SetLance SRL announced that its antimicrobial peptide M33, being developed for people with difficult-to-treat lung infections like pneumonia, is robust enough for industrial production.
Standard treatment for these patients is an intravenous administration of a combination of antibiotics. But such treatments can lead more resistant infectious strains, particularly of Gram-negative bacteria, and doctors are running out of options. SetLance’s M33 might offer an alternative treatment approach.
M33 is an optimized version of an artificial peptide sequence, selected for its efficacy and stability profile. SetLance, an Italian company, started investigating this antimicrobial peptide several years ago, and has since shown encouraging in vitro results against multidrug-resistant Gram-negative bacteria.
With financial support from the European Union for its PneumoNP project, the company is developing a new formulation of M33 that increases its antimicrobial activity, while decreasing issues of artificial peptides such as short half-life, low selectivity for bacteria, and toxicity. Called SET-M33L-PEG, this new formulation aims to fight Gram-negative bacteria in three steps. First, it binds to the lipopolysaccharides (LPS) found on the outer membrane of bacteria, then it forms a helix, and finally it disrupts the membrane, inducing cytoplasm leakage from the bacteria.
When tested in mice with Pseudomonas Aeruginosa-caused lung infections, SET-M33L-PEG induced up to 80 percent survival, SetLance reported in a news release. The drug also healed skin infections when administered topically.
Furthermore, the new M33 formulation seems to be less toxic to human cells than other antimicrobial peptides that are currently being used in the clinic, such as colisin.
An interesting finding was that combining M33 with levofloxacin, a widely used antibiotic, diminished the antimicrobial resistance in the Gram-negative bacteria to restore the effectiveness of levoflaxin. (Levofloxacin is marketed as Quinsair in Europe and Levaquin in the U.S.)
The company has recently taken M33 synthesis from a lab-scale to a commercial scale, and is now able to produce several hundred milligrams per batch, showing that it is robust for industrial production. SetLance is expecting M33 to enter clinical development and testing in early 2018.