Upstream Bio Highlights New Respiratory Drug Verekitug With Trial Data

Author: Benzinga Newsdesk | September 30, 2025 04:26am

Upstream Bio, Inc. (NASDAQ:UPB), a clinical-stage company developing treatments for inflammatory diseases, with an initial focus on severe respiratory disorders, today presented structural and mechanistic data showing verekitug's potent pharmacodynamic activity through its unique approach of targeting the thymic stromal lymphopoietin (TSLP) receptor. Data were presented at the European Respiratory Society (ERS) Congress being held September 27 – October 1, 2025, in Amsterdam, Netherlands.

"We continue to deepen our understanding of verekitug's unique TSLP receptor-targeting mechanism and its role in driving the rapid and durable effects that have been demonstrated to date," said Aaron Deykin, MD, Chief Medical Officer and Head of R&D of Upstream Bio. "In the clinic, we are also now beginning to see that the potency driven by this mechanism of action can translate into a differentiated clinical profile with our recently reported Phase 2 top-line clinical data in patients with chronic rhinosinusitis with nasal polyps where verekitug delivered statistically significant and clinically meaningful effects on multiple endpoints when administered only once every 12 weeks. We look forward to continuing to build the clinical dataset for verekitug with Phase 2 top-line data in severe asthma anticipated in the first quarter of 2026."

Preclinical and clinical data to date demonstrate verekitug's highly potent inhibition of the TSLP receptor. In clinical trials, verekitug has demonstrated rapid, substantial, and sustained TSLP receptor inhibition for up to 24 weeks after the last dose. This unique mechanism of action may translate to a differentiated clinical profile with less frequent dosing as compared to currently approved biologic therapies.

Mechanistic studies were performed to elucidate drivers of this high magnitude of effect seen with verekitug's TSLP receptor inhibition. Data presented are summarized as follows:

• With high affinity binding (KD < 1 pM) to the TSLP receptor, verekitug outcompetes TSLP binding to the TSLP receptor even in the presence of preformed heterodimeric receptor complexes, inhibiting TSLP:TSLP receptor interaction.
• The high-resolution crystal structure reveals that verekitug binds and occupies most of the TSLP binding sites on the TSLP receptor.
• Semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) models indicate that lower abundance and slower turnover of the TSLP receptor compared to the TSLP ligand may drive the greater potency of verekitug, observed in vitro and across clinical datasets, compared to published data for tezepelumab.
• These findings provide a mechanistic explanation for the empirically observed greater potency of targeting the TSLP receptor with verekitug as compared with targeting the TSLP ligand.

Posted In: UPB