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. In an interview with HCPLive, Michael Wechsler, MD, MMSc, professor of medicine and director of the Cohen Family Asthma Institute at National Jewish Health, discussed verekitug's mechanism, VALIANT's design, and the trial's key efficacy and safety findings.

Q&A: Verekitug's TSLP receptor mechanism and VALIANT trial efficacy data

Can you talk about verekitug's mechanism and how it offers potential advantages for asthma?

Verekitug is a novel, unmodified, fully humanized monoclonal antibody that targets the receptor for TSLP, or thymic stromal lymphopoietin. TSLP is an upstream epithelial alarmin, a cytokine that stimulates the activation of a variety of downstream cytokines, particularly interleukin-4, interleukin-5, and interleukin-13, through activation of T helper 2 cells and ILC2 cells. It plays an important role in the activation of type 2 inflammatory pathways in diseases like asthma and chronic sinusitis with nasal polyps. By targeting the TSLP receptor, and it's the only drug in development that targets the TSLP receptor, there are other drugs that target TSLP, but this targets TSLP receptor, it's been shown that 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. We know that the TSLP mechanism and pathway is a robust one. We have great drugs out there like tezepelumab that are effective in asthma and chronic sinusitis with nasal polyps, and now in eosinophilic esophagitis. But the added value here is the extended half-life, and the other benefit, as shown by the data, is the significant robustness of the efficacy. We've now shown efficacy both in the phase 2 VIBRANT study in chronic sinusitis with nasal polyps and now in the current VALIANT study.

Can you give a brief overview of VALIANT's design and anything that's stuck out to you so far?

This was a multicenter, randomized, placebo-controlled phase 2 trial, and patients were randomized to receive one of three different doses of verekitug or placebo. The dosing options were a 100 mg dose every 12 weeks, a 400 mg dose every 24 weeks, or a lower 100 mg dose every 24 weeks, with placebo given on a matching schedule. There were 478 individuals randomized, and the key inclusion criteria were having a history of poorly controlled asthma with an ACQ >1.5, having either 2 exacerbations of asthma in the prior year or 1 emergency room visit with inpatient care over the prior year, or having 1 exacerbation but an exhaled nitric oxide level >50. That enriched for people who have more severe disease and type 2 inflammation. Everyone needed to be on at least a medium to high dose of inhaled steroid for the prior 3 months. The primary outcome was the annualized asthma exacerbation rate from baseline up to week 60, and patients had to have at least 24 weeks of drug exposure, but could get up to 60 weeks. The median time of exposure was about 37 weeks because some patients enrolled at a point when the study was going to close, so everyone got 24 weeks, and when the last patient came in, we stopped doing visits on the other patients, so they got up to 37 weeks. We got some patients up to 60 weeks of treatment.

Can you walk us through the key findings, including how the drug affected exacerbations in eosinophilic versus non-eosinophilic asthma?

There were between 118 and 121 subjects randomized to each arm, so a good sample size, and they met the general criteria for having poorly controlled asthma. The baseline Asthma Control Questionnaire, or ACQ-6, score ranged from around 2.5 to 2.7. At baseline, they had eosinophil counts between 250 and 290 and lung function of around 60%. In the placebo group, the annualized rate was around 1.52 exacerbations per year. All three verekitug doses had a statistically significant and clinically meaningful reduction in exacerbations, ranging from 39% up to 56% in the 100 mg every 12-week dosing, across this broad group of patients, independent of phenotype. When you look at the specific subgroups, what was really exciting for me was to see that in patients with eosinophil counts of 300 or more cells per microliter, 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. There was not a significant reduction in exacerbations in individuals with low eosinophil counts. The less than 150 group did not demonstrate a significant difference. This isn't all too surprising, because in general those patients tend to have fewer exacerbations, and they represent a much smaller proportion of this severe asthma patient population, only about 20%. Most severe asthma patients do have type 2 inflammation and a higher baseline exacerbation rate. So it was very exciting to see the 87% reduction in the high eosinophil group, and even in the high exhaled nitric oxide group, there was a 79% reduction in exacerbations. Excellent outcomes, particularly in the 100 mg every 12-week dosing strategy. Not only was there improvement in exacerbations, there was also significant improvement in other outcomes, including FEV1, or forced expiratory volume in 1 second, a major metric of lung function. The 100 mg every 12-week and the 400 mg every 24-week doses demonstrated efficacy in improving lung function, and even at the 6-month time interval, there was a 100 to 157 mL improvement in lung function, and at the 60-week time frame, the improvement in that smaller subset of patients was between 140 to 150 mL. There was also improvement in Asthma Control Questionnaire scores and exhaled nitric oxide. These are key clinical metrics as well as pharmacodynamic metrics that tell us the drug is working.

All three verekitug dosing arms cut exacerbations significantly, but the every 12-week dose performed best. What do you think the benefits of a dosing schedule like that are?

If you talk to patients, most patients would prefer to take a drug 4 times a year as opposed to 12 times a year or 13 times a year. To me, it allows patients to not think about their underlying disease every month, "Oh, I need to get my shot, I need to get my shot." Every 3 months, it's a little bit out of mind, and they're not worrying about their disease. And who likes to get injections? So it's fewer injections for this patient population. It's an exciting advance, as far as I'm concerned. Significant improvement in exacerbation reduction in the eosinophilic patients, and also a significant improvement in terms of dosing schedule.

Were there any safety concerns or signals that you were keeping an eye on?

No, the drug was very well tolerated, and there was a similar safety profile compared to placebo. In terms of any adverse events, the placebo group, 65% of them had an adverse event, and all three doses of verekitug had some type of adverse event in the 58% to 62% range, so slightly lower, although not significantly different compared to placebo. Most of the adverse events that we saw are things that are observed in asthma clinical trials: nasopharyngitis, headache, bronchitis. These adverse events were generally mild in severity. There were no grade 3 events or greater. There was a high rate of anti-drug antibodies that was observed, but this didn't have any impact in terms of any of the safety or efficacy parameters that were evaluated.

Did you have anything else you felt was important to highlight or add about anything we talked about today?

I think, in general, this is an exciting time to be seeing patients with asthma, seeing patients with COPD, and patients with type 2 inflammation. We have come a long way from 20 years ago. We currently have 7 biologic therapies that have been approved by the US Food and Drug Administration (FDA), and there are many more in development. I'm looking forward to a time when we can actually achieve the ultimate goal in asthma management, that's a cure, getting people into remission and having a sustained remission. That's only going to come with the development of new therapies, new biomarkers, and new strategies, and I think we're well on our way to achieve that type of success in the coming years.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.

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