The exciting data, disclosed in both a poster and an oral presentation by Dr Jonathan Powell from Domainex at the 19th RSC/SCI Medicinal Chemistry Symposium in Cambridge, UK, describe the discovery of three distinct chemical series, all with broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria.
Importantly the Auspherix compounds are active against the so-called ESKAPE pathogens, which are responsible for the majority of hospital infections.
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 antirheumatic medicine.
The focus of the collaboration with Domainex 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 co-ordinated to the central gold atom and have now demonstrated that the physicochemical 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.
Tom Mander, Chief Operating Officer of Domainex, said: “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 multidrug resistant bacterial infections.”
Dr Neil Miller, Auspherix CEO, 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 (MDR) 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,” he added.
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 (QIDP) designation, which offers fast-track status and priority review with the FDA, plus potentially 5 years of additional market exclusivity, thus making our focus on cUTIs an attractive investment proposition.”
