New data in war against resistance

Collaboration develops drug candidates with antibacterial activity

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CAMBRIDGE, U.K. & STEVENAGE, U.K.—Bacteria have become increasingly resistant to existing antibiotics and, as a result, the spread of drug-resistant bacteria has become a significant issue. It is estimated that 50 to 60 percent of hospital-acquired infections (HAIs) in the United States are caused by antibiotic-resistant bacteria, including the so-called ESKAPE pathogens (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa and Enterobacter spp.).
The discovery and development of new antibiotics has slowed in recent decades, and no novel class of antibiotic has been brought to the market in more than 30 years. The World Health Organization (WHO) believes that common infections and minor injuries could become lethal if the need for new antibacterial agents, especially against gram-negative bacteria, are not met.
Domainex and Auspherix have announced new data from their collaboration to develop novel candidate drugs to tackle the growing threat of resistance to antibiotics. Data disclosed in a poster and an oral presentation by Dr. Jonathan Powell from Domainex at the 19th Royal Society of Chemistry Medicinal Chemistry Symposium describe the discovery of three distinct chemical series, all with broad-spectrum antibacterial activity against both gram-positive and gram-negative bacteria. The Auspherix compounds are active against the ESKAPE pathogens. Founding research behind Auspherix’s antibacterial compounds identified auranofin (Ridaura) as being active against gram-positive bacteria. Auranofin is an FDA-approved organogold compound with a long history of clinical use as an anti-rheumatic medicine.
Auspherix Ltd., an anti-infectives company engaged in the discovery and development of a new class of organogold-based antibiotics for difficult to treat or potentially life-threatening infections, has developed a new class of antibiotics that demonstrate potent and broad-spectrum activity against both gram-positive and gram-negative bacteria, including many gram-negative multidrug resistant (MDR) strains. Domainex Ltd., a small-molecule therapeutics company, provides integrated drug research services to global pharmaceutical, biotechnology and academic partners. Its services, which cover a wide span of the drug research value chain from disease target selection to preclinical candidate nomination, include recombinant protein expression and use of its proprietary technology platform and Combinatorial Domain Hunting to identify soluble protein fragments for structural biology and assay development.
The focus of the collaboration has been to develop novel organogold compounds with activity against gram-negative bacteria and deliver a novel class of broad-spectrum antibiotics. Using their medicinal chemistry expertise, the teams at Domainex and Auspherix have explored the structure-activity relationships (SAR) of the two ligands coordinated to the central gold atom and have now demonstrated that the physiochemical properties of the phosphine ligand, in particular, are a key determinant of gram-negative activity. Robust synthetic routes are now in place to enable the team to further explore the chemical space around this organogold chemical template.
According to Tom Mander, chief operating officer of Domainex, “As far as we know, we are the only teams working on the challenging task of developing broad-spectrum antibiotics based on organogold chemistry. In our collaboration with Auspherix, we have made tremendous progress towards identifying novel preclinical drug candidates that address the growing global burden of multi-drug-resistant bacterial infections.”
As Auspherix CEO Dr. Neil Miller said, “This has been a highly productive scientific collaboration with Domainex, and I look forward to seeing the data generated with our lead compounds in rodent infection models as we move towards our goal of identifying a preclinical development candidate from one of our three lead series. We anticipate progressing into human clinical studies in 2019, with an initial focus on the treatment of complicated urinary tract infections (cUTI). Given that our organogold compounds retain activity against multidrug-resistant clinical isolates and they show a low propensity for the emergence of resistance, they have great potential to address the greatest unmet medical need and treat patients suffering from life-threatening drug-resistant infections.
“There is a well-defined clinical and regulatory path to approval for new antibiotic treatments for cUTIs with the opportunity to receive Qualified Infectious Disease Product designation, which offers fast-track status and priority review with the FDA, plus potentially five years’ additional market exclusivity, thus making our focus on cUTIs an attractive investment proposition.”

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