Upstream Bio Inc. (NASDAQ:UPB) shares are trading lower during Friday’s session as the stock reacts to recent developments in its clinical trials.Over the last few days, the stock has plunged more than 54%.The decline follows a report highlighting the company’s results for its asthma treatment.VALIANT Trial Shows 56% Reduction in Asthma AttacksThe VALIANT trial demonstrated statistically significant reductions in the annualized asthma exacerbation rate (AAER) of 56% for the 100 mg every 12 weeks dosing comp ...

Clinical Trial Results - The Phase 2 VALIANT trial demonstrated a 56% reduction in annualized asthma exacerbation rates (AAER) with verekitug dosed at 100 mg every 12 weeks (p<0.0003) and a 39% reduction with 400 mg every 24 weeks (p<0.02) [10] - Significant improvements in lung function were observed, with a 122 mL improvement in FEV1 for the 100 mg dose and a 139 mL improvement for the 400 mg dose [10] - The trial also reported a reduction in exhaled nitric oxide (FeNO) levels, with a 20.4 ppb reduction for the 100 mg dose and a 26.3 ppb reduction for the 400 mg dose [10] - The VALIANT trial enrolled 478 patients across 15 countries, with 91% of participants completing the treatment [21] - Verekitug demonstrated a statistically significant reduction in the annualized asthma exacerbation rate (AAER) at 60 weeks, with a rate of 0.66 for the 100 mg q12w dose compared to 1.52 for placebo, resulting in a rate ratio of 0.44 (95% CI: 0.28, 0.69) [27] - The prebronchodilator forced expiratory volume (FEV1) change from baseline at 60 weeks was 265 mL for the 100 mg q12w dose, significantly higher than the placebo's 143 mL, with a nominal p-value of 0.0003 [27] - At 60 weeks, the FeNO (fractional exhaled nitric oxide) change from baseline was -17.4 ppb for the 100 mg q12w dose, compared to 3.1 ppb for placebo, with a nominal p-value of 0.0003 [27] - The 400 mg q24w dose of Verekitug also showed significant improvements in lung function and FeNO, with a change of -23.3 ppb in FeNO and a nominal p-value of <0.0001 [28] - At 24 weeks, the prebronchodilator FEV1 change for the 400 mg q24w dose was 275 mL, significantly better than the placebo's 142 mL, with a nominal p-value of 0.0119 [31] - The ACQ-6 (Asthma Control Questionnaire) score change at 24 weeks was -1.12 for the 100 mg q12w dose, indicating improved asthma control compared to -0.91 for placebo, with a nominal p-value of 0.0651 [31] - The clinical effects of Verekitug were consistent across various subgroups, including age and sex, with the 100 mg q12w dose showing a rate ratio of 0.40 for patients under 65 years [32] - The overall participant count for the 100 mg q12w group was 121, while the placebo group had 119 participants, ensuring robust data for analysis [27] - The study indicated that secondary endpoints were not powered for statistical significance, highlighting the need for further research [30] - The results suggest that Verekitug may offer a promising new treatment option for asthma patients, with ongoing evaluations of its long-term efficacy and safety [32] - Phase 2 VALIANT study achieved a statistically significant 56% reduction in annualized asthma exacerbation rates (AAER) with verekitug dosed at 100mg every 12 weeks (p<0.0003) and a 39% reduction at 400mg every 24 weeks (p<0.02) [34] - Verekitug demonstrated a 122mL improvement in FEV1 and a 139mL improvement in FEV3, indicating clinically meaningful enhancements in lung function [34] - The treatment resulted in a 20.4ppb reduction in exhaled nitric oxide (FeNO) for the 100mg dose and a 26.3ppb reduction for the 400mg dose, representing a 43.5% and 44.9% reduction versus baseline, respectively [34] Safety and Tolerability - Verekitug demonstrated a treatment-emergent adverse event (TEAE) rate of 62.0% for the 100 mg q12w group and 58.5% for the 400 mg q24w group, compared to 65.5% for the placebo group [25] - The incidence of any serious TEAEs was 4.1% for the 100 mg q12w group and 6.8% for the 400 mg q24w group, while the placebo group had an incidence of 8.4% [25] - The most common TEAE was nasopharyngitis, occurring in 10.7% of the 100 mg q12w group and 7.6% of the 400 mg q24w group [25] - The percentage of participants with any grade 3-5 TEAEs was 6.6% for the 100 mg q12w group and 11.0% for the 400 mg q24w group [25] - The overall incidence of TEAEs was similar across treatment groups, indicating consistent safety profiles [25] - The safety profile of verekitug was consistent with prior studies, indicating it was generally well tolerated [34] Financial and Market Outlook - Upstream Bio has approximately $341.5 million in cash and short-term investments as of December 31, 2025, expected to fund operations through 2027 [12] - The global biologics market for severe asthma and COPD is projected to exceed $35 billion by 2033, indicating a significant commercial opportunity [12] - The company aims to address high unmet needs in severe asthma, CRSwNP, and COPD, with a growing number of biologic therapies entering the market [12] Future Plans and Studies - The company is also conducting the VALOUR long-term extension study and the VIBRANT trial in chronic rhinosinusitis with nasal polyps (CRSwNP), which reported positive results in September 2025 [13] - The Phase 2 trial design included randomized, placebo-controlled methods with registration-enabling endpoints, ensuring robust data collection and analysis [19] - The company plans to conduct integrated analyses of Phase 2 data sets in chronic rhinosinusitis with nasal polyps (CRSwNP) and severe asthma to optimize dosing for Phase 3 trials [38] - Strong execution of the Phase 2 trial in COPD will continue, alongside the initiation of Phase 3 trials in severe asthma and CRSwNP [38] - The company will engage with regulatory agencies and continue accelerated operational planning for the Phase 3 start [38] - Investments in chemistry, manufacturing, and controls (CMC) and device development will be prioritized [38]

Upstream Bio Phase 2 VALIANT Trial Conference Call Summary Company Overview - **Company**: Upstream Bio (NasdaqGS:UPB) - **Focus**: Clinical-stage immunology company targeting severe respiratory diseases, specifically developing Verekitug, a TSLP receptor antagonist [9][10] Industry Context - **Market Opportunity**: - Approximately 1.3 million patients in the U.S. are eligible for biologic therapies for severe asthma, with only 25% currently receiving treatment, indicating significant commercial potential for new biologics [10] - Global peak sales for biologics in severe asthma projected to exceed $12.5 billion by 2033 [11] Key Trial Results - **Trial Name**: VALIANT - **Type**: Phase 2, placebo-controlled, randomized trial - **Participants**: 478 adults with severe asthma [12] - **Dosing Regimens**: - 100 mg every 12 weeks (high dose) - 400 mg every 24 weeks (medium dose) - 100 mg every 24 weeks (low dose) - Placebo [12] Efficacy Findings - **Annualized Asthma Exacerbation Rate (AAER)**: - 100 mg every 12 weeks: 56% reduction in AAER [5] - 400 mg every 24 weeks: 39% reduction in AAER [6] - 100 mg every 24 weeks: 49% reduction in AAER [17] - **Lung Function Improvements**: - 100 mg every 12 weeks: 122 mL improvement in FEV1 and 20.4 ppb reduction in exhaled nitric oxide (FeNO) [5] - 400 mg every 24 weeks: 139 mL improvement in FEV1 and 26.3 ppb reduction in FeNO [6] - **Safety Profile**: Generally well-tolerated with no deaths reported; adverse events similar across treatment groups [16] Strategic Insights - **Differentiation**: Verekitug shows potential for a unique clinical profile compared to existing biologics, with less frequent dosing [7][8] - **Next Steps**: Plans to advance to Phase 3 studies in severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) pending regulatory discussions [23] - **Ongoing Trials**: Enrollment in the VENTURE trial for COPD is over 60% complete, with positive feedback from investigators [10] Market Dynamics - **Competitive Landscape**: The biologics market for asthma is characterized by multiple agents targeting different pathways, allowing for new entrants to capture market share without directly eroding existing products [50] - **Patient Convenience**: Dosing frequency and convenience are critical factors for adoption, with Verekitug's dosing schedule potentially offering a competitive advantage [40][51] Additional Considerations - **Regulatory Engagement**: Future Phase 3 trial designs will be informed by comprehensive data analysis and discussions with regulatory authorities [31][49] - **Antibody Development**: Anti-drug antibodies (ADAs) were observed in 50%-60% of subjects, but their impact on efficacy appears minimal [17][71] Conclusion - Upstream Bio is positioned to leverage the positive results from the VALIANT trial to advance Verekitug into Phase 3 studies, aiming to address significant unmet needs in severe asthma and capitalize on the substantial market opportunity in the biologics space [22][82]

Core Insights - The VALIANT trial for verekitug showed significant reductions in the annualized asthma exacerbation rate (AAER) by 56% for the 100 mg quarterly dosing and 39% for the 400 mg biannual dosing compared to placebo [2] - The drug demonstrated clinically meaningful improvements in lung function and was well-tolerated, with over 90% of eligible patients transitioning to a long-term extension study [2] - The company plans to initiate registrational trials for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) following regulatory interactions [5] Clinical Trial Results - At week 60, verekitug suppressed exhaled nitric oxide (FeNO) by 20.4 ppb (p<0.0003) for the 100 mg quarterly group and by 26.3 ppb (p<0.0001) for the 400 mg biannual group, representing mean reductions of 43.5% and 44.9% from baseline, respectively [3] - A low-dose treatment group (100 mg biannual) showed a statistically significant effect on AAER but lacked consistent improvements in other endpoints [4] - Statistically significant placebo-adjusted improvements in FEV1 and FeNO were observed at week 24 for both dosing regimens [4] Stock Performance and Analyst Consensus - The stock is currently trading 10.2% above its 20-day simple moving average (SMA) and 30.5% above its 100-day SMA, indicating strong short-term momentum [6] - Over the past 12 months, shares have surged 292.24%, and they are closer to their 52-week highs than lows [6] - The stock carries an Outperform Rating with an average price forecast of $49.00, with recent analyst targets ranging from $40.00 to $51.00 [8]

Top-line Results for the Phase 2 VALIANT Trial in Severe Asthma February 11, 2026 © 2026 Upstream Bio, Inc. No Image Disclaimer This presentation 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," ...

Core Insights - Upstream Bio announced positive results from the Phase 2 VALIANT trial for verekitug, showing significant reductions in asthma exacerbation rates and improvements in lung function [2][3][4] Efficacy and Safety - Verekitug demonstrated a 56% reduction in annualized asthma exacerbation rate (AAER) at a dose of 100 mg every 12 weeks and a 39% reduction at 400 mg every 24 weeks compared to placebo [3] - Improvements in lung function were observed, with a placebo-adjusted increase in forced expiratory volume in one second (FEV1) of 122 mL for the 100 mg q12w group and 139 mL for the 400 mg q24w group [4] - The drug also significantly suppressed exhaled nitric oxide (FeNO), with reductions of 20.4 ppb and 26.3 ppb for the respective dosing regimens [4] Patient Enrollment and Future Trials - Over 90% of eligible patients from the VALIANT trial have transitioned to the Phase 2 VALOUR long-term extension study [8] - Upstream Bio plans to advance verekitug into Phase 3 trials for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) following regulatory interactions [6][9] Company Overview - Upstream Bio is focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders, and is advancing verekitug as a unique antagonist targeting the TSLP receptor [19][12] - The company has conducted multiple Phase 2 trials for verekitug, including studies for chronic obstructive pulmonary disease (COPD) and CRSwNP, and is committed to addressing unmet needs in severe asthma treatment [18][19]

Core Insights - Upstream Bio, Inc. is set to report top-line results from the Phase 2 VALIANT trial of verekitug, a treatment targeting the TSLP receptor, on February 11, 2026 [1][2] Group 1: Company Overview - Upstream Bio is a clinical-stage biotechnology company focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders [4] - The company is advancing verekitug, the only known antagonist in clinical development targeting the TSLP receptor, which is involved in inflammatory responses [4] - Upstream Bio aims to address significant unmet needs in patients underserved by current standard care through its development of verekitug [4] Group 2: VALIANT Trial Details - The VALIANT trial is a Phase 2 global, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of verekitug in 478 patients with severe asthma [2] - Participants in the trial were divided into four groups, receiving either 100 mg or 400 mg of verekitug every 24 weeks, 100 mg every 12 weeks, or a placebo, administered subcutaneously [2]

Summary of Upstream Bio's Presentation at Morgan Healthcare Conference Company Overview - **Company**: Upstream Bio - **Focus**: Clinical stage company specializing in immunology, particularly severe respiratory diseases - **Key Product**: Virecetug, a fully human IgG1 targeting the TSLP receptor Core Points and Arguments - **Unique Approach**: Upstream Bio is developing Virecetug by targeting the TSLP receptor, differentiating it from other drugs like Amgen's Tezspire, which targets TSLP itself [2][3] - **Clinical Development**: Virecetug has shown significant pharmacological effects, including: - 100% receptor occupancy for up to 24 weeks post-dose - Significant suppression of disease-related biomarkers such as exhaled nitric oxide (FeNO) and blood eosinophils [6][15] - **Dosing Regimen**: Virecetug can be administered as infrequently as every 12 to 24 weeks, which is a competitive advantage in the market [3][16] - **Market Opportunity**: - The market for chronic rhinosinusitis (CRS) with nasal polyps (NP) is projected to exceed $1 billion in annual biologic sales in the US, with significant growth potential [9] - Despite seven approved biologics for severe asthma, there remains a substantial unmet clinical need, with only 20%-25% of eligible patients currently treated [51] - **Clinical Trials**: - The phase 2 trial for CRS with NP showed a significant reduction in the endoscopic nasal polyp score by 1.8 points and a 76% reduction in the need for surgery or steroids [24] - Upcoming phase 2 trial for severe asthma (Valiant study) aims to assess the efficacy of Virecetug in reducing asthma exacerbations [30][31] Additional Important Content - **Safety Profile**: Virecetug has demonstrated a clean safety profile, consistent with other biologics targeting TSLP [12][25] - **Comparative Efficacy**: Early data suggests Virecetug may have a greater efficacy compared to Tezepelumab, with a predicted maximal effect on exhaled nitric oxide that is 1.5 times greater [18] - **Regulatory Strategy**: Upstream Bio plans to progress to phase 3 trials for both CRS with NP and severe asthma simultaneously, leveraging data from ongoing studies [54] - **Long-term Vision**: The company aims to expand the use of Virecetug across various respiratory diseases, similar to the successful strategy employed by Dupixent [34][35] This summary encapsulates the key points from Upstream Bio's presentation, highlighting the company's innovative approach, clinical advancements, and market potential in the field of respiratory diseases.

2026 J.P. Morgan Healthcare Conference Rand Sutherland, MD, Chief Executive Officer January 2026 © 2026 Upstream Bio, Inc. No Image Disclaimer This presentation contains forward-looking statements of Upstream Bio, Inc. ("Upstream," "the Company," "we," "us," or "our") that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial condition, results of operations, business strategy ...

Company Overview - Upstream Bio, Inc. is a clinical-stage biotechnology company focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders [3] - The company is advancing verekitug, a monoclonal antibody targeting the receptor for thymic stromal lymphopoietin (TSLP), which is involved in inflammatory responses [3] - Verekitug is currently in separate Phase 2 trials for chronic rhinosinusitis with nasal polyps (CRSwNP), severe asthma, and chronic obstructive pulmonary disease (COPD) [3] Upcoming Events - Rand Sutherland, MD, CEO of Upstream Bio, will present at the 44th Annual J.P. Morgan Healthcare Conference on January 12, 2026, at 2:15 p.m. PT [1] - A live webcast of the presentation will be available on Upstream Bio's website, with a replay accessible afterward [2]