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]

Table of Contents As filed with the Securities and Exchange Commission on April 19, 2024 Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Q32 BIO INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) (Primary Standard Industrial Classification Code No.) Delaware 2834 47-3468154 (I.R.S. Employer Identification Number) 830 Winter Str ...