PRS-220 / Palvella Therapeutics - LARVOL DELTA

Preclinical concept studies showing advantage of an inhaled anti-CTGF/CCN2 protein for pulmonary fibrosis treatment. (PubMed, Nat Commun) - "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."

Journal • Preclinical • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CTGF

Study of Single and Multiple Doses of PRS-220 Administered by Oral Inhalation in Healthy Subjects (clinicaltrials.gov) - P1 | N=64 | Completed | Sponsor: Pieris Australia Pty Ltd | Recruiting ➔ Completed

Trial completion

Favorable lung biodistribution profile of CTGF-targeting Anticalin protein PRS-220 for inhaled treatment of IPF patients (ERS 2023) - No abstract available

Clinical • Idiopathic Pulmonary Fibrosis • CTGF

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

Preclinical Profile of PRS-220, a Novel Inhaled Inhibitor of CTGF/CCN2 in Clinical Development for Idiopathic Pulmonary Fibrosis (ATS 2023) - P1 | "Targeting CTGF/CCN2 is a promising treatment approach for IPF as shown in clinical trials with the intravenously delivered monoclonal antibody pamrevlumab. Excellent properties for inhaled lung delivery make PRS-220 a promising treatment option for IPF and support currently ongoing clinical development (NCT05473533)."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • CTGF

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 Announces Presentation of Promising Preclinical Data for PRS-220 at ATS 2023 International Conference (Issuer Direct) - "Pieris Pharmaceuticals...announced the presentation of preclinical data from the Company's inhaled connective tissue growth factor (CTGF) antagonist program, PRS-220, for idiopathic pulmonary fibrosis (IPF) at the annual American Thoracic Society (ATS) International Conference being held in Washington, D.C. May 19-24, 2023. The poster will be presented on May 21, 2023, from 11:30 AM to 1:15 PM (Session A67, P1052) and demonstrates that PRS-220 achieved proof of concept in a silica-induced lung fibrosis mouse model when delivered to the lung by inhalation and outperformed a systemically administered CTGF-targeting monoclonal antibody, reinforcing the transformative potential of a local intervention in this pathway."

Preclinical • Idiopathic Pulmonary Fibrosis

"Excited to be part of @atscommunity, showcasing the latest in the @PierisPharma’s inhaled pipeline at RIS. Today CDO Shane Olwill presented on PRS-220, our novel inhaled CTFG antagonist in the ’Innovators in Fibrosis’ set. Can’t wait for more insightful exchanges at #ATS2023." (@asmousa)

Fibrosis • Immunology

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

Pieris Pharmaceuticals Reports Full-Year 2022 Financial Results and Business Updates (BioSpace) - "PRS-220, inhaled Anticalin protein for idiopathic pulmonary fibrosis (IPF), continues in Phase 1 study; topline results expected in the second half of this year."

P1 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

Study of Single and Multiple Doses of PRS-220 Administered by Oral Inhalation in Healthy Subjects (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Pieris Australia Pty Ltd | Not yet recruiting ➔ Recruiting

Enrollment open

PRS-220, a novel inhaled therapeutic intervention in development for IPF, targets CTGF directly in the lung (ICLAF 2022) - "CTGF/CCN2 has been validated as a novel intervention point for IPF treatment in recent clinical trials with the systemically delivered antibody pamrevlumab. The excellent properties for inhaled lung delivery make PRS-220 a promising treatment option for IPF and merit investigation in clinical studies."

Fibrosis • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease • CTGF

Pieris Pharmaceuticals Announces Dosing of First Subject in Phase 1 Trial of Inhaled CTGF Inhibitor PRS-220 (Pieris Press Release) - "Pieris Pharmaceuticals... announced that the first subject has been dosed in the phase 1 study of PRS-220, an oral inhaled Anticalin protein targeting connective tissue growth factor (CTGF) for the treatment of idiopathic pulmonary fibrosis (IPF) and other forms of fibrotic lung disease. The phase 1 dose escalation study will evaluate the safety, tolerability, and pharmacokinetics of PRS-220 in heathy volunteers....'PRS-220 is the second inhaled respiratory program we have brought into the clinic, and we look forward to reporting the results from this study next year.'"

P1 data • Trial status • Idiopathic Pulmonary Fibrosis

Study of Single and Multiple Doses of PRS-220 Administered by Oral Inhalation in Healthy Subjects (clinicaltrials.gov) - P1 | N=64 | Not yet recruiting | Sponsor: Pieris Australia Pty Ltd | Initiation date: Aug 2022 ➔ Oct 2022

Trial initiation date

Nebulization performance and lung biodistribution profile of PRS-220, an inhaled CTGF antagonist for the treatment of IPF (ERS 2022) - "The excellent properties for inhaled lung delivery make PRS-220 a promising treatment option for IPF."

Fibrosis • Idiopathic Pulmonary Fibrosis • CTGF

Study of Single and Multiple Doses of PRS-220 Administered by Oral Inhalation in Healthy Subjects (clinicaltrials.gov) - P1 | N=64 | Not yet recruiting | Sponsor: Pieris Australia Pty Ltd

New P1 trial

PRS-220, a Novel Inhalable Therapeutic Intervention for IPF, Targeting CTGF Directly in the Lung (ATS 2022) - "The pharmacokinetic profile of PRS-220 upon lung delivery was assessed in lung tissue and plasma of healthy and bleomycin-challenged mice, and biodistribution in lung tissues was investigated by light sheeting imaging. PRS-220 binds with a picomolar affinity to CTGF and shares an overlapping epitope with the clinical-stage, CTGF-targeting antibody pamrevlumab, while demonstrating superior potency compared to the antibody. The promising preclinical profile supports proceeding the development of PRS-220 as a novel, potential best-in-class, inhaled antagonist of CTGF for the treatment of IPF."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • CTGF • TGFB1

Pieris Pharmaceuticals Reports First Quarter 2022 Financial Results and Provides Corporate Update (BioSpace) - "PRS-220, a proprietary inhaled Anticalin protein targeting connective tissue growth factor for the treatment of IPF, remains on track to enter a phase 1 trial in healthy volunteers this year."

New P1 trial • Idiopathic Pulmonary Fibrosis

[VIRTUAL] Development of PRS-220, a potential best-in-class, inhaled CTGF/CCN2 inhibitor for the treatment of IPF (ERS 2021) - "Based on their biophysical properties, Anticalin proteins are well suited for lung delivery as demonstrated by the inhaled PRS-060/AZD1402, currently in Phase 2 studies for asthma...The PK profile and in vivo potency of CTGF-binding Anticalin proteins upon lung delivery were assessed in healthy and bleomycin-challenged mice... Here we report the identification of a novel class of high affinity CTGF inhibitors for treatment of IPF using the Anticalin technology. The preclinical and developability data support further development of PRS-220 as a potential best-in-class inhaled IPF therapy."

Asthma • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • CTGF • TGFB1

Pieris Pharmaceuticals Announces PRS-220 Presentation at ERS Highlighting Preclinical Data for CTGF Inhibitor (Yahoo Finance) - "Pieris Pharmaceuticals, Inc...announced today the presentation of preclinical data for PRS-220...at the European Respiratory Society (ERS) International Congress 2021....The data show that PRS-220 demonstrates a more potent and durable target engagement profile compared to a clinical-stage, systemically delivered anti-CTGF antibody benchmark. Additionally, the targeting of CTGF locally in the lung shows increased attenuation of fibrotic lung remodeling in vivo compared to the systemically delivered antibody. This outcome correlates with superior lung tissue exposure of PRS-220 compared to that of the systemically administered antibody in head-to-head studies, where intratracheally administered PRS-220 efficiently penetrates the fibrotic, interstitial lung tissue of mice. Finally, the drug-like properties data demonstrate the suitability of PRS-220 for delivery to the lung via nebulization."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Respiratory Diseases

Pieris Pharmaceuticals Reports Second Quarter 2021 Financial Results and Provides Corporate Update (Yahoo Finance) - "Announced inhaled program PRS-220 for the treatment of IPF...The Company plans to present initial preclinical data from the program at the European Respiratory Society International Congress 2021 (ERS) in September, and clinical development is expected to begin next year....R&D expenses were $15.8 million for the quarter ended June 30, 2021, compared to $11.3 million for the quarter ended June 30, 2020. The increase reflects higher spending on preclinical activities for PRS-220..."

Commercial • New trial • Preclinical • Idiopathic Pulmonary Fibrosis • Respiratory Diseases

Pieris Pharmaceuticals Announces Inhaled CTGF Inhibitor PRS-220 for Idiopathic Pulmonary Fibrosis and 17 Million Dollar Grant From Bavarian Government To Accelerate Program Development for Post-COVID-19 Pulmonary Fibrosis (Pieris Press Release) - "Pieris Pharmaceuticals...announced the development of PRS-220...for the treatment of idiopathic pulmonary fibrosis (IPF)...The Company also announced it has been selected to receive a 14.2 million euro (approximately 17 million USD) grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy for the research and development of PRS-220 for post-acute sequelae of SARS-CoV-2 infection (PASC) pulmonary fibrosis (PASC-PF)...Clinical development of the program for both indications is expected to begin next year....The grant announced today, intended to support the evaluation of PRS-220 in PASC-PF beyond the intended IPF population...including GLP tox studies, GMP manufacturing, and phase 1 clinical development...Pieris intends to present preclinical data for PRS-220 later this year, around which time the Company also plans to provide further program details in IPF and PASC-PF."

Financing • New P1 trial • Preclinical • Idiopathic Pulmonary Fibrosis • Infectious Disease • Novel Coronavirus Disease