Antibiotics to Treat Multidrug-Resistant Bacterial Infections

Transcription

1 Antibiotics to Treat Multidrug-Resistant Bacterial Infections Copyright 2017 Tetraphase Pharmaceuticals, Inc. C O M P A N Y P R E S E N T A T I O N A p r i l TTPH

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 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 any submission for regulatory approval; whether the results from such trials or studies will be sufficient to warrant submission for regulatory approval; whether submissions will be made and approvals will be received from the United States Food and Drug Administration or equivalent foreign regulatory agencies on a timely basis or at all; whether, if eravacycline obtains approval, it will be successfully distributed and marketed; 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 Deadly Multidrug-Resistant (MDR) Gram-Negative Infections Are A Growing Threat Drug-Resistant Superbugs Are a 'Fundamental Threat', WHO Says by Maggie Fox September 21, 2016 CDC announces 4th superbug case in US patient By Susan Scutti September 9, 2016 September 7, 2016 September 7, 2016 Superbug scourge spreads as U.S. fails to track rising human toll By Ryan McNeill, Deborah J. Nelson and Yasmeen Abutaleb Superbug Explosion Triggers U.N. General Assembly Meeting Antibiotic resistance has grown so dire that it will be the subject of a dedicated global summit later this month October 2016 October 26, 2016 Infectious Disease News: Emergence of colistin resistance represents threatening development Why Can t We Find New Antibiotics? Research gaps lead to dearth of much needed drugs 3

4 Improving Environment for Antibiotic Development Review on AMR Reports CDC 2013 resistance threat report and solutions initiative WHO AMR report and 2015 global action plan President s Council on Science and Technology (PCAST) UN General Assembly Global Awareness and Programs Combined Forces to Address Antibiotic Resistance Legislative Initiatives Gain Act, passed July 2012 Pending DISARM ACT 21 st Century Cures Act Regulatory Pathways FDA updated guidance LPAD, ADAPT Pathway PATH Initiative 4

5 Tetraphase Pharmaceuticals: Corporate Highlights NOVEL ANTIBIOTICS FOR SERIOUS AND LIFE-THREATENING MDR INFECTIONS Late-Stage Pipeline Platform Technology Strong Balance Sheet Strong Leadership Eravacycline in phase 3 Portfolio of differentiated antibiotics Innovation licensed from Harvard Cash runway into 2H 2018 Experienced management team Seeking regulatory approval first in ciai, then in cuti Two phase 1 trials underway with data expected in 2017 Proprietary chemistry enables the creation of novel tetracycline derivatives to treat MDR infections $142M in cash and cash equivalents as of Dec 31, 2016 Track record of success in antiinfective development, regulatory approval and commercialization 5

6 Antibiotics Pipeline from Proprietary Platform Product candidate Route of administration Discovery Preclin Phase 1 Phase 2 Phase 3 Eravacycline Complicated Intra-abdominal Infections IGNITE1 IV completed IGNITE4 IV Complicated Urinary Tract Infections IGNITE2 IV-to-oral completed IGNITE3 IV Oral development Program Oral TP-271 Respiratory infections, CABP IV, Oral TP-6076 Multidrug-resistant infections IV 6

7 Market Opportunity

8 Delayed Use of Appropriate Therapy Burdens Healthcare System In ciai and cuti, over 85% of patients are treated with empiric therapy 1 Empiric Therapy Delayed Appropriate Therapy 3.7 Additional Treatment Days Additional Hospital Days 2 $7,500 in Additional Costs 2 Timely Appropriate Therapy Higher costs for hospital care, particularly with severe resistant Gram-negative infections; primarily driven by room and board and medical care costs 2 1. BioTrends Report, Treatment Trends: Gram-negative Infections (P<0.01) IDWeek 2016 Lodise et al. 8

9 Eravacycline Market Opportunity US and EU ciai and cuti Hospital Market Opportunity:~100 MM Annual Days of Therapy (DOT) = 1 million days of therapy (DOT) 9

10 Eravacycline Market Opportunity US and EU Complicated Intra-abdominal Infections: 40 MM Annual DOT ciai and cuti Hospital Market Opportunity: US and EU ~100 MM Annual DOT Complicated Urinary Tract Infections: 60 MM Annual DOT = 1 million days of therapy (DOT) 10

11 Eravacycline Market Opportunity US and EU Complicated Intra-abdominal Infections: 40 MM Annual DOT 88% is IV treatment Complicated Urinary Tract Infections: 60 MM Annual DOT 56% is IV treatment = 1 million days of therapy (DOT) 11

12 Eravacycline Market Opportunity US and EU Complicated Intra-abdominal Infections: 40 MM Annual DOT 88% is IV treatment High Risk Segment 20 MM Annual DOT Complicated Urinary Tract Infections: 60 MM Annual DOT 56% is IV treatment = 1 million days of therapy (DOT) 12

13 Eravacycline Market Opportunity US and EU Complicated Intra-abdominal Infections: 40 MM Annual DOT 88% is IV treatment Complicated Urinary Tract Infections: 60 MM Annual DOT 56% is IV treatment Empiric treatment for high-risk patients Patients with renal or hepatic-impairment High Risk Segment 20 MM Anual DOT Patients who need combination therapy Patients who have failed first-line therapy Patients with confirmed resistant infections = 1 million days of therapy (DOT) 13

14 Eravacycline Market Opportunity US and EU Complicated Intra-abdominal Infections: 40 MM Annual DOT 88% is IV treatment Eravacycline Opportunity 3.5 MM Annual DOT Complicated Urinary Tract Infections: 60 MM Annual DOT 56% is IV treatment = 1 million days of therapy (DOT) 14

15 ciai: New Drugs Needed for Resistant Infections GRAM-NEGATIVE MARKET OPPORTUNITY ciai needs early, rapid treatment 90% first-line empiric therapy 1 Pip/tazo, quinolones, cephalosporin combinations and carbapenems used primarily 40% of cases require 2 nd line therapy 1 70% % of pathogens targeted when empirically treating ciai patients 2 60% 49% Broad spectrum antibiotics needed Current treatments require combination of drugs to achieve desired bacterial coverage 50% treated with combination therapy 2 13% 32% 7% E. coli K. pneumoniae Enterobacter Acinetobacter ESBLs CREs 1. Internal market research 2. BioTrends Report Treatment Trends Hospital Treated Infections 2015 April JANUARY

16 cuti: New Drugs Needed for Resistant Infections GRAM-NEGATIVE MARKET OPPORTUNITY Gram-negative pathogens primary cause of cuti 85% first-line empiric therapy 1 Quinolones and ceftriaxone primarily used; 20%+ fail initial therapy 2 Antibiotics needed with MDR activity Quinolone resistance rates (20-60%) 3 increasing Combination therapy used 30% 4 Dosing convenience is important 90% % of pathogens targeted when empirically treating cuti patients 5 77% 52% 80% 56% 40% 15% 1. BioTrends Report, Treatment Trends: Gram-negative Infections Internal company estimates 3. WHO April 2014 Global Resistance Report Decision Resources AMR Hospital Data base 5. BioTrends Report Treatment Trends Hospital Treated Infections

17 Eravacycline: Potent Activity Against Bacteria Causing Serious Infections

18 Eravacycline Novel Antibiotic in Phase 3 Trials Novel, fully-synthetic tetracycline being developed for serious infections IV and oral formulations Potent activity against broad spectrum of bacteria: Gram-negative and Gram-positive Anaerobic and atypical MDR: ESBLs, CREs, CRAB, MCR1, VRE, MRSA In phase 3 clinical trials First indication: complicated intra-abdominal infections (ciai) Second indication: complicated urinary tract infections (cuti) Received QIDP and Fast Track designation from U.S. FDA 18

19 Potent Activity Against MDR Gram-Negative Patient Isolates from New York City MIC 90 (µg/ml) ERAVACYCLINE In Vitro MIC 90 Comparison Ceftriaxone Meropenem Gentamicin Ciprofloxacin Tigecycline Eravacycline Source: Abdallah et al; AAC December

20 cuti ciai IV Eravacycline Registration Pathway Complete MAA submission (IGNITE1) Top-line data 3Q17 Complete* Initiated 1Q17 *Primary endpoint not met 20

21 Phase 3 ciai Completed Study Design & Data Summary ERAVACYCLINE Study Design Eravacycline (1.0 mg/kg IV q12h) vs ertapenem (1.0 g IV q24h) in 536 patients Primary endpoint: clinical response at test-of-cure visit (25 to 31 days after initial dose); 10% non-inferiority (NI) margin in microbiological intent-to-treat (micro-itt) population Efficacy Eravacycline met FDA and EMA primary endpoint of non-inferiority to ertapenem Eravacycline was efficacious in patients with difficult-to-treat Gram-negative pathogens Safety Confirmed ESBLs 22/24 (91.7) Confirmed AmpC 8/8 (100) Carbapenem Resistant 6/6 (100) MDR 18/20 (90) Eravacycline was well tolerated and there were no drug-related serious adverse events Microbiology Wide range of bacteria isolated in patients (47.1% Gram-negative, 26.1% Gram-positive, and 26.8% anaerobes; 3 isolates per patient) Data to serve basis of MAA filing expected in 3Q 2017 November

22 Phase 3 ciai Ongoing Study Design NON-INFERIORITY TRIAL (FDA:12.5% margin) POST-TREATMENT EVALUATIONS Eravacycline N=450 (1:1) 1.0 mg/kg IV q12h 4 to 14-Day Dosing Period Primary Endpoint Test of Cure Meropenem 1.0 g IV q8h DAYS 1-14 DAYS DAYS Secondary Endpoint End of Therapy Secondary Endpoint Long-Term Follow Up Top-line data expected in 3Q 2017 Data from IGNITE1 and IGNITE4 to support NDA submission 22

23 Phase 3 cuti Ongoing Study Design ERAVACYCLINE NON-INFERIORITY TRIAL (10% margin) Eravacycline (ERV) 1.5 mg/kg IV q24h IV ORAL POST-TREATMENT EVALUATIONS n=~1000 (1:1) Ertapenem (ERT) 1 g IV q24h Levofloxacin 750 mg q24h DAYS 1-5 DAYS 6-10 Minimum 5 days IV treatment, then eligible to switch to oral levofloxacin Total treatment period: minimum 7 days, maximum 10 days FDA Co-Primary Endpoint Responder Rate (clinical cure and micro success) in micro-itt population at End-of-IV visit Initiated in 1Q 2017; data to support snda for eravacycline FDA Co-Primary Endpoint Responder Rate in micro-itt population at Test-of Cure visit (Day 5-10 post therapy) 23

24 Phase 3 cuti Completed IV-to-Oral Study Design & Data Summary ERAVACYCLINE Study Design Eravacycline (1.5 mg/kg q24h IV, 200 mg BID oral) vs levofloxacin (750 mg q24h IV, 750 mg QD oral) in 908 patients 7 day dosing period: 3 days of IV therapy with potential to transition to oral for remainder Primary endpoint: responder rate 6-8 days post-therapy; 10% NI margin in micro-itt population Efficacy Eravacycline did not achieve its primary endpoint of statistical non-inferiority vs levofloxacin Eravacycline achieved superiority compared to levofloxacin in a subset of patients with quinolone-resistant isolates Safety Eravacycline demonstrated a favorable safety profile Additional Analysis Indicates that longer IV treatment resulted in improved responder rates Patients treated with IV eravacycline achieved higher response rates compared to patients treated with IV levofloxacin Supports overall efficacy result driven by underperformance of oral formulation 24

25 Oral Eravacycline Continuing oral formulation development separately Ongoing phase 1 program Early phase 1 data suggest: Oral dosing regimen used in IGNITE2 leads to lower systemic levels of eravacycline than expected Administration of oral eravacycline in a fasted state results in increased drug exposure Further phase 1 testing underway to evaluate several additional variables associated with optimizing the oral formulation and dosing regimen Update on program findings and next steps planned in Q

26 Eravacycline: Potent Activity Against Key Resistant Bacterial Threats and Convenient Dosing Provide Differentiation Pathogens Eravacycline Plazomicin Meropenem/ Vaborbactam MDR Enterobacteriaceae (ESBL-expressing or Carbapenemase-Resistant) Carbapenemases - inactive; Some ESBLs - modest activity Most ESBLs/ carbapenemases active Anaerobes Acinetobacter (Including Carbapenemase- Resistant) Metallo-Beta lactamase Pseudomonas VRE & MRSA VRE- not active MRSA - active Dosing convenience IV QD or BID 60 mins IV TID 60 mins IV TID 120 mins IV QD 60 mins w/monitoring IV 2g/2g TID 3 hours Active/convenient Intermediate activity/convenience Limited or no activity/convenience Source: Prescribing information for approved products; Public data presentations for investigational products

27 Pipeline Programs

28 Tetraphase Chemistry Technology Offers Novel Development Opportunities PIPELINE PROGRAMS Fully synthetic chemistry that is commercially scalable Over 3,000 novel analogs synthesized 28

29 TP-271: Targeting Respiratory Infections PIPELINE PROGRAMS Potent activity in vitro against Gram-negative and Gram-positive pathogens associated with respiratory tract infections Development program targets respiratory disease caused by bacterial biothreats and antibiotic-resistant public health pathogens Francisella tularensis, Yersinia pestis and Bacillus anthracis Bacterial pathogens associated with community-acquired bacterial pneumonia NIAID funding supports preclinical development, manufacturing and phase 1 clinical, safety and pharmacokinetic evaluation of TP-271 Qualified Infectious Disease Product and Fast Track designation by FDA for both IV and oral formulations Phase 1 clinical trials ongoing; data to be presented mid

30 TP-6076: Targeting MDR Gram-Negative Infections Novel, fully-synthetic antibiotic of the tetracycline class Potent activity in vitro against multidrug-resistant Gram-negative pathogens 55 XDR Acinetobacter baumannii 141 resistant Enterobacteriaceae spp. PIPELINE PROGRAMS Phase 1 clinical trials ongoing; data to be presented mid-2017 Selected to receive $4 million CARB-X funding to support development 30

31 Financial Highlights $142.1M $0 36.9M 41.3M (fully diluted) CASH AND EQUIVALENTS 31-Dec-2016 DEBT 31-Dec-2016 SHARES OUTSTANDING 31-Dec-2016 Non-dilutive U.S. Government funding to support pipeline program development up to $67M (under contract initiated in 2012) up to $39.8M (under contract initiated in 2011) $4M (over 18 months) BARDA (eravacycline) NIAID (TP-271) CARB-X (TP-6076) 31

32 Key Near-Term Milestones Eravacycline Initiate IGNITE3 trial (cuti) 1Q 2017 MAA filing for ciai 3Q 2017 IGNITE4 (ciai) top-line data 3Q 2017 Oral development update 3Q 2017 Pipeline Programs Present TP-271 phase 1 data mid-2017 Present TP-6076 phase 1 data mid