Upstream Bio Reports Positive Top-Line Results from the Phase 2 VIBRANT Trial of Verekitug for the Treatment of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
Upstream Bio (NASDAQ:UPB) announced positive top-line results from its Phase 2 VIBRANT trial evaluating verekitug for treating chronic rhinosinusitis with nasal polyps (CRSwNP). The trial met its primary endpoint with verekitug, dosed every 12 weeks, achieving a significant placebo-adjusted reduction in nasal polyp score of -1.8 (p<0.0001).
The study demonstrated significant improvements in key secondary endpoints, including a -0.8 reduction in nasal congestion score (p=0.0003) and 76% reduction (p=0.03) in need for surgery or systemic corticosteroids. The drug showed a favorable safety profile with no serious adverse events reported. Notably, verekitug's clinical effect appears to meet or exceed that of other biologics in CRSwNP at 24 weeks.
Upstream Bio (NASDAQ:UPB) ha annunciato risultati positivi preliminari dello studio di Fase 2 VIBRANT che ha valutato verekitug nel trattamento della sindrome cronica dei seni paranasali con polipi nasali (CRSwNP). Lo studio ha raggiunto l'endpoint primario: verekitug somministrato ogni 12 settimane ha ottenuto una riduzione del punteggio dei polipi nasali aggiustata per placebo di -1,8 (p<0,0001).
Sono stati rilevati miglioramenti significativi negli endpoint secondari chiave, tra cui una riduzione del punteggio di congestione nasale di -0,8 (p=0,0003) e una riduzione del 76% (p=0,03) della necessit脿 di intervento chirurgico o di corticosteroidi sistemici. Il farmaco ha mostrato un profilo di sicurezza favorevole, senza eventi avversi gravi segnalati. In particolare, l'effetto clinico di verekitug a 24 settimane sembra essere pari o superiore a quello di altri biologici studiati nella CRSwNP.
Upstream Bio (NASDAQ:UPB) anunci贸 resultados positivos preliminares del ensayo de Fase 2 VIBRANT que evalu贸 verekitug para el tratamiento de la rinosinusitis cr贸nica con p贸lipos nasales (CRSwNP). El ensayo cumpli贸 su objetivo primario: verekitug administrado cada 12 semanas logr贸 una reducci贸n del score de p贸lipos nasales ajustada por placebo de -1,8 (p<0,0001).
El estudio mostr贸 mejoras significativas en los principales endpoints secundarios, incluyendo una reducci贸n del score de congesti贸n nasal de -0,8 (p=0,0003) y una reducci贸n del 76% (p=0,03) en la necesidad de cirug铆a o corticosteroides sist茅micos. El f谩rmaco present贸 un perfil de seguridad favorable, sin eventos adversos graves reportados. Cabe destacar que el efecto cl铆nico de verekitug a las 24 semanas parece igualar o superar al de otros biol贸gicos en CRSwNP.
Upstream Bio (NASDAQ:UPB)電� 毵岇劚 牍勲秬牍勲彊鞐�(旖旐彺毽诫彊氚�, CRSwNP) 旃橂鞝滊靹� verekitug鞚� 韽夑皜頃� 2靸� VIBRANT 鞁滍棙鞚� 韱彪澕鞚� 瓴瓣臣臧� 旮嶌爼鞝侅澊霛缄碃 氚滍憸頄堨姷雼堧嫟. 氤� 鞁滍棙鞚� 12欤茧雼� 韴棳頃� verekitug臧� 欤检殧 韽夑皜歆�響滊ゼ 於╈”頄堨溂氅�, 鞙勳暯 氤挫爼 牍勱皶 鞖╈ 鞝愳垬鞐愳劀 -1.8 (p<0.0001)鞚� 鞙犾潣頃� 臧愳唽毳� 氤挫榾鞀惦媹雼�.
欤检殧 2彀� 韽夑皜氤�靾橃棎靹滊弰 鞚橂 鞛堧姅 臧滌劆鞚� 氤挫榾鞙茧┌, 牍勱皶 鞖疙槇 鞝愳垬電� -0.8 (p=0.0003), 靾橃垹 霕愲姅 鞝勳嫚 旖旊ゴ韹办綌鞀ろ厡搿滌澊霌� 頃勳殧靹膘潃 76% 臧愳唽 (p=0.03)毳� 旮半頄堨姷雼堧嫟. 鞚挫儊氚橃潙鞚� 欷戨寑頃� 靾橃鞚� 氤搓碃霅橃 鞎婌晞 鞎堨爠靹� 頂勲韺岇澕霃� 鞏戫樃頄堨姷雼堧嫟. 韸鬼瀳 verekitug鞚� 24欤� 鞁滌爯 鞛勳儊 須臣電� CRSwNP鞐愳劀 雼るジ 靸濍頃� 鞝滌牅霌り臣 霃欕摫頃橁卑雮� 鞖办垬頃� 瓴冹溂搿� 氤挫瀰雼堧嫟.
Upstream Bio (NASDAQ:UPB) a annonc茅 des r茅sultats topline positifs de l'essai de phase 2 VIBRANT 茅valuant verekitug pour le traitement de la rhinosinusite chronique avec polypes nasaux (CRSwNP). L'essai a atteint son crit猫re principal : verekitug, administr茅 toutes les 12 semaines, a obtenu une r茅duction du score des polypes nasaux ajust茅e sur placebo de -1,8 (p<0,0001).
Des am茅liorations significatives ont 茅t茅 observ茅es sur les principaux crit猫res secondaires, notamment une diminution du score de congestion nasale de -0,8 (p=0,0003) et une r茅duction de 76% (p=0,03) du besoin de chirurgie ou de corticost茅ro茂des syst茅miques. Le m茅dicament a pr茅sent茅 un profil d'innocuit茅 favorable, sans 茅v茅nements ind茅sirables graves signal茅s. Il est notable que l'effet clinique de verekitug 脿 24 semaines semble 茅galer ou d茅passer celui d'autres biologiques dans la CRSwNP.
Upstream Bio (NASDAQ:UPB) gab positive Topline-Ergebnisse der Phase-2-Studie VIBRANT bekannt, in der verekitug zur Behandlung der chronischen Rhinosinusitis mit Nasenpolypen (CRSwNP) gepr眉ft wurde. Die Studie erreichte den prim盲ren Endpunkt: verekitug, alle 12 Wochen verabreicht, erzielte eine placebokorrigierte Verringerung des Polypenscores von -1,8 (p<0,0001).
Wesentliche sekund盲re Endpunkte verbesserten sich ebenfalls signifikant, darunter eine Reduktion des Nasenverstopfungs-Scores um -0,8 (p=0,0003) und eine 76%ige Reduktion (p=0,03) des Bedarfs an Operation oder systemischen Kortikosteroiden. Das Medikament zeigte ein g眉nstiges Sicherheitsprofil ohne gemeldete schwerwiegende unerw眉nschte Ereignisse. Auffallend ist, dass die klinische Wirksamkeit von verekitug nach 24 Wochen der anderer Biologika bei CRSwNP zu entsprechen oder diese zu 眉bertreffen scheint.
- None.
- Phase 2 results still require further regulatory discussions and approvals
- Additional clinical trials may be needed before potential commercialization
Insights
Upstream Bio's verekitug shows impressive Phase 2 results for nasal polyps with superior efficacy and convenient 12-week dosing.
The Phase 2 VIBRANT trial results for verekitug represent a potentially significant advancement in chronic rhinosinusitis with nasal polyps (CRSwNP) treatment. The drug demonstrated a placebo-adjusted reduction in nasal polyp score (NPS) of -1.8 (p<0.0001), which appears to meet or exceed efficacy benchmarks set by existing biologics in this space. This is particularly notable given the 12-week dosing interval, which offers a substantial convenience advantage over current therapies typically administered every 2-4 weeks.
The secondary endpoint achievements strengthen the clinical profile: a -0.8 reduction in nasal congestion score (p=0.0003) directly addresses a primary symptom burden for patients, while the 76% reduction in need for surgery or systemic corticosteroids (p=0.03) represents a meaningful clinical outcome with potential healthcare cost implications. The absence of serious adverse events is promising, suggesting a favorable risk-benefit profile.
Mechanistically, verekitug's unique action as the only clinical-stage antibody targeting the TSLP receptor rather than TSLP itself may explain its enhanced potency. This mechanism potentially offers advantages in blocking the inflammatory cascade more effectively at the receptor level.
While these results are promising, it's important to note this remains a Phase 2 trial with 81 participants. The company will need to confirm these findings in larger Phase 3 studies and demonstrate durable efficacy beyond 24 weeks to solidify verekitug's competitive positioning against established biologics like dupilumab and omalizumab in the CRSwNP space.
Upstream Bio's Phase 2 VIBRANT results for verekitug represent a potential differentiated entry into the growing biologics market for CRSwNP. The drug's clinical performance metrics are noteworthy across three dimensions:
First, the -1.8 placebo-adjusted NPS reduction appears competitive with or potentially superior to approved biologics at the same timepoint. For context, dupilumab (Dupixent) showed approximately -1.6 to -1.9 NPS reductions in its pivotal trials, while omalizumab (Xolair) demonstrated -1.0 to -1.1 reductions.
Second, the quarterly dosing schedule offers a significant convenience advantage over existing options that require dosing every 2-4 weeks. This extended interval could substantially improve treatment adherence and patient satisfaction while potentially reducing administration costs.
Third, the 76% reduction in surgical interventions and systemic corticosteroid use has important economic implications beyond symptom improvement, potentially reducing healthcare utilization costs.
From a pipeline perspective, verekitug represents a platform opportunity with the upcoming severe asthma data serving as another significant catalyst. The TSLP pathway's role in multiple inflammatory conditions suggests potential expansion opportunities in other indications.
Key considerations for Upstream Bio include regulatory pathway clarity, manufacturing scale-up capabilities, and commercial positioning strategy against entrenched competitors. The company's interactions with regulatory authorities regarding potential approval pathways will be critical to watch, as will details on durability of effect beyond the 24-week timepoint.
鈥� In this 24-week study, VIBRANT met its primary endpoint, with verekitug dosed every 12 weeks leading to a statistically significant and clinically meaningful reduction from baseline in placebo-adjusted endoscopic nasal polyp score (NPS) of -1.8 (p<0.0001) 鈥�
鈥� Significant and clinically meaningful improvements were observed in key secondary endpoints, including -0.8 (p=0.0003) reduction in nasal congestion score and
鈥� No serious adverse events (SAEs) observed; generally well tolerated safety profile consistent with previous studies 鈥�
鈥� Observed clinical effect on endoscopic NPS in this Phase 2 trial suggests verekitug meets or exceeds that of other biologics in CRSwNP at 24 weeks 鈥�
鈥� Management will host a conference call and webcast today at 8:00 a.m. ET 鈥�
WALTHAM, Mass., Sept. 02, 2025 (GLOBE NEWSWIRE) -- (Nasdaq: UPB), a clinical-stage company developing treatments for inflammatory diseases, with an initial focus on severe respiratory disorders, today announced positive top-line results from the Phase 2 VIBRANT trial evaluating verekitug in participants with chronic rhinosinusitis with nasal polyps (CRSwNP). Verekitug is the only known clinical-stage monoclonal antibody targeting the receptor for thymic stromal lymphopoietin (TSLP).
Over the 24-week treatment period, verekitug, dosed 100mg every 12 weeks, met the primary endpoint and key secondary endpoints, demonstrating statistically significant and clinically meaningful reductions in both endoscopic nasal polyp score (NPS) and nasal congestion score (NCS), with a generally well tolerated safety profile consistent with previous studies. Treatment with verekitug also resulted in a significant reduction in the need for surgery or systemic corticosteroids.
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.
The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful, placebo-adjusted reduction in NPS of -1.8 (p<0.0001) at Week聽24 compared with baseline. The trial also showed a meaningful placebo-adjusted reduction from baseline in the patient-reported NCS, a key secondary endpoint, by -0.8 (p=0.0003).
Significant improvements were also observed in other key secondary endpoints, including sinus opacification as measured by the Lund-Mackay score, reduction in the need for either systemic corticosteroids or nasal polyp surgery, and total symptom score (TSS).
Verekitug was generally well tolerated, demonstrating a favorable safety profile consistent with previous studies, with no SAEs observed.
鈥淭his is an important milestone in the development of verekitug. The VIBRANT trial results demonstrated statistically significant and clinically meaningful benefits with verekitug dosed every 12 weeks, positioning it to potentially advance the standard of care in the treatment of CRSwNP,鈥� said Aaron Deykin, MD, Chief Medical Officer and Head of Research & Development at Upstream Bio. 鈥淭hese results reinforce our earlier observations that verekitug鈥檚 high potency, achieved through targeting the TSLP receptor, has the potential to translate into clinical attributes distinct from those offered by any currently available therapy.鈥澛犅犅�
鈥淭hese results highlight verekitug鈥檚 distinctive profile: significant clinical effect and extended dosing, driven by potency related to the unique mechanism of action. We believe that verekitug has the potential to be an important addition to existing biologic options for the treatment of CRSwNP, a disease where there remains substantial unaddressed clinical need,鈥� stated Rand Sutherland, MD, Chief Executive Officer of Upstream Bio. 鈥淭hese results may also offer insight into verekitug鈥檚 potential clinical utility in other respiratory diseases, including severe asthma. As we prepare to report top-line data in severe asthma in the coming months, we are encouraged by these findings and remain committed to maximizing the opportunity to transform care with verekitug in multiple indications.鈥�
鈥淚n CRSwNP, patients often face persistent nasal obstruction and diminished sense of smell despite repeated courses of systemic corticosteroids or sinus surgery鈥攁ll of which significantly impact quality of life,鈥� said Joseph Han, MD, Professor in the Department of Otolaryngology & Head and Neck Surgery and the Chief for the Division of Allergy at Old Dominion University (Eastern Virginia Medical School), and principal investigator on the VIBRANT trial. 鈥淭he improvements observed with verekitug, including durable nasal polyp reduction and symptom relief with a treatment potentially administered only four times per year, are encouraging. These results suggest verekitug could represent a meaningful advancement in the treatment of this chronically debilitating condition.鈥�
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 further engage with global regulatory authorities on the continued development of verekitug.
Upstream Bio plans to present further details from the VIBRANT trial at an upcoming medical conference.
Conference Call and Webcast Details
Upstream Bio鈥檚 webcast of the Phase 2 VIBRANT top-line results will begin today at 8:00 a.m. ET. The live webcast can be accessed via this or on the Events tab on the Investors section of the Company鈥檚 website at . A replay of the webcast will be available on the website following the call.
About CRSwNP
CRSwNP is a chronic inflammatory disease of the upper airway, marked by inflammation in the nose and sinuses and the presence of nasal polyps. CRSwNP has four main symptoms: runny nose or postnasal drip, nasal congestion, facial pressure and/or pain and loss of smell and/or taste. Despite available treatments such as corticosteroids, surgery and, more recently, biologics, the quality-of-life studies and post-surgical recurrence rates clearly show that many people with CRSwNP have uncontrolled symptoms that are impacting their daily life and current treatments are not meeting their needs. It is estimated that CRSwNP affects up to
Nasal polyps are associated with significant disease burden and debilitating symptoms; it is estimated that over
About the Phase 2 VIBRANT Trial
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聽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.
About Verekitug
Verekitug is a novel recombinant fully human immunoglobulin G1 (IgG1) monoclonal antibody that binds to the TSLP receptor and inhibits proinflammatory signaling initiated by TSLP. It is the only known monoclonal antibody currently in clinical development that targets and inhibits the TSLP receptor. Verekitug is being evaluated in three separate global, placebo-controlled, randomized Phase 2 clinical trials: the VIBRANT trial (NCT06164704) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), the VALIANT trial (NCT06196879) in patients with severe asthma, and the VENTURE trial (NCT06981078) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). 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.
In preclinical studies, verekitug demonstrated high occupancy of the TSLP receptor and potent inhibition of TSLP signaling. Additionally, verekitug inhibited cytokine production from both CD4+ T cells and ILC2 cells and completely suppressed skin allergic reactions in a non-human primate model, suggesting that it may be effective against multiple types of inflammation.
Three Phase 1 clinical trials have been completed for verekitug, including a Phase 1 single-ascending dose (SAD) clinical trial and a Phase 1b multiple-ascending dose (MAD) clinical trial. In these trials, verekitug was well tolerated, had no clinically meaningful immunogenicity, and showed a predictable and consistent pharmacokinetic profile and high subcutaneous bioavailability. In patients with asthma, verekitug led to >
About TSLP and TSLPR Blockade
Thymic Stromal Lymphopoietin (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 (TSLPR) presents an opportunity for a single treatment to impact the drivers of multiple pathological inflammatory processes across a broad set of diseases.
About Upstream Bio
Upstream Bio is a clinical-stage biotechnology company developing treatments for inflammatory diseases, with an initial focus on severe respiratory disorders. The Company is developing verekitug, the only known antagonist currently in clinical development that targets the receptor for thymic stromal lymphopoietin (TSLP), a cytokine which is a clinically validated driver of inflammatory response positioned upstream of multiple signaling cascades that affect a variety of immune mediated diseases. The Company has advanced this highly potent monoclonal antibody into separate Phase 2 trials for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), severe asthma, and chronic obstructive pulmonary disease (COPD). Upstream Bio鈥檚 team is committed to maximizing verekitug鈥檚 unique attributes to address the substantial unmet needs for patients underserved by today鈥檚 standard of care. To learn more, please visit聽.
Forward-Looking Statements
This press release contains 鈥渇orward-looking statements鈥� within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. These statements may be identified by words such as 鈥渁ims,鈥� 鈥渁nticipates,鈥� 鈥渂elieves,鈥� 鈥渃ontinue,鈥� 鈥渃ould,鈥� 鈥渆stimates,鈥� 鈥渆xpects,鈥� 鈥渇orecasts,鈥� 鈥済oal,鈥� 鈥渋ntends,鈥� 鈥渕ay,鈥� 鈥減lans,鈥� 鈥減ossible,鈥� 鈥減otential,鈥� 鈥減redict,鈥� 鈥減roject,鈥� 鈥渟eeks,鈥� 鈥渟hould,鈥� 鈥渢arget,鈥� 鈥渨ill鈥� and variations of these words or similar expressions. Any statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements include, without limitation, express or implied statements regarding: the clinical development of verekitug for the treatment of severe asthma, CRSwNP and COPD, including the timing, progress and results of ongoing and planned clinical trials; expectations for future discussions with regulatory authorities and the potential of the endpoints of the Company鈥檚 clinical trials to produce data that could support submissions for product approval; expectations regarding the differentiation, safety, efficacy, tolerability, or extended dosing interval of verekitug; expectations for the size and growth potential of the market for verekitug in CRSwNP and the Company鈥檚 ability to serve that market; Upstream Bio鈥檚 expected operating expenses and capital expenditure requirements; and participation at upcoming investor conferences and medical congresses. Any forward-looking statements in this press release are based on the Company鈥檚 current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Readers are cautioned that actual results, levels of activity, safety, efficacy, performance or events and circumstances could differ materially from those expressed or implied in the Company鈥檚 forward-looking statements due to a variety of risks and uncertainties, which include, without limitation, risks and uncertainties related to: Upstream Bio鈥檚 ability to advance verekitug through clinical development, and to obtain regulatory approval of and ultimately commercialize verekitug on the expected timeline, if at all; the initiation, timing, progress and results of clinical trials; Upstream Bio鈥檚 ability to fund its development activities and achieve development goals; Upstream Bio鈥檚 dependence on third parties to conduct clinical trials and manufacture verekitug, and commercialize verekitug, if approved; Upstream Bio鈥檚 ability to attract, hire and retain key personnel, and protect its intellectual property; Upstream Bio鈥檚 financial condition and need for substantial additional funds in order to complete development activities and commercialize verekitug, if approved; regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities; Upstream Bio鈥檚 competitors and industry; and other risks and uncertainties described in greater detail under the caption 鈥淩isk Factors鈥� in Upstream Bio鈥檚 most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, as well as any subsequent filings with the SEC. Any forward-looking statements represent Upstream Bio鈥檚 views only as of today and should not be relied upon as representing its views as of any subsequent date. Upstream Bio explicitly disclaims any obligation or undertaking to update any forward-looking statements contained herein to reflect any change in its expectations or any changes in events, conditions or circumstances on which any such statement is based except to the extent required by law, and claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.
Investor and Media Contact: Meggan Buckwell Director, Corporate Communications and Investor Relations [email protected]
FAQ
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