Phase 2 VALIANT: Verekitug Reduces Average Annual Asthma Flare-Ups

In results from the phase 2 VALIANT trial, verekitug met its primary endpoint of statistically significant reductions in annualized asthma exacerbation rate (AAER) compared with placebo.1

The positive topline results were announced by Upstream Bio, Inc, on February 11, 2026, exhibiting clinically meaningful efficacy and a consistent safety profile in adults with severe asthma.1

“Severe asthma, when unable to be controlled by standard of care measures, can significantly and chronically disrupt patients’ quality of life, and put them at risk for potentially life-threatening exacerbation events that can lead to emergency room visits and hospitalizations,” said Michael Wechsler, MD, MMSc, a professor of medicine, and director of the National Jewish Cohen Family Asthma Institute, in a statement. “These data suggest that verekitug can potentially offer patients meaningful improvements in their breathing and asthma symptoms with less frequent dosing than the currently available biologics, and I believe that verekitug could represent an important advancement for individuals living with severe asthma.”1

As of now, verekitug, a novel, high-affinity, fully human monoclonal antibody, is the only known antagonist targeting the receptor for thymic stromal lymphopoietin in clinical stage development. Besides VALIANT, verekitug is currently in phase 2 development in the VIBRANT study for chronic rhinosinusitis with nasal polyps, and VENTURE for chronic obstructive pulmonary disease.1,2

The phase 2 VALIANT trial was a multicenter, randomized, placebo-controlled parallel group study designed to assess the efficacy and safety of subcutaneously administered verekitug. The study consisted of a 4-week screening period, a 60-week treatment period, and a follow-up period ending 16 weeks after the last dosage.1,3

In the trial, study investigators randomized participants in a 1:1:1:1 ratio to receive 100 mg every 12 weeks (Q12W), 400 mg every 24 weeks (Q24W), 100 mg every 24 weeks (Q24W), or placebo. At each dosing visit, all participants received 2 subcutaneous injections to maintain the blinding of different doses.3

VALIANT included a total of 478 patients with severe asthma.1

The study’s primary endpoint of a statistically significant and clinically meaningful reduction at AAER was met at Q12W and Q24W dosing. Veretikug demonstrated a 56% reduction of AAER (P < .0003) at 100 mg Q12W and 39% at 400 mg Q24W compared with placebo.1

At week 60, the placebo-adjusted improvement in lung function, measured by the forced expiratory volume in one second (FEV1), was 122mL with 100 mg Q12W and 139 mL with 400 mg Q24W. Investigators observed suppressed exhaled nitric oxide (FeNO) by 20.4 ppb (P < .0003) at 100 mg Q12W and 26.3 ppb (P <.0001) at 400 mg Q24W. From baseline, these data exhibited a mean reduction of 43.5% (P = .03) in the 100 mg Q12W group and a mean reduction of 44.9% (P = .03) in the 400 mg Q24W group. Additionally, a dosage of 100 mg Q24W demonstrated a statistically significant effect on AAER, but no other endpoints.1

At week 24, in prespecified analysis of secondary outcomes, investigators also noted the significant placebo-adjusted improvements compared to baseline in both FEV1 and FeNO with the 100 mg Q12W and 400 mg Q24W dose regimens.1

Across all active doses, study investigators reported verekitug was generally well tolerated and demonstrated a favorable safety profile consistent with previous studies.1

“We intend to rapidly advance verekitug into Phase 3 trials in severe asthma and CRSwNP. In parallel, we also continue to progress verekitug in our ongoing Phase 2 VENTURE trial in patients with COPD, where we have enrolled more than 60% of patients to date,” said Rand Sutherland, MD, Chief Executive Officer of Upstream Bio, in a statement. “As we transition into a late clinical-stage company pursuing substantial market opportunities, our focus remains on disciplined execution and expanding Upstream Bio’s capabilities to support long-term growth.”1

​​References

1. Upstream Bio Reports Positive Top-line Results from the Phase 2 VALIANT Trial of Verekitug for the Treatment of Severe Asthma — Wed, 02/11/2026 - 06:00. Upstream Bio. Published 2026. Accessed February 11, 2026. https://investors.upstreambio.com/news-releases/news-release-details/upstream-bio-reports-positive-top-line-results-phase-2-valiant

2. Singh D, Brickman CM, Lloyd P, et al. Verekitug, a Novel Antibody Antagonist to the TSLP Receptor in Adults with Asthma: A 32-Week Randomized Phase 1b Multiple Ascending-Dose Trial. Clinical pharmacology and therapeutics. Published online Winter 2025:10.1002/cpt.70156. doi:https://doi.org/10.1002/cpt.70156

3. ‌Clinicaltrials.gov. Published 2026. Accessed February 11, 2026. https://clinicaltrials.gov/study/NCT06196879