Clinical Trial Results - The Phase 2 VALIANT trial demonstrated a 56% reduction in annualized asthma exacerbation rates (AAER) with verekitug dosed at 100 mg every 12 weeks (p<0.0003) and a 39% reduction with 400 mg every 24 weeks (p<0.02) [10] - Significant improvements in lung function were observed, with a 122 mL improvement in FEV1 for the 100 mg dose and a 139 mL improvement for the 400 mg dose [10] - The trial also reported a reduction in exhaled nitric oxide (FeNO) levels, with a 20.4 ppb reduction for the 100 mg dose and a 26.3 ppb reduction for the 400 mg dose [10] - The VALIANT trial enrolled 478 patients across 15 countries, with 91% of participants completing the treatment [21] - Verekitug demonstrated a statistically significant reduction in the annualized asthma exacerbation rate (AAER) at 60 weeks, with a rate of 0.66 for the 100 mg q12w dose compared to 1.52 for placebo, resulting in a rate ratio of 0.44 (95% CI: 0.28, 0.69) [27] - The prebronchodilator forced expiratory volume (FEV1) change from baseline at 60 weeks was 265 mL for the 100 mg q12w dose, significantly higher than the placebo's 143 mL, with a nominal p-value of 0.0003 [27] - At 60 weeks, the FeNO (fractional exhaled nitric oxide) change from baseline was -17.4 ppb for the 100 mg q12w dose, compared to 3.1 ppb for placebo, with a nominal p-value of 0.0003 [27] - The 400 mg q24w dose of Verekitug also showed significant improvements in lung function and FeNO, with a change of -23.3 ppb in FeNO and a nominal p-value of <0.0001 [28] - At 24 weeks, the prebronchodilator FEV1 change for the 400 mg q24w dose was 275 mL, significantly better than the placebo's 142 mL, with a nominal p-value of 0.0119 [31] - The ACQ-6 (Asthma Control Questionnaire) score change at 24 weeks was -1.12 for the 100 mg q12w dose, indicating improved asthma control compared to -0.91 for placebo, with a nominal p-value of 0.0651 [31] - The clinical effects of Verekitug were consistent across various subgroups, including age and sex, with the 100 mg q12w dose showing a rate ratio of 0.40 for patients under 65 years [32] - The overall participant count for the 100 mg q12w group was 121, while the placebo group had 119 participants, ensuring robust data for analysis [27] - The study indicated that secondary endpoints were not powered for statistical significance, highlighting the need for further research [30] - The results suggest that Verekitug may offer a promising new treatment option for asthma patients, with ongoing evaluations of its long-term efficacy and safety [32] - Phase 2 VALIANT study achieved a statistically significant 56% reduction in annualized asthma exacerbation rates (AAER) with verekitug dosed at 100mg every 12 weeks (p<0.0003) and a 39% reduction at 400mg every 24 weeks (p<0.02) [34] - Verekitug demonstrated a 122mL improvement in FEV1 and a 139mL improvement in FEV3, indicating clinically meaningful enhancements in lung function [34] - The treatment resulted in a 20.4ppb reduction in exhaled nitric oxide (FeNO) for the 100mg dose and a 26.3ppb reduction for the 400mg dose, representing a 43.5% and 44.9% reduction versus baseline, respectively [34] Safety and Tolerability - Verekitug demonstrated a treatment-emergent adverse event (TEAE) rate of 62.0% for the 100 mg q12w group and 58.5% for the 400 mg q24w group, compared to 65.5% for the placebo group [25] - The incidence of any serious TEAEs was 4.1% for the 100 mg q12w group and 6.8% for the 400 mg q24w group, while the placebo group had an incidence of 8.4% [25] - The most common TEAE was nasopharyngitis, occurring in 10.7% of the 100 mg q12w group and 7.6% of the 400 mg q24w group [25] - The percentage of participants with any grade 3-5 TEAEs was 6.6% for the 100 mg q12w group and 11.0% for the 400 mg q24w group [25] - The overall incidence of TEAEs was similar across treatment groups, indicating consistent safety profiles [25] - The safety profile of verekitug was consistent with prior studies, indicating it was generally well tolerated [34] Financial and Market Outlook - Upstream Bio has approximately $341.5 million in cash and short-term investments as of December 31, 2025, expected to fund operations through 2027 [12] - The global biologics market for severe asthma and COPD is projected to exceed $35 billion by 2033, indicating a significant commercial opportunity [12] - The company aims to address high unmet needs in severe asthma, CRSwNP, and COPD, with a growing number of biologic therapies entering the market [12] Future Plans and Studies - The company is also conducting the VALOUR long-term extension study and the VIBRANT trial in chronic rhinosinusitis with nasal polyps (CRSwNP), which reported positive results in September 2025 [13] - The Phase 2 trial design included randomized, placebo-controlled methods with registration-enabling endpoints, ensuring robust data collection and analysis [19] - The company plans to conduct integrated analyses of Phase 2 data sets in chronic rhinosinusitis with nasal polyps (CRSwNP) and severe asthma to optimize dosing for Phase 3 trials [38] - Strong execution of the Phase 2 trial in COPD will continue, alongside the initiation of Phase 3 trials in severe asthma and CRSwNP [38] - The company will engage with regulatory agencies and continue accelerated operational planning for the Phase 3 start [38] - Investments in chemistry, manufacturing, and controls (CMC) and device development will be prioritized [38]
Upstream Bio, Inc.(UPB) - 2025 Q4 - Annual Results