Pieris Pharmaceuticals Announces Presentation of Preclinical Data for Inhaled Jagged-1 Inhibitor PRS-400 at ERS
- Category: Proteins and Peptides
- Published on Thursday, 25 August 2022 11:49
- Hits: 831
BOSTON, MA, USA I August 24, 2022 I Pieris Pharmaceuticals, Inc. (NASDAQ:PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin® technology platform for respiratory diseases, cancer, and other indications, today announced the presentation of preclinical data for PRS-400, an inhaled Jagged-1 Anticalin protein the Company is developing for the treatment of muco-obstructive lung diseases, at the European Respiratory Society (ERS) International Congress 2022. The poster is now available for viewing by registered participants, and a copy of the poster is available here. Additionally, the poster will be available for viewing at the conference during a session scheduled on Tuesday, September 6, 2022, 8:30AM - 9:30AM CET.
Jagged-1 is a protein ligand for Notch receptors, which are implicated in mucus-producing cell differentiation. Inhibition of Jagged-1/Notch 2-dependent signaling has been shown to reduce the number of secretory cells in airways, thereby reducing goblet cell metaplasia and mucus hypersecretion in ex vivo and in vivo models. Pieris has generated a suite of inhaled candidates against Jagged-1, including several high-affinity antagonists across different target epitopes as well as biparatopic constructs with enhanced potency. The preclinical data presented show that candidate molecules inhibit Jagged-1-induced Notch 2 signaling in a dose-dependent manner and also demonstrate that PRS-400 reduces mucin expression ex vivo. Additionally, PRS-400 was found in vivo to reduce mucin gene expression and goblet cells in mice with IL-13-induced airway inflammation. These findings suggest that PRS-400 represents a promising opportunity to address muco-obstructive respiratory diseases locally with an attractive therapeutic index.
"PRS-400 is yet another inhaled application of Anticalin proteins for the treatment of respiratory diseases, following PRS-060/AZD1402 for asthma and PRS-220 for idiopathic pulmonary fibrosis," said Shane Olwill, Ph.D., Chief Development Officer of Pieris. "We believe there are broad applications for inhaled inhibition of Jagged-1, which is a highly attractive target in the treatment of muco-obstructive lung diseases, and that local inhibition of the Jagged-1/Notch pathway is vital to avoid safety challenges observed with systemic engagers."
PRS-400 is preclinical program targeting Jagged-1 proteins via oral inhalation for the treatment of muco-obstructive lung diseases. Muco-obstructive lung diseases are often caused by aberrant trans-differentiation of intermediate progenitors towards mucus (goblet) cells at the expense of ciliated cells, further worsening disease by impairing mucociliary clearance. Jagged-1 is a protein ligand for Notch receptors implicated in cell fate specification. In the lung, Jagged-1 acts predominantly through Notch 2 to control the balance of secretory club cells and ciliated cells, regulating mucus production. Inhibiting Jagged-1 redirects lineage specification towards ciliated cells and promotes loss of a majority of club cells, preventing their differentiation into mucus-secreting goblet cells and thereby profoundly reducing mucus cell burden in the epithelium.
About Pieris Pharmaceuticals:
Pieris is a clinical-stage biotechnology company that combines leading protein engineering capabilities and deep understanding into molecular drivers of disease to develop medicines that drive local biology to produce superior clinical outcomes for patients. Our pipeline includes inhalable Anticalin proteins to treat respiratory diseases and locally-activated bispecifics for immuno-oncology. Proprietary to Pieris, Anticalin proteins are a novel class of therapeutics validated in the clinic and by respiratory and immuno-oncology focused partnerships with leading pharmaceutical companies. For more information, visit www.pieris.com.
SOURCE: Pieris Pharmaceuticals