Trius Therapeutics Bio CEO & Investor Conference


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Trius Therapeutics Bio CEO & Investor Conference

  1. 1. Best-in-Class Anti-Infectives
  2. 2. Forward Looking StatementsStatements made in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaningof the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual resultsmay differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limitedto, statements regarding Trius’ ability to successfully complete its ongoing clinical trials and development programs, the expected timingfor reporting of top-line data for the TR701-113 study, Trius’ ability to obtain regulatory approval for tedizolid, market penetration andacceptance of tedizolid and the initiation of clinical studies for Trius’ Gyrase B program. Risks that contribute to the uncertain nature ofthe forward-looking statements include: Trius’ future preclinical studies and clinical trials may not be successful; changes in regulatoryrequirements in the United States and foreign countries may prevent or significantly delay regulatory approval of Trius’ products; Triusmay change its plans to develop and commercialize its product candidates; the FDA may not agree with Trius’ interpretation of the datafrom recently-completed clinical trials of tedizolid; Trius may decide, or the FDA may require Trius, to conduct additional clinical trials orto modify Trius’ ongoing clinical trials; Trius may experience delays in the commencement, enrollment, completion or analysis of clinicaltesting for its product candidates, or significant issues regarding the adequacy of its clinical trial designs or the execution of its clinicaltrials, which could result in increased costs and delays, or limit Trius’ ability to obtain regulatory approval; the third parties with whomTrius has partnered with for the development of tedizolid and upon whom Trius relies to conduct its clinical trials and manufacture itsproduct candidates may not perform as expected; tedizolid may not receive regulatory approval or be successfully commercialized;unexpected adverse side effects or inadequate therapeutic efficacy of tedizolid could delay or prevent regulatory approval orcommercialization; Trius’ may be unable to obtain and maintain intellectual property protection for its product candidates; the loss of keyscientific or management personnel; Trius’ ability to obtain additional financing; and the accuracy of Trius’ estimates regardingexpenses, future revenues and capital requirements. These and other risks and uncertainties are described more fully in Trius’ mostrecent Form 10-K, Forms 10-Q and other documents filed with the United States Securities and Exchange Commission, including thosefactors discussed under the caption “Risk Factors” in such filings. All forward-looking statements contained in this press release speakonly as of the date on which they were made. Trius undertakes no obligation to update such statements to reflect events that occur orcircumstances that exist after the date on which they were made.Trius has filed a registration statement (including a base prospectus) with the United States Securities and Exchange Commission forthe offering to which this communication relates. Before you invest, you should carefully review the prospectus supplement and theaccompanying prospectus, together with the information incorporated by reference therein, as well as any free writing prospectus thatTrius or the underwriters provide you in connection with the offering, for more information about Trius and the offering. Trius files annualreports, quarterly reports and other documents with the Securities and Exchange Commission. You should read the documents wehave filed with the Securities and Exchange Commission for more complete information about Trius. You may get these documents forfree by visiting EDGAR on the Securities and Exchange Commission web site at, or by visiting the Trius Therapeutics’website at 2
  3. 3. Record of Successful Execution All Efficacy and Safety Objectives Achieved •  Unsurpassed efficacy & improved safety with shorter112 Trial Successful course of therapy and better convenience •  Successful efficacy and safety results triggered $5M milestone payment from Bayer Enrollment on track 113 Trial Enrolling •  Top line data expected early 2013 Asia-Pacific/Emerging Markets •  A strong partner with comprehensive development Bayer Deal and commercial infrastructure in Asia •  Accelerates development in skin and lung infections globally Funded through Phase 1 by $28M NIAID ContractGyrB Gram Program •  Broad spectrum potency goals achieved •  IND enabling studies underway 3
  4. 4. Trius Pipeline Tedizolid Development Program Matched with Market Opportunity Product and Dosage Discovery / Target Indications Form Pre-Clinical Phase 1 Phase 2 Phase 3 Oral Tedizolid Phosphate ABSSSI IV/ Oral Tedizolid Phosphate IV/ Oral HAP/VAP Tedizolid Phosphate IV/ Oral Bacteremia GyrB/ParE Drugs for Gram-Negative IV Infections Marine Natural Products Drugs for Gram-Positive & IV Gram-Negative Infections 4
  5. 5. Gram Positive Market Has Doubled in ValueMarket has grown to over $2.5B globally ($1.5B in USA) with declining Vancomycinsusceptibility contributing to growth of branded agents U.S. Sales 2005 – $700MM U.S. Sales 2011 - $1.68B Vibativ (Telavancin) Vancomycin $10M* Tygacil (Tigecycline) Tygacil (Generic) $10MM Vancomycin $186MM* (Tigecycline) (Generic) $148MM $137MM Cubicin Zyvox (Daptomycin) (Linezolid) $114MM Zyvox $640MM (Linezolid) Cubicin $437MM (Daptomycin) $699MM 18% CAGR in Branded Sales from 2005-2011 Each market share point for a branded agent is worth $50MMSource: Company Reports / IMS-National Sales Perspectives; *=Estimate 5
  6. 6. Tedizolid Combining the Strength of Current Products GenericAttribute Linezolid Vancomycin Daptomycin TedizolidIV/OralIn-Vivo BactericidalActive in LungInfectionsOnce Daily TreatmentShort Course ofTherapy 6
  7. 7. Market Research Indicates Formulary Acceptance For Core Indications Priced at Parity Per Course of Priced at Significant Premium Per Therapy to Zyvox Course of Therapy to Zyvox cSSSi cSSSi 60% 40% 30% 40% 30% Pneumonia Pneumonia (HAP/VAP) (HAP/VAP) 80% 20% 50% 20% 30% Endocarditis / Endocarditis / Bacteremia Bacteremia 50% 40% 10% 30% 40% 30% 0% 20% 40% 60% 80% 100% 0% 20% 40% 60% 80% 100% Very Likely Moderately Likely Not At All Likely Very Likely Moderately Likely Not At All Likely Based upon the response of 10 HMO/PBMS and 10 Formulary DirectorsPG Decision Metrics market research of 10 Formulary Directors & 10 HMO/PBMs. Commissioned by Trius in 2009 7
  8. 8. …and Good Placement of the Oral Formulation in the Outpatient Setting Priced at Parity Per Course of Priced at Significant Premium Per Therapy to Zyvox Course of Therapy to Zyvox 100% 100% 90% 90% 90% 90% 80% 80% 70% 70% 60% 60% 50% 50% 40% 40% 30% 30% 20% 20% 10% 10% 10% 10% 0% 0% 0% 0% Tier 1 Tier 2 Tier 3 Tier 1 Tier 2 Tier 3 Based upon the response of 10 HMO/PBMSPG Decision Metrics market research of 10 HMO/PBMs. Commissioned by Trius in 2009. 8
  9. 9. Tedizolid Phosphate Phase 3 Study Design: Oral (112) and IV/Oral (113) Trials Under SPA FDA and EMA Endpoints for Global Registration Safety Analyses PatientScreening 6-Days Tedizolid QD 4-Days Placebo Post Treatment667 Evaluations Randomization 10-Days Linezolid BID Baseline FDA EMA EMA FDA Primary Endpoint Secondary Primary Secondary 48-72 hrs from Baseline Endpoints Endpoint at Endpoint at EOT PTE LFU 9
  10. 10. Primary Outcome: All Current and Contemplated Trial 112Primary Endpoints Achieved in Pre-Specified Analyses Primary Outcome at 48-72 hour visit Treatment Lesion Criteria Tedizolid Linezolid Fever Criteria (200 mg QD 6 days) (600 mg BID 10 days) 112 SPA Primary Endpoint Temperature measurementsNo increase in lesion area required within 24 hrs of 79.5% 79.4%from baseline* 48-72 hr visit* FNIH recommended to FDA to exclude temperature as a component of the primary endpoint and to assess a >20% reduction in lesion size at 48 to 72 hours. Under these pre-specified analysis tedizold shows additional numerical separation from linezolidNo increase in lesion areafrom baseline Temperature excluded** 87.0% 85.4%FNIH Primary Endpoint≥ 20% reduction of lesion Temperature excluded** 78.0% 76.1%are from baseline*** Primary endpoint as agreed to under Study 112 and 113 SPA** FNIH recommendations to FDA: ABSSSI Docket ID: FDA--2010--D--0433 10
  11. 11. Secondary Outcomes: Tedizolid Demonstrates Comparable Efficacy with Shorter Course of Therapy Secondary Outcome at EOT or PTE Treatment Secondary Outcome Tedizolid Linezolid Criteria (200 mg QD 6 days) (600 mg BID 10 days) 112 SPA 69.3% (ITT) 71.9% (ITT) Early clinical failures carried Clinical Response at EOT* forward to EOT* (Day 11) 80.2% (CE) 81.1% (CE) In August 2010 draft guidance the FDA adopted changes to the secondary outcomes of clinical response at the end of therapy (EOT). These were prospectively measured in Study 112 sensitivity analyses and are captured in the Study 113 SPA. 80.7% (ITT) 80.9% (ITT) Clinical Response at EOT* Early clinical failures not carried (Day 11) forward to EOT** 87.5% (CE) 87.1% (CE) Early clinical failures not carried 87.0% (ITT) 87.8% (ITT) 113 SPA forward to EOT** and Clinical Response at EOT* presence/absence of patient (Day 11) reported pain at EOT excluded*/** 94.5% (CE) 95.1% (CE)* Primary and secondary endpoints as agreed to under Study 112 SPA** Consistent with FDA draft ABSSSI Guidance for Industry (August 2010) 11
  12. 12. Tedizolid was Well Tolerated with a Favorable AEProfile Compared to LinezolidTedizolid had a numerically lower rate of drug-related treatment emergent adverse events(TEAE) and a statistically significant lower number of gastrointestinal adverse events Tedizolid Linezolid Adverse Event (200 mg QD 6 Days) (600 mg BID 10 Days) Any Treatment Emergent 40.8% 43.3% Adverse Event (TEAE) Any Drug Related TEAE 24.2% 31.0% Gastrointestinal 16.3%** 25.4% Disorders* * Gastrointestinal AEs include: Diarrhea, Nausea, Vomiting and Dyspepsia ** Statistically significant (p=0.004). No Unexpected Safety Signals •  Liver enzymes/function tests •  QTc 12
  13. 13. Hematology: Tedizolid Had Significantly Lower Impacton Platelets than Linezolid Percent of Patients with Value below the Lower Limit of Normal (LLN) Tedizolid Linezolid Hematology Parameter (200mg QD 6 days) (600mg BID 10 days) Platelets* 9.2% 14.9% Below LLN Platelets – Substantially Abnormal Value 2.3% 4.9% (<75% LLN) * Statistically significant (p=0.038) 13
  14. 14. Phase 3 Trial Summary £  Study 112 design and outcomes are consistent with both FDA and EMA regulatory requirements £  All efficacy and safety objectives of Study 112 were successfully achieved –  Efficacy: All primary and secondary trial endpoints met with a once-daily short course of therapy –  Safety: statistically significant lower incidence in key tolerability and safety parameters –  Successful results triggered $5M milestone payment from Bayer £  Results align with surveyed physician and payer preferences for fast acting drugs with improved tolerability and safety** PG Decision Metrics market research of 10 Formulary Directors & 10 HMO/PBMs. Commissioned by Trius in 2009AMR – Hospital Insight Series, US Data, August 2011Hawk Partners - Target Product Profile Research with 29 US Physicians. Commissioned by Trius, Sept 2011 14
  15. 15. Bayer Strategic Collaboration for Asia-Pacific andEmerging Markets Exclusive license to develop andRetains rights to Obtains key asset for commercialize tedizolid in Asia,largest commercial largest therapeutic Africa, Latin America and the Middle area in licensedopportunity East (ex-Korea) territoryTrius leads Responsible for alldevelopment of global $25M upfront independent regionalclinical studies development $69M in development, regulatoryEnables early and commercial milestones Responsible for allexecution of ex-U.S. marketing activities incommercial strategy its territory 25% of the future development costs in ABSSSI and pneumonia Double digit royalties 15
  16. 16. Gyrase-B Program: Novel Class of Broad Spectrum Antibiotics £  Funded through Phase 1 by $28MM NIAID Contract £  Lead molecules have potent activity against gram-negative and gram-positive bacterial pathogens £  including MRSA, ESBL strains, Pseudomonas, Acinetobacter & Klebsiella (including NDM1) £  Efficacy demonstrated in multiple animal models £  Lung, urinary tract, thigh, septicemia £  Clean nonclinical toxicity and no CYP450 interactions £  Including dog CV telemetry study up to 10x efficacious drug exposure. No effect on all CV parameters (Qtc, HR, BP etc.). £  Clinical studies expected to start 2012 16
  17. 17. Evolution of MICs in Lead Series Against Gram Negativeand Gram Positive Pathogens Antibacterial Potency MIC (µg/mL) Adverse Event 1491 1710 1722 1852 S. aureus 0.008 0.008 0.008 0.008 S. pneumoniae 0.008 0.008 0.008 0.004 E. coli (wt) 0.25 0.13 0.25 0.13 K. pneumoniae (MDR) 2 2 2 1 A. baumannii 0.50 0.25 0.50 0.25 P. aeruginosa (wt) 4 2 1 0.50 Gram + Gram — 17
  18. 18. MIC90 of GyrB/ParE Development Candidate vsComparators against Gram-Positive Pathogens MIC90  of  TR-­‐1852  vs.  G+  isolates   >16   16   >4   >4   >4   14   12   8   MIC90  (µg/ml)   4   10   4   2   8   ciprofloxacin   6   0.25   1   linezolid   4   2   0.5   vancomycin   2   ≤0.001   ≤0.001   daptomycin   0   0.03   TR-­‐1852   Number of isolates is shown in parentheses 18
  19. 19. MIC90 of GyrB/ParE Development Candidate vsComparators against Gram-Negative Pathogens ** * *** *  Includes  ESBL  isolates   **  includes    MDR,  ESBL  isolates   ***  includes  ESBL,  NDM-­‐1,  KPC-­‐2,  KPC-­‐3,  and  randomly  selected  isolates   19
  20. 20. P. aeruginosa MIC90 Results for TR-1852 (50 strains) P.  aeruginosa  MIC90  panel   100   MIC90 = 1 µg/mL 90   80   70  %  strains  cumulaKve   60   1852   Cefepime   50   Cipro   Gent   40   Imipenem   30   20   10   0   0.06   0.125   0.25   0.5   1   2   4   8   16   32   64   128   MIC value µg/mL 20
  21. 21. E. coli Mouse Urinary Tract Infection Model Mouse Ascending UTI Model − E. coli Drugs Dosed IV 10 mg/kg/day 7 Bladder Average Log10 CFU/g Tissue 6 Kidney 5 4 3 2 1 0 C 1852 Levo C 1852 Levo 21
  22. 22. Safety Summary: Clean In-Vitro & In-Vivo to Date£  No CYP450 inhibition – low drug-drug interaction potential£  No Relevant Off-Target Enzyme Activities – bacterial selective£  No Genotoxicity Signals (human cell line)£  Clean in Dog Cardiovascular Study – all parameters including QTc£  Single Dose MTD in Mice & Rats >100 mg/kg£  Rat Chronic 14 Day Dose NOAEL ~50 mg/kg* –  Therapeutic Margin Estimate (~13x)***Pending histopathology, based on gross necropsy, blood biochemistry & hematology**AUC @ NOAEL dose/AUC @ efficacious dose 22
  23. 23. Capitalization Cash & Equivalents (at 9-30-11) $70MM Long Term Debt (at 9-30-11) $0MM Federal Contracts Awarded $60MM Shares Outstanding 38.6MM Market Capitalization (at 2-10-12) $211MM Cash Runway* Q3 2013 * Assumes initiation of global HAP study in 2013 and no additional partnerships 23
  24. 24. Upcoming Goals §  Potential European partnership §  Regulatory agreement enabling initiation of Phase 3 pneumonia study §  IND filing for Gyrase clinical candidate §  Completion of enrollment for 113 Phase 3 ABSSSI trial 24
  25. 25. Best-in-Class Anti-Infectives