Kelun-Biotech and Windward Bio Report Positive Phase 2 Interim Data for Twice-Yearly Asthma Antibody SKB378/WIN378
核心洞察
Interim analysis of the POLARIS-1 Phase 2 portion showed SKB378/WIN378 (搜索) produced dose-dependent FEV1 increases up to 174 mL at Week 24 after a single dose.
The ultra-long-acting anti-TSLP (搜索) antibody demonstrated a half-life of up to 75 days, supporting a twice-yearly dosing schedule in uncontrolled moderate-to-severe asthma (搜索).
SKB378/WIN378 (搜索) was well tolerated with no treatment-related serious adverse events, withdrawals or discontinuations, and adverse events balanced against placebo.
Sichuan Kelun-Biotech (搜索) Biopharmaceutical Co., Ltd. announced that its partner, Windward Bio (搜索), has reported positive interim results from the Phase 2 portion of the POLARIS-1 clinical trial evaluating twice-yearly dosing of SKB378/WIN378 (搜索) in patients with uncontrolled, moderate-to-severe asthma (搜索). The interim analysis, conducted on the first 98 of 147 enrolled patients, demonstrated a half-life of up to 75 days, with clinical effects consistent with twice-yearly dosing.
Lung Function and Biomarker Results at Week 24
At Week 24 after a single dose of SKB378/WIN378 (搜索), the interim analysis showed dose-dependent mean increases in FEV1 of up to 174 mL, with placebo-adjusted mean increases up to 256 mL (p=0.033). The antibody also produced dose-dependent mean reductions in FeNO of up to 24 ppb, or a -43% change (p=0.006), and reductions in mean blood eosinophil count of up to 200 cells/µL, or a -51% change (p<0.0001).
FeNO and blood eosinophils are key markers of inflammation that correlate with asthma (搜索) exacerbations, while FEV1 (forced expiratory volume in one second) is a key measure of lung function. Near maximal effects were observed as early as Week 2 and were sustained through Week 24, indicating a rapid and durable pharmacodynamic response to a single administration.
Safety and Immunogenicity Profile
SKB378/WIN378 (搜索) was well tolerated, with no treatment-related serious adverse events, withdrawals or discontinuations observed as of the cut-off date. Adverse events were balanced between active arms and placebo. Less than 1% of participants experienced injection site reactions, and 2% developed anti-drug antibodies (ADAs), a measure of immunogenicity; ADAs had no impact on the pharmacology of SKB378/WIN378. The results of the interim analysis and population pharmacokinetic modeling support the potential of twice-yearly dosing.
Trial Design and Dosing Strategy
POLARIS-1 (NCT07120503) is an operationally seamless, global Phase 2/3 study of SKB378/WIN378 (搜索) in adults with uncontrolled asthma (搜索) conducted by Windward Bio (搜索). The Phase 2 portion is a 48-week, randomized, double-blind study evaluating three dose levels of SKB378/WIN378 administered subcutaneously against placebo. It is designed to characterize pharmacokinetics, safety, immunogenicity and pharmacodynamic activity, as well as to evaluate effects on lung function and biomarkers of airway inflammation and to inform dose selection for Phase 3 development. The Phase 2 portion enrolled a total of 147 patients, exceeding the initial enrollment target of 120 patients.
Two twice-yearly doses have been selected for the Phase 3 portion of POLARIS-1, which is designed to evaluate the effect of SKB378/WIN378 (搜索) on annualized asthma (搜索) exacerbation rate and other key efficacy measures in patients with severe asthma. The Phase 3 portion has been initiated by Windward Bio (搜索), which plans to begin a second Phase 3 study, POLARIS-2, in the first half of 2027. Data from the Phase 2 portion of POLARIS-1 will be presented at an upcoming medical congress.
A Differentiated Anti-TSLP Mechanism
SKB378/WIN378 (搜索) is a novel fully human, ultra-long-acting monoclonal antibody with a unique binding mode that inhibits thymic stromal lymphopoietin (搜索) (TSLP (搜索)). It was engineered for improved potency, extended half-life and silenced effector function. According to the companies, it is the only known investigational drug that blocks TSLP signaling by binding to two different sites on TSLP, interfering with the binding of TSLP to both of its co-receptors on the cell surface of epithelial cells.
TSLP (搜索) is a clinically validated target that plays a key role in the development and progression of a wide array of immunological diseases, including asthma (搜索), chronic obstructive pulmonary disease (搜索) (COPD), chronic rhinosinusitis with nasal polyps (搜索) and eosinophilic esophagitis (搜索). Beyond POLARIS-1, SKB378/WIN378 (搜索) is being evaluated in the Phase 2 SIRIUS study in COPD.
Dr. Michael Ge, Chief Executive Officer of Kelun-Biotech (搜索), stated: "We are delighted to see that the Phase 2 portion of POLARIS-1 for SKB378/WIN378 (搜索) has achieved positive results, driven by the active efforts of our partner. As a differentiated, ultra-long-acting anti-TSLP (搜索) antibody, SKB378/WIN378 balances efficacy, safety, and patient compliance, and holds the potential to address the unmet clinical needs in moderate-to-severe asthma (搜索)."
Licensing and Development History
SKB378/WIN378 (搜索) started as a co-development project jointly conducted by Kelun-Biotech (搜索) and Harbour BioMed (搜索), with both parties equally sharing global rights. Windward Bio (搜索) licensed the global rights, excluding Greater China and several Southeast and West Asian countries, for the molecule from Kelun-Biotech (also known as SKB378) and Harbour BioMed (also known as HBM9378).