Antibiotics to treat multi-drug-resistant bacterial infections

Forward Looking Statements and Other Important Cautions Any statements in this presentation about future expectations, plans and prospects for the Company, including statements about regarding our strategy, future operations, prospects, plans and objectives, and other statements containing the words believes, anticipates, plans, expects, and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: our ability to obtain marketing approval for and commercialize eravacycline; our efforts to develop an oral formulation of eravacycline; our ability to demonstrate safety and efficacy to the satisfaction of the FDA or comparable regulatory authorities outside the United States in our clinical trials of eravacycline; our commercialization and marketing capabilities; our cash resources; and other factors discussed in the Risk Factors section of our registration statement on Form S-1. In addition, the forward-looking statements included in this presentation represent the Company s views as of July 9, 2013. The Company anticipates that subsequent events and developments will cause the Company s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company s views as of any date subsequent to July 9, 2013. 2

Deadly Multi-Drug-Resistant Gram Negative Infections Are A Growing Threat January 30, 2013 September 14, 2012 NIH superbug claims 7th Victim KPC producing bacteria have emerged as a highly drug resistant Gram-negative bacteria associated with mortality rates ranging from 32% to 48% (SENTRY surveillance program) March 5, 2013 CDC: Deadly, drug-defying CRE bacteria on rise in U.S. hospitals March 5, 2013 Deadly Bacteria That Resist Strongest Drugs Are Spreading Los Angeles County, one of the few places where Klebsiella pneumonia carbapenemase (KPC) is being tracked, detected 356 cases in the second half of 2012. 3

Tetraphase Pharmaceuticals: Overview Pipeline of differentiated antibiotics from proprietary chemistry platform focused on multi-drug resistant (MDR) Gram negative infections Lead product eravacycline in Phase 3 Potential for best in class activity in MDR Gram negative infections Broad spectrum, first line monotherapy IV and potential for oral >3.5 million patient estimated MDR market in the US Two indications for the price of one Two Phase 3 studies can support two indications Optimize reimbursement and commercial uptake $80M in proceeds from IPO, expected to be sufficient to top-line Phase 3 data In addition potential non-dilutive US Government funding of up to $100M 4

Complicated Intra-Abdominal Infections (ciai): New Drugs Needed to Cover Resistant Bacteria Approximately 1.7M Patients in the US (1) 38% of patients treated for ciai Treated EMPIRICALLY for suspicion of Gram Negative (2) 70% have a mixed infection involving Gram-negative and Grampositive pathogens (2) Successfully treated with 1 st line empiric therapy (2) 73% Fail 1 st line empiric therapy (2) 27% % ciai patients with confirmed infection due to specific Gram Negative pathogens (2) 7% 58% 22% 3% P. aeruginosa E. coli K. pneumoniae Acinetobacter 1. Company estimates based on various industry sources 2. Based on physician market survey 5

Complicated Urinary Tract Infections (cuti): New Drugs Needed to Cover Resistant Infections Approximately 4M Patients in the US (1) cuti patients treated EMPIRICALLY for suspicion of GNI (2) 78% 25% of cuti patients treated empirically with therapies that cover MDR Gram negatives (2) Successfully treated with 1 st line empiric therapy (2) 76% Fail 1 st line empiric therapy (2) 24% Increase in resistance to fluoroquinolones (25-30%) Significant market opportunity: QD I.V. (outpatient etc) or I.V./oral step down 1. Company estimates based on various industry sources 2. Based on physician market survey 6

History of Tetracyclines Limited Variety In Semi-synthetic Approach ( )-Chlortetracycline ( )-Doxycycline ( )-Tigecycline H H 3 C 3 C Cl N HO H H O OH O HO H O CH 3 OH NH 2 O H 3 C HO H 3C N H H O OH O HO H O CH 3 OH NH 2 O H 3 C H 3 C H N CH 3 O H 3 C CH N 3 N H H H 3 C H N O OH O HO H O CH 3 OH NH 2 O 1948 1954 1967 1972 2005? H H 3 C 3 C H N HO H H O OH O HO H O CH 3 OH NH 2 O H 3 C CH N 3 H H 3 C H N O OH O HO H O CH 3 OH NH 2 O H 3 C H 3 C CH 3 H N H 3 C CH N 3 H H 3 C H N O OH O HO H O CH 3 OH NH 2 O ( )-Tetracycline ( )-Minocycline PTK-0796 7

Tetraphase Chemistry Technology Offers Novel Antibiotic Development Opportunity Eravacycline TP-834 TP-271 Pseudomonas/Gram -ve 7 8 6 5 4 3 9 11 1 2 10 12 Positions that can be practically modified through conventional semi-synthesis and Tetraphase s technology Positions that can only be practically modified through Tetraphase s technology Fully synthetic chemistry that is commercially scalable Enables Strong IP and barrier to entry 8

Unique Synthesis of Novel Tetracyclines 2800+ novel analogs 50+ novel scaffolds Eravacycline Broad Spectrum IV/Oral TP-271 Monotherapy IV/Oral TP-834 Monotherapy IV/Oral Pseudomonas / Gram -ve Leads 9

Tetraphase Pipeline From Internal Chemistry Platform Program Target Indications Preclinical IND Enabling Studies Phase 1 Phase 2 Phase 3 Eravacycline* Broad Spectrum IV ciai cuti Eravacycline Broad Spectrum Oral Stepdown ciai cuti TP-834 IV/Oral CABP (including MRSA and atypicals) TP-271** IV/Oral Bacterial Biothreats Pseudomonas / Gram-ve Program MDR Gram-negative * Funding from BARDA Biomedical Advanced Research and Development Authority ** Funding from NIAID National Institute of Allergy and Infectious Diseases 10

JUNE 2013 11

MIC90 (µg/ml) ERAVACYCLINE Broad Spectrum Coverage of Gram-Negative Pathogens In Vitro MIC 90 Comparison 32 28 24 20 16 12 8 4 0 Piperacillin/Tazobactam Gentamicin Ceftazidime/Cefotaxime Fluoroquinolone Carbapenem Tigecycline Eravacycline MIC - minimum inhibitory concentration Pip/Tazo and Ceftazidime/Cefotaxime truncated at 32 µg/ml 12

MIC90 in μg/ml ERAVACYCLINE Broad Spectrum Against Gram-Positive Pathogens In Vitro MIC 90 Comparison 8 6 4 2 0 Levofloxacin Daptomycin Linezolid Vancomycin Tigecycline Eravacycline MIC 90 values are truncated at 8 µg/ml 13

MIC90 (µg/ml) ERAVACYCLINE Broad Spectrum Coverage of Anaerobes In Vitro MIC 90 Comparison 16 14 12 10 8 6 4 2 0 Vancomycin Metronidazole Imipenem Tigecycline TP-434 Eravacycline 10-40 isolates/species Vancomycin and Metronidazole MIC 90 values truncated at 16 µg/ml 14

ERAVACYCLINE IV Phase 2 ciai Overview Randomized, double blind study in ciai Primary endpoint: Clinical outcome in the microbiologically evaluable (ME) population at test of cure visit 143 Patients with ciai Randomized (2:2:1) Eravacycline 1.5 mg/kg IV q 24h (ME=42) Eravacycline 1.0 mg/kg IV q 12h (ME=41) Ertapenem 1.0 g IV q 24h (ME=26) 15

Percent Cure ERAVACYCLINE IV Demonstrated Efficacy in Phase 2 Clinical Response at Test of Cure Visit in Microbiologically Evaluable Population 100 90 80 92.9 100 92.3 70 60 50 40 30 20 10 0 TP 1.5 Eravacycline TP 1.0 E Eravacyline 1.5mg/kg q24h 1.0mg/kg q12h Ertapenem 95% CI 80.5-98.5 91.4-100 74.9 99.1 16

ERAVACYCLINE IV Bacteria Isolated in Phase 2 25% of Gram Negative Bacteria Were Multi-Drug-Resistant Other Gram-positive spp., 0.9% Staphylococcus spp., 6.1% Anaerobes, 8.5% Enterococcus spp., 7.5% Escherichia coli, 44.3% Streptococcus spp., 9.0% GN Non-fermentors, 7.5% Other Enterobacteriaceae, 6.1% Klebsiella spp., 9.9% Average of 1.8 isolates/patient (m-mitt population) 17

ERAVACYCLINE IV Minimal Adverse Events Reported Adverse Events Possibly Related to Study Drug* Eravacycline 1.5mg/kg q24h N=53 Eravacycline 1.0mg/kg q12h N=56 Ertapenem N=30 Any Treatment related AE 2 (3.8%) 3 (5.4%) 3 (10.0%) Nausea - 2 (3.6%) 1 (3.3%) Vomiting 1 (1.9%) 1 (1.8%) - Elevated amylase - - 1 (3.3%) Elevated lipase - - 1 (3.3%) Thrombophlebitis - 1 (1.8%) - * ITT population 18

ERAVACYCLINE ORAL Development Plan to Define Oral Dosing Completed Phase I Oral SAD and MAD Single-center, placebo-controlled, double-blinded studies PK is linear; AUC is linear and dose-proportional Orally bioavailable 300mg QD and 100mg BID well tolerated Ongoing studies planned to be completed mid 2013 Phase 1 PK program to evaluate ascending oral doses 19

ERAVACYCLINE Profile of a Well-Differentiated Antibiotic FEATURE Demonstrated clinical efficacy Safe and well tolerated in patients: Minimal GI side effects Convenient dosing: Monotherapy Once daily dosage supported Broad Spectrum Antibiotic Covers gram ve, gram +ve, anaerobes and atypicals Active against difficult-to-treat MDR gram ve pathogens Potential for oral step down therapy 20

ERAVACYCLINE Phase 3 Ready NDA package: one pivotal study in ciai, one in cuti Plan reviewed with FDA at EOP2 meeting in January 2013 Plan follows new FDA Guidance Document ciai Guidance issued September 2012 No longer requires two pivotal studies in the same indication PHASE 3 PROGRAM ciai Non inferiority study IV q12h 3Q2013 cuti Non inferiority study Plan to switch to IV q24h/oral step down Estimated Start: 4Q2013 21

Resistance Increasing for Gram-negative Marketed Products (1) ZOSYN PRIMAXIN MERREM I.V. LEVAQUIN TYGACIL Pfizer; Generics Merck; Generics AZ J&J Pfizer / Wyeth Ampicillin + β- lactamase inhibitor Carbapenem Carbapenem Quinolone Tetracycline 3-4x day IV 3-4x day IV, IM 3-4x day IV 1x day PO, IV 2x day IV 1. As of June 2013 Public Information 22

Gram-negative Compounds In Development (1) Eravacycline Ceftolozane/ Tazobactam Ceftazidime/ Avibactam Ceftaroline/ Avibactam Tetraphase Cubist AZ AZ Phase 3 Phase 3 Phase 3 Phase 3 Tetracycline Cephalosporin + β- lactamase inhibitor Cephalosporin + β- lactamase inhibitor Cephalosporin + β- lactamase inhibitor QD/BID IV Oral 3x/ day IV 3x/day IV 3x day IV Eravacycline has convenient IV dosing with potential for oral step down 1. As of June 2013 Public Information 23

Strong Intellectual Property Estate Exclusive rights from Harvard to proprietary chemistry technology used to create novel fully-synthetic tetracycline analogs Patents for the process for developing novel fully synthetic tetracycline analogs Composition of matter of key intermediates used in the synthesis Composition of matter application pending on eravacycline If issued would extend through at least 2029 24

Experienced Management Team Guy Macdonald President and Chief Executive Officer Patrick Horn, M.D., Ph.D. Chief Medical Officer Joyce Sutcliffe, Ph.D. SVP, Biology David Lubner SVP, Chief Financial Officer Xiao-Yi Xiao, Ph.D. VP, Medicinal Chemistry Magnus Ronn, Ph.D. VP, Pharmaceutical Sciences Leland Webster, Ph.D., M.B.A. VP, Business Development 25

Milestones Initiate Phase 3 ciai study 3Q2013 Complete Oral Phase 1 PK program Mid 2013 Data read-out 2H 2013 Initiate Phase 3 cuti study 4Q2013 Top-line readout from both Phase 3 studies 1Q2015 26

Tetraphase Pharmaceuticals : Summary Pipeline of differentiated antibiotics from proprietary chemistry platform focused on multi-drug resistant (MDR) Gram negative infections Lead product eravacycline in Phase 3 Potential for best in class activity in MDR Gram negative infections Broad spectrum, first line monotherapy IV and potential for oral >3.5 million patient estimated MDR market in the US Two indications for the price of one Two Phase 3 studies can support two indications Optimize reimbursement and commercial uptake $80M in proceeds from IPO, expected to be sufficient to top-line Phase 3 data In addition potential non-dilutive US Government funding of up to $100M 27