Combating Drug-Resistant Infections Globally. Company Presentation

Transcription

1 Combating Drug-Resistant Infections Globally Company Presentation

2 Forward-Looking Statements and Other Important Cautions Any statement in this presentation about our future expectations, plans and prospects, including statements regarding our strategy, future operations, prospects, plans and objectives, and other statements containing the words "anticipates," "believes," "expects," "plans," "will" and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of Actual results may differ materially from those indicated by such forwardlooking statements as a result of various important factors, including: whether XERAVA TM (eravacycline) will be successfully distributed and marketed; whether our cash resources will be sufficient to fund our continuing operations for the period we anticipate; whether clinical trials for our product candidates will be successful; whether the results from such clinical trials or studies will be sufficient to warrant regulatory approval; whether approvals will be received for our clinical candidates from the United States Food and Drug Administration or equivalent foreign regulatory agencies on a timely basis or at all; and other factors discussed in the "Risk Factors" section of our most recent filings with the Securities and Exchange Commission. The forward-looking statements contained in this presentation reflect Tetraphase s current views with respect to future events, and Tetraphase assumes no obligation to update any forward-looking statements except as required by applicable law. 2

3 Multidrug-Resistance (MDR) is a Growing Crisis Superbug From India Spread Far and Fast, Study Finds By Brianna Abbott January 27, 2019 November 6, 2018 How antibiotic resistance can take us back to the dark ages Drug resistant superbugs are killing 33,000 in Europe each year By Kate Kelland November 5, 2018 April 3, 2018 Nightmare bacteria, resistant to almost every drug, stalk U.S. hospitals By Liz Szabo Number of new antibiotics has fallen sharply since 2000 By Julie Kollewe January 23, 2018 April 3, 2018 CDC: Drug-resistant 'nightmare bacteria' pose growing threat By Marilyn Marchione 3

4 Tetraphase Pharmaceuticals: Corporate Highlights Novel Antibiotics for Serious and Life-Threatening MDR Infections Launched in the U.S. Significant Market Opportunity Novel Pipeline Strong Balance Sheet Strong Leadership XERAVA TM (eravacycline) Broad Label in ciai Differentiated Antibiotics Cash runway into Q Experienced management team FDA and EMA approved for treatment of complicated intraabdominal infections (ciai) Product opportunity of up to 2 million patient days of therapy Proprietary platform enables creation of novel tetracycline compounds $108 million in cash and cash equivalents as of Dec. 31, 2018 Track record of success in anti-infective development, regulatory approval and commercialization 4

5 A Strong Pipeline Led by XERAVA Product/Candidate Route of Administration Discovery Preclinical Phase 1 Phase 2 Phase 3 Approved XERAVA Complicated IAI IV TP-271 Respiratory Infections, CABP IV Oral TP-6076 MDR Infections IV TP-2846 Acute Myeloid Leukemia IV 5

6 XERAVA: Novel Antibiotic Approved to Treat Serious Infections Novel, fully-synthetic fluorocycline FDA and EMA approved for complicated intra-abdominal infections Potent activity against broad spectrum of bacteria Gram-negative and Gram-positive Anaerobic and atypical Multidrug-resistant: ESBLs, AmpC, VRE, MRSA ESBL: extended-spectrum beta-lactamase; VRE: vancomycin-resistant enterococci; MRSA: methicillin resistant Staphylococcus aureus; AmpC: AmpC beta-lactamases 6

7 *MIC 90 (ug/ml) XERAVA: Demonstrates Potent In Vitro Coverage XERAVA Tigecycline Ceftazidime Pip/Tazo Meropenem E. coli MDR (n=1388) E. coli, ESBL (n=195) E. coli, CRE (n=277) K. pneumonia MDR (n=956) K. pneumonia, ESBL (n=230) K. pneumonia, CRE (n=1024) A. baumannii MDR (n=1735) A. baumannii, CRAB (n=1792) Multidrug-Resistant Pathogens *MIC 90 : Minimum Inhibitory Concentration: Lowest concentration of the antibiotic at which 90% of the isolates were inhibited Sources: CANWARD 2014, IHMA , IHMA 2015 and IHMA

8 Two Successful Phase 3 Clinical Trials Showing High Clinical Cure Rates Against Resistant Pathogens Baseline Pathogen (No./Total no.) XERAVA % Enterobacteriaceae (277/314) 88.2 CEPH-R (38/42) 90.5 ESBL confirmed (32/36) 88.9 CRE confirmed (1/1) 100 MDR (35/39) 89.7 Acinetobacter species (13/13) 100 CEPH-R (13/13) 100 ESBL confirmed (5/5) 100 CRAB confirmed (3/3) 100 MDR (12/12) 100 Sources: Solomkin J. et al. JAMA Surgery 2017; 152(3): Ditch, et al. Poster 629. Presented at ASM Microbe 2018, Atlanta, GA 8

9 Complicated Intra-Abdominal Infections (ciai) Infection proceeding beyond the source organ into the peritoneal space Sites of Infection (%) in the ICU 3 IAI represents 1 of 5 ICU infections Second most prevalent site of infection in the ICU Respiratory tract Second leading cause of infectious mortality in the ICU Abdominal Bloodstream Renal/urinary tract Second most commonly identified cause of severe sepsis in the ICU Skin Catheter related CNS Others 2.9 Sources: 1. Solomkin JS, et al. Clin Infect Dis. 2010;50: ; 2. Lopez et al. World Journal of Emergency Surgery 2011, 6:7 ; 3. Vincent JL et al. JAMA. 2009;302(21):

10 ESBL Rates Among Enterobacteriaceae Isolates Across U.S. Pacific (9.1%) E. coli 11.2% K. pneumoniae 8.3% K. oxytoca 6.5% P. mirabilis 2.7% USA National (12.2%) E. coli 11.9% K. pneumoniae 16.0% K. oxytoca 10.0% P. mirabilis 4.8% Mountain (12.8%) E. coli 13.2% K. pneumoniae 11.9% K. oxytoca 12.1% P. mirabilis 13.4% WestNorth Central (4.4%) E. coli 5.2% K. pneumoniae 3.2% K. oxytoca 6.5% P. mirabilis 1.7% EastNorth Central (8.8%) E. coli 10.1% K. pneumoniae 8.7% K. oxytoca 9.4% P. mirabilis 3.9% New England (9.7%) E. coli 10.0% K. pneumoniae 11.2% K. oxytoca 13.0% P. mirabilis 1.9% Mid-Atlantic (23.2%) E. coli 20.1% K. pneumoniae 34.7% K. oxytoca 8.6% P. mirabilis 7.2% South Atlantic (19.9%) E. coli 17.6% K. pneumoniae 25.9% K. oxytoca 20.0% P. mirabilis 5.8% Rates from 72 U.S. hospitals in nine regions show variation by region 1 Rates are high and continue to rise 2 Demonstrates importance of using a treatment with broad ESBL coverage E. coli, Escherichia coli; ESBL, extended-spectrum β-lactamase; K. pneumoniae; KPC, Klebsiella pneumoniae carbapenemase; k. oxytoca, Klebsiella oxytoca; P. mirabilis, Proteus miribilis. WestSouth Central (16.2%) E. coli 13.2% K. pneumoniae 26.6% K. oxytoca 3.6% P. mirabilis 4.1% EastSouth Central (8.2%) E. coli 7.6% K. pneumoniae 9.8% K. oxytoca 12.9% P. mirabilis 3.4% Sources: 1. Castanheira et al. Antimicrob Agents Chemother 2014;58: ; 2. Infect Control Hosp Epidemiol Oct;38(10):

11 Days of Therapy CRE Cases A Carbapenem Sparing Drug is Needed Carbapenems are the empiric* drug of choice for ESBL coverage Leads to overuse of carbapenems and increased resistance 18,000,000 Carbapenem Use in U.S. & Europe1 Growth in Carbapenem-resistant Enterobacteriaceae in >3M Admissions in 192 U.S. Hospitals ,000, ,000,000 12,000, ,000, ,000, ,000,000 4,000,000 2,000, National Projection: 227,828 cases *Treatment without specific pathogen diagnosis Sources: 1. Decision Resources AMR Hospital Database; 2. Adapted from Schneider G. SHEA, Spring

12 XERAVA Market Opportunity

13 XERAVA Market Opportunity in the U.S. and EU5 Overall Market 25% High-risk Segment 20% Product Opportunity 40M Days of Therapy 10M Days of Therapy 2M Days of Therapy 88% is IV treatment Patients receiving broad spectrum antibiotics Patients receiving combination Gramnegative and Grampositive agents and anaerobic antibiotics Sources: and 2015 Decision Resources AMR Hospital Database; 2. Internal market research 13

14 XERAVA Focus in the U.S. and EU5 Product Opportunity 2 Million Patient Days of Therapy Second Line Empiric Therapy for Patients: Who have not improved on initial empiric therapy: Empiric Therapy for Patients: Tachypneic Tachycardic At risk of infection with resistant organisms, e.g.: Renally impaired Previous hospitalization Recent ICU stay Elderly LTC facility / SNF Previous C. diff infection 1.2M 400K 400K Hypotensive Febrile For Patients with Confirmed: ESBL AmpC MRSA VRE C. diff Sources: and 2015 Decision Resources AMR Hospital Database; 2. Internal market research 14

15 Comparison of Coverage Points of Differentiation CONTEPO TM ciai indication as monotherapy No need for dose adjusting in renally impaired patients Broad label allowing for empiric therapy Priced for empiric market MDR Enterobacteriaceae (ESBL-expressing) MDR Enterobacteriaceae (AmpC-expressing) MRSA and VRE Anaerobes (i.e. C. diff) Sources: Prescribing information for approved products. Public data presentations for investigational products. Active Intermediate activity or Breakpoint Dependent No 15

16 XERAVA Label: Clear Differentiation Provides Market Opportunities Efficacy Broad label not restricted to patients with limited or no alternative treatment options No need for combination therapy Convenience Twice daily 1mg/kg dosing with a 60 minute infusion No need for Therapeutic Drug Monitoring for any patient groups High clinical cure rates in patients with MDR pathogens, ESBLs, beta-lactamases and Acinetobacter No dose adjustment for patients with impaired renal function Safety Positive safety and tolerability profile No black box warning Ability to use in patients with penicillin and beta-lactam allergies No risk of Clostridium difficile Commercial Opportunity Large, growing patient population ESBL rates as high as 25% in some regions in the U.S. ciais are always polymicrobial and require combination therapy in 50% of patients Carbapenem and beta-lactam combination sparing 16

17 XERAVA Launch

18 XERAVA: Launched in the U.S. XERAVA (eravacycline) for the treatment of complicated intra-abdominal infections in patients 18 years of age and older FDA approved on August 27, 2018 EMA approved on September 20, 2018 Launched in the U.S. in mid-october 2018 Label supports broad use 18

19 Clear Strategy to Ensure XERAVA Commercial Success Susceptibility Testing Focused Launch Strategy Experienced Team Appropriate Patients Differentiated Compound Research Use Only testing material available months before launch (e-strips and discs) Multiple commercial testing options available at launch Hospital-only focused product Targeting top 60% of Gram-negative hospitals at launch Target additional 30% in 2019, leading to 90% of Gram-negative market Management team has >20 years in antibiotic space Sales team has >25 years in the antibiotic space, and has launched >20 hospital products Only company focused on ciai Label allows for empiric treatment Focused on two distinct patient segments: 1) risk of infection with resistant pathogen and 2) high-risk Broad clinical and in vitro coverage of the most prevalent key resistant pathogens No need for TDM No need to dose adjust in renally impaired patients No risk of C. diff 19

20 Breaking the Antibiotic Launch Trends 169 Accounts Ordered Antimicrobial Susceptibility tests (AST) For Research Use Only (RUO) 3 Commercially Available AST Eravacycline Mast Disk by Hardy Diagnostics Eravacycline MIC Strip by Liofilchem Sensititre Plate by Thermo Fisher 400 Formulary Reviews Planned or already approved by end of Q % acceptance rate Speaker Programs 55 Speakers trained and speaking All territories have pulled through programs 70% Accounts Reordering Source: TTPH data as of March 14,

21 Pipeline Programs

22 TP-271: Targeting Respiratory Infections Development program targets respiratory disease caused by bacterial biothreats and antibiotic-resistant public health pathogens Potent activity in vitro against Gram-negative and Gram-positive pathogens associated with respiratory tract infections NIAID funding supports development through phase 1 Qualified Infectious Disease Product and Fast Track designation by FDA for both IV and oral formulations Positive safety and pharmacokinetic data from IV single-ascending and multipleascending dose studies Oral multiple-ascending dose Phase 1 study complete 22

23 TP-6076: Targeting MDR Gram-Negative Infections Potent activity in vitro against multidrug-resistant Gram-negative pathogens, including Acinetobacter baumannii On CDC and WHO list of serious threats Associated with high morbidity and mortality Common infections associated with Acinetobacter spp. VABP/HABP, bloodstream, cuti, cabssti Positive safety and pharmacokinetic data in single- and multiple-ascending dose studies Phase 1 bronchopulmonary disposition study to begin in Q Selected to receive $4 million CARB-X funding to support development 23

24 TP-6076: Targeting MDR Gram-Negative Infections 55 Extremely Drug Resistant Acinetobacter baumannii 141 resistant Enterobacteriaceae spp. Antibiotic MIC 50/90 µg/ml Antibiotic MIC 50/90 µg/ml TP /0.063 Tigecycline 2/4 Minocycline 8/16 Tetracycline >32 Colistin 0.5/4 Meropenem >32 Gentamicin >32 TP /0.5 Tigecycline 0.5/2 Minocycline 8/>32 Tetracycline 16/>32 Colistin 0.25/>32 Meropenem 8/>32 Gentamicin 8/>32 *MIC 50/90 : Minimum Inhibitory Concentration: Lowest concentration of the antibiotic at which 50% and 90% of the isolates were inhibited 24

25 Leadership Team: Seasoned Expertise in Development and Commercialization of Anti-infectives Guy Macdonald President and Chief Executive Officer Larry Edwards Chief Operating Officer Larry Tsai, MD Chief Medical Officer Jacques Dumas, PhD Chief Scientific Officer Christopher Watt Senior Vice President, Finance Maria Stahl Senior Vice President, General Counsel 25

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