Polyphor AG: Polyphor contributes to the progress in understanding Neutrophil Elastase Science
EQS Group-News: Polyphor AG / Key word(s): Scientific publication
Allschwil, Switzerland, July 10, 2017, 09:00 CET
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 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.
- Murepavadin 2,3 (POL7080, entering Phase III / Pivotal registration program), a precision Outer Membrane Protein Targeting Antibiotic (OMPTA) against Pseudomonas Aeruginosa.
- POL6014 4-6 (in Phase Ib), an inhaled inhibitor of neutrophil elastase for the treatment of cystic fibrosis and other neutrophilic lung diseases.
- Balixafortide 7 (POL6326, in Phase Ib), an antagonist of the chemokine receptor CXCR4 for combination treatment in oncology.
Polyphor has applied its Protein Epitope Mimetic (PEM) proprietary technology to discover and optimize fully synthetic cyclopeptide serine protease inhibitors, CXCR4 antagonists and OMPTAs, which resulted, among others, in POL6014, Balixafortide and Murepavidin, respectively.
Polyphor has discovered the OMPTA class and is further developing it, including a broad-spectrum preclinical candidate, to address infections caused by difficult-to-treat, resistant Gram-negative pathogens - one of the most pressing emerging medical needs. The OMPTA represent the first new class of antibiotics against Gram-negative bacteria reaching advanced clinical stage in the last 40 years.
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: Neutrophil Elastase Science