Zumilokibart Rapidly Suppresses FeNO in Phase 1b Asthma Data: Mario Castro, MD

In topline interim phase 1b findings, a single 720-mg subcutaneous dose of zumilokibart (APG777), Apogee Therapeutics' long-acting anti-interleukin-13 (IL-13) monoclonal antibody, produced rapid and sustained suppression of fractional exhaled nitric oxide (FeNO) in patients with mild to moderate asthma, according to Mario Castro, MD, MPH, professor of medicine and chief of the Division of Pulmonary, Critical Care and Sleep Medicine at the University of Kansas School of Medicine. Castro discussed the data, presented at the European Respiratory Society (ERS) International Congress, held in Barcelona from September 5-9, in an interview with HCPLive.

The trial (NCT06920901) randomized 19 patients with baseline FeNO of at least 25 ppb 3:1 to zumilokibart or placebo (14 and 5 patients, respectively).¹ By week 2, patients receiving zumilokibart had a mean FeNO reduction of 45.1 ± 15.7 ppb, a 60.2% ± 4.3% decrease from baseline, compared with 10.6 ± 7.5 ppb (10.2% ± 8.7%) with placebo.¹ Castro said the effect was durable, with mean reductions holding above 40 ppb and 50% through week 32; among the smaller subset of patients with extended follow-up, suppression persisted through week 48, though the evaluable sample had narrowed to 2 patients by that point.

"I consider it a direct measure of airway inflammation," Castro said of FeNO, explaining that the biomarker is believed to reflect IL-13 activity in the airway epithelium and complements lung function testing and phenotyping in guiding treatment.

Zumilokibart was well tolerated: 11 of 14 patients (78.6%) had at least 1 treatment-emergent adverse event, compared with all 5 placebo patients, and neither group had a serious or grade 3/4 event or a discontinuation due to an adverse event.¹ Castro attributed much of the drug's profile to its extended half-life, measured at 75.3 to 77.5 days across doses tested and conferred by a YTE Fc modification that enhances antibody recycling. He said that duration could support dosing as infrequent as every 3 to 6 months, reducing burden on patients and clinicians and potentially helping close the post-exacerbation coverage gap that contributes to hospital readmissions. Apogee is also developing a bispecific candidate combining zumilokibart with an anti-thymic stromal lymphopoietin (TSLP) antibody, aimed at asthma and chronic obstructive pulmonary disease.

Castro noted that elevated FeNO combined with elevated blood eosinophils has separately been shown to predict roughly 2 to 2.5 exacerbations per patient over the following year, reinforcing the biomarkers' combined prognostic value, a relationship also described in a biomarker risk-scale model developed by other investigators.² Looking ahead, Castro said the field is moving toward disease-modifying, and potentially remission-inducing, therapy in severe asthma and COPD, with future interest in earlier use of long-acting biologics, even in childhood, pending additional safety data.

References

1. Castro M, Cole J, DeAngelo J, et al. A single dose of zumilokibart (APG777) durably suppresses FeNO through 32 weeks in patients with mild-to-moderate asthma. Poster presented at: European Respiratory Society (ERS) International Congress; September 5-9, 2026; Barcelona, Spain. Poster PA339.
2. Couillard S, Laugerud A, Jabeen M, et al. Derivation of a prototype asthma attack risk scale centred on blood eosinophils and exhaled nitric oxide. Thorax. 2022;77(2):199-202. doi:10.1136/thoraxjnl-2021-217325