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]