。
該海報的副本可在ASLAN網站的 “出版物” 部分在線查看。
Singh 等人 (2014) Eur Resp Journal 44:1697-1700
Celli BR 等人 (2023) Am J Respir Crit Care Med 207 (9): 1134-1144
Bao K & Reinhardt RL (2015) 細胞因子 75 (1): 25-37
Oishi K 等人 (2020) J Clin Med 9 (8): 2670
