*3.6. Anti-TSLP mAbs*

Similar to IL-33, TSLP is mainly an epithelium-derived alarmin, which plays an upstream role in the initiation of type-2-driven immune responses [71]. In asthma, the number of cells expressing TSLP messenger ribonucleic acid (mRNA) within the airway epithelium and submucosa is markedly increased compared to healthy controls [72]. In a subset of patients with severe asthma, TSLP expression remained enhanced, independent of treatment with high-dose ICS or OCS [73]. Therefore, targeting TSLP signalling represents an intriguing therapeutic strategy in asthma [74].

In a Phase I RCT [53,54] the anti-TSLP mAb fragment ecleralimab (CSJ117) 4 mg was administered via a dry powder inhaler (DPI) for 12 weeks to patients with mild atopic asthma, who exhibited an early asthmatic response (EAR) and late asthmatic response (LAR) to a common inhaled allergen. Ecleralimab did not induce an attenuation in the EAR, as documented by the maximum percentage fall in FEV1 or as time-adjusted area under the curve (AUC), and numerically increased the minimum of the absolute in FEV1 compared to PCB. During the LAR, ecleralimab significantly (*p* < 0.05) reduced the maximum percentage decrease in FEV1 (MD −8.42% (90%CI −15.66–−1.18)) from pre-allergen inhalation challenge and the time-adjusted AUC fall in FEV1 (MD −7.18% (90%CI −11.92–−2.44)), compared to PCB. Patients in the ecleralimab group showed a strong trend towards a significant (*p* = 0.05) increase in the minimum absolute FEV1 during LAR vs. PCB (MD 0.27% (90%CI 0.00–0.55)) [53,54]. No data are available for symptoms control [53,54].
