Upstream Bio announces presentation of data on verekitug’s TSLP receptor

Upstream Bio (UPB) announced the presentation of translational pharmacology modeling data supporting verekitug’s Thymic Stromal Lymphopoietin, TSLP, receptor targeting as a mechanism for greater potency when compared to treatments targeting the TSLP ligand. Data were presented at the European Academy of Allergy & Clinical Immunology, EAACI, Congress taking place June 13-16, 2025, in Glasgow, United Kingdom. Data presented used an in silico system pharmacology modeling approach to provide a mechanism-based understanding for the observed potency of verekitug and are summarized as follows: Semi-mechanistic pharmacokinetic/pharmacodynamic models were built using the same biological and drug-specific parameters for verekitug and tezepelumab and populated with observed clinical data for verekitug and published clinical data for tezepelumab. Across a range of doses, PK/PD model simulations predict complete and sustained inhibition of the TSLP/TSLPR complex with verekitug compared to tezepelumab. Dose-response model simulations predict that potent inhibition of the TSLP/TSLPR complex would result in a greater reduction in fractional exhaled nitric oxide, a biomarker of lung inflammation. Modeling data indicated that the greater predicted reduction of FeNO observed with verekitug, compared with published data for tezepelumab, is potentially driven by lower expression levels of the TSLP receptor over time versus the ligand, as well as slower protein turnover time for the TSLP receptor versus the ligand.