Upstream Bio (UPB) investor relations material

Strategic focus and market opportunity

• Verekitug targets the TSLP receptor, offering a differentiated mechanism and is the only known clinical-stage antagonist with unique pharmacology enabling extended dosing intervals and high potency in severe respiratory diseases.

• Focused on respiratory diseases with high unmet need and commercial potential, including severe asthma, CRSWNP, and COPD, with potential expansion into dermatology and GI indications.

• Multi-billion-dollar market opportunities exist, with the asthma and COPD biologics market projected to exceed $35B globally by 2033.

• Differentiation through broad patient eligibility, potent pharmacology, and infrequent dosing (Q12 or Q24 weeks), offering competitive advantages.

• Leadership team brings deep experience from major biopharma companies, supporting execution of strategic plans.

Clinical development and data highlights

• Verekitug demonstrated rapid, complete, and sustained TSLP receptor occupancy for up to 24 weeks, with significant biomarker suppression and high potency.

• Phase II CRSWNP trial met primary and all key secondary endpoints, including a 1.8-point reduction in nasal polyp score, 0.8 reduction in congestion score, and 76% reduction in need for surgery or steroids, with a favorable safety profile.

• Safety profile remains clean, with no serious adverse events and similar AE rates across groups; >90% of TEAEs were unrelated to study drug.

• Verekitug’s modeled effect on FENO is ~1.5 times greater than tezepelumab, with >300-fold lower EC50/EC90, supporting its differentiated profile.

• Clinical activity was consistent across subgroups, and efficacy at 12-week dosing was similar to other biologics dosed more frequently.

Study design and execution

• Asthma phase II study (Valiant) includes nearly 480 patients, testing three dosing regimens versus placebo, with primary endpoint reduction in annualized asthma exacerbation rate and 85% power to detect a 50% reduction.

• Meticulous study conduct, patient selection, and monitoring to ensure robust, generalizable results.

• Blinded sample size re-estimation confirmed adequacy of trial power; protocol amendments have been minor.

• COPD phase II trial (VENTURE) is currently enrolling, leveraging similar sites and investigator enthusiasm as asthma program.

• Existing capital is expected to fund operations through 2027, supporting ongoing and planned clinical programs.