PRS-400 / Palvella Therapeutics - LARVOL DELTA

Targeting the Jagged-1/Notch pathway for the treatment of muco-obstructive lung diseases (WBC 2025) - "Here we characterize the inhalable Jagged-1 targeting tool Anticalin, PRS-400, in comparison to a monoclonal anti-JAG1 antibody AMG 430 in in vitro (human) and in vivo (murine) models In vitro: PRS-400 dose-dependent suppressed JAG1-notch signalling in a human luciferase reporter system.In human ALI cultures PRS-400 penetrated mucus, suppressed FOXA3+ goblet cell metaplasia and epithelial remodelling induced by IL-13 and IL-17 and restored FOXJ1+ ciliated cells. Targeting the Jagged-1/Notch-2 signalling axis by inhalation, exemplified by PRS-400, shows great potential for the treatment of muco-obstructive lung diseases."

Asthma • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • FOXA3 • IL13 • IL17A • JAG1 • NOTCH2

Targeting the Jagged-1/Notch pathway for the treatment of muco-obstructive lung diseases (WBC 2025) - "Here we characterize the inhalable Jagged-1 targeting tool Anticalin, PRS-400, in comparison to a monoclonal anti-JAG1 antibody AMG 430 in in vitro (human) and in vivo (murine) models. Targeting the Jagged-1/Notch-2 signalling axis by inhalation, exemplified by PRS-400, shows great potential for the treatment of muco-obstructive lung diseases."

Asthma • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • FOXA3 • IL13 • IL17A • JAG1 • NOTCH2

Polygenic Risk Score and Upgrading in Patients With Prostate Cancer Receiving Active Surveillance. (PubMed, JAMA Oncol) - "Multi-ancestry PRS of 451 PCa risk variants (PRS-451) and 400 PCa risk variants (PRS-400) after excluding prostate-specific antigen (PSA)-associated variants...Excluding PSA variants from the PRS revealed an association with smaller prostate size, which has been previously associated with more aggressive tumors. Although PRS may inform active surveillance, it is yet to be seen whether they improve clinical decisions."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

PRS-400 Anticalin® proteins targeting Jagged-1 reduce mucus production in preclinical models of muco-obstructive lung disease (ERS 2023) - No abstract available

Preclinical • Pulmonary Disease • Respiratory Diseases

Pieris Pharmaceuticals Provides Strategic Update and Announces Restructuring (Yahoo Finance) - "AstraZeneca has now informed the Company of its decision to terminate the parties' R&D collaboration agreement and hand back elarekibep along with discontinuing the remaining discovery program...Pieris' management and board of directors have assessed several strategic options, which will include focusing on execution of new or expanded partnerships to advance its therapeutic programs, including cinrebafusp alfa (PRS-343), PRS-220 and PRS-400...Pieris will prioritize capital preservation, with cash, cash equivalents and investments totaling approximately $54.9 million as of June 30, 2023....'One track is accelerating partnering discussions of PRS-220 and PRS-400. A second focal area is diligently selecting the best possible development partner and deal structure to re-initiate clinical development of cinrebafusp alfa, our former lead immuno-oncology asset, which has shown 100% ORR in five patients in a HER2+ gastric cancer trial that was discontinued for strategic reasons."

Commercial • Licensing / partnership • Pipeline update • Asthma • Gastric Cancer • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Pulmonary Delivery of PRS-400 Anti-Jagged-1 Anticalin Proteins Reduce Inflammation-driven Goblet Cell Metaplasia and Mucus Hypersecretion In Vivo (ATS 2023) - "While their binding affinity is similar to that of antibodies, their small size and biophysical properties make Anticalin proteins uniquely suitable for lung delivery via inhalation, as demonstrated by the ongoing evaluation of PRS-060/AZD1402 in a Phase 2 asthma study, and of PRS-220 in a Phase 1 IPF study. Our data demonstrate that Jagged-1-targeting Anticalin proteins potently inhibit Jagged-1/Notch 2 activation in vitro and reduce mucin expression and goblet cell differentiation ex vivo and in vivo. PRS-400 has broad potential as an inhaled therapy for patients with muco-obstructive lung diseases to reduce mucus burden and restore epithelial homeostasis."

Preclinical • Asthma • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • IL13 • NOTCH2

Pieris Pharmaceuticals Reports First Quarter 2023 Financial Results and Business Updates (Issuer Direct) - "Enrollment for elarekibep (PRS-060/AZD1402) Phase 2a study for asthma continues to progress with topline clinical data anticipated by mid-2024; successful safety review completed for 10 mg dose cohort; PRS-220, inhaled Anticalin protein for idiopathic pulmonary fibrosis (IPF), continues in Phase 1 study with topline results expected H2 2023; PRS-400, inhaled Anticalin protein for muco-obstructive respiratory disease, advances toward anticipated development candidate nomination H2 2023; New preclinical data to be presented at the American Thoracic Society (ATS) 2023 International Conference in May 2023 for both PRS-220 and PRS-400."

New P2a trial • New trial • P1 data • P2a data • Preclinical • Asthma • Idiopathic Pulmonary Fibrosis • Immunology • Respiratory Diseases