UPB

– Company rapidly advancing toward Q1 2027 initiation of Phase 3 trials designed to deliver best-in-class efficacy with convenient quarterly dosing in both severe asthma and CRSwNP; End-of-Phase 2 interactions with FDA on track – – Completed enrollment in Phase 2 trial in COPD; data expected in the second half of 2027 – – Clinical data presentations continue to emphasize differentiated profile of verekitug in multiple indications – WALTHAM, Mass., Aug. 11, 2026 (GLOBE NEWSWIRE) -- Upstream Bio, Inc. (Nasdaq: UPB), a clinical-stage company developing treatments for severe inflammatory respiratory diseases, today reported financial results and business updates for the second quarter ended June 30, 2026. The Company highlighted its continued progress in developing verekitug to deliver potential best-in-class efficacy with quarterly dosing across three target indications: severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and chronic obstructive pulmonary disease (COPD). Verekitug is the only known antagonist currently in clinical development that targets and inhibits the thymic stromal lymphopoietin (TSLP) receptor. “We continued to make progress toward the initiation of our Phase 3 trials in severe asthma and CRSwNP in the first quarter of 2027. Our End-of-Phase 2 interactions with the FDA are on schedule, and we look forward to sharing more details about our Phase 3 development plans soon,” said Rand Sutherland, MD, Chief Executive Officer of Upstream Bio. “With more than 500 participants treated in verekitug clinical trials thus far, and with compelling Phase 2 results now demonstrated in both severe asthma and CRSwNP, we have built a substantial and consistent body of clinical evidence supporting verekitug’s potential to deliver durable, best-in-class efficacy with convenient quarterly dosing. In addition, our CMC and device development efforts continue to advance, and we are working diligently to provide options for both at-home and in-office administration at launch.” “I am pleased to share that we have completed enrollment in our ongoing Phase 2 VENTURE trial in COPD, with 481 participants enrolled; data from this important Phase 2 study, expected in the second half of 2027, will provide valuable insights into the potential of verekitug for the treatment of COPD,” added Aaron Deykin, MD, Chief Medical Officer and Head of Research & Development at Upstream Bio. “Additionally, verekitug’s differentiated clinical profile in severe asthma and CRSwNP continues to be reinforced through additional data recently presented at the ATS and EAACI medical congresses, and our team is looking forward to the upcoming late-breaking presentation of our Phase 2 VALIANT trial of verekitug in severe asthma at the ERS Congress in early September. Collectively, these data further strengthen our conviction about the potential for verekitug to advance the standard of care.” Recent Business Highlights Upcoming Initiation of Phase 3 Trials in Severe Asthma and CRSwNP Phase 2 VENTURE Trial in COPD Enrollment Completed Additional Analyses of Phase 2 VIBRANT Trial in CRSwNP Presented at American Thoracic Society (ATS) International Conference 2026 and European Academy of Allergy and Clinical Immunology (EAACI) Congress 2026 Phase 2 VALOUR Long-Term Extension Study in Severe Asthma Second Quarter 2026 Financial ResultsAs of June 30, 2026, Upstream Bio had cash, cash equivalents and short-term investments of $261.3 million, which is expected to fund planned operations through 2027. Research and development expenses were $36.1 million for the quarter ended June 30, 2026, compared to $37.9 million for the same period in 2025. The decrease of $1.8 million was primarily driven by a decrease in manufacturing expenses, partially offset by an increase in personnel-related expenses, including share-based compensation, and an increase in clinical costs related to the Company’s verekitug programs. General and administrative expenses were $7.1 million for the quarter ended June 30, 2026, compared to $7.4 million for the same period in 2025. The decrease of $0.3 million was primarily driven by a decrease in professional fees, partially offset by an increase in personnel-related expenses, including share-based compensation. Net loss was $39.7 million for the quarter ended June 30, 2026, compared to a net loss of $40.0 million for the same period in 2025. Upcoming EventsUpstream Bio expects to participate in the following upcoming medical congresses: European Respiratory Society (ERS) Congress 2026, September 5-9, Barcelona About Upstream BioUpstream Bio is a clinical-stage biotechnology company developing treatments for severe inflammatory respiratory diseases. The Company is developing verekitug, the only known antagonist currently in clinical development that targets and inhibits the receptor for thymic stromal lymphopoietin (TSLP), a cytokine which is a clinically validated driver of inflammatory response positioned upstream of multiple inflammatory pathways. With more than 500 participants treated with verekitug across its clinical development programs and positive Phase 2 results in chronic rhinosinusitis with nasal polyps (CRSwNP) and severe asthma, verekitug has a substantial body of clinical evidence supporting its advancement into Phase 3 development in both diseases. Verekitug is also being evaluated in an ongoing Phase 2 trial in chronic obstructive pulmonary disease (COPD). Upstream Bio is focused on leveraging verekitug’s differentiated mechanism, potency, and potential for extended dosing to develop a treatment which may deliver best-in-class efficacy and quarterly dosing for patients underserved by today’s standard of care. To learn more, please visit www.upstreambio.com. Upstream Bio intends to use the investor relations page on its website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor its website in addition to following press releases, filings with the Securities and Exchange Commission (SEC), public conference calls, presentations and webcasts. Forward-Looking StatementsThis 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 clinical 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 regarding the differentiation, safety, efficacy, tolerability, or extended dosing interval of verekitug; certain activities and next steps to support the Company’s maturation into a late clinical-stage company; expectations regarding regulatory interactions with the FDA on the data from the VIBRANT and VALIANT Phase 2 trials and the outcomes of any such interactions; advancement of the Company’s chemistry, manufacturing and controls and device development efforts and the potential for both at-home and in-office administration at launch; Upstream Bio’s expected operating expenses and capital expenditure requirements, including its cash runway through 2027; and participation at upcoming investor conferences and medical congresses. 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 results of preclinical studies or clinical studies not being predictive of future results in connection with future studies; 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 BuckwellDirector, Corporate Communications and Investor [email protected]

– Company rapidly advancing Phase 3 programs designed to deliver best-in-class efficacy with convenient quarterly dosing in severe asthma and CRSwNP – – End-of-Phase 2 meetings with FDA planned for mid-2026; Phase 3 initiations in both indications expected in Q1 2027 – – Phase 2 VENTURE trial in COPD ongoing; Company to cap further enrollment; data now expected in the second half of 2027 – – Upcoming data presentations at ATS and EAACI to further elaborate the clinical profile of verekitug – WALTHAM, Mass., May 13, 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 first quarter ended March 31, 2026, and highlighted its continued progress in developing verekitug to deliver potential best-in-class efficacy with quarterly dosing across the Company’s three target indications: severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and chronic obstructive pulmonary disease (COPD). Verekitug is the only known antagonist currently in clinical development that targets and inhibits the thymic stromal lymphopoietin (TSLP) receptor. “We continue to make strong progress advancing our clinical programs in severe asthma and CRSwNP to position verekitug as a uniquely differentiated treatment option for these diseases,” said Rand Sutherland, MD, Chief Executive Officer of Upstream Bio. “We are working diligently to deliver best-in-class efficacy with convenient quarterly at-home dosing, a profile that we believe will advance the standard of care for patients and maximize the potential commercial value of verekitug. We are continuing to prepare for our End-of-Phase 2 meetings with the FDA, which we expect to occur in mid-2026, and we remain on track to initiate Phase 3 dosing in both severe asthma and CRSwNP in the first quarter of 2027.” “In addition, our Phase 2 VENTURE study in COPD continues, with more than 400 participants enrolled to date,” continued Dr. Sutherland. “Given our goal to deliver the best efficacy profile possible in all three indications, including COPD, we intend to cap further enrollment in VENTURE as we begin preparations for a Phase 3 trial of a high-dose quarterly regimen in COPD. The placebo-controlled efficacy data from VENTURE, now expected in the second half of 2027, will provide important insights into the potential of verekitug for the treatment of COPD and add to our understanding of the safety and efficacy of this molecule in multiple indications. Across our programs, we remain focused on disciplined execution and generating the data needed to bring a meaningful new treatment option to patients as quickly as possible.” Recent Business Highlights Phase 3 Strategy for High-Dose Quarterly Administration in Broad Patient Populations in Severe Asthma and CRSwNP In February 2026, the Company announced top-line results from the Phase 2 VALIANT trial in severe asthma, which demonstrated significant improvements in asthma exacerbations and lung function with extended dosing. 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 in mid-2026 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. Phase 2 VENTURE Trial in COPD The Company has enrolled more than 400 participants in the Phase 2 VENTURE trial in COPD (NCT06981078). VENTURE is a Phase 2, global, randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to assess the efficacy and safety of verekitug in participants with moderate-to-severe COPD across extended dosing-interval arms of 12 and 24 weeks. The Company plans to cap further enrollment in the VENTURE trial; currently enrolled participants will remain in the study to its completion. Data are now expected in the second half of 2027, and the Company expects that these analyses will provide important insights into the potential impact of verekitug in COPD as it plans a Phase 3 trial of verekitug in COPD. Phase 2 VALOUR Long-Term Extension Study in Severe Asthma Eligible participants with severe asthma who completed the Phase 2 VALIANT clinical trial were offered enrollment in VALOUR (NCT06966479), a long-term extension (LTE) study designed to evaluate the long-term safety and efficacy of verekitug. The study completed enrollment in March 2026 with more than 90% retention of eligible patients from the Phase 2 VALIANT study. Additional Analyses of Phase 2 VIBRANT Data to be Presented at American Thoracic Society (ATS) 2026 International Conference and the European Academy of Allergy and Clinical Immunology Congress 2026 (EAACI) The presentations at ATS and EAACI will feature new data from the Phase 2 VIBRANT trial, including data evaluating verekitug in participants with CRSwNP and comorbid asthma, as well as data on the effect of verekitug on Type 2 inflammatory biomarkers in CRSwNP at ATS. First Quarter 2026 Financial ResultsAs of March 31, 2026, Upstream Bio had cash, cash equivalents and short-term investments of $294.6 million, which is expected to fund planned operations through 2027. Research and development expenses were $36.6 million for the quarter ended March 31, 2026, compared to $25.8 million for the same period in 2025. The increase of $10.8 million was primarily driven by an increase in clinical and manufacturing expenses related to the Company’s verekitug programs as well as an increase in personnel-related expenses, including share-based compensation. General and administrative expenses were $8.1 million for the quarter ended March 31, 2026, compared to $6.8 million for the same period in 2025. The increase of $1.3 million was primarily driven by an increase in personnel-related expenses, including share-based compensation, and professional fees. Net loss was $40.6 million for the quarter ended March 31, 2026, compared to a net loss of $27.3 million for the same period in 2025. The increase of $13.3 million was largely due to increased research and development expenses. Upcoming EventsUpstream Bio expects to participate in the following upcoming investor conferences and medical congresses: American Thoracic Society 2026 International Conference, May 15-20, Orlando, FL Goldman Sachs 47th Annual Global Healthcare Conference, June 8-10, Miami, FL European Academy of Allergy & Clinical Immunology Congress 2026, June 12-16, Istanbul, Turkey Leerink Partners Therapeutics Forum, July 14-15, Boston, MA About Upstream BioUpstream 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 and inhibits 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’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. Upstream Bio intends to use the investor relations page on its website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor its website in addition to following press releases, filings with the Securities and Exchange Commission (SEC), public conference calls, presentations and webcasts. Forward-Looking StatementsThis 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 clinical 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; the Company's decision to cap further enrollment in the Phase 2 VENTURE trial in COPD and expectations regarding the continued participation of currently enrolled participants and the availability of data therefrom; expectations regarding the planned regulatory interactions with the FDA on the data from the Phase 2 VALIANT and VIBRANT trials and the outcomes of any such interactions; expectations regarding the timing of Phase 3 initiation in severe asthma and CRSwNP, including the expected initiation of dosing in the first quarter of 2027; 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, or extended dosing interval of verekitug, including its potential to deliver best-in-class efficacy with quarterly dosing convenience; expectations for the size and growth potential of the market for verekitug and the Company’s ability to serve that market; certain activities and next steps to support the Company’s maturation into a late clinical-stage company; Upstream Bio’s expected operating expenses and capital expenditure requirements, including its cash runway through 2027; and participation at upcoming investor conferences and medical congresses. 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 results of preclinical studies or clinical studies not being predictive of future results in connection with future studies; 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 BuckwellDirector, Corporate Communications and Investor [email protected]

– 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<0.0003) when dosed at 100 mg every 12 weeks and 39% (p<0.02) when dosed at 400 mg every 24 weeks, as compared with placebo. Verekitug demonstrated a favorable safety profile across all doses tested, consistent with previous studies. Additional Analyses of Phase 2 VIBRANT Trial in CRSwNP Presented at 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting Upstream Bio presented additional analyses from the Phase 2 VIBRANT trial of verekitug in patients with CRSwNP at the AAAAI Annual Meeting in February 2026. The analyses further characterized the efficacy and safety profile of verekitug, including evaluations adjusting for the use of rescue therapies, supporting the previously reported significant and clinically meaningful reductions in nasal polyp burden and symptom measures. Dosed 100 mg every 12 weeks, verekitug met the study’s primary endpoint using both the worst-observation carried-forward (WOCF) and primary (treatment policy) analyses, demonstrating a larger placebo-adjusted reduction in nasal polyp score (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. These findings provide additional support for the continued development of verekitug and ongoing planning for Phase 3 registrational studies. Ongoing Enrollment of Phase 2 VENTURE Trial in COPD Enrollment is ongoing in the Phase 2 VENTURE clinical trial in COPD (NCT06981078), which was initiated in July 2025. VENTURE is a Phase 2, global, randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to assess the efficacy and safety of verekitug in participants with moderate-to-severe COPD across extended dosing-interval arms of 12 and 24 weeks. The Company has designed this trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. The VENTURE study is more than 60% enrolled. Fourth Quarter 2025 Financial Results As of December 31, 2025, Upstream Bio had cash, cash equivalents and short-term investments of $341.5 million, which is expected to fund planned operations through 2027. Research and development expenses were $40.2 million for the quarter ended December 31, 2025, compared to $21.8 million for the same period in 2024. The increase of $18.4 million was primarily driven by an increase in clinical and manufacturing expenses related to the Company’s verekitug programs. General and administrative expenses were $6.7 million for the quarter ended December 31, 2025, compared to $5.2 million for the same period in 2024. The increase of $1.5 million was primarily driven by an increase in professional fees and personnel-related expenses, including share-based compensation. Net loss was $42.5 million for the quarter ended December 31, 2025, compared to a net loss of $21.2 million for the same period in 2024. The increase of $21.3 million was largely due to increased research and development expenses. Upcoming Events Upstream Bio expects to participate in the following upcoming investor conferences and medical congresses: Piper Sandler Spring Biopharma Symposium, April 15-16, Boston, MA American Thoracic Society 2026 International Conference, May 15-20, Orlando, FL Goldman Sachs 47th Annual Global Healthcare Conference, June 8-10, Miami, FL European Academy of Allergy & Clinical Immunology, June 12-16, Istanbul, Turkey 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 and inhibits 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’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. Upstream Bio intends to use the investor relations page on its website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor its website in addition to following press releases, filings with the Securities and Exchange Commission (SEC), public conference calls, presentations and webcasts. 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 clinical 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, or extended dosing interval of verekitug; expectations for the size and growth potential of the market for verekitug and the Company’s ability to serve that market; certain activities and next steps to support the Company’s maturation into a late clinical-stage company; expectations regarding the planned regulatory interactions with the FDA on the data from the VIBRANT and VALIANT Phase 2 trials and the outcomes of any such interactions; Upstream Bio’s expected operating expenses and capital expenditure requirements, including its cash runway through 2027; and participation at upcoming investor conferences and medical congresses. 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 results of preclinical studies or clinical studies not being predictive of future results in connection with future studies; 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 [email protected]

– Verekitug provided statistically significant and clinically meaningful reductions in annualized asthma exacerbation rate (AAER) with 100 mg q12 and 400 mg q24 week dosing – – Verekitug also delivered clinically meaningful improvements in lung function (FEV1) and exhaled nitric oxide (FeNO) with both dose regimens – – Verekitug was generally well tolerated, with a safety profile consistent with prior studies – – Over 90% of eligible patients have rolled over to the Phase 2 VALOUR long-term extension study – – Upstream Bio to advance verekitug into Phase 3 trials in severe asthma and CRSwNP following planned regulatory interactions – – Management will host a live webcast today at 8:00 a.m. ET – WALTHAM, Mass., Feb. 11, 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 announced positive top-line results from the Phase 2 VALIANT clinical trial evaluating the safety and efficacy of verekitug in adults with severe asthma. Verekitug is the only known clinical-stage antagonist targeting the receptor for thymic stromal lymphopoietin (TSLP). 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 (q12w) and every 24 week (q24w) dosing, with verekitug demonstrating a reduction in AAER of 56% (p<0.0003) when dosed at 100 mg q12w and 39% (p<0.02) when dosed at 400 mg q24w, as compared with placebo. Placebo-adjusted improvement in lung function, as measured by the forced expiratory volume in one second (FEV1), was 122 mL at week 60 with verekitug 100 mg q12w, and 139 mL at week 60 with 400 mg q24w. At week 60, verekitug also suppressed exhaled nitric oxide (FeNO) compared to placebo by 20.4 ppb (p<0.0003) when dosed at 100 mg q12w, and by 26.3 ppb (p<0.0001) when dosed at 400 mg q24w. These data represented a mean 43.5% (p=0.03) reduction from baseline in the 100 mg q12w group and a mean 44.9% (p=0.03) reduction from baseline in the 400 mg q24w group. A third low-dose treatment group, 100 mg q24w, demonstrated a statistically significant effect on AAER, but did not provide consistent improvements in other endpoints. Additional pre-specified analyses of secondary outcomes at week 24 revealed statistically significant placebo-adjusted improvements compared to baseline in both FEV1 and FeNO with the 100 mg q12w and 400 mg q24w dose regimens. Verekitug was generally well tolerated across all active doses, demonstrating a favorable safety profile consistent with previous studies. “We are excited to share these robust data from VALIANT, which indicate the potential of verekitug’s meaningful clinical effect in severe asthma and provide a strong foundation as we advance verekitug into Phase 3 clinical trials as quickly as possible,” said Aaron Deykin, MD, Chief Medical Officer and Head of Research & Development at Upstream Bio. “We are deeply grateful to the patients, investigators, and study teams whose participation made this progress possible. With the completion of our VALIANT trial, hundreds of patients have now been dosed with verekitug across our clinical programs, providing a growing body of clinical experience that reinforces our confidence in its potential and its differentiated product profile. Together with the positive results from our VIBRANT trial in CRSwNP, we now have an opportunity to incorporate both strong clinical data sets with an in-depth analysis of the aggregate pharmacology findings to guide data-driven decisions about dose selection and trial design for Phase 3.” “These compelling findings from VALIANT strengthen verekitug’s potential to advance the standard of care with a highly competitive efficacy profile and less frequent dosing—an important combination for people living with severe asthma,” stated Rand Sutherland, MD, Chief Executive Officer of Upstream Bio. “We intend to rapidly advance verekitug into Phase 3 trials in severe asthma and CRSwNP. In parallel, we also continue to progress verekitug in our ongoing Phase 2 VENTURE trial in patients with COPD, where we have enrolled more than 60% of patients to date. As we transition into a late clinical-stage company pursuing substantial market opportunities, our focus remains on disciplined execution and expanding Upstream Bio’s capabilities to support long-term growth.” VALIANT (NCT06196879) is a Phase 2 global, randomized, double-blind, placebo-controlled, dose-ranging, parallel group clinical trial that evaluated the safety and efficacy of verekitug for up to 60 weeks, with a minimum of 24 weeks of treatment, in 478 patients with severe asthma. Eligible participants who completed the Phase 2 VALIANT clinical trial were offered enrollment in VALOUR (NCT06966479), a long-term extension (LTE) study designed to evaluate the long-term safety and efficacy of verekitug. Current transition rates indicate more than 90% of eligible patients have rolled over to the Phase 2 VALOUR LTE study. “Severe asthma, when unable to be controlled by standard of care measures, can significantly and chronically disrupt patients’ quality of life, and put them at risk for potentially life-threatening exacerbation events that can lead to emergency rooms visits and hospitalizations,” said Michael Wechsler, MD, MMSc, Professor of Medicine, Director of National Jewish Cohen Family Asthma Institute. “These data suggest that verekitug can potentially offer patients meaningful improvements in their breathing and asthma symptoms with less frequent dosing than the currently available biologics, and I believe that verekitug could represent an important advancement for individuals living with severe asthma.” Upstream Bio designed the VALIANT 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 severe asthma and CRSwNP have commenced, and the Company intends to initiate registrational trials in both indications following planned regulatory interactions. Additional details from the VALIANT trial will be presented at a future medical conference. Webcast Details Upstream Bio’s webcast to discuss the top-line results from the Phase 2 VALIANT trial will begin today at 8:00 a.m. ET. The live webcast can be accessed via this link or on the Events tab on the Investors section of the Company’s website at https://investors.upstreambio.com/news-events/events. A replay of the webcast will be available on the website following the call. About Severe Asthma Severe asthma is a complex, chronic inflammatory disease of the airways characterized by persistent symptoms, recurrent exacerbations, and impaired quality of life despite treatment with high-dose corticosteroids and other long-acting medication that accounts for a disproportionate share of asthma-related costs and healthcare utilization. Severe asthma is a heterogeneous disease driven by multiple inflammatory pathways, including both Type 2 and non-Type 2 mechanisms. Asthma affects approximately 350 million people worldwide, with five to 10 percent suffering from severe asthma. Currently, there are approximately 1.3 million biologic-eligible severe asthma patients in the US, though the use of biologic therapies remains limited relative to the size of the eligible population. We believe new treatment options for severe asthma are needed to further improve control of exacerbations and symptoms, and reduce the treatment burden, such as the need for frequent injections. About the Phase 2 VALIANT Trial The Phase 2 VALIANT trial (NCT06196879) is a global, randomized, placebo-controlled, dose-finding, parallel group clinical trial, designed to assess the efficacy and safety of verekitug in adults with severe asthma. Participants were randomized into one of four groups, receiving either 100 mg of verekitug every 24 weeks, 400 mg of verekitug every 24 weeks, 100 mg of verekitug every 12 weeks, or placebo administered subcutaneously. The study evaluated verekitug’s efficacy in the treatment of severe asthma during a treatment period up to 60 weeks with a minimum of 24 weeks, with the primary endpoint of reduction of the annualized asthma exacerbation rate (AAER). Secondary endpoints included changes in air exhalation, nitric oxide exhalation, and a patient-reported assessment of asthma control, though these were not designed with sufficient power to detect statistically significant effects. 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 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’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 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’s 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 and the Company’s ability to serve that market; certain activities and next steps to support the Company’s maturation into a late clinical-stage company; and participation at upcoming investor conferences and medical congresses. 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 results of preclinical studies, or clinical studies not being predictive of future results in connection with future studies; 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 [email protected]

– Webcast to be held Wednesday, February 11, 2026, at 8:00 a.m. ET – WALTHAM, Mass., Feb. 10, 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 announced it will report top-line results from the Phase 2 VALIANT trial of verekitug, the only known antagonist currently in clinical development that targets and inhibits the thymic stromal lymphopoietin (TSLP) receptor, on Wednesday, February 11, 2026 at 8:00 a.m. ET. The VALIANT trial (NCT06196879) is a Phase 2 global, randomized, double-blind, placebo-controlled, dose-ranging, parallel group clinical trial that evaluated the safety and efficacy of verekitug for up to 60 weeks, with a minimum of 24 weeks of treatment, in 478 patients with severe asthma. Participants were randomized into one of four groups, receiving either 100 mg of verekitug every 24 weeks, 400 mg of verekitug every 24 weeks, 100 mg of verekitug every 12 weeks, or placebo, administered subcutaneously. Webcast Information Upstream Bio’s webcast to discuss the top-line results from the Phase 2 VALIANT trial will begin Wednesday, February 11, 2026, at 8:00 a.m. ET. The live webcast can be accessed via this link or on the Events tab on the Investors section of the Company’s website at https://investors.upstreambio.com/news-events/events. A replay of the webcast will be available on the website following the call. 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’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. Investor and Media Contact: Meggan Buckwell Director, Corporate Communications and Investor Relations [email protected]

– Positive top-line results from VIBRANT Phase 2 trial of verekitug in CRSwNP reported in September showed statistically significant and clinically meaningful effects on primary and key secondary endpoints when administered once every 12 weeks – – On-track to report top-line results from VALIANT Phase 2 trial in severe asthma in the first quarter of 2026 – – Enrollment ongoing in VENTURE Phase 2 trial in COPD; first patient dosed in July – WALTHAM, Mass., Nov. 05, 2025 (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 third quarter ended September 30, 2025, and provided a summary of recent business highlights. 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 chronic rhinosinusitis with nasal polyps (CRSwNP), severe asthma, and chronic obstructive pulmonary disease (COPD). Verekitug’s unique pharmacology may lead to differentiated efficacy and an extended dosing interval as compared to the current standard of care. “During this quarter we reached an important milestone in verekitug’s development and shared positive top-line results from VIBRANT, our Phase 2 trial in CRSwNP, which reinforced verekitug’s differentiated clinical profile, including its potential for efficacy meeting or exceeding that of available biologics, with administration only four times per year,” said Rand Sutherland, MD, Chief Executive Officer of Upstream Bio. “We also continued to bolster our understanding of verekitug through translational research, including with the presentation of new data identifying structural and mechanistic drivers of verekitug’s potent disruption of TSLP signaling by antagonism of the TSLP receptor at the European Respiratory Society Congress in September.” “We remain on track to report top-line results from VALIANT, our Phase 2 trial in severe asthma, in the first quarter of 2026. Guided by these data, and following discussion with regulators, we will be well-positioned to advance our Phase 3 development plans for verekitug in both CRSwNP and severe asthma,” added Dr. Sutherland. “In addition, we continue to make investments in CMC and drug delivery with the goal of further strengthening the clinical profile and utility of verekitug for patients.” Recent Business Highlights and Upcoming Milestones Positive top-line results from the VIBRANT Phase 2 trial in CRSwNP reported in September 2025: Positive top-line results from the VIBRANT Phase 2 trial in CRSwNP showed statistically significant and clinically meaningful effects on multiple endpoints when administered once every 12 weeks. 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). The 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. Significant and clinically meaningful improvements were observed in key secondary endpoints, including -0.8 (p=0.0003) reduction in nasal congestion score and 76% (p=0.03) reduction in need for surgery or systemic corticosteroids. Verekitug was generally well tolerated, demonstrating a favorable safety profile consistent with previous studies, with no serious adverse events (SAEs) observed. The Company has designed this trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. Top-line data from the VALIANT Phase 2 trial in severe asthma expected in the first quarter of 2026: VALIANT is a Phase 2 global, randomized, double-blind, placebo-controlled, parallel group clinical trial designed to assess the efficacy and safety of verekitug in participants with severe asthma in extended dosing interval arms of 12 and 24 weeks. Patient enrollment for VALIANT was completed in June 2025. The Company has designed this trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. Additional program progress: Structural and mechanistic drivers of verekitug’s potent pharmacodynamic activity and differentiated clinical profile were presented at the European Respiratory Society (ERS) Congress in September 2025. Data showed: Verekitug prevents TSLP binding to the TSLP receptor by occupying ligand binding sites. Verekitug outcompetes TSLP in the presence of preformed heterodimeric receptor complexes. These data support the potential of verekitug’s unique mechanism of action to achieve a differentiated therapeutic effect across a broad range of TSLP-driven severe respiratory diseases. Enrollment is ongoing in the VENTURE Phase 2 clinical trial in COPD, in which the first patient was dosed in July 2025. VENTURE is a Phase 2 global, randomized, double-blind, placebo-controlled, parallel group clinical trial designed to assess the efficacy and safety of verekitug in participants with moderate-to-severe COPD in extended dosing interval arms of 12 and 24 weeks. The Company has designed this trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. Third Quarter 2025 Financial Results As of September 30, 2025, Upstream Bio had cash, cash equivalents and short-term investments of $372.4 million, which is expected to fund planned operations through 2027. Research and development expenses were $33.0 million for the quarter ended September 30, 2025, compared to $15.4 million for the same period in 2024. The increase of $17.6 million was primarily driven by an increase in clinical and manufacturing expenses related to the Company’s verekitug programs. General and administrative expenses were $5.5 million for the quarter ended September 30, 2025, compared to $4.1 million for the same period in 2024. The increase of $1.4 million was primarily driven by an increase in personnel-related expenses, including share-based compensation, and professional service fees. Net loss was $33.7 million for the quarter ended September 30, 2025, compared to a net loss of $16.0 million for the same period in 2024. The increase of $17.7 million was largely due to increased research and development expenses. Upcoming Events Upstream Bio expects to participate in the following upcoming investor conferences: 2025 Truist Securities Biopharma Symposium, November 6, 2025, New York, NY Stifel 2025 Healthcare Conference, November 11, 2025, New York, NY TD Cowen Immunology and Inflammation Summit, November 12, 2025, Virtual Piper Sandler 37th Annual Healthcare Conference, December 2, 2025, New York, NY 8th Annual Evercore Healthcare Conference, December 4, 2025, Miami, FL 44th Annual J.P. Morgan Healthcare Conference, January 12-15, 2026, San Francisco, CA 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 and inhibits 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’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. Upstream Bio intends to use the investor relations page on its website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor its website in addition to following press releases, filings with the Securities and Exchange Commission (SEC), public conference calls, presentations and webcasts. 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 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’s 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; Upstream Bio’s expected operating expenses and capital expenditure requirements, including its cash runway through 2027; and participation at upcoming investor conferences and medical congresses. 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 [email protected]

– 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) – – Significant and clinically meaningful improvements were observed in key secondary endpoints, including -0.8 (p=0.0003) reduction in nasal congestion score and 76% (p=0.03) reduction in need for surgery or systemic corticosteroids – – No serious adverse events (SAEs) observed; generally well tolerated safety profile consistent with previous studies – – 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 – – Management will host a conference call and webcast today at 8:00 a.m. ET – WALTHAM, Mass., Sept. 02, 2025 (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 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 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. “This 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,” said Aaron Deykin, MD, Chief Medical Officer and Head of Research & Development at Upstream Bio. “These results reinforce our earlier observations that verekitug’s 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.” “These results highlight verekitug’s 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,” stated Rand Sutherland, MD, Chief Executive Officer of Upstream Bio. “These results may also offer insight into verekitug’s 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.” “In CRSwNP, patients often face persistent nasal obstruction and diminished sense of smell despite repeated courses of systemic corticosteroids or sinus surgery—all of which significantly impact quality of life,” 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. “The 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.” 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’s 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 link or on the Events tab on the Investors section of the Company’s website at https://investors.upstreambio.com/news-events/events. 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 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 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 >50% reductions in fractional exhaled nitric oxide (FeNO) and blood eosinophils that were rapid and sustained for up to 24 weeks after the last dose in the Phase 1b MAD trial. 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’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 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’s 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’s ability to serve that market; Upstream Bio’s 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’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. CONTACT: Investor and Media Contact: Meggan Buckwell Director, Corporate Communications and Investor Relations [email protected]

– On track to report top-line data from Phase 2 trial in chronic rhinosinusitis with nasal polyps (CRSwNP) in the third quarter of 2025 – – Completed enrollment in Phase 2 trial in severe asthma in June 2025; top-line data expected in the first quarter of 2026 – – First patient dosed in Phase 2 trial in chronic obstructive pulmonary disease (COPD) in July 2025 – WALTHAM, Mass., Aug. 06, 2025 (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 second quarter ended June 30, 2025, and provided a summary of recent business highlights. The Company is developing verekitug, the only monoclonal antibody currently in clinical development that targets and inhibits the thymic stromal lymphopoietin (TSLP) receptor, in multiple severe respiratory diseases including CRSwNP, severe asthma, and COPD. Verekitug’s unique pharmacology may lead to differentiated efficacy and an extended dosing interval as compared to the current standard of care. “We continued to build momentum this quarter with strong execution across our clinical development programs for verekitug in severe respiratory diseases,” said Rand Sutherland, MD, Chief Executive Officer of Upstream Bio. “Notably, in June, we completed enrollment in our Phase 2 trial in severe asthma, with top-line data expected in the first quarter of 2026. We also initiated our Phase 2 trial in COPD in July, marking the start of development in a third major respiratory indication. Additionally, we remain on track to report top-line results from our Phase 2 trial in CRSwNP in the third quarter of this year.” “Our development efforts are centered on severe forms of common respiratory diseases where we see significant potential for clinical impact and commercial opportunity,” Dr. Sutherland continued. “We believe verekitug’s differentiated mechanism and extended dosing profile may offer meaningful advantages over biologics currently used to treat these diseases. Our upcoming readouts in CRSwNP and severe asthma represent key program milestones and an opportunity to further demonstrate the potentially unique profile of TSLP receptor inhibition across multiple inflammatory airway diseases.” Upcoming Milestones and Recent Business Highlights Two key upcoming top-line readouts: Top-line data from the VIBRANT Phase 2 trial in patients with CRSwNP expected in the third quarter of 2025: VIBRANT is a Phase 2 global, randomized, double-blind, placebo-controlled, parallel group clinical trial designed to assess the efficacy and safety of verekitug in participants with CRSwNP, dosed every 12 weeks. Patient enrollment for VIBRANT was completed in January 2025. The Company has designed this trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. Top-line data from the VALIANT Phase 2 trial in patients with severe asthma, expected in the first quarter of 2026: VALIANT is a Phase 2 global, randomized, double-blind, placebo-controlled, parallel group clinical trial designed to assess the efficacy and safety of verekitug in participants with severe asthma in extended dosing interval arms of 12 and 24 weeks. Patient enrollment for VALIANT was completed in June 2025. The Company has designed this trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. Program progress: Entered third major respiratory indication with first patient dosed in the VENTURE Phase 2 clinical trial in patients with COPD in July 2025: VENTURE is a Phase 2 global, randomized, double-blind, placebo-controlled, parallel group clinical trial designed to assess the efficacy and safety of verekitug in participants with moderate-to-severe COPD in extended dosing interval arms of 12 and 24 weeks. The Company has designed this trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. Initiated long term extension study (LTE) in severe asthma in May 2025: VALOUR, a Phase 2 LTE, was initiated in eligible participants with severe asthma who have completed the VALIANT Phase 2 trial. Second Quarter 2025 Financial Results As of June 30, 2025, Upstream Bio had cash, cash equivalents and short-term investments of $393.6 million, which is expected to fund planned operations through 2027. Research and development expenses were $37.9 million for the quarter ended June 30, 2025, compared to $14.1 million for the same period in 2024. The increase of $23.8 million was primarily driven by an increase in clinical and manufacturing expenses related to the Company’s verekitug programs. General and administrative expenses were $7.4 million for the quarter ended June 30, 2025, compared to $4.0 million for the same period in 2024. The increase of $3.4 million was primarily driven by an increase in personnel-related expenses, including share-based compensation, and professional service fees. Net loss was $40.0 million for the quarter ended June 30, 2025, compared to a net loss of $14.7 million for the same period in 2024. The increase of $25.3 million was largely due to increased research and development and general and administrative expenses, partially offset by increased interest income. Upcoming Events Upstream Bio expects to participate in the following investor conferences and medical congresses: Stifel Virtual Immunology and Inflammation Forum, September 15–16, 2025 European Respiratory Society, September 27–October 1, 2025, Amsterdam, Netherlands 2025 Truist Securities Biopharma Symposium, November 6, 2025, New York, NY 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’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. Upstream Bio intends to use the investor relations page on its website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor its website in addition to following press releases, filings with the Securities and Exchange Commission (SEC), public conference calls, presentations and webcasts. 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 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’s 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; Upstream Bio’s expected operating expenses and capital expenditure requirements, including its cash runway through 2027; and participation at upcoming investor conferences and medical congresses. 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 [email protected]

– Top-line data from Phase 2 clinical trial of verekitug in patients with chronic rhinosinusitis with nasal polyps expected in the third quarter of 2025 – – Top-line data from Phase 2 clinical trial of verekitug in patients with severe asthma now expected in the first half of 2026 – – First patient in Phase 2 clinical trial of verekitug in patients with chronic obstructive pulmonary disease to be dosed in mid-2025 – WALTHAM, Mass., May 06, 2025 (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 first quarter ended March 31, 2025, and provided a summary of recent business highlights. The Company is developing verekitug, the only monoclonal antibody currently in clinical development that targets and inhibits the thymic stromal lymphopoietin (TSLP) receptor, in multiple severe respiratory diseases including chronic rhinosinusitis with nasal polyps (CRSwNP), severe asthma and chronic obstructive pulmonary disease (COPD). “This quarter we made excellent progress in our development of verekitug, positioning us well to deliver on our upcoming clinical milestones. We are pleased to accelerate our guidance on several near-term events, including the top-line data readout from our Phase 2 clinical trial of verekitug in patients with CRSwNP, expected in the third quarter of this year,” said Rand Sutherland, MD, Chief Executive Officer of Upstream Bio. “In addition, we now anticipate reporting top-line data from our Phase 2 clinical trial in severe asthma in the first half of 2026. We also now expect to dose the first patient in our Phase 2 clinical trial in COPD in mid-2025. We look forward to sharing further updates as we reach these key milestones.” Dr. Sutherland continued, “Verekitug is the only known molecule currently in clinical development targeting the TSLP receptor. Early clinical data suggest that this unique mechanism of action has the potential to meaningfully impact disease activity in patients with these severe respiratory diseases through both differentiated efficacy and an extended dosing interval, and we are testing the therapeutic implications of these observations across our development programs.” First Quarter 2025 and Recent Business Highlights Top-line data from Phase 2 clinical trial in patients with CRSwNP expected in the third quarter of 2025: In January 2025, Upstream Bio completed patient enrollment in its Phase 2 multicenter, randomized, placebo-controlled, parallel group clinical trial designed to assess the efficacy and safety of verekitug in participants with CRSwNP. Top-line data from this clinical trial is expected to be reported in the third quarter of 2025. The Company has designed this trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. Patients were randomized to receive either 100 mg of verekitug or placebo administered subcutaneously every 12 weeks over a 24-week treatment period. The primary endpoint is change from baseline in nasal polyp score (NPS) at week 24, a primary endpoint that has been used in several registrational trials for other biologic treatments for CRSwNP. Secondary endpoints include: nasal congestion score, sinus opacification, difficulty with sense of smell, nasal symptoms, percentage of participants requiring systemic corticosteroids or nasal polyp surgery, time to nasal polyp surgery and/or time to systemic corticosteroids for nasal polyps, total symptom score, and characterization of safety. Top-line data from Phase 2 clinical trial in patients with severe asthma now expected in the first half of 2026: The Company has designed this trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. Upstream Bio also plans to initiate a long-term safety and efficacy extension study (Phase 2 LTE) in certain adult patients with severe asthma following completion of its Phase 2 severe asthma trial with the first patient expected to transition to the LTE study in the second quarter of 2025. First patient dosing in Phase 2 clinical trial in COPD expected in mid-2025: Upstream Bio is initiating development of verekitug in a Phase 2 clinical trial in patients with moderate-to-severe COPD and now expects to dose the first patient in mid-2025. The Company has designed this trial using endpoints that, pending interactions with regulatory authorities, could produce data to support submissions for product approval. First Quarter 2025 Financial Results As of March 31, 2025, Upstream Bio had cash, cash equivalents and short-term investments of $431.4 million, which is expected to fund planned operations through 2027. Research and development expenses were $25.8 million for the quarter ended March 31, 2025, compared to $11.7 million for the same period in 2024. The increase of $14.1 million was primarily driven by an increase in clinical and manufacturing expenses related to the Company’s verekitug program. General and administrative expenses were $6.8 million for the quarter ended March 31, 2025, compared to $4.0 million for the same period in 2024. The increase of $2.8 million was primarily driven by an increase in personnel-related expenses, including share-based compensation, and professional service fees. Net loss was $27.3 million for the quarter ended March 31, 2025, compared to a net loss of $10.9 million for the same period in 2024. The increase of $16.4 million was largely due to increased research and development and general and administrative expenses, partially offset by increased interest income. Upcoming Events Upstream Bio expects to participate in the following investor conferences and medical congresses: Goldman Sachs 46th Annual Global Healthcare Conference 2025, Miami, FL, Upstream Bio presentation on June 11, 2025, at 9:20 a.m. ET European Academy of Allergy and Clinical Immunology (EAACI) Congress 2025, Glasgow, United Kingdom, June 13-16, 2025 About Upstream Bio Upstream Bio is a clinical-stage biotechnology company developing treatments for inflammatory diseases, with an initial focus on severe respiratory disorders. Upstream Bio is developing verekitug, the only known antagonist currently in clinical development that targets the receptor for thymic stromal lymphopoietin, 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. Upstream Bio has advanced this highly potent monoclonal antibody into separate Phase 2 trials for the treatment of severe asthma and chronic rhinosinusitis with nasal polyps and is initiating development in chronic obstructive pulmonary disease. 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. Upstream Bio intends to use the investor relations page on its website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor its website in addition to following press releases, filings with the Securities and Exchange Commission (SEC), public conference calls, presentations and webcasts. 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 clinical 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 safety, efficacy or tolerability of verekitug; Upstream Bio’s expected operating expenses and capital expenditure requirements, including its cash runway through 2027; and participation at upcoming investor conferences and medical congresses. 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. CONTACT: Investor and Media Contact: Meggan Buckwell Director, Corporate Communications and Investor Relations [email protected]