Combining antibacterials to achieve efficacy has been successful historically from an R&D perspective as well as in clinical use. One focused scientific approach of FleurirABX is to identify inhibitors to critical targets in convergent bacterial metabolic pathways, and combine these antibacterial inhibitors to simultaneously inhibit two or more biochemical events where products from both become reactants at a subsequent convergent step. Such inhibition should: achieve substantial antibacterial synergy; overcome resistance to the agents individually or reduce its likelihood; broaden antibacterial spectrum, and improve safety.
We utilize a Renew – Expand – Preserve approach to antibiotic candidate selection and development.
FleurirABX has identified existing marketed antibiotics that exhibit unexpected and patentable properties when used in combination. The component antibiotics have established safety profiles from decades of use, thus mitigating some risks associated with developing novel investigational compounds. And, urgent-threat pathogens are developing resistance to the component antibiotics, diminishing their clinical usefulness individually. These older drugs can have renewed utility in a unique combination.
The combination drugs act synergistically, providing improved antibacterial efficacy beyond that of the individual components. The combinations should not only replace the use of the component drugs in many current indications given the improved profile, but also give broader species coverage and show efficacy against pathogens resistant to the components, thereby expanding utility in additional valuable indications and infections. Reduced dosing of the components in the combination may be afforded by the synergy achieved, resulting in lower drug exposure in the patient and reduced safety liabilities. This approach is also being pursued with combinations of novel chemical entities (NCE), and with combinations of NCEs and approved antiinfectives.
This approach promotes good antibiotic stewardship by extending and expanding the utility of existing antibiotics so that physicians can reserve new monotherapy antibiotics with novel mechanisms for treatment of the most resistant and life-threatening pathogens.