Upstream Bio (UPB) Study result summary

Study design and patient population

• VALIANT was a global, phase II randomized, double-blind, placebo-controlled, dose-ranging trial in 478 adults with severe asthma across 15 countries, with up to 60 weeks of treatment.

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

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

• The study used a double-dummy design and variable treatment period, with all subjects treated at least 24 weeks, some up to 60 weeks.

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

Efficacy results

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

• Both high and medium doses showed clinically meaningful improvements in FEV1 (122 mL and 139 mL, respectively) and FeNO reductions (43.5% and 44.9% from baseline) at week 60.

• Statistically significant improvements in AAER were observed across most subgroups, including age, sex, region, steroid use, and biomarker levels.

• Efficacy was evident as early as 2-4 weeks and maintained over 60 weeks.

• Statistically significant improvements in secondary endpoints (FEV1, FeNO, ACQ, biomarkers) were observed at week 24 for both high and medium doses.

Safety and tolerability

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

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

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

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

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