touchRESPIRATORY coverage of AAAAI 2026:

Q. What is the clinical burden of CRSwNP for patients?

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disorder characterized by sinonasal inflammation, loss of smell, and polyp formation, and is associated with a reduced quality of life. In clinical practice, patients often experience persistent nasal obstruction, impaired sense of smell, facial pressure, and sleep disruption, all of which can significantly affect daily functioning.

Many patients cycle through intranasal corticosteroids, systemic corticosteroids, and surgery, yet continue to have inadequately controlled disease. Recurrence is common, and a substantial proportion of patients have comorbid conditions, such as asthma, which further increases disease burden and complexity of management.

Q. What is the mechanism of action of verekitug, and what was the rationale for investigating it in this indication?

Verekitug is a novel, high-affinity, fully human monoclonal antibody targeting the thymic stromal lymphopoietin receptor (TSLPR). The TSLP signaling pathway functions to initiate a type 2 inflammatory response and has emerged as a key driver of immune activation underlying CRSwNP morbidity. By targeting TSLPR, verekitug is designed to inhibit this upstream pathway and suppress downstream inflammatory activity.

Verekitug’s potent pharmacodynamic activity through its unique approach of targeting the thymic stromal lymphopoietin (TSLP) receptor enables extended interval dosing with administration every 12-week and provides potential for enhanced efficacy relative to TSLP ligand-targeting approaches.  In this regard, verekitug is differentiated from other molecules in development which are modified to extend half-life, but have similar potency to currently-available agents.

Preclinically, verekitug demonstrated superior potency at suppressing TSLP-driven responses, and early clinical data showed sustained reductions in type 2 inflammatory biomarkers, supporting its investigation in CRSwNP.

Q. Could you describe the aims, design, and enrollment criteria of the Phase 2 VIBRANT trial?

VIBRANT (NCT06164704) is a double-blind, randomized phase 2 trial assessing the efficacy and safety of standard of care with either 100mg subcutaneous verekitug or matching placebo every 12 weeks for 24 weeks.

A total of 81 participants were randomized, and baseline characteristics were generally balanced between treatment groups. Key inclusion criteria included adults aged 18–85 years with inadequately controlled CRSwNP, endoscopic nasal polyp score (NPS) ≥5, nasal congestion score (NCS) ≥2, symptoms for at least 8 weeks, and stable standard-of-care therapy. Patients were also required to have a history of nasal polyp surgery or exacerbation requiring systemic corticosteroids in the past 24 months.

The top-line results were originally reported by the sponsor, Upstream Bio, in September of 2025.

Q. What were the primary and secondary endpoints of the study, and how well were they met?

The primary endpoint in VIBRANT was change from baseline in endoscopic nasal polyp score (NPS) at Week 24, and verekitug met this endpoint with a statistically significant and clinically meaningful reduction versus placebo.

The original top-line analysis, reported by Upstream Bio in September 2025, used a conservative “treatment policy” approach, with which the placebo-adjusted reduction in NPS was −1.77 (p<0.0001). In the additional analyses presented at AAAAI using a worst-observation carried-forward (WOCF) approach—which is a commonly used method that adjusts for the use of rescue interventions, such as systemic corticosteroids, surgery, or escalation of background therapy—the treatment effect was −1.95 (p<0.0001).

A similar pattern was observed for key secondary endpoints. For example, nasal congestion score improved by −0.77 (p=0.0003) in the primary analysis and −0.96 (p<0.0001) in the WOCF analysis, as well as difficulty with sense of smell (DSS), which improved by −0.85 (p=0.0002) in the primary analysis and −1.08 (p<0.0001) in the WOCF analysis.

Importantly, these findings need to be interpreted in the context of the study’s previously reported 76% reduction in the need for systemic corticosteroids or nasal polyp surgery with verekitug. The WOCF approach more directly incorporates the clinical impact of those rescue interventions, and in that sense, may better reflect how we think about disease control in practice.

From a clinical perspective, what is reassuring is the consistency across analyses. We see robust improvements in objective measures like polyp size, patient-reported symptoms such as congestion and sense of smell, and a meaningful reduction in rescue interventions—all achieved with dosing every 12 weeks. Taken together, that provides a coherent picture of treatment effect that is highly relevant to how we manage patients with CRSwNP.

Q. What was the safety profile of verekitug at Week 24?

Verekitug was generally well tolerated, with no serious treatment-emergent adverse events observed. Treatment-emergent and treatment-related adverse events occurred more frequently with placebo than with verekitug, and were consistent with disease symptoms, supporting a favourable safety profile through 24 weeks.