TSLP receptor targeting

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Translational Data Illustrate a Mechanism of Greater Potency with Verekitug, a Novel Antibody Antagonist of the TSLP Receptor
Globenewswireยท 2025-06-15 11:45
Core Insights - Upstream Bio, Inc. presented pharmacology modeling data at the EAACI Congress, highlighting the greater potency of verekitug compared to tezepelumab in treating inflammatory diseases [1][3] - Verekitug targets the TSLP receptor, offering a potentially differentiated profile across severe asthma, COPD, and CRSwNP [1][2] Company Overview - Upstream Bio is a clinical-stage biotechnology company focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders [11] - Verekitug is the only monoclonal antibody in clinical development that targets and inhibits the TSLP receptor, which is a key driver of inflammatory responses [2][11] Mechanism of Action - TSLP is a cytokine that initiates the inflammatory cascade, and blocking its receptor can impact multiple inflammatory processes [2][5] - The pharmacokinetic/pharmacodynamic (PK/PD) modeling indicates that verekitug provides complete and sustained inhibition of the TSLP/TSLPR complex, leading to a greater reduction in fractional exhaled nitric oxide (FeNO) compared to tezepelumab [6][8] Clinical Development - Verekitug is currently being evaluated in two Phase 2 clinical trials: the VALIANT trial for severe asthma and the VIBRANT trial for CRSwNP, with plans for a trial in COPD [8][10] - The company anticipates top-line Phase 2 clinical data for CRSwNP in Q3 2025 and for severe asthma in the first half of 2026 [3][8] Preclinical and Clinical Data - Preclinical studies demonstrated that verekitug has high occupancy of the TSLP receptor and effectively inhibits TSLP signaling [9] - Previous clinical trials showed that verekitug was well tolerated and exhibited a predictable pharmacokinetic profile [10]