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 forward-looking 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 additional clinical trials or other studies will be required prior to regulatory approval; whether the results from such 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 forwardlooking statements except as required by applicable law. 2

3 Multidrug-Resistance (MDR) is a Growing Crisis CDC: Drug-resistant 'nightmare bacteria' pose growing threat By Marilyn Marchione April 3, 2018 November 6, 2018 How antibiotic resistance can take us back to the dark ages November 5, 2018 April 3, 2018 Drug resistant superbugs are killing 33,000 in Europe each year By Kate Kelland 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 4, 2018 Rare superbugs more widespread than thought, says CDC By Betsy McKay 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) FDA and EMA approved for treatment of complicated intraabdominal infections (ciai) Broad Label in ciai Product opportunity of up to 2 million patient days of therapy Differentiated Antibiotics Proprietary platform enables creation of novel tetracycline compounds Cash runway into Q $97 million in cash and cash equivalents as of Sept. 30, 2018 Experienced management team 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 Discovery Products 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 IGNITE: Investigating Gram-Negative Infections Treated with Eravacycline Met primary endpoint of clinical cure for IV XERAVA vs. IV ertapenem in 536 patients using 10% noninferiority margin Well-tolerated, no drug-related serious adverse events Met primary endpoint of clinical cure for IV XERAVA vs. IV meropenem in 500 patients using 12.5% noninferiority margin Well-tolerated, no drug-related serious adverse events Achieved high cure rates in patients with Gramnegative pathogens, including resistant isolates Achieved high cure rates in patients with Gramnegative pathogens, including resistant isolates 8

9 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 9

10 Complicated Intra-Abdominal Infections (ciai) Infection proceeding beyond the source organ into the peritoneal space Second most prevalent site of infection in the ICU 1 Second leading cause of infectious mortality in the ICU 1 Second most commonly identified cause of severe sepsis in the ICU 2 Sites of Infection (%) in the ICU IAI represents 1 of 5 ICU infections Respiratory tract Abdominal Bloodstream Renal/urinary tract Skin Catheter related CNS Others 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):

11 Antibiotic Resistance As Resistance Grows, Antibiotic Choices Narrow Gram- Gram+ CR Enterobacteriaceae MDR Acinetobacter baumanni CR Pseudomonas ESBL MRSA VRE Antibiotic Resistance Antibiotic Effectiveness Carbapenems Fluoroquinolones Cephalosporins Penicillins Glycopeptides Sources: Gupta V et al. Poster #352 presented at: ID Week 2016; October 26-30, 2016; New Orleans, LA.; Gupta V et al. Poster #369 presented at: ID Week 2016; October 26-30, 2016; New Orleans, LA.; Hoffman-Roberts H et al. Poster #140 presented at: ASM Microbe 2016; June 16-20, 2016; Boston, MA.; Antibiotic resistance threats in the United States, Centers for Disease Control and Prevention website. http//cdc.gov/ ; Denkinger CM et al. Arch Gerontol Geriatr. 2013; 56(1):

12 No. of Naturally Occurring Enzymes Rise of Extended Spectrum Beta-Lactamase (ESBL) Resistance Unique Beta-Lactamase Sequences Over 1,000 antibiotic-deactivating beta-lactamases have emerged, affecting an ever-broadening range of antibiotics and bacteria ESBLs (TEM/SHV/CTX-M) (TEM/SHV/CTX-M) (OXA) (AmpC) (IMP/VIM/NDM-1) Source: Adapted from Bush K, Jacoby GA. Antimicrob Agents Chemother. 2010;54(3): Year 12

13 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. & Europe Growth in Carbapenem-resistant Enterobacteriaceae in >3M Admissions in 192 U.S. Hospitals 2 16,000,000 14,000,000 12,000,000 10,000, ,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

14 XERAVA Market Opportunity

15 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 Safety High clinical cure rates in patients with MDR pathogens, ESBLs, beta-lactamases and Acinetobacter Positive safety and tolerability profile No black box warning Ability to use in patients with penicillin and beta-lactam allergies No risk of Clostriduim difficile Commercial Opportunity No dose adjustment for patients with impaired renal function 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 βeta-lactam combination sparing 15

16 XERAVA Market Opportunity in the U.S. and EU5 Overall Market 40 MM Days of Therapy 25% High-risk Segment 10 MM Days of Therapy 20% Product Opportunity 2 MM 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 16

17 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: 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 Tachypneic Tachycardic Hypotensive Febrile For Patients with Confirmed: ESBL AmpC MRSA VRE C. diff Sources: and 2015 Decision Resources AMR Hospital Database; 2. Internal market research 17

18 Comparison of Coverage Points of Differentiation Fosfomycin 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 18

19 XERAVA Launch

20 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 Launching in the EU5 beginning in 1H 2019 Label supports broad use 20

21 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 (estrips 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 Gramnegative 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 21

22 Pipeline Programs

23 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 ongoing 23

24 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 24

25 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 25

26 Key Milestones 3Q18 4Q18 1Q19 2Q19 3Q19 FDA approval EU approval U.S. commercial launch EU5 commercial launch TP-271 Phase 1 oral data TP-6076 Phase 1 BAL study 26

27 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 27

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