Development

Windward’s TSLP mAb shows six-month asthma activity after single dose

Windward’s TSLP mAb shows six-month asthma activity after single dose

Positive Phase II interim data from SKB378/WIN378, an anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody engineered for extended half-life, have supported the initiation of a Phase III asthma study, with a single dose producing statistically significant improvements in lung function and inflammatory biomarkers that were sustained through Week 24.

The data come from POLARIS-1, an operationally seamless global Phase II/III trial conducted by Switzerland-based Windward Bio AG, which holds rights outside Greater China and certain Asian markets to the molecule, licensed from China-based Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (HKEX: 06990) and Harbour BioMed. The Phase II portion enrolled 147 adults with uncontrolled asthma across three subcutaneous dose levels versus placebo in a 48-week, randomised, double-blind design; the interim analysis was conducted on the first 98 patients at Week 24 following a single dose.

At that timepoint, SKB378/WIN378 produced dose-dependent mean increases in forced expiratory volume in one second (FEV₁) of up to 174 mL, with a placebo-adjusted mean increase of up to 256 mL (p=0.033). Fractional exhaled nitric oxide (FeNO), a marker of eosinophilic airway inflammation, fell by up to 24 parts per billion, representing a 43% reduction (p=0.006). Blood eosinophil counts declined by up to 200 cells/µL, a 51% reduction (p<0.0001). Windward Bio reported that near-maximal effects were observed as early as Week 2 and were sustained through Week 24. The interim analysis demonstrated a half-life of up to 75 days, which the company said supports population pharmacokinetic modelling for twice-yearly dosing. No treatment-related serious adverse events, withdrawals, or discontinuations were recorded as of the data cut-off; adverse events were balanced across active and placebo arms, fewer than 1% of participants had injection site reactions, and 2% developed anti-drug antibodies with no apparent effect on pharmacology.

The AllSci BriefFree, systematic R&D and deal news. Daily.

SKB378/WIN378 inhibits TSLP by binding simultaneously to two distinct sites on the cytokine, blocking its interaction with both co-receptors on epithelial cell surfaces — a mechanism the company said distinguishes it from tezepelumab (Tezspire), the AstraZeneca and Amgen anti-TSLP antibody approved for severe asthma. The molecule's extended half-life also offers potential twice-yearly dosing.

The Phase III portion of POLARIS-1, which has now been initiated, will evaluate two twice-yearly subcutaneous doses against placebo in patients with severe asthma, with AAER as the primary endpoint. Windward Bio plans to initiate a second pivotal trial, POLARIS-2, in the first half of 2027. SKB378/WIN378 is also being evaluated in the Phase II SIRIUS study in chronic obstructive pulmonary disease. Full Phase II data from POLARIS-1 are to be presented at an upcoming medical congress.


Spot something wrong? Report an issue with this article