Late Breaking Abstract - GB-0895, a high-affinity anti-TSLP mAb, demonstrates prolonged half-life and sustained pharmacological activity supporting every 6-month dosing in asthma

<bold>Background:</bold> Thymic stromal lymphopoietin (TSLP) is a validated therapeutic target in asthma. GB-0895 is a next-generation, subcutaneously administered anti-TSLP monoclonal antibody with ~20-fold higher affinity for TSLP compared to tezepelumab and YTE Fc modifications for extended half-life. <bold>Aims:</bold> To assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of GB-0895 in patients with mild to moderate asthma with blood eosinophils (EOS) ≥150 cells/µL. <bold>Methods and Results</bold> 96 patients received single or multiple subcutaneous doses of GB-0895 (10–1200 mg) or placebo, with 69 patients randomized to GB-0895. The trial remains blinded but group level PK/PD data are available. GB-0895 was well tolerated with no apparent trend in the incidence or severity of adverse events in relationship to dose. GB-0895 demonstrated dose proportional PK and sustained concentrations with a half-life of ~89 days. EOS reductions were observed as early as week 4 at all doses. These reductions were observed through at least 6 months at doses ≥30 mg. A dose-response relationship was evident, with deeper reductions from baseline observed at higher doses, exceeding 50%. Durable decreases were also observed in FeNO, IL-5, and IL-13 for at least 6 months. These biomarker effects are similar to monthly tezepelumab. <bold>Conclusions:</bold> GB-0895 was well tolerated with an extended half-life of ~89 days. A single dose of GB-0895 drives PD biomarker suppression for at least 6 months, reflecting the broad anti-inflammatory effects of the anti-TSLP mechanism seen with tezepelumab. These results support dosing GB-0895 every 6-months for the treatment of severe asthma.