AKAO 2017 Annual Report

13 Plazomicin Development Program We are developing plazomicin, our lead product candidate, for the treatment of serious bacterial infections due to MDR Enterobacteriaceae in patients with limited or no alternative treatment options. These include patients with cUTI, including AP, due to MDR Enterobacteriaceae, including ESBL-producing isolates and CRE. In our Phase 3 EPIC study in patients with cUTI, including AP, plazomicin successfully met FDA- and EMA-specified primary efficacy endpoints and was well tolerated with no new safety concerns, providing evidence of efficacy and safety of plazomicin in this indication. In our other Phase 3 study (CARE) in patients with serious infections due to CRE, a lower rate of mortality or serious disease-related complications was observed for plazomicin compared with colistin therapy and the safety profile of plazomicin was favorable compared to that of colistin. In 2012, the FDA granted fast-track designation for the development and regulatory review of plazomicin to treat serious and life-threatening CRE infections. In 2014, plazomicin received QIDP designation from the FDA. The QIDP designation was created by the GAIN Act, which was part of the FDASIA and provides certain incentives for the development of new antibiotics, including eligibility for priority review and an extension of five years to an existing period of non-patent market exclusivity. In 2017, the FDA granted Breakthrough Therapy designation for plazomicin in patients who have limited or no alternative treatment options for the treatment of BSI caused by certain Enterobacteriaceae, Klebsiella pneumoniae and Enterobacter aerogenes . The FDA has accepted the NDA for substantive review and has granted the NDA Priority Review as well as set a PDUFA target action date of June 25, 2018. We expect a commercial launch of plazomicin in the United States in 2018, if our NDA is approved by the PDUFA date. We also plan to submit an application for marketing authorization in the EU in 2018. Key elements of our clinical development program for plazomicin are outlined in the table below: Completed Phase 3 Clinical Studies Study/Phase Objectives Number Enrolled EPIC/ 3 Primary: Demonstrate the non-inferiority of plazomicin compared with meropenem based on the difference in composite microbiological eradication and clinical cure rate in the microbiological modified intent-to-treat (mMITT) population at both the Day 5 and test-of-cure (TOC) visits in patients with cUTI and AP Secondary : Safety, PK of plazomicin 609 CARE - Cohort 1/ 3 Primary : Evaluate the efficacy of plazomicin as compared to colistin with respect to all-cause mortality or significant disease-related complications at 28 days in patients with serious CRE infections Secondary : Safety, PK of plazomicin 39 CARE - Cohort 2/ 3 Exploratory: Evaluate the efficacy, safety and PK of plazomicin in patients with serious CRE infections 30