Upstream Bio Conference Call Summary Company Overview - **Company**: Upstream Bio (NasdaqGS:UPB) - **Focus**: Clinical stage company developing a monoclonal antibody antagonist of the receptor for TSLP, named verekitug [2][3] Key Points on Drug Development - **Current Trials**: Verekitug is in placebo-controlled Phase 2 trials for severe asthma and other indications [2] - **Efficacy Data**: Recent Phase 2 trial (VALIANT) showed a statistically significant reduction in asthma exacerbation rates across all tested dose regimens, with the high dose (100 mg Q12W) achieving a 56% reduction [4][5] - **Dosing Strategy**: The drug is designed for quarterly dosing, which is expected to provide a competitive advantage over existing treatments [6][8] - **Potency**: Verekitug is approximately 300 times more potent than Tezepelumab, allowing for flexible dosing strategies [8][19] Phase 3 Preparation - **Data Analysis**: The company is currently analyzing Phase 2 data to inform dose selection for Phase 3 trials, aiming to maximize efficacy while minimizing dosing frequency [3][7] - **Regulatory Alignment**: The company plans to finalize its Phase 3 strategy after discussions with regulators, expected to occur in Q3 2026 [12][20] Long-term Extension Study - **Patient Retention**: Over 90% of patients from the Phase 2 trial have rolled over into the long-term extension study, allowing for extended follow-up and additional data collection [17][18] Competitive Landscape - **Market Positioning**: Upstream Bio differentiates itself by targeting the receptor for TSLP, while many competitors focus on the ligand. The company believes understanding the pharmacology of its molecule is crucial for successful Phase 3 trials [19][20] - **Emerging Competition**: The company is aware of competitors like Generate and Glaxo, but emphasizes its unique approach and data-driven strategy [19][21] Market for Biologics in Asthma - **Market Dynamics**: The asthma treatment market is converging around a limited set of targets (TSLP, IL-13, IL-5, IgE). The company aims to innovate within this space by delivering a differentiated clinical profile [23][24] - **Patient Preferences**: Quarterly dosing is viewed favorably, and any reduction in efficacy could lead to decreased patient preference for less frequent dosing [25] COPD Opportunity - **Trial Enrollment**: Enrollment in the VENTURE COPD trial is over 60%. The company is considering potential changes to the study based on new data from the asthma trials [27][32] - **Target Population**: The focus is on patients with an eosinophilic phenotype, as they are expected to respond best to Type 2 immunomodulators [32][36] Financial Position - **Cash Reserves**: The company ended the last quarter with $341 million in cash, providing a runway through 2027 to support ongoing and future trials [50] Future Catalysts - **Upcoming Events**: The company plans to initiate Phase 3 trials for severe asthma and CRSwNP by the beginning of next year, with further updates on the COPD program expected as data becomes available [41][42] Device Development - **Formulation and Delivery**: The company has developed a highly concentrated formulation (200 mg/mL) to facilitate a single injection delivery system, which is crucial for patient comfort and compliance [42][43]

Summary of Upstream Bio FY Conference Call Company Overview - **Company**: Upstream Bio (NasdaqGS:UPB) - **Focus**: Development of verekitug, a long-acting TSLP (thymic stromal lymphopoietin) targeting therapy for asthma and other Type 2 inflammatory conditions Key Points and Arguments Clinical Data and Efficacy - **Phase 2 VALIANT Data**: Verekitug demonstrated a 56% reduction in asthma exacerbations at a 100 mg Q12W dosing and a 39% reduction at 400 mg Q24W, meeting primary endpoints [3][5][7] - **Comparison with Tezspire**: Efficacy data for verekitug is comparable to Tezspire, which also showed a 56% reduction in asthma exacerbations with monthly dosing [4][5] - **Lung Function Improvements**: Statistically significant improvements in lung function and reductions in exhaled nitric oxide (FeNO) were observed across dosing regimens [5][6] - **Dosing Preferences**: Physicians prefer Q12W dosing over Q24W, indicating a market demand for more frequent dosing without sacrificing efficacy [4][11] Future Development Plans - **Phase 3 Trials**: Upstream Bio is preparing for Phase 3 trials in severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), aiming to start by the end of the year [21][22] - **Regulatory Strategy**: The company is working on regulatory briefing books and plans to utilize robust data from Phase 2 trials to support its Phase 3 applications [21][80] - **Potential Market Position**: Upstream aims to be the second long-acting drug to market for severe asthma and potentially the first for CRSwNP, leveraging its strong efficacy profile [22][80] Safety and Immunogenicity - **Safety Profile**: Verekitug has shown a clean safety profile consistent with other biologics in the space, with an ADA (anti-drug antibody) prevalence of 50%-60% [31][32] - **Impact of ADAs**: The presence of ADAs does not appear to significantly affect drug exposure or efficacy, as the drug has demonstrated strong efficacy despite ADA presence [31][32][36] Competitive Landscape - **Market Competition**: Upstream faces competition from Tezepelumab, which is already on the market. The company believes its robust data set and potential for a differentiated dosing regimen will provide a competitive edge [79][80] - **Analysis of Other Trials**: Upstream is aware of the nuances in statistical approaches used in competitor trials and aims to ensure its data is robust and compelling [51][52] COPD Indication - **Phase 2 VALIANT Trial for COPD**: Enrollment is progressing well, with over 60% of patients enrolled. The company is considering potential changes to the trial design based on insights gained from asthma data [65][68] - **Focus on Type 2 Inflammation**: The COPD trial is designed to target patients with higher eosinophil counts, reflecting a focus on Type 2 inflammation, which is less prevalent in the general COPD population [77][78] Additional Important Insights - **Dosing Strategy**: The company is exploring the possibility of higher dosing regimens for both asthma and COPD, which could enhance efficacy [24][70] - **Device Development**: Upstream is developing a concentrated formulation compatible with auto-injector platforms, aiming for a seamless launch with Phase 3 formulations [40][41] - **Regulatory Considerations**: The company is cautious about trial designs and regulatory paths, emphasizing the importance of robust data to support future submissions [82][85] This summary encapsulates the critical insights from Upstream Bio's FY conference call, highlighting the company's strategic direction, clinical data, and competitive positioning in the biopharmaceutical landscape.

Core Insights - Upstream Bio, Inc. presented additional data from the Phase 2 VIBRANT clinical trial for verekitug, showing significant efficacy in treating chronic rhinosinusitis with nasal polyps (CRSwNP) [1][2] - The trial demonstrated a placebo-adjusted reduction in endoscopic nasal polyp score (NPS) of -1.95 (p < 0.0001) and a reduction in nasal congestion score (NCS) of -0.96 (p < 0.0001) [1][2] - The company plans to initiate Phase 3 trials for CRSwNP and severe asthma, highlighting verekitug's potential to improve treatment standards for serious respiratory diseases [2][3] Company Overview - Upstream Bio is a clinical-stage biotechnology company focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders [11] - Verekitug is a novel monoclonal antibody targeting the thymic stromal lymphopoietin (TSLP) receptor, which plays a key role in inflammatory responses [8][11] - The company aims to address unmet needs in patients with conditions like CRSwNP and severe asthma through innovative therapies [11] Clinical Trial Details - The VIBRANT trial was a global, randomized, double-blind, placebo-controlled study involving 81 adults with CRSwNP, assessing the efficacy and safety of verekitug over 24 weeks [7] - Participants received 100 mg of verekitug or placebo every 12 weeks, with primary and secondary endpoints focused on nasal polyp scores and other symptoms [7] - The trial's design and endpoints are intended to support future regulatory submissions for product approval [3][7] Efficacy and Safety - Verekitug reduced the need for surgery or systemic corticosteroids by 76% (p = 0.03) compared to placebo, indicating a strong therapeutic effect [1][2] - The treatment was generally well tolerated, with no serious adverse events (SAEs) reported, reinforcing its favorable safety profile [1][2] Future Directions - Upstream Bio is preparing to initiate registrational trials for verekitug in CRSwNP and severe asthma, following planned interactions with regulatory authorities [3] - The company believes verekitug's unique mechanism of action and dosing schedule could significantly enhance the standard of care for patients with serious respiratory diseases [2]

Core Insights - Upstream Bio, Inc. is set to present new analyses from the Phase 2 VIBRANT trial of verekitug for chronic rhinosinusitis with nasal polyps (CRSwNP) at the AAAAI Congress 2026 [1][2] - Verekitug is a novel monoclonal antibody targeting the TSLP receptor, which plays a significant role in inflammatory responses [3][4] - The company is advancing verekitug through multiple Phase 2 clinical trials for various inflammatory diseases, including CRSwNP, severe asthma, and chronic obstructive pulmonary disease (COPD) [5][6] Presentation Details - The presentation titled "Efficacy and Safety of Verekitug (UPB-101) in Chronic Rhinosinusitis with Nasal Polyps: Results of the Phase 2 VIBRANT Trial" will be delivered by Dr. Joseph Han [2] - Scheduled for March 1, 2026, from 9:45 am to 10:45 am EST at the Convention Center, Level 2, Hall E [2] About Verekitug - Verekitug is the only known antagonist in clinical development that targets the TSLP receptor, inhibiting proinflammatory signaling [3][6] - TSLP is a key cytokine in allergic and inflammatory diseases, making it a strategic target for therapeutic intervention [4][6] Company Overview - Upstream Bio focuses on developing treatments for inflammatory diseases, particularly severe respiratory disorders [6] - The company aims to address unmet medical needs with its innovative monoclonal antibody, verekitug, which is currently in various stages of clinical trials [6]

Core Insights - Upstream Bio, Inc. is a clinical-stage biotechnology company focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders [2] Company Overview - Upstream Bio is developing verekitug, a monoclonal antibody that targets the receptor for thymic stromal lymphopoietin (TSLP), which is a key driver of inflammatory responses [2] - Verekitug is currently in separate Phase 2 trials for chronic rhinosinusitis with nasal polyps (CRSwNP), severe asthma, and chronic obstructive pulmonary disease (COPD) [2] - The company aims to address significant unmet medical needs for patients who are underserved by existing treatments [2] Upcoming Events - Rand Sutherland, CEO of Upstream Bio, will participate in investor conferences in March 2026, including: - TD Cowen 46 Annual Health Care Conference on March 4, 2026, at 9:50 a.m. ET [3] - 2026 Leerink Partners Global Healthcare Conference on March 9, 2026, at 1:40 p.m. ET [3] - Live webcasts of these presentations will be available on Upstream Bio's website [1]

Core Viewpoint - Upstream Bio Inc. shares have experienced a significant decline of over 54% following recent clinical trial results for its asthma treatment, indicating potential concerns among investors regarding the company's competitive positioning in the market [1][3]. Clinical Trial Results - The VALIANT trial reported a statistically significant 56% reduction in the annualized asthma exacerbation rate (AAER) for the 100 mg every 12 weeks dosing compared to placebo, alongside improvements in lung function and a high transition rate of over 90% of eligible patients to the long-term extension study [2]. Analyst Insights - Analyst William Blair noted that while biomarker results for verekitug appeared strong, the lower exacerbation reduction at the 400 mg Q6M dosing raised concerns about its competitive positioning against other candidates in Phase II/III development [3]. - Analyst Matt Phipps commented that the nearly 50% drop in shares is perceived as excessive, as the thymic stromal lymphopoietin (TSLP) space is viewed as a winner-take-all scenario for the first to commercialize a Q6M dosing regimen [4]. Stock Performance and Momentum - Currently, Upstream Bio's stock is trading 10.2% above its 20-day simple moving average (SMA) and 30.5% above its 100-day SMA, indicating strong short-term momentum, with a 12-month surge of 292.24% [4]. - The stock's Relative Strength Index (RSI) is at 45.37, indicating neutral territory, while the MACD is below its signal line, suggesting bearish pressure [5]. Analyst Consensus and Price Targets - The stock holds a Strong Buy rating with an average price forecast of $49.00, with recent analyst actions including targets of $51.00, $43.00, and $40.00 from Mizuho, LifeSci Capital, and Evercore ISI Group respectively [6]. - As of the latest publication, Upstream Bio shares were down 11.33% at $12.69, with key resistance at $33.50 and key support at $12.00 [6].

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," ...