Upstream Bio's TSLP Antagonist Verekitug Enters Global Phase 2 Trial for COPD

Upstream Bio announced dosing of the first participant in the global phase 2 trial evaluating verekitug in chronic obstructive pulmonary disease (COPD). The trial, VENTURE (NCT06981078), is will evaluate the efficacy and safety of verekitug administered once every 12 or 24 weeks in approximately 670 adults with moderate-to-severe COPD. The study expands the investigational therapy's potential into a third inflammatory respiratory condition, according to a company statement.

_{Courtesy of Upstream Bio}

Verekitug is a fully human IgG1 monoclonal antibody that selectively targets the thymic stromal lymphopoietin (TSLP) receptor, a central upstream node in type 2 inflammation. TSLP receptor blockade has been clinically validated in asthma, and recent research suggests that TSLP also contributes to the pathogenesis and exacerbations of COPD. According to Upstream Bio, verekitug is currently the only biologic in development that targets the TSLP receptor directly in COPD.

“There are emerging data indicating that TSLP plays an important role in driving the pathobiology of COPD and the exacerbations that many patients with this disease experience,” Aaron Deykin, MD, chief medical officer and head of R&D at Upstream Bio, said in the statement. “Given the results observed in our preclinical and early clinical studies in asthma, we believe that as the only known biologic in development targeting the TSLP receptor, verekitug may have the potential to advance COPD treatment with less frequent dosing and differentiated efficacy as compared to currently approved biologic therapies."

The randomized, double-blind, placebo-controlled trial is evaluating verekitug 100 mg every 12 weeks or 400 mg every 24 weeks compared to placebo over treatment periods of 60 to 108 weeks. The primary endpoint is the annualized rate of moderate or severe COPD exacerbations. Secondary endpoints include daily symptom scores and lung function metrics, including forced expiratory volume in 1 second. The company noted that participants will be enrolled regardless of blood eosinophil count (BEC), however, the primary VENTURE analysis will focus on those with elevated BEC at screening. The efficacy of verekitug in study participants without eosinophilia will be investigated in planned exploratory analyses, according to the Upstream Bio statement.

COPD is characterized by progressive airflow obstruction and frequent exacerbations. Environmental insults such as viruses and pollutants may initiate airway inflammation through epithelial cell activation of TSLP, which in turn drives downstream cytokines including IL-4, IL-5, IL-13, IL-17, and IgE.² Elevated levels of TSLP and TSLP receptor expression have been reported in COPD, particularly among individuals with severe disease.² By blocking the receptor upstream in this inflammatory cascade, verekitug may modulate multiple inflammatory pathways simultaneously.¹

Verekitug has previously demonstrated favorable safety and pharmacokinetics in phase 1 trials, including predictable subcutaneous bioavailability and a sustained pharmacodynamic response. In a multiple-ascending dose study in asthma, verekitug led to greater than 50% reductions in fractional exhaled nitric oxide (FeNO) and BECs that persisted for up to 24 weeks after the final dose. Preclinical studies also showed suppression of cytokine production from CD4+ T cells and ILC2 cells, and inhibition of allergic skin responses in non-human primates.¹

The broader development program for verekitug includes 2 fully enrolled phase 2 trials in chronic rhinosinusitis with nasal polyps and severe asthma. Upstream Bio expect to release top-line data from the trials in Q3 2025 and Q1 2026, respectively. A long-term extension study, VALOUR, was also initiated in May 2025 to follow adults completing the asthma trial, according to the statement.

If successful, verekitug could offer a differentiated therapeutic option for patients with COPD, particularly those with eosinophilic inflammation, while also reducing dosing frequency compared to current biologics, the company stated.

References

1. Upstream Bio announces first patient dosed in phase 2 clinical trial of verekitug in chronic obstructive pulmonary disease (COPD). News release. Upstream Bio. July 8, 2025. Accessed July 11, 2025. https://investors.upstreambio.com/news-releases/news-release-details/upstream-bio-announces-first-patient-dosed-phase-2-clinical

2. Therapeutic targeting of thymic stromal lymphopoietin (TSLP) in asthma and COPD: A technical overview. BPS Bioscience. Accessed July 11, 2025. https://bpsbioscience.com/therapeutic-targeting-of-tslp-in-asthma-and-copd