SKB BIO's (06990) partner Windward Bio AG has unveiled encouraging interim results from the Phase 2 segment of the POLARIS-1 trial, evaluating SKB378/WIN378 for asthma treatment, with the Phase 3 portion already underway.

SKB378/WIN378 is a novel fully human ultra-long-acting monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), engineered with enhanced potency, an extended half-life, and silenced effector function. It holds the distinction of being the only investigational therapy known to block TSLP signaling through dual-site binding, disrupting the interaction between TSLP and its two co-receptors on epithelial cells.

Where the study stands

POLARIS-1 (NCT07120503) is a seamless global Phase 2/3 study conducted by Windward Bio, designed to assess SKB378/WIN378 in adults with uncontrolled asthma. The Phase 2 segment, a 48-week randomized double-blind trial, focused on evaluating the pharmacokinetics, safety, immunogenicity, and pharmacodynamic activity of three subcutaneous dose levels versus placebo, providing the basis for Phase 3 dose selection. The study also measured effects on lung function and airway inflammation biomarkers, enrolling 147 patients—exceeding the initial target of 120—with the interim analysis based on data from the first 98 participants.

The Phase 3 portion is currently assessing two twice-yearly dosing regimens of SKB378/WIN378 versus placebo, focusing on the annualized rate of asthma exacerbations as the primary endpoint in patients with severe asthma.

Key interim findings

At week 24 after a single dose, the interim analysis revealed dose-dependent increases in forced expiratory volume in one second (FEV1), with a maximum mean improvement of 176mL, rising to 256mL after placebo adjustment (p=0.033). Fractional exhaled nitric oxide (FeNO) showed a dose-dependent reduction, with a maximum mean decrease of 24 parts per billion, equivalent to a 43% reduction (p=0.006). Blood eosinophil counts (EOS) fell by up to 200 cells/µL, corresponding to a 51% reduction (p<0.0001). FEV1 serves as a critical measure of lung function, while FeNO and EOS are key inflammatory markers linked to asthma exacerbations. These effects were observed nearly at their maximum as early as week 2 and remained sustained through week 24.

The interim data also indicated a half-life of up to 75 days, with the results and population pharmacokinetic modeling supporting a twice-yearly dosing schedule.

Safety profile and next steps

SKB378/WIN378 demonstrated a favorable tolerability and safety profile, with no treatment-related serious adverse events, withdrawals, or discontinuations observed up to the data cutoff. Adverse event rates were comparable between the treatment and placebo groups, and injection site reactions occurred in fewer than 1% of cases. The anti-drug antibody rate stood at 2%, a measure of immunogenicity that did not impact the drug's pharmacological characteristics.

Windward Bio has initiated the Phase 3 portion of POLARIS-1, adopting two twice-yearly dose regimens to evaluate the impact on the annualized asthma exacerbation rate and other key efficacy outcomes in severe asthma patients. Additionally, the company plans to launch a second Phase 3 study, POLARIS-2, in the first half of 2027. The Phase 2 data from POLARIS-1 is scheduled for presentation at an upcoming medical conference. SKB378/WIN378 was initially developed by SKB BIO in collaboration with Harbour Biomed Holdings, with both parties sharing global rights.