AKAO 2017 Annual Report

9 Research and Development Pipeline The following table summarizes the status of plazomicin and our other preclinical and research programs: Plazomicin Overview Our lead product candidate is plazomicin, a next generation aminoglycoside designed by our scientists to overcome the most common aminoglycoside resistance mechanisms, the aminoglycoside modifying enzymes (“AMEs”). Aminoglycosides have been used successfully for the treatment of serious bacterial infections for more than 50 years. As a class, aminoglycosides have several important characteristics including rapid bactericidal activity, well-characterized pharmacokinetics (“PK”), a lack of metabolism in humans, and excellent solubility and stability. However, the spread of resistance to currently marketed aminoglycosides has decreased their clinical utility. We developed plazomicin by chemically modifying an existing aminoglycoside, sisomicin, a natural product isolated from bacteria, to shield the regions of the molecule that are targeted by the enzymes responsible for aminoglycoside resistance. As a result of these modifications, plazomicin has the potential to remain active against MDR organisms where most other major drug classes, including commercially available aminoglycosides such as gentamicin and amikacin, have limited activity. Based on this profile, we are developing plazomicin as an intravenous (“IV”) therapy for the treatment of serious bacterial infections due to MDR Enterobacteriaceae, including ESBL-producing Enterobacteriaceae and CRE, which the CDC considers to be among the most serious and urgent resistance threats to public health. We consider the following to be key attributes that support the clinical utility and commercial value of plazomicin: • Met the objective of non-inferiority compared to meropenem in the Phase 3 EPIC trial in patients with cUTI and AP for the FDA-specified primary efficacy endpoint, and achieved superiority for the EMA-specified primary efficacy endpoint. Plazomicin was well tolerated with no new safety concerns identified in this trial. Plazomicin demonstrated non-inferiority to meropenem in our Phase 3 EPIC trial based on the primary efficacy endpoint of combined microbiological eradication and clinical cure for the FDA and was superior to meropenem based on the primary endpoint of microbiological eradication for the EMA. Plazomicin showed comparable or higher cure rates to meropenem in the subgroups of patients with infection caused by ESBL-producing and/or aminoglycoside-resistant Enterobacteriaceae.