32-week data from a multiple ascending-dose study with verekitug, a novel antibody to the human TSLP receptor (TSLPR), in adults with asthma

<bold>Background:</bold> Verekitug, a novel, highly potent, recombinant, fully human monoclonal antibody targeting TSLPR, is in development as a potential therapy for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Interim data analysis has been presented previously; here we present the full 32-wk data. <bold>Methods:</bold> A randomized, double-blind, placebo-controlled, multiple ascending-dose study was conducted in adults with mild to moderate asthma and ≥200 eosinophils (EOS) cells/µL or ≥150 EOS cells/µL with FeNO >25. Four dosing cohorts, each with 6 active and 2 placebo participants (pts), were enrolled: 100mg SC Q4Wx3; 200mg SC Q4Wx3; 300mg SC Q12Wx2; 25mg SC Q12Wx1. Pts were observed for 32 wks after randomization. <bold>Results:</bold> 32 pts (16F, 16M) were randomized (24 active, 8 placebo). There was no dose-related increase in AE incidence. All doses produced 100% TSLPR occupancy and substantial reductions from baseline in indices of airway inflammation within 2 wks of treatment. The 100mg dose resulted in a 54% and 54% mean percent change from baseline at 12 wks in FeNO and EOS, respectively; both of which were sustained at 24 wks after last dose. PK/PD modeling shows that verekitug is highly potent with an FeNO EC90 of ≈0.07 µg/mL. Median trough serum concentration >FeNO EC90 is predicted to be maintained with 100mg SC Q12W and 400mg SC Q24W. <bold>Conclusions:</bold> Verekitug was well tolerated and safe at all dose levels tested. Reductions in FeNO and EOS were rapid, substantial, and sustained. These data inform the phase 2 development of verekitug as a potential therapy for severe asthma and CRSwNP at dose intervals of up to 24 wks.