ALLSCHWIL, Switzerland—Privately held Polyphor Ltd. has announced that it has received a Seeding Drug Discovery Award of 2.3 million Swiss francs (approximately $2.28 million) from the Wellcome Trust to advance the development of broad-spectrum, gram-negative preclinical antibiotic product candidates. The award will help support the development over the next 18 to 24 months of novel antibiotics based on Polyphor’s new product class, Outer Membrane Protein Targeting Antibiotics (OMPTA), which have shown efficacy in attacking the most resistant strains of gram-negative pathogens.
Concern about antimicrobial resistance has been growing over the past few decades. Antibiotic resistance occurs naturally, but widespread misuse of antibiotics in humans and animals is accelerating the process. A growing number of infections—pneumonia, malaria and tuberculosis, for example—are becoming difficult to treat, and the antibiotics used are becoming less effective. According to the Infectious Diseases Society of America, the cost to the U.S. healthcare system alone of antibiotic-resistant infections is $21 billion to $34 billion each year, and more than eight million additional hospital days. And while the threat of these drug-resistant bacteria continues to grow, fewer and fewer drug companies are willing to assume the regulatory burden of creating new solutions to this problem because such drugs are less profitable than ones like asthma or diabetes, which patients will take for years.
Bacteria are classified as gram-negative or gram-positive. Gram-negative bacteria are particularly alarming because their structure allows them to find ever new ways to be resistant and can transfer genetic materials to make other bacteria become drug-resistant as well. Most antibiotics currently being developed have mechanisms similar to those already on the market, so novel antibiotics are needed particularly to fight multidrug resistant (MDR) gram-negative bacteria.
Of particular concern is Pseudomonas aeruginosa, a gram-negative bacterium that accounts for 8 percent of hospital-acquired infections in the United States, according to the U.S. Centers for Disease Control and Prevention, and which is listed as of one of the six most dangerous drug-resistant microbes (the “ESKAPE” pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) by the Infectious Diseases Society of America. The first member of the class of Polyphor’s OMPTA-class of antibiotics is murepavadin (POL7080), which is being developed for the treatment of serious Pseudomonas aeruginosa infections associated with ventilator-associated bacterial pneumonia. Polyphor is currently in discussion with the U.S. Food and Drug Administration and the European Medicines Agency on a regulatory path towards market approval for murepavadin.
Polyphor has shown that its broad-spectrum antibiotics are efficacious against other MDR gram-negative pathogens, both in vitro and in vivo, belonging to the ESKAPE pathogens, including isolates resistant to colistin, which is often used as the last resort antibiotic. According to the company, the new compound series is currently in advanced lead optimization phase and the program should deliver the first development candidates entering clinical testing within the next two years.
“The resistance of bacteria to antibiotics is a growing and significant global public health issue,” Giacomo Di Nepi, CEO of Polyphor, said in a press release. “The support from Wellcome will help us advance our novel broad-spectrum antibiotics even more expeditiously towards the first clinical trial. Today’s award is yet another validation of our breakthrough antibiotic research which already resulted in murepavadin, a precision antibiotic for the treatment of Pseudomonas aeruginosa infections, close to enter pivotal clinical studies. The award from Wellcome exemplifies Polyphor’s strategy of translating innovative research into new medicines that address major unmet needs.”
Wellcome Trust is the world’s largest biomedical research funding charity, with substantial experience and commitment in antibacterial research and development. “Already hundreds of thousands of people every year die from drug-resistant infections,” said Dr. Ann Mills-Duggan, part of Wellcome’s Innovations Division, in a statement. “If nothing is done, this will increase to millions of people every year by 2050. A healthy pipeline of alternative treatments is a vital part of tackling this serious global health problem. This Seeding Drug Discovery award to Polyphor will contribute to this pipeline by supporting the development of a new class of antibiotics.”