Core Insights - Upstream Bio has initiated a Phase 2 clinical trial, VENTURE, to evaluate the efficacy and safety of verekitug in patients with moderate-to-severe COPD, marking the expansion of its global development program into a third indication [1][3] - Verekitug is a novel antibody antagonist targeting the TSLP receptor, which plays a significant role in the inflammatory response associated with allergic and inflammatory diseases [2][6] - The trial aims to assess the annualized rate of moderate or severe COPD exacerbations as the primary endpoint, with secondary endpoints including changes in symptoms and lung function [4] Company Overview - Upstream Bio is a clinical-stage biotechnology company focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders [17] - The company is advancing verekitug, the only known monoclonal antibody in clinical development targeting the TSLP receptor, through multiple Phase 2 trials for CRSwNP, severe asthma, and COPD [9][17] - The company aims to address unmet needs in patient populations underserved by current standard treatments [18] Clinical Trial Details - The VENTURE trial is a randomized, double-blind, placebo-controlled study involving approximately 670 adults with moderate-to-severe COPD, with treatment periods ranging from 60 to 108 weeks [3][4] - Participants will receive either verekitug at doses of 100 mg every 12 weeks, 400 mg every 24 weeks, or a placebo [3] - The trial is designed to potentially support regulatory submissions based on the data collected [4] Current Research and Development - Upstream Bio has completed enrollment in separate Phase 2 trials for CRSwNP and severe asthma, with top-line data expected in the third quarter of 2025 and the first quarter of 2026, respectively [5] - Preclinical studies have shown that verekitug effectively inhibits TSLP signaling and demonstrates potential efficacy against various types of inflammation [10][11] Disease Context - COPD is a chronic inflammatory disease that significantly impacts airflow and is associated with high morbidity and mortality, being the fourth leading cause of death globally [12][14] - The prevalence of COPD is projected to increase due to ongoing exposure to risk factors and an aging population [14] - Current treatments for COPD include inhaled steroids and bronchodilators, with biologics emerging as new treatment options [16]

Core Insights - Upstream Bio, Inc. presented pharmacology modeling data at the EAACI Congress, highlighting the greater potency of verekitug compared to tezepelumab in treating inflammatory diseases [1][3] - Verekitug targets the TSLP receptor, offering a potentially differentiated profile across severe asthma, COPD, and CRSwNP [1][2] Company Overview - Upstream Bio is a clinical-stage biotechnology company focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders [11] - Verekitug is the only monoclonal antibody in clinical development that targets and inhibits the TSLP receptor, which is a key driver of inflammatory responses [2][11] Mechanism of Action - TSLP is a cytokine that initiates the inflammatory cascade, and blocking its receptor can impact multiple inflammatory processes [2][5] - The pharmacokinetic/pharmacodynamic (PK/PD) modeling indicates that verekitug provides complete and sustained inhibition of the TSLP/TSLPR complex, leading to a greater reduction in fractional exhaled nitric oxide (FeNO) compared to tezepelumab [6][8] Clinical Development - Verekitug is currently being evaluated in two Phase 2 clinical trials: the VALIANT trial for severe asthma and the VIBRANT trial for CRSwNP, with plans for a trial in COPD [8][10] - The company anticipates top-line Phase 2 clinical data for CRSwNP in Q3 2025 and for severe asthma in the first half of 2026 [3][8] Preclinical and Clinical Data - Preclinical studies demonstrated that verekitug has high occupancy of the TSLP receptor and effectively inhibits TSLP signaling [9] - Previous clinical trials showed that verekitug was well tolerated and exhibited a predictable pharmacokinetic profile [10]

Upstream Bio (UPB) FY 2025 Conference June 11, 2025 09:20 AM ET Speaker0 Good morning. We'll continue with the next session. I'm Paul Choi, and I cover the biotech sector here at Goldman Sachs. It's my pleasure to have, upstream bio here for our next session. To my left here is Brand Sutherland. And what maybe what we'll do is have Brand kick it off with a bit of an overview of Upstream, maybe a little bit of background on it and sort of what the company's maybe special sauce is. Speaker1 Sure. Well, you, P ...

Core Insights - Upstream Bio, Inc. is focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders, and will present new data on June 15, 2025, at the EAACI Congress 2025 in Glasgow, UK [1][2] Group 1: Presentation Details - The presentation will discuss translational pharmacology modeling data that supports the targeting of the TSLP receptor with verekitug, showing greater potency compared to treatments targeting the TSLP ligand [1][2] - The presenting author is Ashish Kalra, PhD, Vice President of Translational Research at Upstream Bio, and the poster number is D3.113 [2] Group 2: TSLP and TSLPR Blockade - Thymic Stromal Lymphopoietin (TSLP) is a key cytokine in the inflammatory response for diseases like asthma, and blocking TSLP signaling is a validated therapeutic strategy [3] - TSLP activation initiates a cascade of inflammatory responses, making TSLPR blockade a potential single treatment for multiple inflammatory diseases [4] Group 3: About Verekitug - Verekitug is a novel fully human IgG1 monoclonal antibody that inhibits TSLP receptor signaling and is currently the only mAb in clinical development targeting this receptor [5][8] - It is being evaluated in two Phase 2 clinical trials: the VALIANT trial for severe asthma and the VIBRANT trial for chronic rhinosinusitis with nasal polyps, with an additional trial for COPD being initiated [5][9] - Preclinical studies indicate verekitug has high receptor occupancy and effectively inhibits TSLP signaling, suggesting potential efficacy against various inflammatory conditions [6] Group 4: Clinical Trials and Development - Three clinical trials for verekitug have been completed, showing it was well tolerated with no significant immunogenicity and a consistent pharmacokinetic profile [7] - The company aims to address unmet needs in patients with severe respiratory disorders through the development of verekitug [9]

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 a monoclonal antibody named verekitug, which targets the receptor for thymic stromal lymphopoietin, a key cytokine involved in inflammatory responses [3] - Verekitug is currently in separate Phase 2 trials for severe asthma and chronic rhinosinusitis with nasal polyps, with plans to initiate development for chronic obstructive pulmonary disease [3] Upcoming Events - Rand Sutherland, MD, CEO of Upstream Bio, will participate in a fireside chat at the Goldman Sachs 46th Annual Global Healthcare Conference on June 11, 2025, at 9:20 a.m. ET [1] - A live webcast of the event will be available on the company's website, with a replay posted afterward [2]

Core Insights - Upstream Bio, Inc. has appointed Stacy Price as Chief Technology Officer to enhance its technical operations and product development for verekitug, a treatment for severe respiratory disorders [1][2] - The company is preparing to initiate a third clinical program for verekitug, which targets the receptor for thymic stromal lymphopoietin, a key driver of inflammatory responses [2][3] - Upstream Bio is committed to addressing unmet medical needs in severe respiratory diseases through the development of verekitug, which is currently in Phase 2 trials for severe asthma and chronic rhinosinusitis with nasal polyps [3] Company Overview - Upstream Bio 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 that is the only known antagonist in clinical development targeting the receptor for thymic stromal lymphopoietin [3] - Upstream Bio aims to maximize the unique attributes of verekitug to meet the substantial unmet needs of patients underserved by current standard care [3]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from _________________ to _________________ Commission File Number: 001-42366 UPSTREAM BIO, INC. (Exact Name of Registrant as Specified in its Charter) (State or oth ...

Upstream Bio Reports First Quarter 2025 Financial Results and Accelerates Guidance on All Clinical Programs – 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 dose ...

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Financial Performance - The company reported net losses of $62.8 million and $20.5 million for the years ended December 31, 2024 and 2023, respectively, with an accumulated deficit of $190.8 million as of December 31, 2024[587]. - The net loss for the year ended December 31, 2024 was $62.8 million, compared to a net loss of $20.5 million in 2023, reflecting an increase of $42.3 million[615]. - The company expects to continue incurring significant net operating losses for the foreseeable future, depending on the timing of expenditures on research and development activities[588]. - The company has incurred significant net operating losses and negative cash flows since inception, indicating a need for additional financing to support ongoing operations[590]. Cash and Investments - The company has cash, cash equivalents, and short-term investments totaling $470.5 million, which are expected to fund operations through 2027[587]. - As of December 31, 2024, the company had cash, cash equivalents, and short-term investments totaling $470.5 million[626]. - The company believes its existing cash, cash equivalents, and short-term investments will fund operating expenses through 2027[638]. Initial Public Offering (IPO) - The company completed its IPO in October 2024, issuing 17,250,000 shares at a public price of $17.00 per share, resulting in net proceeds of $268.8 million after deducting underwriting discounts and commissions[586]. Research and Development - The company is developing verekitug, currently in Phase 2 trials for severe asthma and chronic rhinosinusitis with nasal polyps, with top-line data expected in the second half of 2025 and 2026, respectively[585]. - Research and development expenses are expected to increase as the company advances verekitug through clinical trials, with higher costs anticipated in later stages of development[603]. - Research and development expenses increased to $63.0 million in 2024 from $31.8 million in 2023, driven by a $23.8 million increase in expenses for the verekitug program[617]. - The company expects increased research and development and general administrative expenses as it advances its product candidates through clinical trials[635]. - The company incurred approximately $51.0 million in direct external expenses for the development of verekitug for severe asthma since its nomination[621]. Revenue and Collaboration - The company has not generated any revenue from product sales and does not expect to do so in the foreseeable future, relying on collaboration revenue from the Maruho License Agreement[601]. - Collaboration revenue from related parties was $2.4 million for both years ended December 31, 2024 and 2023, primarily related to clinical trials for severe asthma[616]. Operating Expenses - The total operating expenses for 2024 were $80.1 million, up from $42.5 million in 2023, marking an increase of $37.6 million[615]. - General and administrative expenses rose to $17.2 million in 2024 from $10.7 million in 2023, with personnel expenses increasing by $4.5 million due to higher headcount[622]. - The company expects general and administrative expenses to increase in the future as it expands its infrastructure and headcount to support ongoing research and development[609]. Financing Activities - The company has received total gross proceeds of $400.0 million from the issuance of Series A and Series B redeemable convertible preferred stock[586]. - The company anticipates financing operations through equity offerings, debt financings, and collaborations until substantial product revenue is generated[639]. - The company provided $129.6 million in net cash from financing activities during the year ended December 31, 2023, including $80.0 million from the issuance of Series A Preferred Stock[634]. Lease and Payments - The company entered into a three-year lease agreement for office space with an initial base rent of approximately $0.7 million for the first year[648]. - The company has made annual payments to Lonza of $0.5 million and $0.4 million for the years ended December 31, 2024 and 2023, respectively, related to the Lonza License Agreement[600]. - Annual payments to Lonza under the Lonza License Agreement were $0.4 million for the year ended December 31, 2023[647]. Stock and Valuation - The company issued stock option awards with performance-based vesting conditions to key executives, with stock-based compensation recognized upon achievement of performance conditions in February 2023 and April 2024[657]. - Prior to the IPO in October 2024, the estimated fair value of the company's common stock was determined by the board of directors, considering third-party valuations and other relevant factors[658]. - The company classified Series A and Series B preferred stock tranche rights as liabilities, initially recorded at fair value upon issuance[659]. - Changes in the fair value of preferred stock tranche right liabilities were recognized as a component of other income in the consolidated statements of operations until settled[660]. - The fair value of Series A preferred stock tranche right liability was determined using a probability-weighted expected return method, with significant assumptions impacting valuation[663]. - The fair value of Series B preferred stock tranche right liability was determined using an option pricing model, with the fair value of Series B Preferred Stock as a key assumption[664]. Regulatory and Reporting Status - The company is classified as a "smaller reporting company," with a market value of common stock held by non-affiliates less than $700 million and annual revenue below $100 million[668]. - The company has elected not to "opt out" of the extended transition period for new accounting standards, which may affect comparability with other public companies[667]. - The company may continue to rely on exemptions from certain disclosure requirements as a smaller reporting company, including reduced obligations regarding executive compensation[668]. - The company is not required to provide quantitative and qualitative disclosures about market risk due to its status as a smaller reporting company[669].