AKAO 2017 Annual Report

5 • Potential for more convenient administration as a once-daily, 30-minute IV therapy compared to other IV antibiotics administered multiple times per day with infusion times up to three hours. In particular, this supports the potential for plazomicin outpatient therapy. • Potential to reduce the health care costs associated with the treatment of such infections. In January 2018, we announced positive Phase 1 top-line results for our orally-administered antibacterial candidate, C-Scape, which is a combination of ceftibuten, an approved third generation cephalosporin, and clavulanate, an approved -lactamase inhibitor. We believe that C-Scape has the potential to address a serious unmet need for an effective oral treatment for patients with cUTI, including AP, caused by ESBL-producing Enterobacteriaceae. The Phase 1 top-line results demonstrated that, in healthy subjects, C-Scape was well tolerated across all doses studied, with no drug-drug interactions observed between the previously approved compounds when dosed in combination. These results are supportive of further evaluation and we currently plan to initiate a single pivotal Phase 3 study in patients with cUTI, including AP, who are suitable for treatment with oral antibiotics, in 2018. the Biomedical Advanced Research and Our C-Scape program is funded in part by a contract with Development Authority (“BARDA”) for up to $18.0 million, of which $12.0 million is committed. The C-Scape drug combination was granted QIDP designation by the FDA for the treatment of cUTI, including AP, in January 2017. We currently plan to leverage a 505(b)(2) regulatory path to support the potential initiation of a single pivotal Phase 3 trial in 2018. ESBL-producing Enterobacteriaceae are often resistant to currently available oral therapies. In 2017, the WHO identified ESBL as a Global Priority 1 Pathogen: Critical Need for Research and Development of New Antibiotics. The lack of adequate oral therapies often leads to hospitalization for intravenous therapy. New oral agents with activity against ESBL-producing organisms are needed to reduce hospitalization and reliance on carbapenems. The goal of the C-Scape development program would be to treat certain MDR infections in the outpatient and possibly step-down settings. CRE and ESBL-producing Enterobacteriaceae are two of many types of MDR gram-negative pathogens threatening patients. Bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii also pose “serious” resistance threats, according to the CDC, and also drive a great need for new, safe, and effective antibiotics. We have assembled the expertise and capabilities required, including chemistry and microbiology, to develop new agents for the treatment of gram-negative infections. Our research and development pipeline includes small molecule and antibody programs that target gram-negative pathogens as well as other disease areas. These programs include our collaboration with the Bill & Melinda Gates Foundation which provides for up to $20.5 million in grant funding and equity investments, of which $13.2 million has been committed or invested, to further develop our antibody platform and discover monoclonal antibody candidates against gram-negative bacteria, including those that cause neonatal sepsis. Strategy Our strategy is to discover, develop, and commercialize new antibacterials for the treatment of gram-negative bacterial infections. Key elements of our strategy are as follows: • Obtain regulatory approval of plazomicin in both the United States and the EU. We are seeking approval in the U.S. for plazomicin to treat cUTI, including AP, and BSI due to certain Enterobacteriaceae in patients who have limited or no alternative treatment options. In January 2018, we announced that the FDA has accepted the NDA for substantive review and granted the NDA Priority We also intend to submit a Marketing Review with a PDUFA target action date of June 25, 2018. Authorization Application (“MAA”) to the EMA in 2018. • Rapidly progress a second antibacterial targeting high unmet need gram-negative infections. We are developing C-Scape, an innovative combination of ceftibuten, an approved third generation cephalosporin, and clavulanate, an approved -lactamase inhibitor, that we believe could offer a potential oral therapy to treat patients with MDR gram-negative infections such as cUTIs due to ESBL- producing pathogens. The program has positive top-line Phase 1 results and has the potential to enter Phase 3 in 2018. In January 2017, C-Scape received QIDP designation from the FDA.