April 23, 2019
Synspire Pharmaceuticals SNSP 113 Demonstrates Improvement in Abnormal Cystic Fibrosis Mucus and Pulmonary Disease
Synspira Therapeutics SNSP 113 Demonstrates Improvement in Abnormal Cystic Fibrosis Mucus and Pulmonary Disease
Targets Mucus Structure and Improves Airway Clearance
Reduces Pulmonary Markers of Inflammation
FRAMINGHAM, Mass., April 23, 2019 — Synspire Pharmaceuticals, a clinical-stage biopharmaceutical company dedicated to improving the lives of people with cystic fibrosis and other rare diseases, today announced the results of a publication exploring the efficacy of SNSP113 as a potential treatment for improving lung function in people with cystic fibrosis. The publication, “A glycopolymer improves viscoelasticity and mucociliary transport of abnormal cystic fibrosis mucus” was published in the April issue of The Journal of Clinical Investigation and evaluated a number of mechanisms where SNSP113 could impact abnormal mucus structure and improve mucus clearance.
“Improving mucus clearance is a critical challenge for protecting people with CF and other pulmonary diseases from life threatening infections and progressive pulmonary decline,” said Dr. Steven M. Rowe, MD MSPH, Director, Cystic Fibrosis Research Center at the University of Alabama at Birmingham. “New therapies that target the underlying mechanisms of mucus abnormalities and reduce pulmonary accumulation of hyperconcentrated mucus may contribute to improving chronic infections, airway function and patient quality of life.”
Researchers evaluated the mucus properties of SNSP113 (poly (acetyl, arginyl) glucosamine (PAAG)), a first-in-class inhaled glycopolymer with a broad spectrum mechanism of action, to normalize mucin structure, reduce mucus viscoelasticity and improve mucus clearance of the lungs.
Results of the studies showed that SNSP113 treatment produced a significant reduction in CF patient sputum viscosity and elasticity, approaching levels seen in sputum obtained from normal volunteers. Furthermore, this change in sputum properties directly resulted in improved mucus clearance and ciliary beat frequency in animal models. Inhalation of nebulized SNSP113 in animal models of CF resulted in mucociliary transport. Researchers showed that with SNSP113 treatment mucin polymers took on a more linear extended structure, comparable to that found in normal lungs.
SNSP113 was also observed to localize to the epithelial surface to reduce adhesion between adherent mucins and the lung surface. This localized surface activity is likely the source of SNSP113’s observed ability to remove mucus plugs from cystic fibrosis animal models. Twice-weekly inhalation of SNSP113 in a cystic fibrosis ferret model also showed a significant reduction in markers of pulmonary inflammation, specifically reduction in neutrophils (P < 0.0001) and several inflammatory markers.
“Accumulation of abnormally thick mucus and inflammation in the lungs may be a trigger of lung disease in cystic fibrosis and other pulmonary diseases,” said Robert Gallotto, President and Chief Executive Officer, Synspira Therapeutics. “SNSP113 has a novel mechanism of action disrupting both mucus and biofilm structure and represents a new therapeutic option against the cascade of events that lead to progressive pulmonary decline and pulmonary exacerbations. We look forward to continuing to study SNSP113 and its potential to improve pulmonary function in patients with CF.”
Increased mucus viscosity and delayed mucociliary clearance is linked to progressive decline in pulmonary function in patients with cystic fibrosis (CF) and other progressive pulmonary diseases. Mucins, the chief structural component of mucus, are negatively charged glycoproteins that protect the epithelial surface of human airways. In CF, mucin structure is abnormal, contributing to mucus that is hyperviscous and adheres to lung epithelium leading to chronic infections, biofilm accumulation and inflammation, hall¬marks of progressive pulmonary diseases.
About SNSP113
The company’s lead product, SNSP113, is a first-in-class inhaled glycochemistry-based therapeutic with a broad spectrum mechanism of action intended to target the underlying cascade of events that lead to progressive pulmonary disease or other life-threatening pulmonary conditions, such as pulmonary infections with nontuberculous Mycobacteria (NTM), Burkholderia cepacia complex (BCC), Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus (MRSA). SNSP113 is designed to normalize mucin viscosity and improve mucus transport to increase airway clearance. SNSP113 disrupts the cohesion of bacterial biofilms and interacts with the cell walls of invading bacteria to increase their permeability, reduce their viability and potentiate the efficacy of antibiotics. These actions of SNSP113 lead to a reduction in the inflammatory cascade of neutrophils that can lead to pulmonary damage and fibrosis. Progressive pulmonary disease leads to overwhelming symptoms, impacts quality of life (QoL) and results in debilitating progressive lung decline. Synspire is planning to initiate a study in cystic fibrosis patients with SNSP113 in 2019, a trial that is supported in part by a development award from the Cystic Fibrosis Foundation Therapeutics, Inc.
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Company Contact:
info@synspirepharmaceuticals.com