Verekitug Cuts Polyp Size in Severe CRSwNP, With Joseph Han, MD

At the 2026 annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI), Joseph Han, MD, from Old Dominion University, presented new data from the phase 2 VIBRANT trial evaluating verekitug (UPB-101), a fully human monoclonal antibody targeting the thymic stromal lymphopoietin (TSLP) receptor, in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP).

“What's nice about targeting TSLP receptor is that you're still targeting the same epithelial alarm in TSLP, but specifically you're targeting the receptor,” Han told HCPLive during the meeting. “The benefit of targeting the receptor is that the monoclonal antibody binds to the receptor longer, so the half-life ends up being longer. In this study, what we were able to do is show that by blocking the TSLP receptor and giving a sub-Q injection every 3 months, instead of every month or 2 months.”

The double-blind, placebo-controlled VIBRANT trialrandomized 81 patients with severe CRSwNP (endoscopic nasal polyp score [NPS] ≥5) who had previously undergone endoscopic sinus surgery or required or were intolerant to systemic corticosteroids. Participants received standard of care plus either 100 mg subcutaneous verekitug (n = 41) or placebo (n = 40) every 12 weeks for 24 weeks.

The primary endpoint, change from baseline in total NPS at week 24, was met. Verekitug demonstrated a least squares mean difference vs placebo of −1.77 (95% CI, −2.51 to −1.03; P <.0001). Han noted that the magnitude of polyp reduction, approaching a 2-point difference from baseline, is clinically meaningful in a population with high baseline disease burden.

Key secondary endpoints also showed statistically significant and clinically relevant improvements at week 24. Compared with placebo, verekitug reduced the nasal congestion score by −0.77 (P =.0003), the total symptom score by −4.29 (P =.0018), and the difficulty with sense of smell scoreby −0.85 (P =.0002). Imaging outcomes also improved, with a −8.1 change in the Lund-Mackay score (P <.0001).

Treatment reduced the odds of requiring rescue endoscopic sinus surgery or systemic corticosteroids by 76% compared with placebo (P =.03). According to Han, improvements in polyp size and congestion are directly linked to reductions in acute exacerbations and downstream interventions, reinforcing the potential disease-modifying impact of targeting TSLP signaling upstream in the inflammatory cascade.

Safety findings were favorable. Treatment-related adverse events occurred more frequently in the placebo arm (7.5%) than in the verekitug arm (2.5%), supporting the tolerability of the 12-week dosing strategy.

With these positive phase 2 results, the program is advancing to phase 3 evaluation. Han cautioned that definitive positioning relative to approved biologics will require head-to-head data or cross-trial comparisons following completion of phase 3 studies. However, he noted that the magnitude and consistency of effect across symptom, endoscopic, and imaging endpoints are encouraging.

“The results are in line with targeting TSLP, and the results seem to be very similar to what we saw with Waypoint,” Han said.

Relevant disclosures include GlaxoSmithKline, LLC., Medtronic, Inc., Regeneron Healthcare Solutions, Inc., GENZYME CORPORATION, Optinose US, Inc., Medtronic, Inc., AstraZeneca Pharmaceuticals LP, and AERIN MEDICAL INC.

References

Han J, Skarzynski P, Talreja N, et al. Efficacy and Safety of Verekitug (UPB-101) in Chronic Rhinosinusitis With Nasal Polyps: Results of the Phase 2 VIBRANT Trial. Journal of Allergy and Clinical Immunology. 2026;157(2):AB432. doi:https://doi.org/10.1016/j.jaci.2025.12.966