Harbour BioMed has announced that its partner, Windward Bio, has reported positive interim results from the phase 2 portion of the POLARIS-1 clinical trial, which evaluates twice-yearly dosing of HBM9378/WIN378 in asthma.
HBM9378/WIN378 is a novel human, ultra-long-acting monoclonal antibody with a unique binding mode to inhibit thymic stromal lymphopoietin (TSLP). It was engineered for improved potency, extended half-life and silenced effector function. It is the only known investigational drug that blocks TSLP signalling 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.
POLARIS-1 is an operationally seamless, global phase 2/3 study. The phase 2 portion of the study is a 48-week, randomised, double-blind study evaluating three dose levels of HBM9378/WIN378 against placebo. It is designed to evaluate the pharmacokinetics, safety, immunogenicity, and pharmacodynamic activity of HBM9378/WIN378 in patients with uncontrolled moderate-to-severe asthma. The study also evaluates the effects of HBM9378/WIN378 on lung function and biomarkers of airway inflammation and informed dose selection for phase 3 development. The phase 2 portion of the study enrolled 147 patients, with the interim analysis conducted on the first 98 patients.
The interim analysis demonstrated at Week 24 after a single dose of HBM9378/WIN378, a dose-dependent mean increases in FEV1 of up to 174 mL, as well as dose-dependent mean reductions in FeNO of up to 24 ppb.
Reductions in mean blood eosinophil count (EOS) of up to 200 cells/µL were noted, with near maximal effects seen as early as Week 2 and sustained through Week 24.
HBM9378/WIN378 was well tolerated with favourable safety results, and there were 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 HBM9378/WIN378. The results of the interim analysis and population pharmacokinetic modelling support the potential of twice-yearly dosing of HBM9378/WIN378.
“We are very encouraged by the positive phase 2 results of HBM9378/WIN378 and its continued progression into phase 3 development,” said Jingsong Wang, founder, chairman and CEO of Harbour BioMed.
“HBM9378/WIN378 is an ultra-long-acting fully human monoclonal antibody against TSLP generated from our H2L2 Harbour Mice platform. 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.”
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 annualised asthma exacerbation rate and other key efficacy measures in patients with severe asthma. The phase 3 portion of the study has been initiated by Windward Bio who 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.