Sichuan Kelun-Biotech Biopharmaceutical 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 SKB378/WIN378 in asthma.

SKB378/WIN378 is a novel fully 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 signaling by binding to two different sites on TSLP, interfering with 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, randomized, double-blind study evaluating three dose levels of SKB378/WIN378 against placebo. It is designed to evaluate the pharmacokinetics, safety, immunogenicity, and pharmacodynamic activity of SKB378/WIN378 in patients with uncontrolled moderate-to-severe asthma. The study also evaluates the effects of SKB378/WIN378 on lung function and biomarkers of airway inflammation and informs dose selection for Phase 3 development. The Phase 2 portion of the study enrolled a total of 147 patients, exceeding the initial enrollment target of 120 patients, with the interim analysis conducted on the first 98 patients.

The interim analysis demonstrated the following at Week 24 after a single dose of SKB378/WIN378:

Dose-dependent mean increases in FEV1 of up to 174 mL (placebo-adjusted mean increase up to 256 mL, p=0.033).

Dose-dependent mean reductions in FeNO of up to 24 ppb (or -43 per cent change, p=0.006).

Reductions in mean blood eosinophil count (EOS) of up to 200 cells/µL (or -51 per cent change, p<0.0001).

Near maximal effects seen as early as Week 2 and sustained through Week 24.

SKB378/WIN378 was well tolerated with favorable 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 per cent of participants experienced injection site reactions, and 2 per cent 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 of SKB378/WIN378.

Dr. Michael Ge, Chief Executive Officer of Kelun-Biotech, stated: "We are delighted to see that the Phase 2 portion of POLARIS‑1 for SKB378/WIN378 has achieved positive results, driven by the active efforts of our partner. As a differentiated, ultra-long-acting anti-TSLP antibody, SKB378/WIN378 balances efficacy, safety, and patient compliance, and holds the potential to address the unmet clinical needs in moderate-to-severe asthma."