Columbotai Biotech (06990): SKB378/WIN378 achieved positive results in the treatment of asthma in phase 2 and phase 3 studies initiated
According to Zhitong Financial App, Columbotai Biotech (06990) announced that the company's partner Windward Bio AG (Windward Bio) has announced that SKB378/WIN378 (an all-human ultra-long-acting monoclonal antibody targeting thymic matrix lymphopoietin (TSLP)) achieved positive interim results in phase 2 of the POLARIS-1 clinical trial for the treatment of asthma. The Phase 3 portion of POLARIS-1 has also been launched.
SKB378/WIN378 is a novel all-human ultra-long-lasting monoclonal antibody. It has a unique binding pattern and can effectively inhibit TSLP. The antibody has been engineered to have stronger efficacy, extended half-life, and functional silencing. SKB378/WIN378 is currently the only known drug under development that blocks its signaling pathway through two-site binding to TSLP, which can interfere with the binding of TSLP to its two co-receptors on the surface of epithelial cells.
POLARIS-1 (NCT07120503) is a seamless global phase 2/3 clinical study conducted by Windward Bio to evaluate SKB378/WIN378 for adult patients with uncontrolled asthma. The phase 2 portion of the study was a 48-week randomized, double-blind study that mainly assessed the pharmacokinetics, safety, immunogenicity, and pharmacodynamic activity of the three dose levels of SKB378/WIN378 subcutaneously compared to placebo, and provided a basis for dose selection for the phase 3 study. The study also assessed the effects of SKB378/WIN378 on lung function and biomarkers of airway inflammation. A total of 147 patients were enrolled in phase 2, exceeding the initial enrollment target of 120 cases. The mid-term analysis was based on data from the first 98 patients. Phase 3 is evaluating the efficacy of two doses of SKB378/WIN378 compared with placebo, given twice a year. The main end point was the annual rate of acute asthma attacks in patients with severe asthma.
Interim analysis results showed that in the 24th week after a single dose of SKB378/WIN378 administration: (i) first-second forced expiratory volume (FEV1) showed a dose-dependent average increase of up to 176 mL (up to 256 mL after placebo correction) (p=0.033); (ii) the nitric oxide fraction (FeNO) of exhaled nitric oxide (FeNO) decreased by a dose-dependent average of 24 billion parts (43% reduction percentage, p=0.006); (iii) eosinophilic acidophilic cells Average (EOS) decreased, highest drop Up to 200 cells/µL (51% reduction percentage, p<0.0001).
FEV 1 is a key indicator of lung function, while FenO and EOS are key inflammatory markers associated with acute asthma attacks. The above effects were observed close to maximum as early as week 2 and continued until week 24. Mid-term analysis showed a half-life of up to 75 days. Interim analysis results and population pharmacokinetic models supported SKB378/WIN378 to adopt a twice-yearly dosing regimen.
SKB378/WIN378 is well tolerated and safe. As of the data cutoff date, no serious treatment-related adverse events, withdrawal or discontinuation were observed. The treatment group had a similar incidence of adverse events to the placebo control group. The incidence of reaction at the injection site is less than 1%, and the incidence of anti-drug antibodies is 2% (this indicator is used to evaluate immunogenicity and has no effect on the pharmacological characteristics of SKB378/WIN378).
The phase 3 portion of Polaris-1 has been initiated by Windward Bio to determine the use of two dosage regimens with two doses per year to assess the effects of SKB378/WIN378 on the annual acute incidence rate of asthma and other key efficacy indicators in patients with severe asthma. Additionally, Windward Bio plans to launch the second phase 3 clinical study Polaris-2 in the first half of 2027. The data from the Phase 2 study of POLARIS-1 will be presented at an upcoming medical conference.
SKB378/WIN378 was initially jointly developed by the company and Hebo Pharmaceutical Holdings Co., Ltd., and both parties shared their global interests.