Announcement • Jun 15
Upstream Bio Presents New Responder Analyses Demonstrating Clinically Meaningful Improvements in CRSwNP in Significant Majority of Participants Treated with VIBRANT in the Phase 2 Vibrant Trial At EAACI 2026
Upstream Bio, Inc. presented new responder analyses from the Phase 2 VIBRANT trial of verekitug in participants with chronic rhinosinusitis with nasal polyps (CRSwNP). Verekitug, administered once every three months, led to clinically meaningful improvements in nasal polyp score (NPS) in approximately 80% of participants. Majority of verekitug-treated participants experienced clinically meaningful improvements across key secondary endpoints, including 72% in nasal congestion and 83% in CRSwNP total symptom score. Verekitug administered every three months achieved a placebo-adjusted reduction in NPS of -1.95. 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 severe, inadequately controlled CRSwNP, despite treatment with standard-of-care intranasal steroids. The VIBRANT trial demonstrated the efficacy of verekitug administered every 12 weeks in participants with uncontrolled, severe CRSwNP, in improving NPS, sinonasal symptoms, and sinus disease. The new responder analyses evaluated the proportion of participants who achieved predefined thresholds for clinically meaningful improvements across efficacy endpoints at Week 24. Key findings included: Nasal Polyp Score (Primary endpoint): 79% of verekitug-treated participants, or approximately four in five treated, achieved clinically meaningful improvements in NPS at week 24, compared to 24% in the placebo group (odds ratio [95% CI], 12.06 [4.09–35.53]). Nasal Congestion Score: 72% of verekitug-treated participants demonstrated at least one point of improvement in nasal congestion, a key secondary endpoint, compared to 39% in the placebo group (odds ratio [95% CI]: 3.99 [1.50–10.59]; p=0.0046). Total Symptom Score: 83% of verekitug-treated participants demonstrated at least four points of improvement in total symptom score, a key secondary endpoint, compared to 37% in the placebo group (odds ratio [95% CI]: 8.57 [2.86–25.67]). Difficulty with sense of smell (Loss of smell): 69% of verekitug-treated participants demonstrated at least one point of improvement in sense of smell, a key secondary endpoint, compared to 21% in the placebo group (odds ratio [95% CI]: 8.52 [2.97–24.45]). Lund-Mackay score: 78% of verekitug-treated participants demonstrated at least five points of improvement in the Lund-Mackay score, a key secondary endpoint measuring extent of sinus disease by CT scan, compared to 12% in the placebo group (odds ratio [95% CI]: 25.38 [6.86–93.83]). Verekitug demonstrated significant and clinically meaningful improvements in key secondary endpoints, including 76% (p=0.03) reduction in the need for surgery or systemic corticosteroids compared with placebo. Verekitug was generally well tolerated, demonstrating a favorable safety profile consistent with previous studies, with no serious adverse events observed during the trial. Upstream Bio designed the VIBRANT trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. 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.
