A phase 1 study of SHR-1905, a long-acting anti-TSLP monoclonal antibody, in healthy subjects and patients with asthma

<bold>Introductions:</bold> SHR-1905 is a humanized monoclonal antibody against thymic stromal lymphopoietin (TSLP). We aimed to investigate the safety, tolerability, PK, and PD of SHR-1905 in healthy subjects (HSs) and patients (pts) with asthma. <bold>Methods:</bold> In this double-blind, single-ascending-dose, phase 1 study in China (<ext-link>NCT04905602</ext-link>), HSs were randomized 4:1 to receive SHR-1905 or placebo (50, 100, 200, 400, and 600 mg; n=10 per dose cohort), and asthma pts were randomized 2:1 to receive SHR-1905 or placebo (mild asthma, 200 mg; moderate-severe asthma, 100 and 600 mg; n=12 per dose cohort). <bold>Results:</bold> SHR-1905 was safe and well-tolerated, with all treatment-related adverse events being mild to moderate. Peak concentrations were observed 8.5-15.0 days after dosing of 50-600 mg SHR-1905 in HSs, and mean t1/2 was 82.9-106 days. SHR-1905 exposure increased dose-proportionally. PK profiles in asthma pts were similar to those in HSs. Compared to placebo, SHR-1905 significantly reduced the levels of eosinophils, fractional exhaled nitric oxide, thymus and activation-regulated chemokine, and eotaxin-3, while significantly improving level of forced expiratory volume in one second in asthma pts (Fig). <bold>Conclusion:</bold> SHR-1905 showed favorable safety, tolerability, PK and PD profiles. Its long half-life supported extended dosing intervals (every 24 or 12 weeks) compared with clinically available anti-TSLP antibodies. <bold>Supporting information:</bold> Figure Mean (SD) change of biomarkers (EOS, FeNO, FEV1) from baseline following a single subcutaneous dose in patients with moderate-to-severe asthma