Upstream Bio (UPB) Study result summary

Study design and patient population

• The Phase 2 VALIANT trial was a global, randomized, double-blind, placebo-controlled, dose-ranging study in 478 adults with severe asthma across 15 countries, with up to 60 weeks of treatment and balanced baseline characteristics.

• Participants were randomized to receive verekitug 100 mg every 12 weeks, 400 mg every 24 weeks, 100 mg every 24 weeks, or placebo, using a double-dummy design to maintain blinding.

• The primary endpoint was annualized asthma exacerbation rate (AAER); secondary endpoints included FEV1, FeNO, and asthma control questionnaire (ACQ) scores.

• Over 90% of eligible patients transitioned to the VALOUR long-term extension study, and 91% completed treatment in VALIANT.

• Baseline characteristics reflected an uncontrolled severe asthma population, and discontinuation rates were similar across arms.

Efficacy results

• Verekitug 100 mg every 12 weeks reduced AAER by 56% (p<0.0003), and 400 mg every 24 weeks reduced AAER by 39% (p<0.02) versus placebo.

• Placebo-adjusted FEV1 improvements at week 60 were 122 mL (100 mg q12w) and 139 mL (400 mg q24w); FeNO was reduced by 20.4 ppb and 26.3 ppb, respectively.

• Both dose regimens showed mean FeNO reductions of over 43% from baseline at week 60, with early and sustained improvements in FEV1 and FeNO seen as early as week 2.

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

• The 100 mg every 24 weeks group showed significant AAER reduction but less consistent improvements in other endpoints.

Safety and tolerability

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

• Incidence of treatment-emergent and serious adverse events was similar across groups, with no deaths reported.

• Most common adverse events included nasopharyngitis, bronchitis, headache, and urinary tract infection; bronchitis was more frequent in higher dose groups.

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

• Verekitug's safety profile was consistent with previous studies, and anti-drug antibodies did not impact safety.