Preclinical concept studies showing advantage of an inhaled anti-CTGF/CCN2 protein for pulmonary fibrosis treatment
Vanessa Neiens,
Eva-Maria Hansbauer,
Thomas J. Jaquin,
Janet K. Peper-Gabriel,
Poornima Mahavadi,
Mark E. Snyder,
Maximilian J. Grill,
Cornelia Wurzenberger,
Antonio Konitsiotis,
Adriana Estrada-Bernal,
Kristina Heinig,
Athanasios Fysikopoulos,
Nicolas Schwenck,
Stefan Grüner,
Denis Bartoschek,
Theresia Mosebach,
Sandra Kerstan,
Joe Wrennall,
Marleen Richter,
Kentaro Noda,
Konrad Hoetzenecker,
Janette K. Burgess,
Robert Tarran,
Claudia Wurzenberger,
Karl-Robert Wichmann,
Jonas Biehler,
Kei W. Müller,
Andreas Guenther,
Oliver Eickelberg,
Mary F. Fitzgerald,
Shane A. Olwill,
Gabriele Matschiner and
Marina Pavlidou ()
Additional contact information
Vanessa Neiens: Pieris Pharmaceuticals GmbH
Eva-Maria Hansbauer: Pieris Pharmaceuticals GmbH
Thomas J. Jaquin: Pieris Pharmaceuticals GmbH
Janet K. Peper-Gabriel: Pieris Pharmaceuticals GmbH
Poornima Mahavadi: Justus Liebig University (JLU) Giessen
Mark E. Snyder: University of Pittsburgh
Maximilian J. Grill: Ebenbuild GmbH
Cornelia Wurzenberger: Pieris Pharmaceuticals GmbH
Antonio Konitsiotis: Pieris Pharmaceuticals GmbH
Adriana Estrada-Bernal: University of Pittsburgh
Kristina Heinig: Pieris Pharmaceuticals GmbH
Athanasios Fysikopoulos: Pieris Pharmaceuticals GmbH
Nicolas Schwenck: Pieris Pharmaceuticals GmbH
Stefan Grüner: Pieris Pharmaceuticals GmbH
Denis Bartoschek: Pieris Pharmaceuticals GmbH
Theresia Mosebach: Pieris Pharmaceuticals GmbH
Sandra Kerstan: Pieris Pharmaceuticals GmbH
Joe Wrennall: University of North Carolina Department of Cell Biology & Physiology
Marleen Richter: Pieris Pharmaceuticals GmbH
Kentaro Noda: University of Pittsburgh
Konrad Hoetzenecker: Medical University of Vienna
Janette K. Burgess: Department of Pathology and Medical Biology
Robert Tarran: University of North Carolina Department of Cell Biology & Physiology
Claudia Wurzenberger: Pieris Pharmaceuticals GmbH
Karl-Robert Wichmann: Ebenbuild GmbH
Jonas Biehler: Ebenbuild GmbH
Kei W. Müller: Ebenbuild GmbH
Andreas Guenther: Justus Liebig University (JLU) Giessen
Oliver Eickelberg: University of Pittsburgh
Mary F. Fitzgerald: Pieris Pharmaceuticals GmbH
Shane A. Olwill: Pieris Pharmaceuticals GmbH
Gabriele Matschiner: Pieris Pharmaceuticals GmbH
Marina Pavlidou: Pieris Pharmaceuticals GmbH
Nature Communications, 2025, vol. 16, issue 1, 1-20
Abstract:
Abstract Inhaled therapeutics have high potential for the treatment of chronic respiratory diseases of high unmet medical need, such as idiopathic pulmonary fibrosis (IPF). Preclinical and early clinical evidence show that cellular communication network factor 2 (CCN2), previously called connective tissue growth factor (CTGF), is a promising target for the treatment of IPF. In recent phase 3 clinical trials, however, systemic CCN2 inhibition failed to demonstrate a clinically meaningful benefit. Here, we present the preclinical profile of the inhaled anti-CCN2 Anticalin® protein PRS-220. Our study demonstrates that efficient pulmonary delivery directly translates into superior efficacy in relevant models of pulmonary fibrosis when compared to systemic CCN2 inhibition. Moreover, we present a holistic approach for the preclinical characterization of inhaled PRS-220 from state-of-the art in vitro and in vivo models to novel human ex vivo and in silico models, highlighting the advantage of inhaled drug delivery for treatment of respiratory disease.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58568-x
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DOI: 10.1038/s41467-025-58568-x
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