CONFIDENTIAL

Accelerating Drug Development through Drug & Companion Diagnostic Co-Development

Mark Roberts PhD Director, Diagnostics Development

Covance Central Laboratory Services

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Our Environment Today

Pressured Cycle of Dependencies

The pressures are the same across the marketplace… why are some companies succeeding while others continue to struggle?

Patients

Pharma

Sites CMOs, etc

CROs

R&D Cost Pressures

Funding Needed For Innovation

TargetScarcity

ConsumerPrice

Pressure

Regulations

Patent Cliffs

Healthcare Models

PartnershipsEmerging Markets

PricePressures

Market Realities

+

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Drugs Don’t Work for all Patients

Antidepressants

Cancer Drugs

Diabetes Drugs

Arthritis Drugs

Asthma Drugs

Source : Personalized Medicine Coalition

Estimated $350 billion wasted in 2011

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The Future Is ……… Personalized Medicine

Providing

the right treatment

for the right person

at the right time

in the right dose

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The New Drug Development Paradigm

Personalized Medicine

Companion Diagnostics are integral to the new Personalized Medicine paradigm

Personalized Medicine

Targeted Therapeutic Biomarker

An “in vitro” device that provides information that is essential for the safe and effective use of a corresponding therapeutic product” Source : US Food & Drug Administration

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• Many ‘Companion’ Diagnostics developed after a drug is on market

• Retrospective validation using banked samples: potential IRB / informed consent issues / new trial

• Drug manufacturer unlikely to change labeling unless required to do so by FDA : may consider extra testing / expense to be a detriment to clinical use

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CDx: Historical Perspective

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• Better understanding of the genetic and polypharmacy causes of adverse reaction

• Increasing utility of pre-dosing patient stratification through understanding of ‘pathway’ targets

• Targeted therapy improves clinical outcome – Enhanced safety profile : and reduced liability claims?– Enhanced therapeutic efficacy

• Enhanced healthcare economics

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CDx: A New Perspective

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FDA :Drug & CDx Co-Development

“In most circumstances, if use of an in vitro companion diagnostic device is essential for the safe and effective use of a therapeutic product,

the IVD companion diagnostic device and therapeutic product should be approved or

cleared contemporaneously by FDA for the use indicated in the therapeutic product labeling,”

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Drug / CDx co-development successes

Targets ALK mutation in NSCLC

Occurs in 4% - 5% of patients

Tumor shrinkage in 83% of ALK +ve patients (4-5% of NSCLC)

Drug and CDx (Abbott) launched in 2011

Targets V600E mutated BRAF in advanced melanoma

Occurs is ca. 60% of mm patients

Drug and device approved together in 2011

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QUESTION:

What role do you see CROs playing in the development of companion diagnostics over the coming years?

Voice of the Client Survey : 2011

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• Clients had not considered CROs role – Dx focused• Clients continue to define their needs (lack clarity)• Clients voiced the need for:

– Capabilities: Fill the gap where clients lack ability or expertise

– Flexibility: Resource flexibility under an outsource model– Integration: Providers able to integrate services are

valuable– CDx vision & direction: Clients are struggling and need a

partner with vision AND capabilities to guide their path forward

Summary of VOC Feedback

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TodayYesterday

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Charting a New Model

Diagnostic

Devices

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Drugs & Biologics

Diagnostic

Devices

The future of Healthcare will require a new mindset:Products and industries once considered separate and distinct

move to integration

Drugs & BiologicsIntegrated with

Diagnostics

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Why Rx / CDx Co-Development?

Potential to:

enhance therapeutic efficacy

increase safety & reduce risk

Speed-up development process

improve trial design

increase commercial success

improve trial design

enhance safety profile

enhance therapeutic efficacy

accelerate trial outcome

Increase commercial success

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Hurdles Under the New Model

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Understanding the diagnostic industry

Choosing a Diagnostics Partner

Complex Trial Execution

Managing the co-development process

Regulatory uncertainty around CDx

Intellectual property issues

Success Begins with the Right Partners

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Global Diagnostics Market

• $ 44 billion in 2011• > 5% CAGR to $62 billion in 2016

• Largest Players

– Roche $ 7.4 billion– Siemens $ 5.2 billion – Danaher $ 4.4 billion– Abbott $ 4.3 billion

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Companion Diagnostics Market

World Companion Diagnostics Market 2010-2021 ($Billions)

(incl. the sales of testing kits and testing service revenues).

“Companion Diagnostics World Market 2011-2021”, VisionGain (2011)

1.3 1.6 1.9 2.32.8

3.44.2

5.2

6.4

7.8

9.5

11.4

0.0

2.0

4.0

6.0

8.0

10.0

12.0

2010

2011

2012

2013

2014

2015

2016

2017

2018

2019

2020

2021

Year

Sal

es (

$B)

CAGR 21.6%

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• Nature of Diagnostic Target (biomarker)• Required Turn around Time of Result• Channel to Market• Economics

Considerations in Choice of Commercial Partner

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Rx / CDx Co-Development Value for Stakeholders

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Stake Holder Benefit

BioPharma Companies

• Reduced Drug Development Costs• Improved safety-efficacy profile of drug• Increased cost effectiveness of drug• Accelerated regulatory approval• Competitive advantage (differentiated therapeutic)• Rescued drugs• Premium pricing for “targeted” drug

Dx Companies

• New market opportunities• Develop new partnership with Pharma companies• Premium pricing for CDx• Increase distribution of their product

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Hurdles Under the New Model

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Understanding the diagnostic industry

Choosing a Diagnostics Partner

Complex Trial Execution

Managing the co-development process

Regulatory uncertainty around CDx

Intellectual property issues

Success Begins with the Right Partners

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Leveraging Complementary Competencies

CRO Dx Partner

Sole focus of supporting Clinical Development

Focus on delivering innovative Dx products

Experienced collaborator for novel assays, technologies and

Dx devices

Experienced in assay development & technology

Complementing competencies•Technical agility•Global reach

•Commitment to quality•Experience in Project Management

Complementing competencies•Deep technical proficiency

•Limited reach•Experience in product development

•Experience in Regulatory Submission

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CDx

Rx / CDx Co-Development

Strategic Agility• Medical Device Partner

• Technology/Platform

• Global Reach

• Intellectual Property

• Regulatory Path

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IVD

Pharma

Par

tner

ship P

artnership

Partnership

Unbiased approach enables a straightforward path to commercialization

CRO

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Technology leadership

Global Execution

Sample Handling / Storage Expertise

Regulatory Experience

Strong Commercial Partnerships

CRO Partner Expertise Required

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(4) Needs a partner for IVD manufacturing and global commercialization

(1) Biomarker identification & CDx development

(3) Already has an assay development/ commercialization partner

(2) Assay development and validation

(5) Requires single strategic partner with broad capabilities/expertise

Drug Development

Biomarker/CDx Development

Discovery Pre-Clinical Phase I Phase II Phase IIINDA

Submission

Biomarker Discovery & Development

CDx Assay Feasibility

CDx Development & Validation

Regulatory Submission & CDx Launch

Flexibility and access along the continuum is critical

Your Partnership Needs

CDx Development Stages

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Examples of CDx Validation and Rx / CDx Co-Development

Mark Roberts PhD Director, Diagnostics Development

Covance Central Laboratory Services

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Collaboration on a CDx Clinical Validation

Clinical Candidate

Proprietary CDx

CommercialPlatform

USAEurope

Asia-PacChina

Platform expanded for global clinical studies

Collaborative assay evaluation & troubleshooting

CDx validation

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Dx Partner

Pharma Client

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Global Reach & Data Combinability

Global Consistency

1 instrument 1 technologist 1 point in time Same reagents globally

Fewer Laboratories = Higher Quality Data

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Points to consider in Rx / CDx Co-Development

• CDx manufacturer distinct from Rx client

• Parties may have different priorities

• All parties need to be at the table

• Not all assays are created equal :

● Assay must be very robust in order to be ‘plug and play’

● Development assays require more attention

Rx / CDx : A different business model

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CDx

Rx / CDx Co-Development

Strategic Agility• Medical Device Partner

• Technology/Platform

• Global Reach

• Intellectual Property

• Regulatory Path

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IVD

Pharma

Par

tner

ship P

artnership

Partnership

Unbiased approach enables a straightforward path to commercialization

CRO

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“Delivering on the promise of Personalized Medicine requires Precision Co-Development”

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Thank You

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