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Polyphor contributes to the progress in understanding Neutrophil Elastase Science
Daniel Obrecht, CSO of Polyphor, said: "Despite existing therapies there is still high unmet medical need for the treatment of chronic neutrophilic inflammation associated with high levels of free NE which ultimately leads to lung destruction and loss of pulmonary function.
Polyphor values the collaboration with academic partners to increase the understanding of NE and its quantification methods in disease-relevant lung matrix".
POL6014 is a potent inhaled NE inhibitor currently in clinical development in a Multiple Ascending Dose study in CF. Recently, promising data of a Single Ascending Dose study were presented at ECFS in Sevilla, showing a high concentration of POL6014 accompanied by strong inhibition of NE in sputum.
Polyphor is investing to better understand the science of NE inhibition as NE is considered one of the major determinants of chronic inflammation and tissue damage in neutrophilic lung diseases like CF or NCFB. NE released from activated neutrophils induces degradation of elastin and collagen, IL-8 production and mucin secretion, which eventually leads to lung destruction, resulting in the development of serious chronic lung diseases. A central role in the pathophysiology of CF and other neutrophilic lung diseases has been attributed to NE as high NE levels have been detected in sputa and these levels correlate with disease severity (as measured by FEV1%pred reduction)1.
Inhibition of pulmonary NE may greatly contribute to reduce the local inflammatory process and favor maintenance of tissue integrity, lung function and quality of life of patients suffering from bronchiectasis.
1. Mayer-Hamblett N. et al. Association between pulmonary function and sputum biomarkers in Cystic Fibrosis. Am. J. Respir. Crit. Care Med. V175: 822-828, 2007.
2. Armaganidis A, et al. Pharmacokinetic and efficacy analysis of Murepavadin (POL7080) co-administered with standard-of-care (SOC) in a Phase II study in patients with ventilator associated pneumonia (VAP) due to suspected or documented Pseudomonas aeruginosa infection. Poster 1308, ECCMID 2017.
3. Machacek M, et al. Population pharmacokinetics modeling of Murepavadin (POL7080) and simulation of target attainment in a population with ventilator-associated pneumonia due to infection with Pseudomonas aeruginosa. Poster 1307, ECCMID 2017.
4. Lacey N. et al. A novel neutrophil elastase inhibitor, POL6014, for therapeutic potential in cystic fibrosis and airways disease characterised by neutrophil-dominated inflammation. Poster. NACFC, 2016.
5. Barth. P. et al. A randomised, double-blind, placebo-controlled, parallel-group, dose-escalation Phase I study in healthy volunteers (HV) of inhaled single doses (SD) of POL6014, a potent and selective human neutrophil elastase. Poster, ECFS, 2017.
6. Hooftman, L. et al. A randomised, double-blind, placebo-controlled, parallel-group, dose-escalation study of inhaled single doses of POL6014, a highly potent and selective reversible inhibitor of human neutrophil elastase (NE), in cystic fibrosis (CF) patients. Oral Communication, ECFS, 2017.
7. Gil-Martin et al. Phase Ib study of the combination of Balixafortide (a CXCR4 inhibitor) and Eribulin in HER2-negative metastatic breast cancer patients. Poster, ASCO 2017.
Document title: Neutrophil Elastase Science
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