HBM HOLDINGS-B (02142) has announced that its partner, Windward Bio AG, has reported positive interim results from the Phase II portion of the POLARIS-1 clinical trial evaluating HBM9378/WIN378 for the treatment of asthma. The Phase III segment of POLARIS-1 has also been initiated, marking an important step forward for this investigational therapy.
HBM9378/WIN378 is a novel, fully human ultra-long-acting monoclonal antibody targeting thymic stromal lymphopoietin, a key driver of allergic inflammation. Engineered for enhanced potency, extended half-life, and silenced effector function, this antibody employs a distinctive binding pattern to effectively inhibit TSLP activity. It is currently the only investigational drug known to block the TSLP signaling pathway by binding to two distinct sites, thereby interfering with the interaction between TSLP and its two co-receptors at the epithelial cell surface.
The POLARIS-1 trial is a seamless global Phase II/III study sponsored by Windward Bio, designed to evaluate HBM9378/WIN378 in adult patients with uncontrolled asthma. The Phase II portion is a 48-week, randomized, double-blind study that primarily assesses the pharmacokinetics, safety, immunogenicity, and pharmacodynamic activity of three dose levels of subcutaneously administered HBM9378/WIN378 relative to placebo, while also informing dose selection for the Phase III trial. Additionally, the study evaluates the impact of the therapy on lung function and airway inflammation biomarkers.
A total of 147 patients were enrolled in the Phase II segment, exceeding the original enrollment target of 120, with the interim analysis based on data from the first 98 patients. The Phase III portion is currently assessing the efficacy of two twice-yearly dosing regimens of HBM9378/WIN378 versus placebo, with the primary endpoint being the annualized rate of asthma exacerbations in patients with severe asthma.
The interim analysis revealed that after a single dose of HBM9378/WIN378 at week 24, patients experienced a dose-dependent mean increase in forced expiratory volume in one second, reaching up to 174 mL, with a placebo-adjusted mean increase of up to 256 mL. Additionally, there was a dose-dependent mean reduction in fractional exhaled nitric oxide, with a maximum decrease of 24 parts per billion, representing a 43% reduction. The study also showed a mean reduction in blood eosinophil counts of up to 200 cells per microliter, a 51% decrease from baseline.
These findings are particularly notable as FEV1 serves as a key indicator of lung function, while FeNO and EOS are critical inflammatory markers associated with asthma exacerbations. Notably, near-maximal effects were observed as early as week two and were sustained through week 24. The interim analysis also demonstrated a half-life of up to 75 days, supporting the feasibility of a twice-yearly dosing schedule.
The tolerability and safety profile of HBM9378/WIN378 was generally favorable. As of the data cutoff date, no treatment-related serious adverse events, withdrawals, or discontinuations were observed. Adverse event rates were comparable between the treatment and placebo groups, with injection site reactions occurring in less than 1% of patients and an anti-drug antibody incidence of 2%, indicating minimal impact on the drug's pharmacological characteristics.
With the Phase III portion of POLARIS-1 now underway, Windward Bio plans to launch a second Phase III study, POLARIS-2, in the first half of 2027. The comprehensive data from the Phase II portion of POLARIS-1 will be presented at an upcoming medical conference.