26
1 The Future of Anti-Infectives November 14, 2012 2012 Credit Suisse Healthcare Conference

Trius nov12confpresentation

Embed Size (px)

Citation preview

Page 1: Trius nov12confpresentation

1

The Future of Anti-Infectives

November 14, 2012

2012 Credit Suisse Healthcare Conference

Page 2: Trius nov12confpresentation

2

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.

Page 3: Trius nov12confpresentation

3

Investment highlights

• Focus on novel antibacterial compounds for serious infections

• Tedizolid completing confirmatory ESTABLISH-2 Phase 3 trial

– ESTABLISH-1 trial met all primary and secondary endpoints

– De-risked asset with high efficacy & superior safety

• Bayer collaboration to generate additional clinical data

• Broad spectrum gyrase program entering clinic in 2013

• Significant potential near-term catalysts

Page 4: Trius nov12confpresentation

4

Pre-clinicalPre-clinical Phase 1Phase 1 Phase 2Phase 2 Phase 3Phase 3

Tedizolid Phosphate

Oral

IV/Oral

HAP/VAP IV

Bacteremia IV/Oral

GyrB/ParE

Gram- Infections IV

ABSSSI

Trius pipeline

Page 5: Trius nov12confpresentation

5

Strong growth in MRSA* treatment days

Source: AMR (United States market) *methicillin-resistant Staphylococcus aureus

Total hospital treatment days in US

(Vancomycin, Linezolid and Daptomycin)

2005 2006 2007 2008 2009 2010

16.7M

21.1M 21.0M 22.2M

24.0M 25.8M

Page 6: Trius nov12confpresentation

6

Increasing resistance to vancomycin

Resistance of MRSA against Vancomycin

Source: Theravance Company Report, April 2010 & AMR (United States market).

AMR - Hospital Insight Series, US Data, August 2011

2.8% 3.3%

3.8%

9.2%

11.1%

2005 2006 2007 2008 2009

Page 7: Trius nov12confpresentation

7

Physician attitude on vancomycin is changing

Source: AMR - Hospital Insight Series, US Data, August 2011

51% 39%

9%

6% 8%

48%

CubicinZyvoxVancomycin

Percent of physicians reporting decreased or increased prescriptions

Less

M

ore

Page 8: Trius nov12confpresentation

8

Tedizolid: highly differentiated oxazolidinone

Tedizolid Linezolid (Zyvox)

Week 1 Week 2 Week 1 Week 2

Page 9: Trius nov12confpresentation

9

Strong product profile

Attribute Linezolid Vancomycin Daptomycin Tedizolid

IV/Oral

In-Vivo Bactericidal

Active in Lung

Infections

Once Daily

Treatment

Short Course of

Therapy

Generic

X

X

X

X

X

X X

X

X

Page 10: Trius nov12confpresentation

10

Tedizolid Attributes Align Well With Market Need

Source: Datamonitor.

Key unmet needs for antibacterials

Activity against Gram-

negative pathogens

Activity against

resistant pathogens

Shorter treatment

courses

Lower cost of

therapy

Improved safety and

tolerability profile

Oral/IV switch

Incre

asin

g l

evel

of

imp

ort

an

ce

Tedizolid

Page 11: Trius nov12confpresentation

11

29%

38%

9%11%

5% 6%3%

-12pp

-3pp

-10pp

-2pp -2pp 0pp

-25%

50%

Tedizolid Vancomycin Cubicin Zyvox Teflaro Tygacil Other

% P

ati

en

ts P

res

cri

be

d

Future Usage

Change from Current

Tedizolid Profile Shifts Share From Both Vancomycin and Zyvox

D13: Now, please think about your prescribing for these same patients if Product X were also available, considering the fact that trials would be

ongoing for hospital-acquired pneumonia at the time Product X becomes available.

Original

Allocation 50% 12% 21% 7% 8% 3%

Allocation of Common Agents for Treatment of MRSA Overall (n=165)

Trius Quantitative Study, 2012

Page 12: Trius nov12confpresentation

12

Generic Linezolid Has a Modest Impact on Tedizolid

29%

40%

7%

11%

5% 5%3%

23%

14%

38%

7% 6%5% 5% 2%

0%

50%

Tedizolid GenericLinezolid Vancomycin Cubicin Zyvox Tefla

r

o Tygacil Other

% P

hys

icia

ns

Impact of Generic Linezolid on Treatment of MRSA ABSSSI (n=165)

BrandedZyvox:TedizolidCostperDayofTherapySameasZyvox

GenericLinezolid:TedizolidCostperDayofTherapySameasZyvox

C2: Now, please think about your prescribing for these same patients if Product X were also available, using your previous answers as a

reference.

E3: How would the availability of generic linezolid impact your use of Product X in your next 20 MRSA ABSSSI patients at that point? Please

assume that the price of Product X would be the same as branded Zyvox (linezolid) per day. Trius Quantitative Study, 2012

Page 13: Trius nov12confpresentation

13

Phase 3 trial design: ESTABLISH-1 (oral), ESTABLISH-2 (IV/PO)

2o

EMA

1o

EMA

Tedizolid

Linezolid

1x 200mg

2x 600mg

n=667

1o

FDA

2o

FDA

Placebo

Post-Treatment Evaluations

END-POINTS FOR GLOBAL REGISTRATION

Safety Analysis

Non-inferiority trail design vs Linezolid

Page 14: Trius nov12confpresentation

14

1o endpoint achieved: current & expected guidance

Lesion Criteria (Area)

No increase from baseline

Fever Criteria (Temperature)

Measurements required

Lesion Criteria (Area)

≥20% reduction from baseline

Fever Criteria (Temperature)

Excluded*

79.5%

78.0%

79.4%

76.1%

Current Guidelines* Expected Guidelines**

Tedizolid

Linezolid

* Primary endpoint as agreed to under Study 112 and 113 SPA

** FNIH recommendations to FDA: ABSSSI Docket ID: FDA-2010-D-0433

Page 15: Trius nov12confpresentation

15

Significantly lower impact on platelets

2.3% 4.9%

9.2%*

14.9%*

TedizolidLinezolid

75% - 100% LLN (112-150K/μL)

<75% LLN (<112K/μL)

* Statistically significant difference

Page 16: Trius nov12confpresentation

16

Phase 3: lower rates of adverse events

TEAE = Treatment Emergent Adverse Event

Gastrointestinal AEs incl. diarrhea, nausea, vomiting & dyspepsia

* Statistically significant difference: p = 0.004

43.3%

31.0%

25.4%

40.8%

24.2%

16.3%*

Any TEAE Drug-Related TEAE GI Disorder

Linezolid Tedizolid

Page 17: Trius nov12confpresentation

17

Clinical studies show DDI advantage over linezolid

Phase 1 - Tyramine:

• Tedizolid similar to placebo. No dietary restrictions necessary

• Linezolid induces 5-fold increase in tyramine sensitivity

Phase 1 - Noradrenergic:

• Tedizolid similar to placebo. No increase in mean blood pressure

• Linezolid induces 113% increase in mean blood pressure

No monoamine oxidase mediated interactions

Page 18: Trius nov12confpresentation

18

Tedizolid showed no interactions with SSRIs

Mouse Head Twitch Study

13 Tedizolid Placebo

13

(30X human exposure)

Linezolid

69

(1X human exposure)

Page 19: Trius nov12confpresentation

19

Differences between ESTABLISH-1 and 2

• IV to oral switch: minimum 1-day of IV dosing

– Slightly higher exposure for tedizolid IV (~8%)

– No differences expected in efficacy or safety

• Patient demographics

– ESTABLISH-1: 80% US; ESTABLISH-2: 50% US

• X-US patients have statistically larger lesions (ESTABLISH-1)

• Tedizolid response rate vs linezolid enhanced in larger lesions

Page 20: Trius nov12confpresentation

20

Rapid efficacy in severe cellulitis

0 cm2 0 cm2 337cm2

Screen Day 3 Day 10

Page 21: Trius nov12confpresentation

21

High cellulitis efficacy at both FDA + EMA endpoints*

*Clinical cure at days 17-21

98%

82%

91%

78%

EMA EndpointFDA Endpoint

Tedizolid

Linezolid

Difficult to treat deep tissue infections

Page 22: Trius nov12confpresentation

22

Tedizolid on track toward market

* With Priority Review afforded by the GAIN Act

• ESTABLISH-2 enrollment completion: Q4 2012

• ESTABLISH-2 top line data: H1 2013

• ABSSSI NDA filing: H2 2013

• Potential NDA approval: mid 2014*

Page 23: Trius nov12confpresentation

23

Gyrase: broad spectrum antibacterial program

• Potent activity against gram negative and gram positive pathogens

• Novel chemical class, broad IP rights

• Funded through Phase 1 from 5-year $28M NIAID contract

• Expected to enter clinic 2013

• First data roll out at ICAAC (9/12): 14 posters, 1 oral presentation

Page 24: Trius nov12confpresentation

24

Strong balance sheet

Cash and Marketable Securities (9/30/12) $71M

Long-term Debt (9/30/12) $0M

Shares Outstanding (11/1/12) 39.4M

Page 25: Trius nov12confpresentation

25

Investment highlights

• Focus on novel antibacterial compounds for serious infections

• Tedizolid completing confirmatory ESTABLISH-2 Phase 3 trial

– ESTABLISH-1 trial met all primary and secondary endpoints

– De-risked asset with high efficacy & superior safety

• Bayer collaboration to generate additional clinical data

• Broad spectrum gyrase program entering clinic in 2013

• Significant potential near-term catalysts

Page 26: Trius nov12confpresentation

26

The Future of Anti-Infectives

November 14, 2012

2012 Credit Suisse Healthcare Conference