Upstream Bio Presents Additional Analyses from the Phase 2 VIBRANT Trial of Verekitug in Chronic Rhinosinusitis with Nasal Polyps at 2026 AAAAI Annual Meeting

Rhea-AI Summary

Upstream Bio (Nasdaq:UPB) presented additional Phase 2 VIBRANT data for verekitug in chronic rhinosinusitis with nasal polyps (CRSwNP) at the AAAAI 2026 meeting. WOCF-adjusted analyses showed a placebo-adjusted NPS reduction of -1.95 (p < 0.0001) and NCS reduction of -0.96 (p < 0.0001) at Week 24.

The trial (n=81) also reported a 76% reduction in need for surgery or systemic corticosteroids (p=0.03), an acceptable safety profile with no SAEs observed, and plans to initiate Phase 3 registrational trials in CRSwNP and severe asthma.

Positive

• NPS reduction of -1.95 (placebo-adjusted, WOCF)
• NCS reduction of -0.96 (placebo-adjusted, WOCF)
• 76% reduction in surgery or systemic steroid use (p=0.03)
• Every 12-week dosing at 100 mg
• No SAEs observed in the 24-week trial

Negative

• Small Phase 2 sample size of 81 adults
• Results are Phase 2 only; registrational trials pending

Key Figures

NPS reduction (WOCF): -1.95 (p<0.0001) NPS reduction (primary): -1.77 (p<0.0001) NCS reduction (WOCF): -0.96 (p<0.0001) +5 more

8 metrics

NPS reduction (WOCF) -1.95 (p<0.0001) Placebo-adjusted primary endpoint in Phase 2 VIBRANT at week 24

NPS reduction (primary) -1.77 (p<0.0001) Placebo-adjusted primary analysis in Phase 2 VIBRANT at week 24

NCS reduction (WOCF) -0.96 (p<0.0001) Placebo-adjusted nasal congestion score key secondary endpoint

NCS reduction (primary) -0.77 (p=0.0003) Placebo-adjusted nasal congestion score primary analysis

Rescue intervention reduction 76% (p=0.03) Reduced need for surgery or systemic corticosteroids vs placebo

Dose regimen 100 mg every 12 weeks Verekitug dosing schedule in VIBRANT trial

Trial duration 24 weeks Phase 2 VIBRANT efficacy and safety evaluation period

Participants 81 adults CRSwNP patients enrolled in Phase 2 VIBRANT

Market Reality Check

Price: $7.68 Vol: Volume 1,394,474 is below...

low vol

$7.68 Last Close

Volume Volume 1,394,474 is below the 20-day average of 2,295,062, suggesting a muted trading response so far. low

Technical Shares at $7.685 are trading below the 200-day MA at $19.17 and far under the 52-week high of $33.68.

Peers on Argus

UPB is down 2.78% while close biotech peers are mixed: SYRE up 1.39%, QURE down ...

UPB is down 2.78% while close biotech peers are mixed: SYRE up 1.39%, QURE down 8.49%, RAPP down 1.09%, VERV roughly flat. No clear sector-wide pattern supports today’s move.

Previous Clinical trial Reports

4 past events · Latest: Feb 26 (Positive)

Same Type Pattern 4 events

Date	Event	Sentiment	Move	Catalyst
Feb 26	VIBRANT poster preview	Positive	+2.1%	Announced upcoming AAAAI late-breaking poster with adjusted VIBRANT efficacy analyses.
Feb 11	VALIANT top-line data	Positive	-47.2%	Reported positive Phase 2 VALIANT severe asthma results with significant exacerbation reduction.
Sep 02	VIBRANT top-line data	Positive	+18.3%	Announced Phase 2 VIBRANT CRSwNP success with significant nasal polyp and congestion score reductions.
Jul 08	COPD trial start	Positive	-0.7%	Dosed first patient in Phase 2 VENTURE COPD trial, expanding verekitug to a third indication.

Pattern Detected

Clinical trial news has produced mixed reactions: some positive CRSwNP updates lifted the stock, while the severe asthma Phase 2 readout coincided with a sharp selloff, yielding an overall average move of -6.89% on such headlines.

Recent Company History

Recent history shows a steady stream of verekitug clinical milestones across CRSwNP, severe asthma, and COPD. Positive Phase 2 VIBRANT CRSwNP data on Sep 2, 2025 drove an 18.27% gain, while the severe asthma VALIANT top-line on Feb 11, 2026 saw a -47.18% move despite meeting endpoints. An AAAAI VIBRANT analysis preview on Feb 26, 2026 produced a modest 2.07% rise. Today’s detailed VIBRANT analyses extend this clinical narrative as the company plans Phase 3 trials.

Historical Comparison

-6.9% avg move · Across 4 clinical-trial headlines, UPB’s average move was -6.89%. Today’s -2.78% reaction to additio...

clinical trial

-6.9%

Average Historical Move clinical trial

Across 4 clinical-trial headlines, UPB’s average move was -6.89%. Today’s -2.78% reaction to additional VIBRANT CRSwNP analyses sits within this historical volatility range.

Clinical updates show progression from initial Phase 2 VIBRANT CRSwNP success and VALIANT asthma data toward planned Phase 3 programs in CRSwNP and severe asthma while maintaining an active COPD Phase 2 trial.

Market Pulse Summary

This announcement strengthens the Phase 2 VIBRANT dataset, showing improved placebo-adjusted reducti...

Analysis

This announcement strengthens the Phase 2 VIBRANT dataset, showing improved placebo-adjusted reductions in nasal polyp and congestion scores and a 76% cut in surgery or systemic steroid use. Together with prior CRSwNP and severe asthma results, it supports advancing verekitug into Phase 3 across multiple respiratory indications. Investors may track upcoming registrational trial starts, longer-term safety data, and how verekitug’s every-12-week dosing compares clinically with existing biologics.

Key Terms

endoscopic nasal polyp score (NPS), nasal congestion score (NCS), systemic corticosteroids, serious adverse events (SAEs), +2 more

6 terms

endoscopic nasal polyp score (NPS) medical

"Primary endpoint of endoscopic nasal polyp score (NPS) showed reduction..."

An endoscopic nasal polyp score (NPS) is a numeric rating doctors give after looking inside the nose with a tiny camera to judge how large and obstructive nasal polyps are. Think of it like measuring how much a road is blocked by debris; a higher score means more blockage. Investors watch NPS because it’s a standard, measurable outcome in clinical trials and regulatory reviews that shows whether a treatment meaningfully reduces symptoms and can drive product approval and sales.

nasal congestion score (NCS) medical

"including reduction in nasal congestion score (NCS) by -0.96..."

A nasal congestion score (NCS) is a simple numeric measure used in clinical trials to quantify how blocked a person’s nose feels, often recorded by the patient on a short scale like a “thermometer” for stuffiness. Investors watch NCS because it gives a standardized way to show whether a nasal therapy or device actually improves symptoms, which directly affects regulatory approval prospects, marketability, and potential sales.

systemic corticosteroids medical

"including nasal polyp surgery, systemic corticosteroids, or escalation..."

Systemic corticosteroids are prescription medicines that mimic natural steroid hormones and are taken by mouth or given by injection to reduce inflammation and calm the immune system throughout the whole body. They matter to investors because they can drive large prescription sales and strongly influence clinical trial outcomes, safety warnings, regulatory approvals and insurance coverage; like a master switch that eases symptoms but can cause significant side effects that affect a drug’s market value.

serious adverse events (SAEs) medical

"favorable safety profile consistent with previous studies, with no SAEs observed."

Serious adverse events (SAEs) are significant negative outcomes, such as severe health issues, hospitalizations, or death, that occur during a medical study or treatment. For investors, SAEs matter because they can signal potential risks associated with a product or company, potentially affecting its reputation, regulatory approval, or financial performance. Recognizing SAEs helps gauge the safety and reliability of medical-related investments.

randomized, double-blind, placebo-controlled technical

"a Phase 2 global, randomized, double-blind, placebo-controlled, parallel group..."

A "randomized, double-blind, placebo-controlled" process is a method used to test the effectiveness of a new treatment or intervention. Participants are randomly assigned to different groups, with one receiving the real treatment and the other a fake version, called a placebo. Neither the participants nor the researchers know who is receiving which, which helps ensure unbiased results. For investors, this rigorous approach increases confidence that the findings are accurate and not influenced by guesswork or bias.

Phase 2 technical

"VIBRANT (NCT06164704) was a Phase 2 global, randomized..."

Phase 2 is the mid-stage clinical trial where a new drug or treatment is tested in a larger group of patients to see if it works and to keep checking safety after initial human testing. Think of it as a field test that proves whether a product actually delivers its promised benefit. Investors watch Phase 2 closely because its results strongly influence a medicine’s chances of reaching the market, the size of its potential sales, and the company’s valuation.

AI-generated analysis. Not financial advice.

– Primary endpoint of endoscopic nasal polyp score (NPS) showed reduction of -1.95 (p < 0.0001) in new analysis with adjustment for concomitant rescue therapy use –

– Secondary endpoints also provided strong efficacy data in new analyses, including reduction in nasal congestion score (NCS) by -0.96 (p < 0.0001) –

WALTHAM, Mass., March 01, 2026 (GLOBE NEWSWIRE) -- Upstream Bio, Inc. (Nasdaq:UPB), a clinical-stage company developing treatments for inflammatory diseases, with an initial focus on severe respiratory disorders, today presented additional data from the Phase 2 VIBRANT clinical trial evaluating verekitug in participants with chronic rhinosinusitis with nasal polyps (CRSwNP). The additional analyses incorporated a worst-observation carried-forward (WOCF) statistical approach to adjust for concomitant rescue therapy use, including nasal polyp surgery, systemic corticosteroids, or escalation of background treatments. The data support previously reported positive top-line results and were presented in a late-breaking poster session at the American Academy of Allergy Asthma & Immunology (AAAAI) 2026 Annual Meeting in Philadelphia.

Dosed 100 mg every 12 weeks, verekitug met the study’s primary endpoint using both the WOCF and primary (treatment policy) analyses, demonstrating an improved placebo-adjusted reduction in NPS 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 also showed a placebo-adjusted reduction in the patient-reported NCS, a key secondary endpoint, of -0.96 (p < 0.0001) in the WOCF analysis as compared to -0.77 (p = 0.0003) in the primary analysis.

As previously reported in the top-line results, verekitug reduced the need for surgery or systemic corticosteroids by 76% (p = 0.03) compared with placebo, and was generally well tolerated, demonstrating a favorable safety profile consistent with previous studies, with no SAEs observed.

“The strong results in clinical effect we saw in these additional analyses are an important validation of verekitug’s impact on endpoints that take into consideration the use of rescue medication, which was substantially reduced with verekitug treatment in VIBRANT. As this approach more closely aligns with that used in other recent studies of agents in CRSwNP, it also enhances our understanding of verekitug’s potential to add to the existing armamentarium for this serious disease. The presentation of these data continues to reinforce verekitug’s differentiated profile, comprising robust clinical activity with far less-frequent dosing, relative to currently available biologics as a potential treatment of CRSwNP,” said Aaron Deykin, MD, Chief Medical Officer and Head of Research & Development at Upstream Bio. “As we prepare to initiate our Phase 3 trials in CRSwNP and severe asthma, we believe that verekitug’s unique mechanism of action and differentiated product profile could position it to significantly advance the standard of care for people with serious respiratory diseases.”

“The magnitude of improvement observed with verekitug across both analytical approaches, along with the previously reported reduction in rescue interventions, suggests the potential for meaningful benefit for people living with chronic rhinosinusitis with nasal polyps,” 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. “Additionally, the efficacy outcomes we observed in VIBRANT, combined with the every 12-week dosing interval, suggest that verekitug could represent a valuable new treatment option for people living with this challenging condition.”

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. Planning activities for Phase 3 trials in CRSwNP and severe asthma have commenced, and the Company intends to initiate registrational trials in both indications, following planned regulatory interactions.

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 4% of the general population, of whom 40% have uncontrolled disease.

Nasal polyps are associated with significant disease burden and debilitating symptoms; it is estimated that over 40% of people with severe asthma also have CRSwNP and that up to 70% of people with CRSwNP also have asthma, demonstrating a strong association between the two conditions.

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 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 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 recently completed positive VIBRANT trial (NCT06164704) in patients with CRSwNP and 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.

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 evaluated this highly potent monoclonal antibody in separate Phase 2 trials for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), severe asthma, and an ongoing Phase 2 trial in chronic obstructive pulmonary disease (COPD). Upstream Bio’s team is committed to maximizing verekitug’s unique attributes to address the substantial unmet needs for patients underserved by today’s standard of care. To learn more, please visit www.upstreambio.com.

Forward-Looking Statements
This press release contains “forward-looking statements” 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 “aims,” “anticipates,” “believes,” “continue,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “predict,” “project,” “seeks,” “should,” “target,” “will” 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 global development of verekitug for the treatment of severe asthma, CRSwNP and COPD, including the initiation, 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’s clinical trials to produce data that could support submissions for product approval; expectations regarding the differentiation, safety, efficacy, tolerability, and/or extended dosing interval of verekitug; and expectations for the size and growth potential of the market for verekitug in CRSwNP and the Company’s ability to serve that market. Any forward-looking statements in this press release are based on the Company’s 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’s forward-looking statements due to a variety of risks and uncertainties, which include, without limitation, risks and uncertainties related to: Upstream Bio’s 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’s ability to fund its development activities and achieve development goals; Upstream Bio’s dependence on third parties to conduct clinical trials and manufacture verekitug, and commercialize verekitug, if approved; Upstream Bio’s ability to attract, hire and retain key personnel, and protect its intellectual property; Upstream Bio’s 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’s competitors and industry; and other risks and uncertainties described in greater detail under the caption “Risk Factors” in Upstream Bio’s 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’s 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
ir@upstreambio.com

FAQ

What was the primary endpoint result for verekitug in the VIBRANT trial (UPB) presented March 2026?

The primary endpoint showed a placebo-adjusted NPS reduction of -1.95 using WOCF (p < 0.0001). According to Upstream Bio, this WOCF analysis adjusted for rescue therapy use and corroborates the previously reported primary (treatment policy) result at Week 24.

How did verekitug affect nasal congestion score (NCS) in the Phase 2 VIBRANT study for UPB?

Verekitug produced a placebo-adjusted NCS reduction of -0.96 in the WOCF analysis (p < 0.0001). According to Upstream Bio, this secondary endpoint improvement aligns with the primary outcome and accounts for concomitant rescue therapy use at Week 24.

Did verekitug reduce the need for surgery or systemic corticosteroids in VIBRANT (UPB)?

Yes. Verekitug reduced the need for surgery or systemic corticosteroids by 76% versus placebo (p = 0.03). According to Upstream Bio, this finding was reported in the topline and reinforced in the additional WOCF-adjusted analyses.

What safety findings did Upstream Bio report for verekitug in the March 1, 2026 VIBRANT update?

The company reported no serious adverse events observed in the 24-week trial and a generally favorable safety profile. According to Upstream Bio, safety was consistent with prior studies, supporting tolerability at the 100 mg every-12-weeks dose.

When will Upstream Bio (UPB) start Phase 3 trials for verekitug in CRSwNP and severe asthma?

Upstream Bio has commenced planning and intends to initiate registrational Phase 3 trials following regulatory interactions. According to Upstream Bio, Phase 3 initiation will proceed after planned discussions with regulators, with timelines subject to those interactions.