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]

Group 1 - The article discusses Upstream Bio, Inc. (UPB) and its focus on treating respiratory disorders through TSLP targeting differentiation [2] - The author, Terry Chrisomalis, has extensive experience in the biotech sector and runs the Biotech Analysis Central service, which provides in-depth analysis of pharmaceutical companies [2] - Biotech Analysis Central offers a library of over 600 biotech investing articles and a model portfolio of more than 10 small and mid-cap stocks [2] Group 2 - The article does not provide any specific financial data or performance metrics related to Upstream Bio, Inc. or the biotech industry [1][3][4]

Summary of Upstream Bio FY Conference Call (December 04, 2025) Company Overview - **Company**: Upstream Bio (NasdaqGS:UPB) - **Focus**: Transition from early-stage clinical development to mid-stage development, particularly in the field of chronic rhinosinusitis (CRS) and severe asthma treatments Key Accomplishments - Transition to mid-stage development highlighted by the release of Phase 2 placebo-controlled data for the drug **Virectib** in chronic rhinosinusitis with nasal polyps [5][6] - Strong efficacy demonstrated with Virectib, showing significant clinical validation and a promising dosing schedule of every 12 weeks [5][6] Drug Mechanism and Competitive Landscape - **Virectib** is a monoclonal antibody targeting the TSLP receptor, which is expressed at lower levels compared to the ligand targeted by competitors like Amgen's Tezspire [7][8] - Virectib's pharmacological profile allows for greater efficacy, with a predicted effect on exhaled nitric oxide suppression approximately 50% greater than Tezepelamab [7][8] - Unique position as the only drug targeting the TSLP receptor in development [8] Clinical Data and Future Trials - Phase 2 Vibrant study showed a 1.8-point reduction in endoscopic nasal polyp score, significant reductions in nasal congestion, and improvements in sinusitis [17][18] - Positive data from CRS trials boosts confidence for upcoming asthma data release in Q1 2026, with plans to initiate Phase 3 trials for both indications simultaneously [19][21] - Anticipated efficacy in asthma trials is aimed at achieving a 50% reduction in annualized asthma exacerbation rates, comparable to existing biologics [23][24] Regulatory Strategy - Plans to engage with the FDA for regulatory interactions based on robust data from both CRS and asthma trials [19][34] - Potential for a single Phase 3 trial for each indication if data supports it [34] COPD Program - Ongoing Phase 2 trial for COPD with a focus on a broad patient population, including those with lower eosinophil counts [36][39] - Insights from Tezepelamab's Phase 2 program suggest TSLP is a promising target for COPD treatment [37][38] Market Position and Future Outlook - Upstream Bio aims to differentiate itself through robust efficacy and extended dosing intervals, with a focus on patient convenience and clinical significance [32][33] - The company is optimistic about its competitive positioning against existing therapies and the potential for significant market impact with its upcoming data releases [19][21][24]

Summary of Conference Call on Upstream Bio and Verekitug Company and Industry Overview - **Company**: Upstream Bio - **Industry**: Biopharmaceuticals, specifically focusing on treatments for asthma and chronic rhinosinusitis with nasal polyps Key Points and Arguments 1. **Upcoming Data Readouts**: The company anticipates significant data readouts in Q1 2026 for Verekitug, particularly regarding asthma treatment efficacy, following the completion of enrollment on June 9, 2023, for a 24-week study [1][2][3] 2. **Efficacy Expectations**: The target for success in the asthma study is a 50% reduction in exacerbation rates on a placebo-adjusted basis, with hopes to achieve this through both quarterly and biannual dosing regimens [4][6] 3. **Potency of Verekitug**: The drug is characterized by its high potency, which has been demonstrated in previous studies, suggesting it could deliver best-in-class efficacy with extended dosing intervals [5][6][19] 4. **Comparison with Competitors**: The company aims to differentiate Verekitug from existing biologics like Tezspire and Dupixent by offering a unique dosing schedule and potentially superior efficacy [26][28] 5. **Clinical Trial Design**: The design of the trials is informed by previous data, with a focus on replicating successful outcomes seen in other biologics while adhering to regulatory standards [12][13][28] 6. **Market Penetration Challenges**: Despite the large market for asthma treatments, less than 10% of patients currently use biologics, attributed to factors such as patient eligibility based on eosinophil counts and market access issues [30][31] 7. **Regulatory Strategy**: The company plans to engage with regulatory agencies to potentially run concurrent studies for asthma and chronic rhinosinusitis, which is a unique approach compared to typical staggered study designs [29] Additional Important Insights 1. **Biomarker Relevance**: Exhaled nitric oxide (FeNO) levels are highlighted as a significant biomarker for predicting asthma exacerbations, with Verekitug expected to show superior results in this area compared to competitors [19][20] 2. **Patient Population**: The trials are designed to include patients with a history of exacerbations, ensuring that the study population is representative of those most likely to benefit from treatment [11][12] 3. **Future Development Plans**: The company is optimistic about the potential for Verekitug to address unmet needs in both asthma and chronic rhinosinusitis, with plans for robust data collection to inform future phase 3 trials [22][23] This summary encapsulates the critical discussions and insights from the conference call, focusing on the strategic positioning of Upstream Bio and its product Verekitug within the biopharmaceutical landscape.

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, the only known antagonist in clinical development targeting the receptor for thymic stromal lymphopoietin (TSLP), which is a key driver of inflammatory responses [2] - The company has advanced verekitug into separate Phase 2 trials for chronic rhinosinusitis with nasal polyps (CRSwNP), severe asthma, and chronic obstructive pulmonary disease (COPD) [2] - Upstream Bio aims to address significant unmet needs for patients who are underserved by current standard care [2] Upcoming Events - Rand Sutherland, CEO of Upstream Bio, will participate in the Piper Sandler 37th Annual Healthcare Conference on December 2, 2025, at 4:30 p.m. ET [3] - The company will also be present at the 8th Annual Evercore Healthcare Conference on December 4, 2025, at 10:25 a.m. ET [3] - Live webcasts of these presentations will be available on Upstream Bio's website, with replays posted afterward [1][3]

Upstream Bio Conference Call Summary Company Overview - **Company**: Upstream Bio (NasdaqGS:UPB) - **Event**: First annual I&I Summit - **Date**: November 12, 2025 Key Industry Insights Drug Development and Efficacy - Upstream Bio presented positive Phase 2 data for **verekitug**, an antibody targeting the **TSLP receptor**, showing long pharmacodynamic activity with a dosing schedule of Q12 weeks [3][5][6] - The drug demonstrated a **76% reduction** in systemic corticosteroid use and surgery needs in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) [9][10] - The data indicated that there was no plateau in efficacy at 24 weeks, suggesting potential for continued improvement in longer studies [4][8] Clinical Trial Progression - Upstream Bio is advancing towards Phase 3 trials for both CRSwNP and severe asthma, with plans to analyze data from both indications contemporaneously to inform dose selection [11][12] - The company aims to initiate Phase 3 programs as quickly as possible, contingent on data analysis and regulatory feedback [31] Competitive Landscape - Upstream Bio differentiates itself from competitors by targeting the **TSLP receptor** rather than the ligand, which is the approach taken by other companies [34][35] - The competitive landscape includes drugs from GSK and ILOS, which are reportedly behind Upstream Bio in development timelines [32][34] Additional Important Points Pharmacodynamics and Dosing - The pharmacodynamic profile of verekitug suggests that it maintains receptor occupancy for up to **24 weeks** after the last dose, which is critical for sustained efficacy [24][22] - The company is exploring the potential for extended dosing intervals (Q24 weeks) while ensuring that efficacy is not compromised [17][22] Regulatory Considerations - Upstream Bio is focused on obtaining robust data to support regulatory negotiations, with a primary endpoint of asthma exacerbation reduction set at **50% or greater** [26][28] - The company is preparing for potential discussions with regulators regarding the design of future trials, including considerations for secondary endpoints like lung function improvement [30][31] Future Data Releases - Upcoming data from the Phase 2 trials is expected in Q1, with plans to present findings at major medical meetings such as QuadAI and ATS in the first half of the following year [38] This summary encapsulates the critical insights and developments discussed during the Upstream Bio conference call, highlighting the company's strategic direction and competitive positioning within the biotech industry.

Summary of Upstream Bio Conference Call Company Overview - Upstream Bio is a clinical stage company focused on severe respiratory diseases, specifically developing virecotug, a monoclonal antibody targeting the TSLP receptor [1][4] Core Points and Arguments Product Differentiation - Virecotug is unique as it targets the TSLP receptor rather than the ligand, which is the approach taken by other companies [1][36] - This receptor-targeting strategy is expected to provide specific pharmacological benefits, potentially leading to superior efficacy and extended dosing intervals [2][36] Clinical Trials and Data - The company is conducting multiple Phase II trials for virecotug in chronic rhinosinusitis with nasal polyps (CRS with NP), severe asthma, and chronic obstructive pulmonary disease (COPD) [2][3] - Recent Phase II trial data for CRS with NP showed a primary endpoint achievement with a reduction in the endoscopic nasal polyp score by 1.8 points, alongside significant secondary endpoint results [9][21] - The upcoming Phase II trial data for severe asthma is expected in Q1 of next year, with a focus on a 50% reduction in asthma exacerbations as a primary endpoint [3][28] Market Opportunity - The market for biologics in the targeted indications is projected to exceed $35 billion by the mid-2030s, indicating substantial commercial potential [4][30] - There is a growing trend towards the use of biologics in CRS with NP and severe asthma, with existing products like dupilumab and tezepelumab already approved [30][31] Safety and Efficacy - Virecotug has demonstrated a favorable safety profile consistent with other biologics in the same space, showing high tolerability [13][21] - The drug's pharmacological modeling suggests a greater effect on exhaled nitric oxide compared to existing treatments, indicating potential for improved efficacy [16][19] Future Directions - Upstream Bio plans to continue its clinical development and is well-funded through 2027, allowing for further trial execution and preparation for Phase III studies [4][48] - The company is considering the potential for commercialization independently, leveraging its understanding of the market dynamics and patient needs [45][46] Additional Important Content - The company has a robust team with extensive experience in respiratory disease clinical development [4] - There is potential for virecotug to be used in other therapeutic areas such as dermatology and gastrointestinal diseases in the future [32] - The competitive landscape is acknowledged, but Upstream Bio believes it has a timeline and data advantage over other companies in the same field [43][44]

Financial Performance - As of September 30, 2025, the company reported net losses of $33.7 million for the three months ended September 30, 2025, compared to $16.0 million for the same period in 2024, indicating a 110.6% increase in losses year-over-year[114] - The company has incurred significant net operating losses and negative cash flows since inception, with net losses of $101.0 million for the nine months ended September 30, 2025, compared to $41.6 million for the same period in 2024, representing a 142.4% increase[114] - The net loss for the nine months ended September 30, 2025, was $101.0 million, compared to a net loss of $41.6 million in 2024, reflecting an increase of 143.0%[153] Revenue and Collaboration - The company has not generated any revenue from product sales since inception and does not expect to do so in the foreseeable future, relying instead on collaboration revenue from the Maruho License Agreement[129] - During the nine months ended September 30, 2025, the company received $2.1 million from Maruho, compared to $1.2 million during the same period in 2024, reflecting a 75% increase[127] - Collaboration revenue for the three months ended September 30, 2025, was $0.7 million, an increase of 12.5% from $0.6 million in the same period of 2024[146] - For the nine months ended September 30, 2025, collaboration revenue was $2.2 million, up 24.4% from $1.8 million in 2024[154] Expenses - Research and development expenses for the three months ended September 30, 2025, were $33.0 million, up 113.6% from $15.4 million in 2024, primarily due to increased costs associated with the verekitug program[147] - Research and development expenses for the nine months ended September 30, 2025, totaled $96.6 million, a 134.7% increase from $41.2 million in 2024, driven by higher costs in the verekitug program[155] - General and administrative expenses increased to $5.5 million for the three months ended September 30, 2025, compared to $4.1 million in 2024, reflecting a rise of 36.3% driven by higher personnel costs[151] - General and administrative expenses totaled $19.7 million for the nine months ended September 30, 2025, up from $12.0 million in 2024, reflecting a $7.7 million increase[159][160] - Total operating expenses for the nine months ended September 30, 2025, were $116.4 million, a significant increase of 118.9% from $53.2 million in 2024[153] Cash and Investments - The company has an accumulated deficit of $291.8 million and cash, cash equivalents, and short-term investments totaling $372.4 million as of September 30, 2025, which is expected to fund operations through 2027[114] - Net cash used in operating activities was $102.6 million for the nine months ended September 30, 2025, compared to $39.6 million in 2024[164][165] - Net cash used in investing activities was $152.4 million for the nine months ended September 30, 2025, compared to $101.4 million in 2024[168][169] - Interest income rose to $4.1 million for the three months ended September 30, 2025, a 41.4% increase from $2.9 million in 2024, attributed to higher balances in investments[152] - Interest income increased to $13.3 million for the nine months ended September 30, 2025, compared to $7.0 million in 2024, an increase of $6.3 million[162] Future Expectations - The company expects general and administrative expenses to rise as it increases headcount and expands infrastructure to support ongoing research and development[137] - The company anticipates increased R&D and administrative expenses as it advances verekitug through clinical trials and potential future product candidates[172] - The company expects to fund operations through a combination of equity offerings, debt financings, and collaborations, as it does not expect to generate revenue from product sales for several years[172][175] Clinical Development - The company reported positive top-line results in the Phase 2 trial for chronic rhinosinusitis with nasal polyps (CRSwNP) in September 2025 and anticipates reporting data from the severe asthma Phase 2 trial in Q1 2026[112] - Research and development expenses are expected to increase significantly as the company advances verekitug through clinical trials, with costs associated with later-stage trials generally being higher[131] - The company has incurred approximately $86.8 million in direct external expenses for the development of verekitug for severe asthma, COPD, and CRSwNP since their development candidate nominations[158] Agreements and Royalties - The company is required to pay mid-single-digit percentage royalties on aggregate worldwide net sales of any product developed that contains the compound verekitug as an ingredient[124] - The company has entered into multiple agreements, including the Astellas Asset Purchase Agreement and the Maruho License Agreement, to support the development and commercialization of verekitug[120][125] Company Classification - The company is classified as an "emerging growth company" under the JOBS Act, allowing it to adopt new accounting standards at the same time as private companies[190] - The company is also a "smaller reporting company," which may continue if its market value is below $250 million or annual revenue is below $100 million[191] - As a smaller reporting company, the company can present only the two most recent fiscal years of audited financial statements in its Annual Report on Form 10-K[191] - The company has reduced disclosure obligations regarding executive compensation due to its status as a smaller reporting company[191] - The company is not required to provide quantitative and qualitative disclosures about market risk as a smaller reporting company[192]