Upstream Bio to Present Phase 1b Trial Data of Verekitug in Asthma at ERS Congress

Upstream Bio, Inc., a clinical-stage company developing treatments for inflammatory diseases, has recently unveiled promising data from its Phase 1b trial of verekitug, an investigational antagonist targeting the Thymic Stromal Lymphopoietin (TSLP) receptor. This presentation was made at the European Respiratory Society (ERS) Congress 2024 in Vienna, Austria.

The Phase 1b trial spanned 32 weeks and involved multiple ascending doses of verekitug in adults with asthma. The new data from this study showed significant reductions in key inflammation biomarkers such as IL-5 (Interleukin 5) and IgE (immunoglobulin E). These findings align with previous reports showing decreases in blood eosinophils and fractional exhaled nitric oxide (FeNO).

Predictive pharmacodynamic (PD) and pharmacokinetic (PK) modeling based on these observations indicate that verekitug may exhibit high potency in asthma patients. The models predict that verekitug could achieve an approximately 1.5-fold greater reduction in FeNO compared to tezepelumab, a similar medication. Furthermore, the modeling suggests that dosing of verekitug at 100 mg every 12 weeks or 400 mg every 24 weeks could maintain effective serum levels for over 95% of the dosing interval. This supports ongoing Phase 2 trials examining these dosing intervals in severe asthma patients.

Verekitug was well tolerated at all tested dose levels and demonstrated rapid and substantial treatment effects. In one dose, it achieved 100% TSLP receptor occupancy, and within 12 weeks, it resulted in up to a 54% reduction in FeNO and a 65% reduction in blood eosinophils. These effects were maintained for up to 24 weeks post-treatment.

Dr. Aaron Deykin, Chief Medical Officer and Head of R&D at Upstream Bio, expressed confidence in the differentiated product profile of verekitug. He highlighted the rapid and sustained reductions in disease-related biomarkers, which are predictive of fewer exacerbations—an important clinical outcome for asthma patients. Dr. Deykin emphasized the potential of verekitug to improve clinical outcomes and enhance patient care.

The oral presentation of the data took place on September 9, 2024, under the session titled "Recent advances in biological treatments for asthma and chronic obstructive pulmonary disease."

The Phase 1b multiple ascending dose (MAD) study was a multicenter, randomized, double-blind, placebo-controlled trial involving adults with mild to moderate asthma and elevated blood eosinophils. It included four dosing cohorts: 100 mg every 4 weeks, 200 mg every 4 weeks, 300 mg every 12 weeks, and a 25 mg single dose. Participants were monitored for 32 weeks post-randomization.

Thymic Stromal Lymphopoietin (TSLP) is a cytokine that plays a crucial role in the inflammatory response in allergic and inflammatory diseases like asthma. Blocking TSLP signaling has been clinically validated as an effective therapeutic strategy. TSLP activation triggers the inflammatory cascade, affecting downstream targets such as IL-4, IL-5, IL-13, IL-17, and IgE. By targeting the TSLP receptor, a single treatment like verekitug has the potential to impact multiple inflammatory processes.

Verekitug is a novel, fully human immunoglobulin G1 (IgG1) monoclonal antibody that inhibits proinflammatory signaling initiated by TSLP. It is the only known antagonist targeting the TSLP receptor currently in clinical development. Three Phase 1 trials, including 32 asthma patients, have shown that verekitug is well-tolerated, exhibits a predictable pharmacokinetic profile, and has high subcutaneous bioavailability.

Currently, verekitug is being evaluated in two Phase 2 clinical trials. The VALIANT trial involves approximately 436 severe asthma patients, while the VIBRANT trial includes around 70 patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Both trials are placebo-controlled, multi-national, and randomized, focusing on different dosing intervals and primary endpoints related to disease exacerbation and nasal polyp scores.

Upstream Bio is dedicated to developing treatments for inflammatory diseases, particularly severe respiratory disorders. By leveraging the unique attributes of verekitug, the company aims to address unmet needs in severe asthma and CRSwNP, with broader potential applications in other inflammatory diseases.