Verekitug Reduces Asthma Exacerbations Up to 87%, With Michael Wechsler, MD

Verekitug, an investigational monoclonal antibody that targets the thymic stromal lymphopoietin (TSLP) receptor, met its primary endpoint in the phase 2 VALIANT trial, reducing annualized asthma exacerbation rates by as much as 56% overall and 87% in patients with elevated eosinophil counts. The results, from Upstream Bio's ongoing development program in severe asthma, were presented at the European Respiratory Society (ERS) Congress 2026 in Barcelona.

"Even low concentrations of verekitug are sufficient to saturate the TSLP receptors, and therefore abrogate some of the TSLP signaling, and this allows for longer dosing intervals," Michael Wechsler, MD, MMSc, professor of medicine and director of the Cohen Family Asthma Institute at National Jewish Health, said in an interview with HCPLive.

A Novel Approach to Targeting TSLP

TSLP is an upstream epithelial alarmin that drives activation of interleukin-4, interleukin-5, and interleukin-13 through T helper 2 cells and ILC2 cells, playing a central role in the type 2 inflammatory pathways implicated in asthma and chronic sinusitis with nasal polyps (CRSwNP). While other therapies, including tezepelumab, target TSLP itself, verekitug is the only agent in development that targets the TSLP receptor directly. Wechsler noted that the added benefit is an extended half-life alongside a robust efficacy signal, building on what he described as an already well-validated pathway.

VALIANT Trial Design

VALIANT was a multicenter, randomized, placebo-controlled phase 2 trial that enrolled 478 adults with poorly controlled asthma, defined by an Asthma Control Questionnaire (ACQ) score >1.5, along with either 2 exacerbations or 1 emergency department visit with inpatient care in the prior year, or 1 exacerbation plus an exhaled nitric oxide level >50. All participants required a medium to high dose inhaled corticosteroid for at least 3 months prior to enrollment. Patients were randomized to 1 of 3 verekitug doses, 100 mg every 12 weeks, 400 mg every 24 weeks, or 100 mg every 24 weeks, or to placebo. The primary outcome was the annualized asthma exacerbation rate through week 60, with a minimum of 24 weeks of drug exposure required; median exposure across the trial was approximately 37 weeks.

Efficacy Findings by Eosinophil Status

Baseline ACQ-6 scores ranged from 2.5 to 2.7, with eosinophil counts between 250 and 290 cells/microliter and lung function near 60%. The placebo arm had an annualized exacerbation rate of approximately 1.52, while all 3 verekitug doses produced statistically significant and clinically meaningful reductions, ranging from 39% to 56%, independent of phenotype. The effect was more pronounced among patients with eosinophil counts ≥300 cells/microliter.

"In the patients who had high eosinophil counts, there was an 87% reduction in exacerbations. This is really exciting. It's best in class as far as I'm concerned, for demonstrating a reduction in exacerbations," Wechsler said. Patients with eosinophil counts <150 cells/microliter, who represent roughly 20% of the severe asthma population, did not show a significant reduction. Verekitug also improved forced expiratory volume in 1 second (FEV1), with 100 to 157 mL gains at 6 months, along with improvements in ACQ scores and exhaled nitric oxide levels.

Check out the companion piece: Verekitug's Quarterly Dosing Cuts Asthma Burden, With Michael Wechsler, MD

Editor’s Note: Wechsler reports relevant disclosures with Upstream Bio and is principal investigator on the VALIANT trial.

References

1. Upstream Bio Reports Positive Top-line Results from the Phase 2 VALIANT Trial of Verekitug for the Treatment of Severe Asthma. GlobeNewswire. February 11, 2026. https://www.globenewswire.com/news-release/2026/02/11/3236073/0/en/Upstream-Bio-Reports-Positive-Top-line-Results-from-the-Phase-2-VALIANT-Trial-of-Verekitug-for-the-Treatment-of-Severe-Asthma.html

2. Upstream Bio Presents Results from the Phase 2 VALIANT Trial of Verekitug for the Treatment of Severe Asthma in Oral Presentation at ERS Congress 2026. GlobeNewswire. September 8, 2026. https://www.globenewswire.com/news-release/2026/09/08/3357341/0/en/upstream-bio-presents-results-from-the-phase-2-valiant-trial-of-verekitug-for-the-treatment-of-severe-asthma-in-oral-presentation-at-ers-congress-2026.html