Shares of Upstream Bio (NASDAQ: UPB) fell about 23% after the company disclosed results from the Phase 2 VALIANT trial evaluating verekitug for severe asthma. The clinical-stage biotech reported that both dosing regimens tested in VALIANT met the trial's primary endpoint but produced different magnitudes of benefit.
According to the company, the 100mg dose administered every 12 weeks (q12w) reduced the annualized asthma exacerbation rate (AAER) by 56%. The alternate regimen, 400mg given every 24 weeks (q24w), produced a 39% reduction in AAER. Both results were statistically significant versus placebo, but only the 100mg q12w profile produced an effect size the company and analysts compared to existing therapies.
TD Cowen analyst Yaron Werber, M.D. summarized the data, saying: "Ph2 asthma data was mixed. Verekitug led to 56% AAER reduction at 100mg Q12W & 39% at 400mg Q24W; both stat sig but only Q12W looks Tezspire-like."
The VALIANT study also reported lung function improvements. Placebo-adjusted changes in forced expiratory volume in one second (FEV1) at week 60 measured +122 mL for the 100mg q12w dose and +139 mL for the 400mg q24w dose. The company stated that verekitug was generally well tolerated across the doses evaluated.
Despite the market reaction, Upstream Bio plans to advance verekitug into Phase 3 development for both severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) following regulatory interactions. The company is also continuing a Phase 2 VENTURE trial in patients with chronic obstructive pulmonary disease (COPD), which has enrolled more than 60% of its targeted participants.
Enrollment momentum from VALIANT carried into longer-term follow-up: the company reported that over 90% of eligible participants from VALIANT have joined VALOUR, the long-term extension study. Upstream Bio said VALIANT was designed with endpoints that could, subject to regulatory discussions, support future product approval filings.
The mixed efficacy across dosing regimens, ongoing regulatory dialogue and the company's plan to progress multiple programs in parallel set the framework for upcoming clinical and commercial milestones. Market participants reacted strongly to the differentiated dosing data, driving the near-term share movement.