B32-49 Early and Sustained Suppression of FeNo With a Single Dose of Zumilokibart (APG777), a Novel Half-Life-Extended Anti-Il-13 Antibody, in Patients With Mild-to-Moderate Asthma

Introduction

IL-13 is a key cytokine driving type 2 airway inflammation and increased expression of fractional exhaled nitric oxide (FeNO), which are strongly associated with exacerbations and impaired lung function in patients with asthma. Zumilokibart (APG777) is a novel, half-life-extended anti-IL-13 monoclonal antibody designed to achieve early peak drug exposures that are sustained over an extended dosing interval. The ∼77-day half-life of zumilokibart is conferred through a YTE amino acid modification in the Fc region that increases FcRn-mediated antibody recycling. Here we present interim results from an ongoing phase 1 study evaluating the safety, pharmacokinetics (PK), and magnitude and durability of FeNO suppression following a single dose of zumilokibart in adults with mild-to-moderate asthma (NCT06920901).

Methods

Participants with mild-to-moderate asthma and baseline FeNO ≥25 ppb were randomized 3:1 to receive a single subcutaneous dose of 720 mg zumilokibart or placebo. Evaluation of safety and tolerability was the primary objective; PK and FeNO were also assessed at multiple timepoints.

Results

This analysis included 19 adults (mean age 44.5 years; 42.1% female). Through Week 16, adverse events (AEs) were generally mild, and no grade 3 or serious AEs were observed. Zumilokibart demonstrated a PK profile consistent with previous studies, achieving a maximum serum concentration (Cmax) 15 days after dosing. Zumilokibart led to rapid suppression of FeNO, with maximal mean absolute reduction (±SE) of 45.1±15.7 ppb (vs. 10.6±7.5 ppb with placebo) and -60.2% (±4.3) change from baseline (vs. -10.2% (±8.7) with placebo) at Week 2 after dosing. Mean FeNO reduction from baseline >40 ppb was maintained at all timepoints from Week 2 through Week 16 following a single dose of zumilokibart. For zumilokibart-treated participants with follow-up data available from weeks 20 to 32 (N = 2-11), durable FeNO suppression was observed through Week 32.

Conclusions

Zumilokibart was well tolerated, with an optimized PK profile that supports evaluation of every 3- or 6-month dosing in patients with moderate-to-severe asthma. These results, together with the durable suppression of FeNO observed after a single dose, reinforce the conviction for IL-13 inhibition in asthma and support further clinical investigation with zumilokibart, as monotherapy as well as in combination with other half-life-extended monoclonal antibodies, for the treatment of obstructive airway diseases.

This abstract is funded by: Apogee Therapeutics