Upstream Bio (UPB) investor relations material

Company overview and strategy

• Clinical-stage immunology company developing verekitug, a high-potency TSLP receptor antagonist for severe respiratory diseases.

• Completed Phase 2 trials in severe asthma and CRSWNP; ongoing Phase 2 in COPD.

• Targeting large commercial opportunities, with asthma and COPD markets projected to exceed $35B globally by 2033.

• Phase 3 trials in severe asthma and CRSWNP planned for Q1 2027, with capital to fund operations through 2027.

• Leadership team has deep experience in biotech and pharma.

Verekitug mechanism and clinical profile

• Verekitug is a fully human IgG1 antibody, uniquely inhibiting TSLP signaling with ~300-fold greater potency than tezepelumab.

• Demonstrated robust efficacy and favorable safety in ~500 participants across Phase 1 and 2 trials.

• Every 12-week dosing showed strong clinical benefit in both severe asthma and CRSWNP.

• PK modeling predicts higher quarterly doses will further increase efficacy and coverage.

• Immunogenicity profile shows no meaningful impact on safety or efficacy.

Market opportunity and product positioning

• Severe asthma, CRSWNP, and COPD represent significant unmet needs and commercial potential.

• Efficacy is the primary driver for HCPs in biologic selection; dosing convenience is valued but not at the expense of efficacy.

• Quarterly at-home dosing with a single high-dose injection is designed to maximize patient convenience and commercial value.

• Market research confirms most value is captured by moving to quarterly dosing, with minimal gains from less frequent dosing.