Financial Performance - Upstream Bio reported a net loss of $33.7 million for Q3 2025, compared to a net loss of $16.0 million in Q3 2024, reflecting an increase of $17.7 million primarily due to higher research and development expenses[11]. - Upstream Bio's total operating expenses for Q3 2025 were $38.5 million, compared to $19.5 million in Q3 2024, reflecting an increase driven by research and development activities[21]. Research and Development - Research and development expenses for Q3 2025 were $33.0 million, up from $15.4 million in the same period last year, marking an increase of $17.6 million driven by clinical and manufacturing costs related to verekitug programs[9]. - The company is investing in CMC and drug delivery to enhance the clinical profile and utility of verekitug for patients[2]. Clinical Trials - Positive top-line results from the VIBRANT Phase 2 trial in chronic rhinosinusitis with nasal polyps (CRSwNP) showed a statistically significant reduction in placebo-adjusted endoscopic nasal polyp score of -1.8 (p<0.0001) after 24 weeks[3]. - Key secondary endpoints in the VIBRANT trial showed a reduction in nasal congestion score of -0.8 (p=0.0003) and a 76% (p=0.03) reduction in the need for surgery or systemic corticosteroids[7]. - Verekitug demonstrated a favorable safety profile with no serious adverse events reported during the VIBRANT trial[7]. - The VALIANT Phase 2 trial in severe asthma is on track to report top-line results in Q1 2026, with patient enrollment completed in June 2025[5]. - Enrollment is ongoing in the VENTURE Phase 2 trial for chronic obstructive pulmonary disease (COPD), with the first patient dosed in July 2025[8]. Financial Position - Cash, cash equivalents, and short-term investments totaled $372.4 million as of September 30, 2025, which is expected to fund operations through 2027[9].

Core Insights - Upstream Bio, Inc. reported positive top-line results from the VIBRANT Phase 2 trial of verekitug in chronic rhinosinusitis with nasal polyps (CRSwNP), demonstrating significant efficacy and a favorable safety profile [1][5] - The company is on track to report results from the VALIANT Phase 2 trial in severe asthma in the first quarter of 2026, with ongoing enrollment in the VENTURE Phase 2 trial for chronic obstructive pulmonary disease (COPD) [1][4][12] - Financial results for Q3 2025 show a net loss of $33.7 million, with increased research and development expenses primarily related to verekitug programs [8][10][19] Recent Business Highlights - The VIBRANT Phase 2 trial met its primary endpoint with a statistically significant reduction in placebo-adjusted endoscopic nasal polyp score of -1.8 (p<0.0001) [5] - Key secondary endpoints showed a reduction in nasal congestion score of -0.8 (p=0.0003) and a 76% (p=0.03) reduction in the need for surgery or systemic corticosteroids [5] - Structural and mechanistic data presented at the European Respiratory Society Congress highlighted verekitug's unique mechanism of action in disrupting TSLP signaling [2][12] Upcoming Milestones - Top-line data from the VALIANT Phase 2 trial in severe asthma is expected in Q1 2026, with the trial designed to assess efficacy and safety in extended dosing intervals of 12 and 24 weeks [4] - Enrollment is ongoing in the VENTURE Phase 2 trial for COPD, with the first patient dosed in July 2025 [1][12] Financial Overview - As of September 30, 2025, Upstream Bio had cash, cash equivalents, and short-term investments totaling $372.4 million, expected to fund operations through 2027 [8] - Research and development expenses for Q3 2025 were $33.0 million, up from $15.4 million in the same period in 2024, reflecting increased clinical and manufacturing costs [8][10] - General and administrative expenses rose to $5.5 million in Q3 2025, compared to $4.1 million in Q3 2024, driven by personnel-related costs [9]

Core Insights - Upstream Bio, Inc. is a clinical-stage biotechnology company focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders [2] - The company is advancing its lead candidate, verekitug, which targets the receptor for thymic stromal lymphopoietin (TSLP), into Phase 2 trials for chronic rhinosinusitis with nasal polyps, severe asthma, and chronic obstructive pulmonary disease [2] Upcoming Events - Rand Sutherland, CEO of Upstream Bio, will participate in several investor conferences in November 2025, including the Truist Securities BioPharma Symposium on November 6, Stifel 2025 Healthcare Conference on November 11, and TD Cowen Immunology and Inflammation Summit on November 12 [1][3] - Live webcasts of the presentations will be available on Upstream Bio's website, with replays posted afterward [1]

Core Insights - Upstream Bio, Inc. is advancing its clinical-stage monoclonal antibody, verekitug, which targets the TSLP receptor, showing potential for treating severe respiratory diseases [1][10] - Recent data presented at the European Respiratory Society Congress indicate verekitug's unique mechanism of action may lead to differentiated therapeutic effects across various TSLP-driven inflammatory diseases [1][2] Mechanism of Action - Verekitug prevents TSLP from binding to its receptor by occupying ligand binding sites and outcompetes TSLP even in the presence of preformed receptor complexes [1][6] - The high affinity of verekitug (KD < 1 pM) allows it to inhibit proinflammatory signaling initiated by TSLP effectively [6][8] Clinical Development - Verekitug has shown rapid and sustained TSLP receptor inhibition for up to 24 weeks post-administration, indicating a potential for less frequent dosing compared to existing biologic therapies [2][9] - The recently completed VIBRANT trial demonstrated that a single dose of 100 mg verekitug every 12 weeks met both primary and secondary endpoints in patients with chronic rhinosinusitis with nasal polyps [7][10] - Ongoing trials include the VALIANT trial for severe asthma and the VENTURE trial for moderate-to-severe chronic obstructive pulmonary disease (COPD) [7][10] Preclinical and Clinical Data - Preclinical studies have shown verekitug's high occupancy of the TSLP receptor and its ability to inhibit cytokine production from CD4+ T cells and ILC2 cells [8] - In Phase 1 trials, verekitug was well tolerated and demonstrated significant reductions in fractional exhaled nitric oxide (FeNO) and blood eosinophils in asthma patients [9] Company Overview - Upstream Bio is focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders, with verekitug being the only known antagonist targeting the TSLP receptor currently in clinical development [10]

Upstream Bio Conference Call Summary Company Overview - Upstream Bio is a clinical-stage biotechnology company focused on developing Viraqita, the only known antagonist of the TSLP receptor in clinical development [2][3] - The company is currently funded through a successful IPO last year, with funding expected to last until 2027 [3][4] Product Development - Viraqita is being developed for three indications: 1. Chronic rhinosinusitis with nasal polyps (CRSwNP) 2. Severe asthma 3. Chronic obstructive pulmonary disease (COPD) - The company is in Phase 2 trials for all three indications, aiming to support a Biologics License Application (BLA) with these trials [3][4] Unique Mechanism of Action - Upstream Bio targets the TSLP receptor rather than the ligand, which is a significant differentiation from competitors [5][6] - Viraqita can fully occupy 100% of free TSLP receptors within two weeks and maintain this occupancy for up to 24 weeks after the last dose [6] Clinical Data and Efficacy - The Phase 2 trial for CRSwNP has shown promising results, with Viraqita's efficacy potentially meeting or exceeding that of other biologics in the market [14][15] - The dosing interval for Viraqita is every 12 weeks, which is significantly less frequent than competitors like Tezepelumab (13 times a year) and Dupilumab (26 times a year) [15][16] - The delta nasal polyp score (NPS) for Viraqita was -1.8, compared to -1.7 for Tezepelumab and -1.6 for Dupilumab, indicating competitive efficacy [15] Trial Design and Regulatory Considerations - The trial design follows FDA guidance with a placebo-controlled approach and includes endpoints such as change in endoscopic nasal polyp score and nasal congestion score [12][13] - The company aims for the nasal polyps data to serve as one of two pivotal studies for BLA submission [12] Patient Population and Baseline Characteristics - The patient population in the trial was designed to be similar to those in other studies, with comparable disease severity and eosinophil counts [17][18] - The lack of prior steroid use in some patients could indicate a more severe population, but this is not seen as a significant tailwind [19] Future Outlook - The company is optimistic about the read-through of nasal polyp data to asthma, with expectations of similar efficacy and a less frequent dosing regimen [21][22] - Upcoming data in asthma is anticipated to provide further insights into the drug's potential [22]

Core Insights - 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 its lead candidate, verekitug, which targets the receptor for thymic stromal lymphopoietin (TSLP), into Phase 2 trials for chronic rhinosinusitis with nasal polyps, severe asthma, and chronic obstructive pulmonary disease [3] - The CEO, Rand Sutherland, will participate in a fireside chat at the Stifel 2025 Virtual Immunology and Inflammation Forum on September 15, 2025 [1] Company Overview - Upstream Bio is dedicated to addressing unmet medical needs in patients underserved by current treatments [3] - Verekitug is the only known antagonist in clinical development targeting TSLP, a key cytokine in inflammatory responses [3] - The company aims to leverage verekitug's unique properties to improve patient outcomes in various immune-mediated diseases [3] Event Information - A live webcast of the CEO's fireside chat will be available on the company's website, with a replay posted afterward [2]

Core Points - Upstream Bio is hosting a conference call to discuss the Phase II VIBRANT top-line results of their lead asset, Verekitug [1][4] - The call includes forward-looking statements regarding the company's expectations and beliefs about future events [2] - Comparisons of Verekitug against existing treatments are based on third-party published data, with caution advised due to differences in trial designs and patient characteristics [3] Company Overview - Upstream Bio's CEO, Dr. Rand Sutherland, and Chief Medical Officer, Dr. Aaron Deykin, are present to discuss the results and future plans for Verekitug [4] - The agenda includes an overview of the results and a detailed review of the Phase II VIBRANT clinical study top-line results [4]

Summary of Upstream Bio Phase Two Vibrant Top-Line Results Conference Call Company Overview - **Company**: Upstream Bio - **Lead Asset**: Virecotag, an antagonist of the TSLP receptor - **Focus**: Severe respiratory diseases, including chronic rhinosinusitis with nasal polyps (CRS with NP), severe asthma, and COPD [7][24] Industry Context - **Market Size**: Sales of therapies for CRS with NP exceed $1 billion annually and are projected to grow due to new agents and expanded use [9] - **Current Treatments**: Comparison with existing treatments like Tezepelumab and Dupilumab, highlighting the need for more frequent dosing in other agents [6][20][21] Key Clinical Trial Results - **Trial Design**: Phase Two, randomized, double-blind, placebo-controlled trial with 81 participants [11][12] - **Primary Endpoint**: Significant reduction in endoscopic nasal polyp score (NPS) by 1.8 points and nasal congestion score (NCS) by 0.8 points at 24 weeks [16][17] - **Secondary Endpoints**: Improvements in sinus opacification, total symptom score, and a 76% reduction in the need for steroids or surgery [17][22] - **Safety Profile**: Virecotag was well tolerated with no serious adverse events reported; common treatment emergent adverse events included upper respiratory infections and sinusitis [15][16] Mechanism of Action - **Potency**: Virecotag is approximately 300-fold more potent than Tezepelumab due to its unique mechanism targeting the TSLP receptor [8] - **Dosing Interval**: Administered every 12 weeks, significantly less frequent than other biologics [6][20] Future Development Plans - **Upcoming Trials**: - Valiant trial in severe asthma expected to report top-line data in Q1 2026 [7][25] - Ongoing Venture trial in COPD [7] - **Potential Expansion**: Plans to explore Virecotag's efficacy in other therapeutic areas, including dermatology and gastrointestinal diseases [7] Market Opportunity - **Unmet Need**: High interest among allergists and ENT specialists for biologics targeting TSLP in CRS with NP [9] - **Commercial Strategy**: Focus on maximizing the value of Virecotag across multiple indications with substantial unmet needs [7][24] Additional Insights - **Subgroup Analysis**: Preliminary data suggests consistent efficacy across various patient subgroups, including those with comorbid asthma [19][40] - **Long-term Efficacy**: Anticipation of greater treatment effects with longer studies, as seen with other agents [38][46] Conclusion - **Overall Sentiment**: Positive trial results reinforce the potential of Virecotag as a differentiated treatment option for CRS with NP and other respiratory diseases, with a favorable safety profile and significant clinical benefits [22][24]

VIBRANT Phase 2 Study Results - The Phase 2 VIBRANT study of verekitug in CRSwNP met the primary endpoint, demonstrating a statistically significant reduction in Nasal Polyp Score (NPS) of -1.8 (p<0.0001) [11, 71, 85] - Key secondary endpoints were also met, including a Nasal Congestion Score (NCS) reduction of -0.8 (p=0.0003) [11, 71, 85] and a 76% reduction in the need for surgery or systemic steroids (p=0.03) [11, 71, 85] - Verekitug, dosed every 12 weeks, showed clinical activity at week 24 similar to tezepelumab dosed every 4 weeks [14, 65] - In the VIBRANT trial, 93% of subjects completed the study [38] Safety and Tolerability - Verekitug was generally well tolerated, with no serious adverse events (SAEs) observed [11, 71, 85] - The incidence of adverse events (AEs) was similar across treatment groups, with treatment-emergent adverse events (TEAEs) related to study treatment occurring more frequently in the placebo group [48] Verekitug's Potential - Upstream Bio is developing verekitug as an antagonist of the TSLP receptor, with the goal of achieving rapid, complete, and sustained receptor occupancy for up to 24 weeks after the last dose [21] - Current biologics sales in CRSwNP alone are estimated to exceed $1 billion globally [29] - Upstream Bio is studying verekitug across multiple indications with high unmet need, including severe asthma (VALIANT trial, topline data expected in Q1 2026) and COPD (VENTURE trial, currently enrolling) [22, 23]

Core Insights - Upstream Bio, Inc. announced positive top-line results from the Phase 2 VIBRANT trial for verekitug, demonstrating significant efficacy in treating chronic rhinosinusitis with nasal polyps (CRSwNP) [1][6][12] Study Results - The VIBRANT trial met its primary endpoint with a statistically significant placebo-adjusted reduction in endoscopic nasal polyp score (NPS) of -1.8 (p<0.0001) at Week 24 [1][4] - Key secondary endpoints showed a reduction in nasal congestion score (NCS) by -0.8 (p=0.0003) and a 76% reduction (p=0.03) in the need for surgery or systemic corticosteroids [1][2][5] - The trial involved 81 adults and was designed as a global, randomized, double-blind, placebo-controlled study over 24 weeks [3][12] Safety Profile - Verekitug was generally well tolerated, with no serious adverse events (SAEs) reported, consistent with previous studies [1][5][6] Mechanism and Potential - Verekitug is a monoclonal antibody targeting the thymic stromal lymphopoietin (TSLP) receptor, which is unique in its mechanism of action compared to existing therapies [1][13][18] - The results suggest that verekitug could advance the standard of care for CRSwNP and may have potential applications in other respiratory diseases, including severe asthma [6][7][18] Future Plans - Upstream Bio plans to engage with global regulatory authorities for further development and potential product approval of verekitug [7][12] - The company will present additional details from the VIBRANT trial at an upcoming medical conference [8]