Nasdaq: AKAO. Cowen Health Care Conference March 3, 2015

Transcription

1 Nasdaq: AKAO Cowen Health Care Conference March 3, 2015

2 Forward Looking Statements Forward-Looking Statements This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, prospective products, potential market size and market share, availability of funding, clinical trial results, product approvals and regulatory pathways, research and development costs, timing, strategies for completion and likelihood of success for our business activities, including in particular our Phase 3 trial evaluating plazomicin, plans and objectives of management for future operations, and future results of current and anticipated products, are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to our business in general, see our Form 10-Q for the fiscal quarter ended September 30, 2014, filed with the Securities and Exchange Commission on November 10, 2014 and our future periodic reports on Form 10-K or Form 10-Q. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. This presentation concerns drugs that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration (FDA). It is currently limited by Federal law to investigational use, and no representation is made as to its safety or effectiveness for the purposes for which it is being investigated. 1

3 Developing Antibacterial Medicines Targeting Growing Unmet Medical Needs Founded around in-house antibacterial R&D expertise Focused on multi-drug resistant, gram-negative bacterial infections with high mortality Based in South San Francisco, CA; Nasdaq: AKAO Plazomicin lead product with strong commercial opportunity High unmet medical need current therapy of carbapenem-resistant Enterobacteriaceae (CRE) infections associated with high mortality rate Growing demand growing drug resistance leading to more CRE infections Value-based pricing supported by targeted reductions in high mortality rate and cost of care for affected patients Favorable sales model target infectious disease specialists in hospitals Status Phase 3 trial: first patient in Q Exciting discovery programs targeting drugs to treat gram-negative bacterial infections LpxC inhibitor Bactericidal antibody Substantial non-dilutive funding including $104MM BARDA contract Proven leadership team with a track record of drug discovery, global approvals and launches 2

4 Proven Leadership Team Kenneth Hillan, M.B., Ch.B Chief Executive Officer Ian Friedland, MD Chief Medical Officer Extensive background in drug discovery & development and product commercialization Derek Bertocci Chief Financial Officer Christine Murray VP, Regulatory Affairs 3

5 Multi-Drug Resistant, Gram-Negative Bacteria A serious global health threat Antibiotic-Resistant Infections Lead to 23,000 Deaths a Year, C.D.C. Finds Last-line antibiotics losing ability to kill superbugs in EU 4

6 Strong Momentum Towards Improving the Funding, Regulatory, and Commercial Prospects for Antibiotics Selected Recent Activities CDC Threat Report GAIN Act FDA Guidance PCAST Report Sept Executive Order DISARM Act ADAPT Act PATH Act Impact Enhanced awareness of urgent need for new antibiotics Additional market exclusivity Increased federal R&D funding Faster, more flexible regulatory pathways Potential for significant pricing power in patient populations with resistant infections 5

7 Market & Regulatory Developments Support for antibacterial drugs and R&D Increased M&A Activity Merck acquires Cubist for $9.5B (Dec. 2014) Actavis acquires Durata for $0.7B (Oct. 2014) Positive Regulatory Activity FDA approval of ZERBAXA (ceftolozane/tazobactam) for cuti and ciai infections (Dec. 2014) FDA approval of AVYCAZ (ceftazidime/avibactam) for cuti and ciai infections for patients with few or no alternative treatment options (Feb. 2015) 6

8 Pipeline Discovery Phase 1 Phase 2 Phase 3 Target: Carbapenem-Resistant Enterobacteriaceae (CRE) Plazomicin Targets: Pseudomonas aeruginosa & Acinetobacter baumannii LpxC Inhibitors Antibacterial Antibody Target: Gram-negative bacteria Discovery Engine 7

9 Multi-Drug Resistance & Carbapenem Resistant Enterobacteriaceae (CRE) 8

10 Carbapenem Resistant Enterobacteriaceae (CRE) An urgent threat to public health RESISTANCE: CRE are resistant to nearly all of the antibiotics we have SPREAD OF RESISTANCE: CRE easily transfer their antibiotic resistance to other bacteria PREVALENT AND GROWING: CRE prevalence has increased dramatically over the last 10 years DEATH: CRE kill up to 1 in 2 patients who develop bloodstream infections IMPACT: Significant impact to both individual patients and hospital systems CDC Vital Signs, March 2013, 9

11 Evolution of Multi-Drug Resistance CRE bacteria are resistant to multiple classes of antibiotics Enterobacteriaceae* Profiles Evolution of Resistance Antibiotic Class Generally Susceptible MDR CRE Aminoglycosides Fluoroquinolones Cephalosporins Carbapenems Inactive vs. high % strains Active vs. high % strains * Key species within Enterobacteriaceae family include Klebsiella pneumoniae, E. coli, Enterobacter spp. 10

12 Cumulative Survival CRE Infections Associated with significant mortality Survival by Antibiotic Susceptibility K. pneumoniae Bloodstream Infections Mortality By Treatment Regimen K. pneumoniae Bloodstream Infections** Susceptible Cephalosporin-resistant, carbapenem susceptible Carbapenem-resistant Regimen All-Cause Mortality 0.6 Colistin*** 46% * p = Total Length of Stay (days) * From log-rank test for comparison of survival distribution in patients with carbapenem resistant versus ESBL/susceptible K. pneumoniae Tigecycline*** 47% Aminoglycoside*** 38% Combination Therapy 37% ** Carbapenemase-producing Klebsiella pneumoniae *** Agents active in vitro Ben-David, et al. Clin. Microbiol. Infect 2012; 18: Daikos et al. Expert Rev. Anti. Infect. Ther. 2012, 10:

13 Plazomicin: A Next Generation Aminoglycoside AMEs (aminoglycoside modifying enzymes) co-travel with other resistance mechanisms, including carbapenemases AMEs ) AMEs AMEs Plazomicin is engineered to overcome clinically relevant AMEs that inactivate existing aminoglycosides AMEs AMEs Plazomicin retains potent activity vs. multi-drug resistant strains, including carbapenem and aminoglycoside-resistant strains 12

14 Plazomicin Granted Qualified Infectious Disease Product (QIDP) Designation by FDA in Dec QIDP designation created by Generating Antibiotic Incentives Now (GAIN) Act QIDP provides incentives for development of new antibiotics: Priority review and eligibility for FDA s fast track program Additional five years of market exclusivity Plazomicin granted QIDP designation for 5 indications: Hospital-acquired bacterial pneumonia (HABP) Ventilator-associated bacterial pneumonia (VABP) Complicated intra-abdominal infections (ciai) Complicated urinary tract infections (cuti) Catheter-related bloodstream infections 13

15 Plazomicin Pre-clinical and clinical data 14

16 Plazomicin Has Shown Superior Potency Against CRE In vitro Activity vs. Clinical Isolates of CRE Compound Class N MIC 50 (µg/ml) MIC 90 (µg/ml) Plazomicin Aminoglycoside Gentamicin Aminoglycoside Amikacin Aminoglycoside Ciprofloxacin Fluoroquinolone Ceftazidime Cephalosporin >128 Piperacillin/tazobactam Penicillin/Betalactamase inhibitor 731 >128 >128 Tigecycline Glycycline Colistin/polymyxin B Polymyxin Susceptible Non-Susceptible MIC 50 and MIC 90 (minimum inhibitory concentration in μg/ml) reflect the lowest concentrations at which the drug inhibits growth of 50% and 90% of the bacteria, respectively. N=number of strains within the overall set of 807 bacterial strains tested vs. the given antibiotic. CLSI 2012 susceptibility criteria were used except for tigecycline and colistin, for which EUCAST 2013 criteria were used because CLSI criteria were not available. Isolates selected had an MIC 2 µg/ml for any type 2 carbapenem, a value defined as non-susceptible for this class according to CLSI. Data includes clinical isolates from three studies: 1) J Chemother Aug;24(4):191-4, 2) J Antimicrob Chemother Jan;66(1):48-53, 3) J Antimicrob Chemother Oct;65(10):

17 Logarithmic Change in CFU /g Infected Tissue Plazomicin Has Superior Activity Against CRE in Mouse Infection Model Human Equivalent Dose Plazomicin Colistin Prodrug Tigecycline 1 0 Initial Infection Load (Stasis) Multiple of Human Dose, by Total Plasma Exposure (AUC) CFU = Bacterial Colony Forming Unit Each data series represents a CRE clinical isolate tested in model (n=9) Superior activity of plazomicin against CRE in mouse tissue infection model supports hypothesis that plazomicin may have superior activity in patients 16

18 Demonstrated Efficacy in Phase II cuti trial Similar efficacy to active comparator levofloxacin and an acceptable safety profile Trial Design Protocol: Multi-national, randomized, double-blind study in complicated urinary tract infection and acute pyelonephritis (cuti/ap) Study Drugs: Plazomicin (10 or 15 mg/kg) vs. levofloxacin (750 mg) N = 145 patients By-Patient Microbiological Response Plazomicin 10 mg/kg Plazomicin 15 mg/kg Microbiologically Evaluable (ME) Levofloxacin 750 mg Primary Outcome* N Eradication, n (%) 6 (86%) 31 (89%) 17 (81%) Modified Intent-to-Treat (MITT)** N Eradication, n (%) 6 (50%) 31 (61%) 17 (59%) Safety Similar adverse event rates across plazomicin and levofloxacin arms. No drug-related SAEs in the plazomicin arm. Class-related adverse events included: Nephrotoxicity: Minor changes in serum creatinine in 5.2% of evaluable plazomicin patients versus 4.5% in the levofloxacin arm Ototoxicity: mild, permanent tinnitus & mild, transient vertigo (N=1 each) * Microbiological Eradication **Eradication rates in MITT population reflect lack of test-of-cure cultures for some patients 17

19 Plazomicin Phase 3 study design, rationale and timeline 18

20 Phase 3 Study Design Pathogen-specific, randomized, open-label, active comparator controlled Presumed or Documented CRE Infection (Bloodstream Infection or Pneumonia) Plazomicin-based regimen 1:1 (n = ~360) Colistin-based regimen Primary Endpoint 28 day all-cause mortality Secondary Endpoints Safety Assessments Pharmacoeconomic Assessments Both regimens will include addition of either meropenem or tigecycline Plazomicin dose may be adjusted by therapeutic drug monitoring (TDM) via a proprietary in vitro assay Presumed infections: based on identification of a carbapenemase-producing Enterobacteriaceae (CRE) 19

21 Phase 3 Trial Status Update Targeting 72 sites across the EU, U.S. and Latin America All US sites and the majority of European sites activated All sites expected to be activated by Q Enrollment: First patients dosed in Q Goal to obtain top line data in the first half of 2017 Trial enrollment slower than anticipated Evaluation and implementation of strategies to increase recruitment ongoing 20

22 Plazomicin Commercial opportunity 21

23 Attractive Commercial Opportunity for Plazomicin High Unmet Medical Need (CRE) Up to 50% mortality in bloodstream infections Current therapies inadequate Resistance growing on a global basis Strong Market Share Potential Mortality benefit over comparator Potent activity vs. broad spectrum of CRE isolates Favorable physician response Use in definitive and empiric setting Value-Based Pricing Favorable Business Model Superior efficacy Allows sparing of currently overused antibiotics Narrow patient population limits budget impact to any given hospital Pharmacoeconomic cost savings anticipated (e.g., reduction in ICU days) Concentrated market in resistance hotspots facilitates targeted sales approach Development costs limited as Phase 3 program partially funded by award from BARDA Favorable healthcare system developments (e.g., Pew Trusts Forum) 22

24 Two Key Plazomicin Addressable Patient Segments US and EU-5 Estimated Inpatient Cases in 2013: Bloodstream Infections and Pneumonia Definitive Treatment: Confirmed CRE 4.7 M Total Inpatients bacteriaceae 25 % 2.5 % X Entero- X carbapenem- = resistance ~30K* CRE cases * Total of ~110K CRE cases when urinary tract and intra-abdominal infections included Empiric Treatment: Risk of CRE 4.7 M Total Inpatients 80% 23 % X X Infectious Disease = empiric treatment (ID) consult ~850K Empiric, ID consult cases Proxy for the number of more complicated cases and/or serious infections A subset of these patients will be deemed to be at risk for CRE (expected to rise over time) Decision Resources, Arlington Medical Resources, primary literature, CDC & ECDC, TEST Surveillance Database, and company internal analysis 23

25 Plazomicin is Well-Positioned vs. Key Late-Stage Competitors Drug / Company Status KPC Mechanism Coverage* MBL CRE Focus Superiority Study Plazomicin Phase 3 Indications** CRE in BSI HAP/VAP Zerbaxa / Cubist Avycaz / AZ & Forest Carbavance / The Medicines Company Eravacycline / Tetraphase Marketed Approved Phase 3 Phase 3 cuti ciai HAP/VAP cuti ciai HAP/VAP (Phase 3) cuti CRE (Phase 2) cuti ciai Potentially HAP Plazomicin is the only agent targeting a mortality benefit in CRE * KPC: Klebsiella pneumonia carbapenemase, MBL: Metallo-beta-lactamase; **BSI: bloodstream infection, HAP/VAP: hospital and ventilator-acquired pneumonia, cuti: complicated urinary tract infection, ciai: complicated intra-abdominal infection 24

26 Discovery Engine Two lead preclinical programs targeting gram-negative bacterial infections LpxC inhibitor Antibody program 25

27 LpxC Inhibitors: Novel Mechanism of Action with Significant Potential New class of bactericidal antibiotics LpxC is an essential enzyme required for outer membrane synthesis in gram-negative bacteria Potent activity vs. P. aeruginosa No pre-existing resistance One candidate, ACHN-975, advanced into clinical trials in 2012 Multiple dose study halted due to local tolerability reaction Additional candidates currently undergoing preclinical evaluation In vitro Activity vs. Clinical Isolates of P. aeruginosa Compound MIC 50 (µg/ml) MIC 90 (µg/ml) ACHN Tobramycin 1 >32 Ciprofloxacin 0.5 >4 Ceftazidime 8 >32 Imipenem 2 >16 Colistin 1 4 Susceptible Non-Susceptible 26

28 Therapeutic Antibody Program Initial target candidate profile: Monotherapy treatment for serious gram-negative infections Hypothesis-driven approach focused on functionally important targets on the bacterial cell surface (targets not being disclosed at this time) Potential benefits: o Direct bacterial killing o Favorable safety profile typically associated with monoclonal antibodies o Antibody PK profile with a half-life that could support a single-dose cure 27

29 Corporate Overview 28

30 Key Future Value Drivers Plazomicin Phase 3 clinical trial Interim assessment of efficacy Top line data Potential additional clinical trials Research Programs Investigational new drug application ( IND ) - Expected 2016 Proof of concept for therapeutic antibody 29

31 Financial Snapshot Listed on NASDAQ March 2014 AKAO - Top Institutional Shareholders: (09/30/2014) Shares (000 s) Fidelity Management & Research Company 2,630 Domain Associates, L.L.C. 2,021 Venrock 1,746 Wellcome Trust 1,575 ARCH Venture Partners 1,419 Versant Ventures 1,281 Omega Fund Management (US) 886 NASDAQ Symbol: AKAO Market Cap (as of 03/02/2015): $192M Shares o/s (as of 09/30/2014): 17.7M Price per Share (as of 03/02/2015): $ week high: $ week low: $ Mo Avg Daily Trading Vol. (shares) 81,057 Cash & Equivalents (09/30/2014) $72M Analyst Coverage Cantor Dan Brims Needham Alan Carr Credit Suisse Jason Kantor Wedbush Heather Behanna Cowen Ritu Baral William Blair Katherine Xu Gabelli & Co. Kevin Kedra SunTrust Edward Nash 30

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