Upstream Bio, Inc. · NASDAQ:UPB
Upstream Bio — European Respiratory Society (ERS) Congress 2025
9 slides from Upstream Bio's conference presentation, September 2025
Slide 1: Mechanistic drivers for potent pharmacodynamic activity of verekitug
No Image Mechanistic drivers for potent pharmacodynamic activity of verekitug, a novel anti-human thymic stromal lymphopoietin receptor (TSLPR) antibody Fatema Chowdhury, PhD; Ashish Kalra, PhD; Sumathi Sivapalasingam, MD; Aaron Deykin, MD Upstream Bio, Inc., Waltham, MA, USA European Respiratory So
Slide 2: Acknowledgments, funding, and disclosures
No Image Acknowledgments, funding, and disclosures Acknowledgments Under the direction of the authors, medical writing assistance was provided by Luciana Gardner, MSc, of Parexel International, and supported by Upstream Bio, Inc. Funding and disclosures This study was funded by Upstream Bio, Inc., W
Slide 3: Verekitug, targeting TSLPR, can substantially reduce biomarkers of airway inflammation
No Image Verekitug, targeting TSLPR, can substantially reduce biomarkers of airway inflammation • TSLP is a key upstream driver of airway inflammation in chronic respiratory diseases such as asthma, CRSwNP, and COPD Phase 1 clinical study data in patients with mild to moderate asthma • Verekitug is
Slide 4: Verekitug binds to TSLPR with a sub-picomolar affinity and inhibits TSLP-TSLPR complex formation
No Image Verekitug binds to TSLPR with a sub-picomolar affinity and inhibits the formation of TSLP-TSLPR complex Blocks the necessary priming step for heterodimeric complex formation with IL-7Rα Mechanism of TSLP-induced signaling4 TSLP binding to TSLPR Verekitug binding to TSLPR in the presence of
Slide 5: Verekitug outcompetes TSLP in the preformed heterodimeric complex and blocks STAT5 signaling
No Image Verekitug outcompetes TSLP in the preformed heterodimeric complex and blocks STAT5-mediated TSLP/TSLPR signaling Verekitug blocks pSTAT5 mediated signaling Control IgG does not inhibit receptor complex formation even when cells were pre-incubated with TSLP 80 TSLP pre-incubation Relative re
Slide 6: Verekitug blocks TSLP/TSLPR interaction by occupying majority of the TSLP ligand binding sites
No Image Verekitug blocks TSLP/TSLPR interaction by occupying majority of the TSLP ligand binding sites TSLP Verekitug (Fab) TSLP interaction sites Verekitug (heavy and light chains) interaction sites Fab, fragment antigen-binding region. 6
Slide 7: Superior potency of verekitug over tezepelumab may stem from targeting receptor with lower abundance
No Image Superior potency of verekitug over tezepelumab may stem from targeting receptor with lower abundance and slower turnover Semi-mechanistic PK/PD modeling co-fit with phase 1 clinical data Model overview5–7 TSLP/TSLPR inhibition TSLPR concentration Verekitug binding 100 Verekitug Tezepelumab
Slide 8: Conclusions
No Image Conclusions • Verekitug (KD < 1 pM) outcompetes TSLP binding to TSLPR in a preformed heterodimeric complex • Verekitug binds and occludes the majority of TSLP binding sites on TSLPR, blocking TSLP interaction with the binding pocket of the TSLPR • A semi-mechanistic PK/PD model indicates th
Slide 9: References
No Image References 1. Numazaki M, et al. J Pharmacol Exp Ther. 2022;380:26–33. 2. Corren J, et al. N Engl J Med. 2017;377: 936–946. 3. Deykin A, et al. Eur Res J. 2024;64(suppl 68):OA3651. 4. Verstraete K, et al. Nat Commun. 2017;8:14937. 5. Ly N, et al. J Clin Pharmacol. 2021;61:901–912. 6. Sundne
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