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Fighting the rise of antimicrobial resistance
STEVENAGE, U.K.—Aimed at meeting the urgent need for new antibiotics to fight a worldwide healthcare crisis of rising antimicrobial resistance (AMR), British private biotechnology company Auspherix Ltd. has developed a novel class of antibacterials from its organogold chemistry platform which show low propensity for the emergence of resistance. If successful, the formula offers new hope in the battle against antibiotic-resistant bacteria, with a chance to save thousands of lives—and set the tone for a new worldwide policy on fighting infection.
The company’s new class of antibiotics are differentiated from current antibiotics by their chemical structure and distinct antibacterial profile.
“Our pipeline comprises three structurally distinct series of organogold small molecules, with potent and broad spectrum activity against gram-positive and gram-negative bacteria, including life-threatening multidrug resistant (MDR) pathogens,” states Auspherix CEO Neil Miller. “We are currently in the lead optimization phase and are on track to progress a development candidate from one of our three lead series into human clinical studies by early 2019, with an initial focus on treating complicated urinary tract infections (cUTI).”
Two million people acquire serious drug-resistant bacterial infections per year, with 23,000 deaths in the U.S., alone, according to Miller. Furthermore, AMR has the potential to kill 10 million people globally in 2050, at an estimated cost of $100 trillion. And there have been no new classes of antibiotics on the market in 30 years, Miller says, adding that the greatest unmet need is MDR.
Auspherix co-founders Ian Charles and Dr. Dagmar Alber have been the vanguard of renewed interest in developing new classes of antibiotics in response to the global healthcare crisis. The idea behind the company’s work came about some six years ago when a team headed by Charles and Alber embarked on a discovery program that used phenotypic assays to identify antibacterial compounds with drug-like properties that had activity against bacterial communities in various life forms. This research identified auranofin (Ridaura)—an FDA- approved antirheumatic agent with a long history of clinical use—as being active against gram-positive bacteria in planktonic, biofilm and persister forms.
Mechanistic investigations are still ongoing, but both in-house data and recent publications from several academic groups suggest that auranofin’s antibacterial activity is likely due to a complex mechanism of action involving modulation of multiple cellular pathways.
Auranofin’s structure comprises a central gold(I) atom bound to two ligands, a sugar thiol and a trialkylphosphine, according to the research. Auspherix has applied its chemistry expertise to modify both of these gold ligands to create novel chemical compounds which, in comparison to auranofin itself, inhibit both gram-positive and gram-negative bacteria, including life-threatening MDR pathogens which include the ESKAPE pathogens (that encompasses the six pathogens with growing multidrug resistance: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species).
Its organogold antibacterials have also been shown to have a rapid bactericidal (killing rather than growth inhibition) activity against gram-negative bacteria, researchers say.
The choice of cUTI as a lead clinical indication reflects a number of factors including high unmet medical need, the profile of Auspherix’s compounds and the significant commercial opportunity.
For instance, there is a high prevalence of pathogenic gram-negative bacteria in patients with cUTIs. Also, there is an increasing proportion of cUTI patients who have a MDR infection that is not sensitive to standard-of-care antibiotics.
“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,” says Miller.
In addition to its cUTI program, Auspherix plans to explore additional indications such as complicated intra-abdominal infections and nosocomial pneumonia.