Harbour BioMed's TSLP Antibody HBM9378 Delivers 24-Week Asthma Control After Single Dose, Supporting Twice-Yearly Regimen
核心洞察
Harbour BioMed (搜索) partner Windward Bio (搜索) reported positive interim Phase 2 results for HBM9378/WIN378, an ultra-long-acting anti-TSLP monoclonal antibody, in uncontrolled moderate-to-severe asthma (搜索).
A single dose produced dose-dependent FEV1 increases up to 174 mL (placebo-adjusted up to 256 mL, p=0.033) sustained through Week 24, with a half-life of up to 75 days.
The drug was well tolerated with no treatment-related serious adverse events, withdrawals or discontinuations, and less than 1% injection site reactions and 2% anti-drug antibodies.
Harbour BioMed (搜索) (HKEX: 02142) announced that its partner Windward Bio (搜索) has reported positive interim results from the Phase 2 portion of the POLARIS-1 clinical trial of HBM9378/WIN378, an ultra-long-acting anti-thymic stromal lymphopoietin (搜索) (TSLP) monoclonal antibody, in patients with uncontrolled moderate-to-severe asthma (搜索). The interim analysis, conducted on the first 98 of 147 enrolled patients, showed rapid and sustained improvements in lung function and airway inflammation after a single dose, with pharmacokinetic data supporting a potential twice-yearly dosing schedule.
Single Dose Produces Durable Lung Function and Biomarker Gains
At Week 24 after a single dose, HBM9378/WIN378 produced dose-dependent mean increases in forced expiratory volume in one second (FEV1) of up to 174 mL, with placebo-adjusted mean increases of up to 256 mL (p=0.033). The drug also drove dose-dependent mean reductions in fractional exhaled nitric oxide (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).
According to the company, near maximal effects were observed as early as Week 2 and were sustained through Week 24. FeNO and blood eosinophils are key markers of airway inflammation that correlate with asthma (搜索) exacerbations, while FEV1 is a standard measure of lung function. The interim analysis also demonstrated a half-life of up to 75 days, and population pharmacokinetic modeling supported the feasibility of twice-yearly administration.
Favorable Safety and Immunogenicity Profile
HBM9378/WIN378 was well tolerated, with no treatment-related serious adverse events, withdrawals, or discontinuations observed as of the data cut-off date. Adverse events were balanced between the active arms and placebo. Less than 1% of participants experienced injection site reactions, and 2% developed anti-drug antibodies (ADAs), a measure of immunogenicity; the company reported that ADAs had no impact on the pharmacology of HBM9378/WIN378.
A Distinct Binding Mode Against TSLP
HBM9378/WIN378 is a fully human, ultra-long-acting monoclonal antibody engineered for improved potency, extended half-life, and silenced effector function. It is described as 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. The antibody was generated from Harbour BioMed (搜索)'s H2L2 Harbour Mice® platform.
"We are very encouraged by the positive Phase 2 results of HBM9378/WIN378 and its continued progression into Phase 3 development," said Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed (搜索). "The significant and sustained improvements in lung function and airway inflammation observed with a single dose, together with its potential for twice-yearly dosing, further reinforce the therapeutic potential of this molecule. We are fully confident in the clinical potential of this novel biotherapeutic."
Trial Design and Phase 3 Progression
POLARIS-1 is an operationally seamless, global Phase 2/3 study. The Phase 2 portion is a 48-week, randomized, double-blind study evaluating three dose levels of HBM9378/WIN378 against placebo in patients with uncontrolled moderate-to-severe asthma (搜索). It was designed to assess pharmacokinetics, safety, immunogenicity, and pharmacodynamic activity, as well as effects on lung function and biomarkers of airway inflammation, and to inform dose selection for Phase 3 development. Enrollment reached 147 patients, exceeding the initial target of 120.
Two twice-yearly doses have been selected for the Phase 3 portion of POLARIS-1, which is designed to evaluate the effect of HBM9378/WIN378 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.