Upstream Bio (UPB) Corporate presentation summary

Company overview and strategy

• Focuses on severe respiratory diseases with a unique clinical-stage TSLP receptor antagonist, verekitug, showing rapid, complete, and sustained receptor occupancy for up to 24 weeks after dosing.

• Verekitug is being studied in multiple high unmet need indications: CRSWNP (Phase 2 complete), severe asthma (Phase 2 ongoing), and COPD (Phase 2 ongoing).

• All clinical trials are randomized, placebo-controlled, and designed with registrational endpoints.

• TSLP biology supports potential expansion into dermatology and gastrointestinal indications.

• Asthma and COPD markets are projected to exceed $35B globally by the mid-2030s, with existing capital expected to fund operations through 2027.

Verekitug mechanism and differentiation

• Verekitug is the only known clinical-stage antagonist of the TSLP receptor, offering high potency and extended dosing intervals (every 12 or 24 weeks).

• Demonstrates rapid, complete, and sustained TSLP receptor occupancy, with significant suppression of disease biomarkers (FENO and eosinophils) in asthma patients.

• Phase 2 CRSWNP trial showed clinical activity meeting or exceeding other approved biologics at 24 weeks with less frequent dosing.

• Verekitug’s potency is approximately 300-fold greater than tezepelumab, a TSLP ligand-targeting biologic.

• Pharmacology enables potential for enhanced efficacy and less frequent dosing compared to ligand-targeting approaches.

Clinical data and trial results

• Phase 2 VIBRANT study in CRSWNP met primary and key secondary endpoints, with significant reductions in nasal polyp and congestion scores, and a 76% reduction in need for surgery or steroids.

• Verekitug was generally well tolerated in both Phase 1 and 2 studies, with no serious adverse events and a safety profile similar to placebo.

• Substantial and sustained pharmacodynamic effects observed for up to 24 weeks after last dose, including >50% reduction in FENO and eosinophils.

• Clinical activity was consistent across all subgroups, including those with comorbid asthma and prior nasal polyp surgery.

• Verekitug dosed every 12 weeks delivered efficacy at week 24 similar to tezepelumab dosed every 4 weeks.