Trius Therapeutics Bio CEO & Investor Conference

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Best-in-Class Anti-Infectives

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Transcript of Trius Therapeutics Bio CEO & Investor Conference

Page 1: Trius Therapeutics Bio CEO & Investor Conference

Best-in-Class Anti-Infectives

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Forward Looking Statements

Statements made in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding Trius’ ability to successfully complete its ongoing clinical trials and development programs, the expected timing for reporting of top-line data for the TR701-113 study, Trius’ ability to obtain regulatory approval for tedizolid, market penetration and acceptance of tedizolid and the initiation of clinical studies for Trius’ Gyrase B program. Risks that contribute to the uncertain nature of the forward-looking statements include: Trius’ future preclinical studies and clinical trials may not be successful; changes in regulatory requirements in the United States and foreign countries may prevent or significantly delay regulatory approval of Trius’ products; Trius may change its plans to develop and commercialize its product candidates; the FDA may not agree with Trius’ interpretation of the data from recently-completed clinical trials of tedizolid; Trius may decide, or the FDA may require Trius, to conduct additional clinical trials or to modify Trius’ ongoing clinical trials; Trius may experience delays in the commencement, enrollment, completion or analysis of clinical testing for its product candidates, or significant issues regarding the adequacy of its clinical trial designs or the execution of its clinical trials, which could result in increased costs and delays, or limit Trius’ ability to obtain regulatory approval; the third parties with whom Trius has partnered with for the development of tedizolid and upon whom Trius relies to conduct its clinical trials and manufacture its product 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 or commercialization; Trius’ may be unable to obtain and maintain intellectual property protection for its product candidates; the loss of key scientific or management personnel; Trius’ ability to obtain additional financing; and the accuracy of Trius’ estimates regarding expenses, future revenues and capital requirements. These and other risks and uncertainties are described more fully in Trius’ most recent Form 10-K, Forms 10-Q and other documents filed with the United States Securities and Exchange Commission, including those factors discussed under the caption “Risk Factors” in such filings. All forward-looking statements contained in this press release speak only as of the date on which they were made. Trius undertakes no obligation to update such statements to reflect events that occur or circumstances 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 for the offering to which this communication relates. Before you invest, you should carefully review the prospectus supplement and the accompanying prospectus, together with the information incorporated by reference therein, as well as any free writing prospectus that Trius or the underwriters provide you in connection with the offering, for more information about Trius and the offering. Trius files annual reports, quarterly reports and other documents with the Securities and Exchange Commission. You should read the documents we have filed with the Securities and Exchange Commission for more complete information about Trius. You may get these documents for free by visiting EDGAR on the Securities and Exchange Commission web site at www.sec.gov, or by visiting the Trius Therapeutics’ website at www.triusrx.com.

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Record of Successful Execution

Bayer Deal

Asia-Pacific/Emerging Markets •  A strong partner with comprehensive development

and commercial infrastructure in Asia •  Accelerates development in skin and lung infections

globally

Enrollment on track •  Top line data expected early 2013 113 Trial Enrolling

All Efficacy and Safety Objectives Achieved •  Unsurpassed efficacy & improved safety with shorter

course of therapy and better convenience •  Successful efficacy and safety results triggered $5M

milestone payment from Bayer

112 Trial Successful

Funded through Phase 1 by $28M NIAID Contract •  Broad spectrum potency goals achieved •  IND enabling studies underway

GyrB Gram Program

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Trius Pipeline

Tedizolid Development Program Matched with Market Opportunity

Product and Target Indications

Dosage Form

Discovery / Pre-Clinical Phase 1 Phase 2 Phase 3

Tedizolid Phosphate ABSSSI

Tedizolid Phosphate HAP/VAP

Tedizolid Phosphate Bacteremia

GyrB/ParE Drugs for Gram-Negative Infections

Marine Natural Products Drugs for Gram-Positive & Gram-Negative Infections

Oral

IV/Oral

IV/ Oral

IV/ Oral

IV

IV

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Zyvox (Linezolid) $437MM

Cubicin (Daptomycin)

$114MM

Vancomycin (Generic) $137MM

Tygacil (Tigecycline)

$10MM

U.S. Sales 2005 – $700MM

Source: Company Reports / IMS-National Sales Perspectives; *=Estimate

Tygacil (Tigecycline)

$148MM

Vancomycin (Generic) $186MM*

Cubicin (Daptomycin)

$699MM

Zyvox (Linezolid) $640MM

Vibativ (Telavancin)

$10M*

U.S. Sales 2011 - $1.68B

18% CAGR in Branded Sales from 2005-2011 Each market share point for a branded agent is worth $50MM

Market has grown to over $2.5B globally ($1.5B in USA) with declining Vancomycin susceptibility contributing to growth of branded agents

Gram Positive Market Has Doubled in Value

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Tedizolid Combining the Strength of Current Products

Attribute Linezolid Vancomycin Daptomycin Tedizolid

IV/Oral

In-Vivo Bactericidal

Active in Lung Infections

Once Daily Treatment

Short Course of Therapy

Generic

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50%

80%

60%

40%

20%

40%

10%

0% 20% 40% 60% 80% 100%

Very Likely Moderately Likely Not At All Likely

Market Research Indicates Formulary Acceptance For Core Indications

Priced at Parity Per Course of Therapy to Zyvox

Priced at Significant Premium Per Course of Therapy to Zyvox

cSSS

i Pn

eum

onia

(H

AP/

VAP)

En

doca

rdit

is /

Ba

cter

emia

30%

50%

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40%

20%

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30%

30%

30%

0% 20% 40% 60% 80% 100%

Very Likely Moderately Likely Not At All Likely

cSSS

i

PG Decision Metrics market research of 10 Formulary Directors & 10 HMO/PBMs. Commissioned by Trius in 2009

Based upon the response of 10 HMO/PBMS and 10 Formulary Directors

Pneu

mon

ia

(HA

P/VA

P)

Endo

card

itis

/

Bact

erem

ia

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…and Good Placement of the Oral Formulation in the Outpatient Setting

Priced at Parity Per Course of Therapy to Zyvox

Priced at Significant Premium Per Course of Therapy to Zyvox

0%

90%

10%

0%

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Tier 1 Tier 2 Tier 3

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Tier 1 Tier 2 Tier 3

PG Decision Metrics market research of 10 HMO/PBMs. Commissioned by Trius in 2009.

Based upon the response of 10 HMO/PBMS

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4-Days Placebo 6-Days Tedizolid QD

Tedizolid Phosphate Phase 3 Study Design: Oral (112) and IV/Oral (113) Trials Under SPA

Post Treatment Evaluations

Patient Screening

Randomization

FDA and EMA Endpoints for Global Registration

10-Days Linezolid BID

Safety Analyses

Baseline

EMA Primary

Endpoint at PTE

FDA Primary Endpoint 48-72 hrs from Baseline

EMA Secondary Endpoint

LFU

FDA Secondary Endpoints

at EOT

667

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Primary Outcome at 48-72 hour visit

112 SPA Primary Endpoint No increase in lesion area from baseline*

Temperature measurements required within 24 hrs of

48-72 hr visit* 79.5% 79.4%

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 linezolid

No increase in lesion area from baseline Temperature excluded** 87.0% 85.4%

FNIH Primary Endpoint ≥ 20% reduction of lesion are from baseline**

Temperature excluded** 78.0% 76.1%

Primary Outcome: All Current and Contemplated Trial 112 Primary Endpoints Achieved in Pre-Specified Analyses

Lesion Criteria Fever Criteria Tedizolid (200 mg QD 6 days)

Linezolid (600 mg BID 10 days)

* Primary endpoint as agreed to under Study 112 and 113 SPA ** FNIH recommendations to FDA: ABSSSI Docket ID: FDA--2010--D--0433

Treatment

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Secondary Outcome at EOT or PTE

112 SPA Clinical Response at EOT*

(Day 11)

Early clinical failures carried forward to EOT*

69.3% (ITT) 71.9% (ITT)

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.

Clinical Response at EOT* (Day 11)

Early clinical failures not carried forward to EOT**

80.7% (ITT) 80.9% (ITT)

87.5% (CE) 87.1% (CE)

113 SPA Clinical Response at EOT*

(Day 11)

Early clinical failures not carried forward to EOT** and

presence/absence of patient reported pain at EOT excluded*/**

87.0% (ITT) 87.8% (ITT)

94.5% (CE) 95.1% (CE)

Secondary Outcome Criteria Tedizolid (200 mg QD 6 days)

Linezolid (600 mg BID 10 days)

Treatment

* Primary and secondary endpoints as agreed to under Study 112 SPA ** Consistent with FDA draft ABSSSI Guidance for Industry (August 2010)

Secondary Outcomes: Tedizolid Demonstrates Comparable Efficacy with Shorter Course of Therapy

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* Gastrointestinal AEs include: Diarrhea, Nausea, Vomiting and Dyspepsia ** Statistically significant (p=0.004).

No Unexpected Safety Signals •  Liver enzymes/function tests •  QTc

Adverse Event Tedizolid (200 mg QD 6 Days)

Linezolid (600 mg BID 10 Days)

Any Treatment Emergent Adverse Event (TEAE) 40.8% 43.3%

Any Drug Related TEAE 24.2% 31.0%

Gastrointestinal Disorders* 16.3%** 25.4%

Tedizolid was Well Tolerated with a Favorable AE Profile Compared to Linezolid

Tedizolid had a numerically lower rate of drug-related treatment emergent adverse events (TEAE) and a statistically significant lower number of gastrointestinal adverse events

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* Statistically significant (p=0.038)

Percent of Patients with Value below the Lower Limit of Normal (LLN)

Hematology Parameter Tedizolid (200mg QD 6 days)

Linezolid (600mg BID 10 days)

Platelets* Below LLN 9.2% 14.9%

Platelets – Substantially Abnormal Value (<75% LLN)

2.3% 4.9%

Hematology: Tedizolid Had Significantly Lower Impact on Platelets than Linezolid

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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 2009 AMR – Hospital Insight Series, US Data, August 2011 Hawk Partners - Target Product Profile Research with 29 US Physicians. Commissioned by Trius, Sept 2011

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Retains rights to largest commercial opportunity Trius leads development of global clinical studies Enables early execution of ex-U.S. commercial strategy

Obtains key asset for largest therapeutic area in licensed territory Responsible for all independent regional development Responsible for all marketing activities in its territory

$25M upfront $69M in development, regulatory and commercial milestones 25% of the future development costs in ABSSSI and pneumonia

Exclusive license to develop and commercialize tedizolid in Asia,

Africa, Latin America and the Middle East (ex-Korea)

Double digit royalties

Bayer Strategic Collaboration for Asia-Pacific and Emerging Markets

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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

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Evolution of MICs in Lead Series Against Gram Negative and 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 —

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MIC90 of GyrB/ParE Development Candidate vs Comparators against Gram-Positive Pathogens

TR-­‐1852  

daptomycin  

vancomycin  

linezolid  

ciprofloxacin  

0  

2  

4  

6  

8  

10  

12  

14  

16  

≤0.001  ≤0.001  

0.03  

8  

0.5   2  

>16  

0.25   1  

4  

2  4  

>4   >4   >4  

MIC

90  (µ

g/ml)  

MIC90  of  TR-­‐1852  vs.  G+  isolates  

Number of isolates is shown in parentheses

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*  Includes  ESBL  isolates  **  includes    MDR,  ESBL  isolates  ***  includes  ESBL,  NDM-­‐1,  KPC-­‐2,  KPC-­‐3,  and  randomly  selected  isolates  

* **

***

MIC90 of GyrB/ParE Development Candidate vs Comparators against Gram-Negative Pathogens

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P. aeruginosa MIC90 Results for TR-1852 (50 strains)

MIC value µg/mL

0  

10  

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100  

0.06   0.125   0.25   0.5   1   2   4   8   16   32   64   128  

%  strains  c

umulaK

ve  

P.  aeruginosa  MIC90  panel  

1852  

Cefepime  

Cipro  

Gent  

Imipenem  

MIC90 = 1 µg/mL

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0

1

2

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C 1852 Levo C 1852 Levo

Aver

age

Log 1

0 CF

U/g

Tis

sue

E. coli Mouse Urinary Tract Infection Model

Mouse Ascending UTI Model − E. coli Drugs Dosed IV 10 mg/kg/day

Bladder

Kidney

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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

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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

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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

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Best-in-Class Anti-Infectives