January 17, 2018
Synspire Pharmaceuticals Novel Glycopolymer Proves Effective Against Antibiotic Resistance
CAMBRIDGE, Mass.– Synspire Pharmaceuticals, a privately held company developing a new class of inhaled glycopolymer-based therapeutics for the treatment of pulmonary disease, today announced the results of a study exploring poly-N (acetyl, arginyl) glucosamine (PAAG) as a potential new treatment for methicillin-resistant Staphylococcus aureus (MRSA). The full study, “In Vitro Activity of Novel Glycopolymer Against Clinical Isolates of Multidrug-Resistant Staphylococcus aureus,” is published in PLOS ONE.
The study was conducted by Synedgen, a pioneering biotechnology company using the science of glycomics to discover and develop polysaccharide-based drugs that enhance and mimic the innate immune system. Synspira has an exclusive license from Synedgen to the Glycomics Technology Platform for the development of inhaled therapeutics in pulmonary indications.
MRSA is a contagious bacterial infection, often resistant to numerous antibiotics, making it increasingly challenging to treat. More than 2 million people in the U.S. every year acquire serious antibiotic-resistant MRSA infections. The prevalence of MRSA in patients with cystic fibrosis (CF) is increasing steadily and is a significant contributor to pulmonary decline.
Synspire is developing SNSP113 as part of its new class of glycopolymers to serve as an adjunctive therapy to traditional antibiotic strategies to treat MRSA and multidrug-resistant (MDR) infections. The results of the study demonstrate the antibacterial activity of PAAG against clinical isolates of methicillin and mupirocin-resistant Staphylococcus aureus (S. aureus) and its ability to dramatically reduce the amount of antibiotic required to kill the bacteria.
“The study published today explores how PAAG can enhance the efficacy of current antibiotics used to treat MRSA, a common pathogen in patients with cystic fibrosis, who face frequent complications from MDR bacteria,” said Shenda Baker, Ph.D., Board Member, Synspire. “PAAG is the active component in Synspire’s inhaled pulmonary candidate, SNSP113, which is currently in a Phase 1 clinical trial for the treatment of CF.”
The study showed antibacterial efficacy of PAAG against clinical isolates of MRSA and mupirocin resistant S. aureus. These results demonstrate that PAAG rapidly permeabilizes the bacteria to both directly kill MRSA and is synergistic with antibiotics, reducing the minimum inhibitory concentration (MIC) below levels where bacteria are considered resistant and resensitizing bacteria to the antibiotic. In addition, in a prior study published in PLOS ONE, PAAG improved the effectiveness of antibiotics against Burkholderia cepaciacomplex.
“This new class of glycopolymers may provide a new tool in the battle against multidrug-resistant bacteria,” stated John Uhrig, Postdoctoral Fellow at the Division of Infectious Disease at the Medical College of Wisconsin. “PAAG’s ability to permeabilize bacteria reduces their ability to respond to a variety of antibiotic challenges, and thus has tremendous potential for treating MDR infections.”
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 nontuberculous Mycobacteria(NTM), Burkholderia cepacia complex (BCC), Pseudomonas aeruginosaor 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. Synspira is expected to initiate SNSP113 Phase 2 trials in 2019.
About Cystic Fibrosis
Cystic fibrosis (CF) is a progressive genetic disease that causes persistent lung infections and chronic inflammation of pulmonary tissue leading to permanent lung damage and ultimately resulting in respiratory failure. CF is characterized by the accumulation of thick, sticky mucus in the lungs and clogged airways which impede breathing. Bacteria are not easily cleared and create protective biofilms that are difficult for antibiotics to penetrate and often lead to the emergence of multi-drug resistant bacteria. More than 30,000 people in the United States, and a similar number in Europe, live with cystic fibrosis.