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Upstream Bio, Inc. Presents New Data from Phase 2 Vibrant Trial of Verekitug Demonstrating Improvement in Asthma Symptom Control in Participants with CRSwNP and Comorbid Asthma
Upstream Bio, Inc. presented new data from the Phase 2 VIBRANT trial evaluating verekitug in participants with chronic rhinosinusitis with nasal polyps (CRSwNP). The data, presented in two posters at the American Thoracic Society 2026 International Conference in Orlando, FL, demonstrated the positive effect of verekitug in participants with CRSwNP and comorbid asthma, as well as its impact on type 2 inflammatory biomarkers in blood and nasal secretions. Approximately 60% of the 81 participants in the VIBRANT trial had comorbid asthma. Among participants with comorbid asthma, verekitug 100 mg administered every 12 weeks led to improvement in asthma symptom control at Week 24, with a placebo-adjusted least squares mean reduction in ACQ-6 of -0.9 (95% CI: -1.6 to -0.2; nominal p=0.014) compared with placebo—well above the minimal clinically important change in ACQ-6 of -0.5. Verekitug also led to improvements in NPS at Week 24 in participants with and without comorbid asthma, consistent with the previously reported VIBRANT top-line results. In participants with comorbid asthma, generally greater improvements were observed across sinonasal symptom measures, including nasal congestion score (NCS), total symptom score (TSS), difficulty with sense of smell (DSS), and Lund-Mackay score, compared with participants without comorbid asthma. Among participants with comorbid asthma, verekitug reduced the need for rescue systemic corticosteroids or CRSwNP surgery by 83% (nominal p=0.027) compared with placebo. In a separate post hoc analysis, verekitug 100 mg administered every 12 weeks led to rapid and sustained reductions in key type 2 inflammatory cytokines, including IL-4, IL-5, and IL-13, in both blood and nasal secretions over 24 weeks of treatment with generally greater reductions observed in nasal secretions. Verekitug also reduced additional mediators of local inflammation and fibrotic activity, including periostin, thymus and activation-regulated cytokine (TARC), macrophage-derived chemokine (MDC), and eotaxin-3, shedding light on the mechanisms by which a thymic stromal lymphopoietin (TSLP) receptor blockade may benefit patients with inflammatory airway disease. Verekitug reduced blood eosinophils by 50% as early as Week 2, with reductions sustained through Week 24. Reductions in IgE were observed beginning at Week 4 and continued to decline through Week 24. The magnitude of IL-5 reduction in blood correlated with the magnitude of reduction in blood eosinophils following verekitug treatment (Pearson r=0.68). VIBRANT (NCT06164704) was a Phase 2 global, randomized, double-blind, placebo-controlled, parallel group clinical trial that evaluated the efficacy and safety of verekitug over 24 weeks in 81 adults with CRSwNP. Upstream Bio designed the VIBRANT trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. The Company plans to initiate dosing in Phase 3 registrational trials in both CRSwNP and severe asthma in the first quarter of 2027. The Phase 2 VIBRANT trial (NCT06164704) was a global, randomized, placebo-controlled, parallel group clinical trial, which was designed to assess the efficacy and safety of verekitug in adults with CRSwNP who were receiving concurrent intranasal corticosteroid therapy. Participants received either 100 mg of verekitug or placebo subcutaneously every 12 weeks for 24 weeks. The primary endpoint was change in endoscopic nasal polyp score at Week 24, a primary endpoint that has been used in several registrational trials for other biologic treatments for CRSwNP. Secondary endpoints included: nasal congestion score, sinus opacification, difficulty with sense of smell, total symptom score, percentage of participants requiring systemic corticosteroids or nasal polyp surgery, and time to first such interventions up to Week 24. Verekitug is a novel recombinant fully human immunoglobulin G1 (IgG1) monoclonal antibody that binds to the thymic stromal lymphopoietin (TSLP) receptor and inhibits proinflammatory signaling initiated by TSLP. It is the only known antagonist currently in clinical development that targets and inhibits the TSLP receptor. TSLP is a cytokine that is a key driver of the inflammatory response in major allergic and inflammatory diseases, such as asthma, where disruption of TSLP signaling has been clinically validated as an effective therapeutic strategy. TSLP activation is one of the first events in the inflammatory cascade stimulated by allergens, viruses and other triggers, initiating the activation of downstream targets such as IL-4, IL-5, IL-13, IL-17 and IgE. Because TSLP is a target upstream in the inflammatory cascade, blocking the TSLP receptor presents an opportunity for a single treatment to impact the drivers of multiple pathological inflammatory processes across a broad set of diseases. Verekitug has advanced into three separate global, placebo-controlled, randomized Phase 2 clinical trials, including the positive VIBRANT trial (NCT06164704) in patients with CRSwNP and the positive VALIANT trial (NCT06196879) in patients with severe asthma. The VENTURE trial (NCT06981078) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) is ongoing. Additionally, in May 2025, Upstream Bio initiated the VALOUR trial (NCT06966479), a long-term extension study in eligible participants with severe asthma who completed the VALIANT Phase 2 clinical trial.