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]

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]