Upstream Bio (UPB) investor relations material

Study design and patient population

• The Phase II VALIANT trial was a global, randomized, double-blind, placebo-controlled study enrolling 478 adults with severe asthma across 15 countries, with treatment durations up to 60 weeks.

• Participants had uncontrolled severe asthma, FEV1 30%-80% predicted, and recent exacerbations despite standard therapy, with balanced baseline characteristics across groups.

• Patients were randomized to verekitug 100 mg q12w, 400 mg q24w, 100 mg q24w, or placebo.

• Over 90% of eligible patients transitioned to the VALOUR long-term extension study.

• 91% of participants completed treatment, with similar discontinuation rates across arms.

Efficacy results

• Verekitug 100 mg q12w reduced annualized asthma exacerbation rate (AAER) by 56% (p<0.0003) and 400 mg q24w by 39% (p<0.02) versus placebo; 100 mg q24w reduced AAER by 49%.

• Both high and medium doses showed placebo-adjusted FEV1 improvements at week 60 (122 mL and 139 mL) and FeNO reductions (20.4 ppb and 26.3 ppb), with over 43% mean FeNO reduction from baseline.

• Efficacy on lung function and biomarkers was evident as early as 2-4 weeks and maintained over 60 weeks.

• Statistically significant, dose-related improvements in secondary endpoints and biomarkers were observed at 24 weeks.

• Treatment effects were consistent across clinically relevant subgroups, including age, sex, region, steroid use, and biomarker levels.

Safety and tolerability

• Verekitug was generally well tolerated across all dose regimens, with a safety profile consistent with previous studies.

• Incidence of adverse events and serious TEAEs was similar across groups; no deaths occurred.

• Most common TEAEs included nasopharyngitis, bronchitis, headache, and urinary tract infection.

• Anti-drug antibodies (ADAs) were observed in 50%-60% of subjects, stable over time, with no impact on safety or efficacy.

• One case of anaphylaxis occurred in a placebo patient.