HBM HOLDINGS-B (02142): Positive interim results from the Phase II clinical trial of HBM9378/WIN378 for the treatment of asthma and the initiation of Phase III study.

HBM HOLDINGS-B (02142) announced that its partner Windward Bio AG (Windward Bio) has released positive interim results from the Phase II portion of the POLARIS-1 clinical trial for HBM9378/WIN378, a fully human long-acting monoclonal antibody targeting thymic stromal lymphopoietin (TSLP) for the treatment of asthma. The Phase III portion of POLARIS-1 has also been initiated. HBM9378/WIN378 is an innovative fully human long-acting monoclonal antibody with a unique binding mode that effectively inhibits TSLP. This antibody has been engineered for enhanced potency, prolonged half-life, and functional silencing. HBM9378/WIN378 is currently the only known investigational drug that blocks the TSLP signaling pathway through dual-site binding, interfering with the binding of TSLP to its two co-receptors on the surface of epithelial cells. POLARIS-1 (NCT07120503) is a seamless global Phase II/III clinical study conducted by Windward Bio, aiming to evaluate HBM9378/WIN378 in adult patients with uncontrolled asthma. The Phase II portion is a 48-week randomized, double-blind study primarily assessing the pharmacokinetics, safety, immunogenicity, and pharmacodynamic activity of subcutaneously administered HBM9378/WIN378 at three dosage levels compared to a placebo, and providing rationale for dosage selection in the Phase III study. The study also evaluates the effects of HBM9378/WIN378 on lung function and biomarkers of airway inflammation. A total of 147 patients were enrolled in the Phase II portion, exceeding the initial target of 120, with the interim analysis based on data from the first 98 patients. The Phase III portion is currently evaluating the efficacy of two dosing regimens of HBM9378/WIN378 administered biannually compared to a placebo, with the primary endpoint being the annualized rate of acute asthma exacerbations in patients with severe asthma. The interim analysis results show that at week 24 after a single dose of HBM9378/WIN378: (i) The forced expiratory volume in one second (FEV1) showed a dose-dependent mean increase, reaching up to 174 mL (the maximum placebo-corrected mean increase was 256 mL, p=0.033); (ii) The fractional exhaled nitric oxide (FeNO) showed a dose-dependent mean decrease, with the maximum reduction of 24 parts per billion (percentage reduction of 43%, p=0.006); and (iii) The eosinophil count (EOS) showed a mean reduction, with the maximum decrease of 200 cells/L (percentage reduction of 51%, p<0.0001). FEV1 is a key indicator of lung function, while FeNO and EOS are key inflammatory markers associated with acute asthma exacerbations. These effects were observed to approach their maximum as early as week 2 and persisted until week 24. The interim analysis indicated a half-life of up to 75 days. These interim analysis results and the population pharmacokinetic model support a biannual dosing regimen for HBM9378/WIN378. HBM9378/WIN378 was well-tolerated and demonstrated good safety; as of the data cutoff date, no treatment-related serious adverse events, withdrawals, or discontinuations were observed. The incidence of adverse events was comparable between the treatment and placebo groups. The incidence of injection site reactions was below 1%, and the occurrence of anti-drug antibodies was 2% (this measure is used to assess immunogenicity and has no impact on the pharmacological characteristics of HBM9378/WIN378). The Phase III portion of POLARIS-1 has adopted two dosing regimens administered biannually to evaluate the impact of HBM9378/WIN378 on the annualized rate of acute asthma exacerbations and other key efficacy endpoints in patients with severe asthma. The Phase III portion has been initiated by Windward Bio, which plans to launch a second Phase III clinical study, POLARIS-2, in the first half of 2027. Data from the Phase II study of POLARIS-1 will be presented at an upcoming medical conference.