Upstream Bio Highlights Phase 3 Development Strategy for Verekitug and Reports Fourth Quarter and Full Year 2025 Financial Results

– Company to pursue Phase 3 development strategy designed to deliver best-in-class efficacy with a high-dose quarterly regimen in broad patient populations in both severe asthma and CRSwNP –

– Company plans to initiate dosing in Phase 3 trials in both severe asthma and CRSwNP in Q1 2027 –

– Reported positive top-line results from Phase 2 VALIANT trial of verekitug in patients with severe asthma in February 2026, demonstrating significant improvements in asthma exacerbations and lung function –

– Presented additional analyses from Phase 2 VIBRANT trial at AAAAI, reinforcing verekitug’s therapeutic potential in CRSwNP –

– Strong cash position of $341.5 million expected to fund planned operations through 2027 –

WALTHAM, Mass., March 26, 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 reported financial results for the fourth quarter and full year ended December 31, 2025, and highlighted its Phase 3 development strategy for verekitug in severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The Company is developing verekitug, the only known antagonist currently in clinical development that targets and inhibits the thymic stromal lymphopoietin (TSLP) receptor, in multiple severe respiratory diseases including severe asthma, CRSwNP, and chronic obstructive pulmonary disease (COPD).

“Upstream Bio continues to make strong progress, highlighted by our recent positive Phase 2 VALIANT study of verekitug in patients with severe asthma,” said Rand Sutherland, MD, Chief Executive Officer of Upstream Bio. “This trial demonstrated compelling efficacy data and a favorable safety profile with extended dosing, and we believe this combination could represent a meaningful advance over currently available biologic therapies. We are working diligently to move verekitug into Phase 3 development and to realize its potential to become a leading medicine for the treatment of severe asthma and CRSwNP.”

“Since reporting the top-line results from VALIANT, we have analyzed data from approximately 500 participants treated in our Phase 1 and 2 clinical trials, and this comprehensive dataset supports verekitug’s potential to deliver best-in-class efficacy with doses as high as 400 mg administered quarterly in a single injection, in both severe asthma and CRSwNP,” continued Dr. Sutherland. “As a result of this work and comprehensive market research indicating that a profile that delivers best-in-class efficacy with quarterly dosing maximizes the potential commercial value of verekitug, we are prioritizing a Phase 3 development strategy that focuses on maximizing efficacy in both indications, without biomarker restriction, while also delivering the convenience of quarterly at-home administration. We will provide additional details on the study design following engagement with the U.S. Food and Drug Administration (FDA) later this year, and we plan to initiate dosing in both Phase 3 programs in the first quarter of 2027.”

Recent Business Highlights

• Phase 3 Strategy for High-Dose Quarterly Administration in Broad Patient Populations in Severe Asthma and CRSwNP Supported by Analyses of Phase 2 Trial Results
  • Evaluation of exposure-response relationships across multiple clinical endpoints in both severe asthma and CRSwNP supports the Company’s intent to study a high-dose quarterly regimen of verekitug of up to 400 mg, administered in a single injection.
    • As observed in Phase 2 trials, patients in the highest exposure group consistently demonstrated the highest clinical benefit in both severe asthma, as measured by forced expiratory volume in 1 second (FEV1), and CRSwNP, as measured by the nasal congestion score (NCS) after treatment with 100 mg every 12 weeks.
    • Pharmacokinetic (PK) modeling from all patients treated with verekitug indicates that, at doses above 100 mg every 12 weeks, 85% to 96% of patients at 200 mg every 12 weeks and 400 mg every 12 weeks, respectively, are predicted to have verekitug concentrations sufficient to achieve near-maximal suppression of exhaled nitric oxide throughout the quarterly dosing interval.
  • Observed positive treatment responses across both high and low eosinophil subgroups in severe asthma and CRSwNP reinforce verekitug’s continued development in a broad population of patients in both indications.
  • Immunogenicity in Phase 2 trials was consistent with previous experience, and meaningful differences in either safety or efficacy were not observed in patients with anti-drug antibodies as compared to those without.
  • The Company’s market research, conducted with healthcare providers, payers, and patients, consistently indicates that efficacy is the primary driver of clinical impact and commercial success in severe asthma and CRSwNP, that healthcare providers are unwilling to trade off any aspect of safety or efficacy for extended dosing, and that the majority of value generated by dosing convenience is captured by moving from every 2- or 4-week dosing to quarterly dosing. These findings support the Company’s development strategy focused on delivering high efficacy with quarterly dosing convenience.
  • The Company plans to meet with regulators later this year to gain alignment on Phase 3 plans for verekitug in severe asthma and CRSwNP and expects to initiate both registrational studies in the first quarter of 2027.

• Positive Phase 2 VALIANT Trial in Severe Asthma Results Reported
  • Top-line results from the Phase 2 VALIANT trial in severe asthma reported in February 2026 demonstrated significant improvements in asthma exacerbations and lung function with extended dosing.
  • In this randomized, placebo-controlled study, VALIANT met the study’s primary endpoint of a statistically significant and clinically meaningful reduction in the annualized asthma exacerbation rate (AAER) with both every 12 week and every 24 week dosing, with verekitug demonstrating a reduction in AAER of 56% (p