Presented at the annual meeting of the American Society of Microbiology, June 1-5, 2017, New Orleans, LA, USA

Is Associated With Improved Survival and Safety Compared to Colistin in Serious Carbapenemresistant Enterobacteriaceae (CRE) Infections: Results of the CARE Study Lynn E. Connolly 1, Adrian M. Jubb 1, Bridget O Keeffe 1, Alisa W. Serio 1, Alex Smith 1, Jonathan Gall 1, Kevin M. Krause 1, James A. McKinnell 2, Epaminondas Zakynthinos 3, Valerie Riddle 4, and George L. Daikos 5 1 Achaogen, South San Francisco, CA, USA; 2 LA BioMed at Harbor-UCLA Medical Center, Los Angeles, CA, USA; 3 University Hospital, Larissa, Greece; 4 BioPharmAdvisors LLC, Parrish, FL, USA; 5 University of Athens, Athens, Greece Presented at the annual meeting of the American Society of Microbiology, June 1-5, 2017, New Orleans, LA, USA 1

Disclosures This presentation concerns a drug that is under clinical investigation and which has not yet been approved by any regulatory authority, including the US Food and Drug Administration (FDA) This drug is currently limited by law to investigational use, and no representation is made as to the safety or effectiveness for the purposes for which it is being investigated This presentation contains certain forward-looking statements reflecting Achaogen s current beliefs and expectations made pursuant to the safe harbor provisions of United States law, including, but not limited to, Achaogen s expectations relating to potential regulatory approval of plazomicin. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors that may cause Achaogen s actual results, performance or achievements to be materially different from those implied by the forward-looking statements L.E. Connolly, A.M. Jubb, B. O Keeffe, A.W. Serio, A. Smith, J. Gall, and K.M. Krause are employees of and stockholders in Achaogen V. Riddle is President/Owner of BioPharmAdvisors LLC, a paid contractor to Achaogen J.A. McKinnell, E. Zakynthinos, and G.L. Daikos have received honoraria and served on advisory boards for Achaogen 2

Is a Next-generation Aminoglycoside for the Potential Treatment of MDR Enterobacteriaceae Structure protects it from most AMEs that inactivate other aminoglycosides 1 AMEs co-travel with other resistance mechanisms, including β-lactamases and carbapenemases 1 Inhibits bacterial protein synthesis and is rapidly bactericidal 2 Potent in vitro activity against: ESBL-producing Enterobacteriaceae 3 Carbapenem-resistant Enterobacteriaceae 3,4 Aminoglycoside-resistant Enterobacteriaceae 5 IV, once-daily 30-minute infusion AMEs ) AMEs Structure of plazomicin AMEs AMEs AMEs AME, aminoglycoside-modifying enzyme; ESBL, extended-spectrum b-lactamase; IV, intravenous; MDR, multidrug resistant. 1. Ramirez MS, Tolmasky ME. Drug Resist Updat. 2010;13:151-171. 2. Thwaites M, et al. ASM Microbe 2016. Poster 571. 3. Galani I, et al. J Chemother. 2012;24:191-194. 4. Livermore DM, et al. J Antimicrob Chemother. 2011;66:48-53. 5. Almaghrabi R, et al. Antimicrob Agents Chemother. 2014;58:4443-4451. 3

Combating Antibiotic-resistant Enterobacteriaceae (CARE) A Phase 3 Study Evaluating the Efficacy and Safety of in the Treatment of Patients With Serious Infections due to Carbapenem-resistant Enterobacteriaceae (CRE) Primary Objective Evaluate the efficacy of plazomicin compared with colistin a in the treatment of BSI or HABP/VABP due to CRE based on primary endpoint: Day 28 all-cause mortality or significant disease-related complications (SDRC) b a or colistin in combination with adjunctive therapy of meropenem or tigecycline. b Within 7 days: New/worsening ARDS, new lung abscess or empyema, new-onset septic shock; persistence of bacteremia 5 days (BSI only); new-onset bacteremia (HABP/VABP only). This trial is registered at ClinicalTrials.gov: NCT01970371. ARDS, acute respiratory distress syndrome; BSI, bloodstream infection; HABP, hospital-acquired bacterial pneumonia; VABP, ventilator-associated bacterial pneumonia. 4

CARE Study Design Screening Treatment Follow-up Cohort 1: BSI, HABP/VABP Randomization 1:1 15 mg/kg q24h as 30-minute infusion (with TDM) Documented or presumed CRE infection Plus meropenem or tigecycline TOC EOS LFU Cohort 2: BSI, HABP/VABP, cuti/ap Colistin 300-mg loading dose; 5 mg/kg/d divided q8h or q12h as 60-minute infusion Documented or presumed CRE infection (with broader eligibility criteria) 15 mg/kg q24h as 30-minute infusion (with TDM) Adjunctive therapy per investigator s choice a TOC EOS LFU Up to 96 hours 7-14 days IV study drug therapy a Adjunctive therapy per investigator for BSI, HABP/VABP patients only; optional oral step-down after 4 days IV for cuti/ap. AP, acute pyelonephritis; cuti, complicated urinary tract infection; EOS, end of study; LFU, late follow-up; q8h, every 8 hours; q12h, every 12 hours; q24h, every 24 hours; TDM, therapeutic drug management; TOC, test of cure. 7 days from last dose IV study drug Day 28 Day 60 5

CARE Patient Disposition (Randomized Cohort 1) N = 39 ITT n = 18 All randomized patients n = 21 Colistin n = 18 MITT/Safety Patients who received any amount of study drug n = 21 MITT/Safety n = 17 mmitt Patients with CRE isolated from studyqualifying baseline specimen who received 1 dose of study drug n = 20 mmitt Primary efficacy analysis population included patients with BSI or HABP/VABP due to CRE. CRE defined as meropenem MIC of 4 µg/ml, or a meropenem MIC of 2 µg/ml and disk diffusion zone 19 mm on central laboratory testing. ITT, intent to treat; MIC, minimum inhibitory concentration; MITT, modified intent to treat; mmitt, microbiological modified intent to treat. 6

CARE Baseline Characteristics (Randomized Cohort 1) Well Balanced Across Treatment Groups Overall Baseline Characteristic (mmitt Population) (N = 17) Colistin (N = 20) Age, years, mean ± SD 66.7 ± 12 63.1 ± 19 Male, n (%) 12 (70.6) 10 (50.0) APACHE II score, n (%) Infection type, n (%) Baseline pathogens, n (%) Creatinine clearance, n (%) a Initial adjunctive therapy, n (%) 15 to 20 21 to 30 >30 BSI HABP/VABP Monomicrobial Polymicrobial >90 ml/min 90 ml/min CRRT Meropenem Tigecycline 10 (58.8) 6 (35.3) 1 (5.9) 14 (82.4) 3 (17.6) 14 (82.4) 3 (17.6) 4 (23.5) 7 (41.2) 4 (23.5) 6 (35.3) 11 (64.7) a Cockcroft-Gault estimation; baseline central laboratory data not available for subset of patients in each arm. 11 (55.0) 9 (45.0) 0 (0.0) 15 (75.0) 5 (25.0) 17 (85.0) 3 (15.0) 10 (50.0) 6 (30.0) 2 (10.0) 9 (45.0) 11 (55.0) APACHE II, Acute Physiology and Chronic Health Evaluation II; CRRT, continuous renal replacement therapy; SD, standard deviation. 7

CARE Efficacy Results (Randomized Cohort 1) Reduced Mortality at Day 28 for Versus Colistin BSI and HABP/VABP (mmitt Population) Difference (colistin minus plazomicin) (90% CI) Patients (%) 60 50 40 30 20 26.5 (-0.7 to 51.2) 28.2 (0.7 to 52.5) 23.5% 50.0% 11.8% 40.0% Colistin 10 0 4/17 10/20 2/17 8/20 All-cause mortality at Day 28 or significant complications All-cause mortality at Day 28 Two-sided 90% confidence interval (CI) calculated based on the unconditional exact method. 8

CARE Efficacy Results (Randomized Cohort 1) Reduced Mortality at Day 28 and SDRCs for Versus Colistin in Key Subgroups of Interest Subgroup of Interest (mmitt Population) (N = 17) n/n1 (%) ACM at Day 28 or SDRCs Colistin (N = 20) n/n1 (%) APACHE II score 15-20 2/10 (20.0) 5/11 (45.5) APACHE II score 21-30 2/7 (28.6) 5/9 (55.6) Adjunctive meropenem a 1/6 (16.7) 5/10 (50.0) Adjunctive tigecycline a 3/12 (25.0) 6/11 (54.5) a 1 patient in each treatment group switched adjunctive therapy and was counted as having received both meropenem and tigecycline. Percentages are calculated as n (number of patients in specified category)/n1 (number of patients in the specified subgroup). ACM, all-cause mortality; SDRC, significant disease-related complications. 9

CARE Efficacy Results (Randomized Cohort 1) Reduced Mortality at Day 28 for Versus Colistin in BSI BSI Subgroup (mmitt Population) Difference (colistin minus plazomicin) (90% CI) 60 39.0 (9.4 to 65.5) 32.9 (4.0 to 60.1) 53.3% Patients (%) 50 40 30 20 14.3% 40.0% Colistin 10 0 All-cause mortality at Day 28 or significant complications 7.1% 2/14 8/15 1/14 6/15 All-cause mortality at Day 28 Two-sided 90% CI calculated based on the unconditional exact method. 10

CARE Efficacy Results (Randomized Cohort 1) Sustained Survival Benefit in -treated Patients With BSI 100 60-day Survival in BSI Subgroup (mmitt Population) HR for death (plazomicin:colistin) (90% CI) 0.37 (0.15 to 0.91) Patients alive (%) 80 60 40 + + + Colistin 20 0 + Censored 0 10 20 30 40 50 60 Days Estimate of hazard ratio (HR) calculated as plazomicin:colistin based on Cox proportional hazards regression model. 11

CARE Efficacy Results (Randomized Cohort 1) Favorable Microbiological Response Higher in BSI Patients Treated With Versus Colistin BSI Subgroup (mmitt Population) Favorable response (%) 100 90 80 70 60 50 40 30 20 10 0 92.9% 92.9% 60.0% 53.3% 13/14 9/15 13/14 8/15 EOT TOC Colistin A favorable microbiological response for BSI requires confirmed negative results in 2 consecutive blood cultures measured on separate study days, with no recurrence on or prior to the specified visit. EOT, end of treatment (Day 7-14); TOC, test of cure (7 days ±2 days after EOT). 12

CARE Patient Disposition (Observational Cohort 2) N = 30 ITT n = 30 Safety n = 27 mmitt n = 14 BSI n = 9 HABP/VABP n = 4 cuti Cohort 2 included patients with BSI or HABP/VABP due to CRE who were ineligible for Cohort 1, as well as patients with cuti due to CRE. ITT, intent to treat; mmitt, microbiological modified intent to treat. 13

CARE Baseline Characteristics (Observational Cohort 2) Cohort 2 Is Distinct From Cohort 1 Baseline Characteristic (mmitt Population) (N = 17) n (%) Cohort 1 Cohort 2 Colistin (N = 20) n (%) (N = 27) n (%) Age, mean ± SD 66.7 ± 12 63.1 ± 19 63.3 ± 17 Male 12 (70.6) 10 (50.0) 21 (77.8) APACHE II score a <15 15 to 20 21 to 30 >30 Infection type Baseline pathogens Creatinine clearance b BSI HABP/VABP cuti Monomicrobial Polymicrobial >90 ml/min 90 ml/min CRRT 0 (0.0) 10 (58.8) 6 (35.3) 1 (5.9) 14 (82.4) 3 (17.6) 0 14 (82.4) 3 (17.6) 4 (23.5) 7 (41.2) 4 (23.5) 0 (0.0) 11 (55.0) 9 (45.0) 0 (0.0) 15 (75.0) 5 (25.0) 0 17 (85.0) 3 (15.0) 10 (50.0) 6 (30.0) 2 (10.0) 11/23 (47.8) 7/23 (30.4) 5/23 (21.7) 0 (0.0) 14 (51.9) 9 (33.3) 4 (14.8) 14 (51.9) 13 (48.1) 8 (29.6) 14 (51.9) 3 (11.1) Initial adjunctive therapy a Meropenem Tigecycline Other 6 (35.3) 11 (64.7) 0 (0.0) a 4 cuti patients in Cohort 2 did not receive adjunctive therapy or have APACHE II score collected. b Cockcroft-Gault estimation; baseline central laboratory data not available for subset of patients in each arm. 9 (45.0) 11 (55.0) 0 (0.0) 4/23 (17.4) 17/23 (73.9) 2/23 (8.7) APACHE II, Acute Physiology and Chronic Health Evaluation II; CRRT, continuous renal replacement therapy; SD, standard deviation. 14

CARE Efficacy Results (Observational Cohort 2) Low Mortality in BSI Subgroup Supportive of Findings in Cohort 1 BSI Subgroup (mmitt Population) Patients (%) 40 35 30 25 20 15 10 5 0 35.7% 30.0% 14.3% 10.0% 5/14 3/10 2/14 1/10 All-cause mortality at Day 28 or significant complications Overall (All CRE) CRE without Acinetobacter or Pseudomonas co-infection All-cause mortality at Day 28 All patients meeting primary endpoint due to SDRC alone had persistent CRE bacteremia on or after Day 5 Additional gram-negative pathogens include Acinetobacter spp. and Pseudomonas aeruginosa, which were an exclusion criterion for Cohort 1. SDRC, significant disease-related complications. 15

CARE Overall Summary of AEs and SAEs Favorable Safety Profile for Versus Colistin Adverse Event (Safety Population) (N = 18) n (%) Cohort 1 Cohort 2 Colistin (N = 21) n (%) (N = 30) n (%) AE 16 (88.9) 21 (100.0) 26 (86.7) Study drug-related 5 (27.8) 9 (42.9) 5 (16.7) Led to discontinuation of study drug 2 (11.1) 1 (4.8) 3 (10.0) Related to renal function 6 (33.3) 11 (52.4) 9 (30.0) SAE 9 (50.0) 17 (81.0) 20 (66.7) Study drug-related 1 (5.6) 4 (19.0) 0 (0.0) Led to death (up to Day 60 visit) 8 (44.4) 13 (61.9) 12 (40.0) Related to renal function 2 (11.1) 6 (28.6) 1 (3.3) No study drug-related deaths and no events of ototoxicity were reported AE, adverse event; SAE, serious adverse event. 16

CARE Laboratory Parameters Associated With Renal Function Lower Incidence and Magnitude of Serum Creatinine Increases for Versus Colistin Number of patients 9 8 7 6 5 4 3 2 1 0 Cohort 1 (Safety Population) (n(n=12) = 2/12) Colistin (n (N=16) = 8/16) Majority (6/9) of serum creatinine increases in Cohort 2 patients were <1.0 mg/dl Serum creatinine increase 0.5 to <1.0 mg/dl 1.0 to <1.5 mg/dl 1.5 to <2.0 mg/dl 2.0 to <3.0 mg/dl Baseline serum creatinine defined as the last central laboratory measurement prior to the first dose of study drug. Patients starting CRRT prior to baseline were excluded from the analysis, as were all postbaseline serum creatinine measurements collected after start of CRRT. 17

CARE Conclusions Patients with serious CRE infections had high mortality and disease-related complications When used as part of a combination regimen, plazomicin treatment was associated with reduced all-cause mortality at Day 28 overall, and in the subgroup of BSI patients, compared with colistinbased treatment The survival benefit in plazomicin-treated BSI patients was sustained through Day 60 The higher microbiological response rate in plazomicin-treated BSI patients supports the mortality benefit observed The low mortality rate in Cohort 2 BSI patients is supportive of findings in Cohort 1 was associated with a favorable safety profile compared with colistin, including lower incidence and magnitude of serum creatinine elevations when used as part of a combination regimen for the treatment of life-threatening infections due to CRE Data from the CARE study suggest that plazomicin could offer an important new potential treatment option for patients with serious infections due to CRE 18

Acknowledgments The authors thank the investigators, patients, and families involved in this clinical trial program This project has been funded in whole or in part with Federal funds from the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of Health and Human Services, under Contract No. HHSO100201000046C Medical writing support was provided by Jean Turner of PAREXEL and funded by Achaogen 19