Upstream Bio, Inc.(UPB) - 2025 Q2 - Quarterly Results

Executive Summary & Company Overview Upstream Bio is a clinical-stage biotech developing verekitug for inflammatory diseases, with ongoing Phase 2 trials and upcoming data readouts Company Profile and Strategic Focus Upstream Bio is a clinical-stage biotechnology company focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders - Upstream Bio is a clinical-stage company developing verekitug, the only monoclonal antibody currently in clinical development that targets and inhibits the thymic stromal lymphopoietin (TSLP) receptor[1] - The company's initial focus is on severe respiratory disorders, including chronic rhinosinusitis with nasal polyps (CRSwNP), severe asthma, and chronic obstructive pulmonary disease (COPD)[1] - Verekitug's unique pharmacology is believed to offer differentiated efficacy and an extended dosing interval compared to current standard of care biologics[1][2] Key Clinical Development Highlights Upstream Bio reported significant progress in its clinical development programs for verekitug, including completing enrollment for the severe asthma trial and initiating the COPD trial, while remaining on track for key data readouts - Completed enrollment in Phase 2 trial in severe asthma (VALIANT) in June 2025; top-line data expected in the first quarter of 2026[1][2] - First patient dosed in Phase 2 trial in chronic obstructive pulmonary disease (COPD) (VENTURE) in July 2025, marking entry into a third major respiratory indication[1][2] - On track to report top-line data from Phase 2 trial in chronic rhinosinusitis with nasal polyps (CRSwNP) (VIBRANT) in the third quarter of 2025[1][2] Clinical Development Programs Upstream Bio is advancing verekitug through multiple Phase 2 clinical trials for severe respiratory disorders, with several key data readouts anticipated Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) Program The VIBRANT Phase 2 trial for CRSwNP completed patient enrollment in January 2025, with top-line data anticipated in the third quarter of 2025 - Top-line data from the VIBRANT Phase 2 trial in CRSwNP expected in Q3 2025[3] - VIBRANT is a global, randomized, double-blind, placebo-controlled, parallel group clinical trial assessing verekitug efficacy and safety, dosed every 12 weeks[3] - Patient enrollment for VIBRANT was completed in January 2025[3] Severe Asthma Program The VALIANT Phase 2 trial for severe asthma completed enrollment in June 2025, with top-line data expected in Q1 2026 - Top-line data from the VALIANT Phase 2 trial in severe asthma expected in Q1 2026[4] - VALIANT is a global, randomized, double-blind, placebo-controlled trial assessing verekitug efficacy and safety with extended dosing intervals of 12 and 24 weeks[4] - Initiated long term extension study (VALOUR) in severe asthma in May 2025 for eligible participants who completed the VALIANT trial[9] Chronic Obstructive Pulmonary Disease (COPD) Program Upstream Bio entered a third major respiratory indication with the initiation of the VENTURE Phase 2 clinical trial for moderate-to-severe COPD in July 2025 - First patient dosed in the VENTURE Phase 2 clinical trial in patients with COPD in July 2025, marking entry into a third major respiratory indication[9] - VENTURE is a global, randomized, double-blind, placebo-controlled trial designed to assess verekitug efficacy and safety in moderate-to-severe COPD with extended dosing intervals of 12 and 24 weeks[9] Second Quarter 2025 Financial Results Upstream Bio reported a strong cash position expected to fund operations through 2027, despite increased operating expenses and a larger net loss in Q2 2025 Cash Position and Runway As of June 30, 2025, Upstream Bio maintained a strong cash position, which is projected to fund its planned operations through 2027 Cash, Cash Equivalents and Short-Term Investments | Metric | Amount (Millions) | | :-------------------------------- | :------------------ | | Cash, cash equivalents and short-term investments (June 30, 2025) | $393.6 | - The current cash position is expected to fund planned operations through 2027[6] Operating Expenses Operating expenses significantly increased in Q2 2025 compared to Q2 2024, driven primarily by higher clinical and manufacturing costs for verekitug programs and increased personnel-related expenses Operating Expenses (Three Months Ended June 30) | Expense Category | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (Millions) | Change (%) | | :----------------------- | :----------------- | :----------------- | :---------------- | :--------- | | Research and development | $37.9 | $14.1 | +$23.8 | +168.8% | | General and administrative | $7.4 | $4.0 | +$3.4 | +85.0% | - Increase in R&D expenses was primarily due to increased clinical and manufacturing expenses related to verekitug programs[6] - Increase in G&A expenses was primarily driven by higher personnel-related expenses, including share-based compensation, and professional service fees[7] Net Loss Upstream Bio reported a substantially larger net loss in Q2 2025 compared to the same period in 2024, mainly attributable to the increased research and development and general and administrative expenses Net Loss (Three Months Ended June 30) | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (Millions) | Change (%) | | :------- | :----------------- | :----------------- | :---------------- | :--------- | | Net loss | $(40.0) | $(14.7) | $(25.3) | +172.1% | - The increase in net loss was largely due to increased research and development and general and administrative expenses, partially offset by increased interest income[8] Corporate Information This section provides an overview of Upstream Bio's mission, upcoming investor events, and important disclosures regarding forward-looking statements About Upstream Bio Upstream Bio is dedicated to developing verekitug, a highly potent TSLP receptor antagonist, to address significant unmet needs in inflammatory diseases, particularly severe respiratory disorders, leveraging its unique mechanism of action - Upstream Bio is a clinical-stage biotechnology company developing treatments for inflammatory diseases, with an initial focus on severe respiratory disorders[11] - Verekitug is the only known antagonist currently in clinical development that targets the receptor for thymic stromal lymphopoietin (TSLP), a clinically validated driver of inflammatory response[11] - The company is committed to maximizing verekitug's unique attributes to address substantial unmet needs for patients underserved by today's standard of care[11] Upcoming Events & Investor Relations Upstream Bio plans to participate in several investor conferences and medical congresses in Q3 and Q4 2025 and utilizes its investor relations website as a primary channel for disclosing material nonpublic information - Upstream Bio expects to participate in the Stifel Virtual Immunology and Inflammation Forum (September 15–16, 2025), European Respiratory Society (September 27–October 1, 2025), and 2025 Truist Securities Biopharma Symposium (November 6, 2025)[10] - The company intends to use the investor relations page on its website (www.upstreambio.com) for disclosing material nonpublic information and complying with Regulation FD[12] Forward-Looking Statements This section contains standard forward-looking statements, highlighting risks and uncertainties related to the clinical development, regulatory approval, funding, and commercialization of verekitug, as well as other business risks - Statements regarding the timing, progress, and results of ongoing and planned clinical trials for verekitug are forward-looking[13] - Risks include Upstream Bio's ability to advance verekitug through clinical development, obtain regulatory approval, fund development activities, and its dependence on third parties[13] - Readers are cautioned that actual results could differ materially due to various risks and uncertainties detailed in the company's SEC filings[13][14] Condensed Consolidated Financial Statements This section presents Upstream Bio's condensed consolidated financial statements, including the balance sheet and statements of operations, for the periods ended June 30, 2025 Condensed Consolidated Balance Sheet The balance sheet provides a snapshot of Upstream Bio's financial position, showing a decrease in total assets and stockholders' equity from December 31, 2024, to June 30, 202