Upstream Bio Reports Positive Phase 2 Data for Verekitug in Nasal Polyps and Severe Asthma

Upstream Bio Inc. (Nasdaq:UPB) presented additional data from its Phase 2 VIBRANT clinical trial evaluating verekitug in patients with chronic rhinosinusitis with nasal polyps at the American Academy of Allergy Asthma & Immunology 2026 Annual Meeting in Philadelphia on Sunday. The company also reported top-line results from its Phase 2 VALIANT trial evaluating verekitug in adults with severe asthma.

The new VIBRANT analysis incorporated a worst-observation carried-forward statistical approach to adjust for concomitant rescue therapy use, including nasal polyp surgery, systemic corticosteroids, or escalation of background treatments. Verekitug, dosed at 100 mg every 12 weeks, met the study's primary endpoint in both the WOCF and primary analyses. The drug demonstrated a placebo-adjusted reduction in endoscopic nasal polyp score of -1.95 (p < 0.0001) in the WOCF analysis as compared to a reduction of -1.77 (p < 0.0001) in the primary analysis at week 24.

The trial showed a placebo-adjusted reduction in the patient-reported nasal congestion score of -0.96 (p < 0.0001) in the WOCF analysis as compared to -0.77 (p = 0.0003) in the primary analysis. Verekitug reduced the need for surgery or systemic corticosteroids by 76% (p = 0.03) compared with placebo. No serious adverse events were observed during the trial.

The VIBRANT trial enrolled 81 adults with chronic rhinosinusitis with nasal polyps. Participants received either 100 mg of verekitug or placebo subcutaneously every 12 weeks for 24 weeks.

In the VALIANT trial for severe asthma, the placebo-controlled, randomized study followed patients for up to 60 weeks and met its primary endpoint, demonstrating statistically significant reductions in annualized asthma exacerbation rate with multiple dosing regimens. The trial reported a 56% reduction in AAER with 100 mg every 12 weeks, a 39% reduction with 400 mg every 24 weeks, and a 49% reduction with 100 mg every 24 weeks.

The 100 mg every-12-weeks regimen was associated with a 122 mL improvement in FEV1 and a 20.4 parts-per-billion reduction in FeNO, described as a 43.5% mean reduction from baseline. The 400 mg every-24-weeks regimen was associated with a 139 mL FEV1 improvement and a 26.3 ppb FeNO reduction, described as a 44.9% reduction from baseline. Treatment effects on biomarkers and lung function appeared early—FeNO reductions were described as evident by week 2—and were maintained through 60 weeks.

VALIANT was a Phase 2 randomized, double-blind, placebo-controlled, parallel-group trial enrolling adults with severe asthma across the U.S. and 14 other countries. A total of 478 participants were randomized across four arms: verekitug 100 mg every 12 weeks (121 patients), verekitug 400 mg every 24 weeks (118 patients), verekitug 100 mg every 24 weeks (120 patients), and placebo (119 patients).

Verekitug was described as generally well-tolerated across dosing regimens, with treatment-emergent adverse events and serious TEAEs reported as similar across groups. Anti-drug antibodies were observed in 50–60% of subjects without clear safety or efficacy impact.

Upstream Bio stated it plans to initiate Phase 3 registrational trials in chronic rhinosinusitis with nasal polyps and severe asthma following planned regulatory interactions. The company is also conducting a Phase 2 trial in chronic obstructive pulmonary disease. Verekitug is a monoclonal antibody that binds to the thymic stromal lymphopoietin receptor and inhibits proinflammatory signaling.