A proof-of-mechanism trial in asthma with lunsekimig, a bispecific NANOBODY molecule.

Therefore, dual blockade of these cytokines may result in an enhanced response compared to single targeting and has the potential to break efficacy ceilings in asthma.

因此，这些细胞因子的双重阻断可能会比单一靶向产生更强的反应，并有可能打破哮喘治疗的效能上限。

This study assessed the safety and tolerability of lunsekimig, a bispecific NANOBODY molecule that blocks TSLP and IL-13, and its effect on type 2 (T2) inflammatory biomarkers and lung function in asthma.

本研究评估了双特异性NANOBODY分子lunsekimig的安全性和耐受性，该分子阻断TSLP和IL-13，并研究了其对2型（T2）炎症生物标志物和哮喘患者肺功能的影响。

Methods

This was a phase 1b, single-dose (subcutaneous lunsekimig 400 mg or placebo), randomised (2:1), double-blind, proof-of-mechanism study in 36 participants with mild-to-moderate asthma and elevated exhaled nitric oxide fraction (F ENO; ≥25 ppb), a marker of airway inflammation.

这是一项1b期、单剂量（皮下注射lunsekimig 400 mg或安慰剂）、随机（2:1）、双盲、机制验证研究，在36名轻度至中度哮喘患者中进行，这些患者呼出的一氧化氮分数（FENO；≥25 ppb）升高，是气道炎症的一个标志。

The primary end-point was safety and tolerability through day 71.

主要终点是第71天的安全性和耐受性。

The main pharmacodynamic secondary end-point was change from baseline in F ENO at day 29.

主要药效学次要终点是第29天基线时F ENO的变化。

Results

Lunsekimig was well tolerated, with no serious treatment-emergent adverse events.

Lunsekimig 被良好地耐受，未出现严重的治疗相关不良事件。

F ENO was significantly reduced from day 8 through day 29 after a single dose, with change from baseline of -40.9 (90% CI -55.43- -26.39) ppb (p<0.0001) versus placebo at day 29.

单剂量给药后，从第8天至第29天，F ENO 显著降低，基线变化为 -40.9 (90% 置信区间 -55.43- -26.39) ppb (p<0.0001)，与第29天的安慰剂组相比。

Blood-based T2 biomarkers at day 29 were significantly reduced from baseline.

第29天的血液T2生物标志物从基线显著减少。

Lung function, particularly small airway dysfunction, was numerically improved at day 29, most notably in participants with impaired lung function at baseline.

特别是在第29天，小气道功能障碍有所改善，这在基线时肺功能受损的参与者中尤为显著。

Conclusions

A single dose of lunsekimig was well tolerated, significantly suppressed T2 inflammation and improved lung function in mild-to-moderate asthma.

单剂量的lunsekimig耐受性良好，显著抑制了轻度至中度哮喘的T2炎症，并改善了肺功能。