Immune-MediatedInflammatory Diseases

CLINICAL DEVELOPMENT SERVICES

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The new inflammation paradigm

Solutions for your success

An interconnected perspective

High-quality data—forbetter answers, sooner

05Your partner for a new IMID paradigm

Table of contents

The new inflammationparadigm Growing markets, increasing opportunitiesIMIDs: Immune-Mediated Inflammatory Diseases

Global impact of IMIDs

A new understanding of inflammation has changed thedrug development landscape for several major diseases affecting millions of people worldwide. These include:

• Asthma

• Chronic obstructive pulmonary disease (COPD)

• Psoriasis

• Rheumatoid arthritis (RA)

• Systemic lupus erythematosus (Lupus)

• Inflammatory bowel disease (IBD) (includes ulcerative colitis and Crohn’s disease)

Drug development has traditionally focused on treating the symptoms of each disease separately, with limited integration of research and clinical trial design.

Today, the discovery that these conditions share a common underlying immune system response mechanism is driving a new, interconnected approach:targeting these immune-mediated inflammatory diseases(IMIDs) as a unified area focused on mechanism-baseddisease modification.

Growing markets, increasing opportunities

IMIDs represent a significant and escalating global threatin terms of morbidity, mortality, and quality of life.

This represents a growing opportunity to develop newtreatments designed to modify these disease states; enternew markets; and expand market share.

Covance has aligned our medical, scientific, and operationalresources to support your drug development needs underthis new IMID paradigm.

Immune-Mediated InflammatoryDiseases

Asthma Psoriasis Rheumatoidarthritis

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GlobalImpact:

Covance global IMID experience

RA

COPD

IBD

Psoriasis

Asthma

Lupus

Asthma affects 15% of theglobal adult population.Source: World Health Organization.

Psoriasis affects 2-5% of the global population.Source: World Psoriasis Day consortium.

The total annual cost of RA is estimated at €45 billion inEurope and $54 billion in theUnited States.Source: Kobelt G. in Rheumatoid Arthritis (2009).

• 112 IMID clinical trials since 2007• 6,101 sites worldwide• 61,975 patients

Solutions toyour IMID drugdevelopmentchallenges

Solutions for your successIntegrated capabilities aligned with your needsTo gain competitive advantage in the IMID drug developmentmarket, you need to overcome the operational challenges that can slow your progress and reduce the possibilities for understandingyour compound's safety and efficacy.

Covance’s integrated capabilities span the full range of services, resources, and expertise you need to conduct effective and cost-efficient IMID studies that enable you to make better decisions faster—based on high-quality primary data.

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Placebo response rates

Investigator interest

Site performance

Patient retention

Objective endpoints

Patient compliance

PRO reporting

Challenge: If your trial is conducted at a low-performing site, it can have a detrimentaleffect on your study timelines, data quality,and clinical ROI.Covance solution:Using our Xcellerate®

platform, we will provide customized recommendations for selecting and monitoringthe most appropriate site, investigator, and location to deliver patient enrollment—helping to reduce the drain on your resources,decrease your trial timelines, and enhance your clinical ROI. With our robust network of clinical trial sites and investigators, we can also quickly deploy standby sites to keepyour trial on track, even when unexpectedproblems arise.

Challenge: High placebo response rates observed in IMID trials (e.g., psoriasis 14-20%; RA 30%; ulcerative colitis >30%)can mask treatment effects, putting the success of your drug at risk. Covance solution:High placebo responserates in IMID trials are often related to "eligibility creep"—a significant risk in trialswhen disease severity is evaluated using subjective self-reporting or investigator assessment methods. Covance helps you reduce placebo response rates through carefulstudy evaluation, investigator training, and bymonitoring investigator and site performanceusing our Xcellerate® platform.

Challenge: Patient reported outcomes play a crucial role in the differentiation of new products in the crowded IMID market. Improper selection of PROs can result inmissed opportunities for differentiation, PROlabel claims, and accurate patient assessment. Covance solution: Drawing on our combinedGHEOR and clinical development experienceand resources, Covance offers an integrated approach to PRO strategy and management.We help indentify PROs which are targeted at creating differentiation and guide our clientsthrough the PRO label claim process. We alsooffer PRO management in the clinical trials toensure translation and ePRO readiness for anyclinical trial scenario.

Challenge: Because many new IMID therapies are injectable biologics, self-administration can be challenging for patients, leading to noncompliance and/or reduced drug efficacy. Covance solution: As your clinical trial partner, we ensure that your study subjects areproperly trained and monitored throughoutthe screening period and entire trial.

Challenge: The use of objective endpointmeasurements in IMID clinical trials (e.g., radiographic imaging (RA) and lesion photographs (psoriasis)) can enhance the precision and accuracy of your data, but they often require specializedassessment techniques.Covance solution:Leveraging our imagingexperience in oncology studies, Covance canperform a centralized review and analysis ofimages obtained for your objective endpointsto reduce data variability.

Challenge: In the highly competitive IMIDclinical trial arena—where the demands oninvestigators are high, the pool of subjects is limited, and study durations are oftenlong—investigator interest may be lackingand difficult to maintain.Covance solution: Covance will providecustomized recommendations for recruitingand retaining qualified investigators. Wehave the experience needed to tailor yourstudy protocol, sample size requirements, investigator remuneration, and other elements to drive instructor engagementthroughout your clinical trial.

Challenge: IMID clinical trials are oftenlengthy and involve complex protocols, making it difficult to retain subjects for the entire duration of the study.Covance solution: Covance proactively"pressure tests" each protocol and study and recommends a customized mix of approaches and tools to promote continued study participation.

Integrated in-house IMIDcapabilities

Central LaboratoryServices

Market Access & GHEOR

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An interconnected perspectiveIntegrated capabilities across IMIDs and a full range of drug development services Like you, Covance targets IMIDs as an interconnected area that requires an interconnected approach—commercially, medically, and operationally.

Our unique integrated approach offers valuable opportunities to leverage our medical and operational experience across related diseases, enabling you to benefit from our strategic insight and obtain faster, high-quality results. Our broad range of integrated Phase I-IV drug development services includes:

• Clinical trial monitoring and project management

• Site services

• Data management

• Biometrics and medical writing

• Central laboratory services

• Quality assurance and control

• Patient safety

• Regulatory submissions

Early Clinical Services

Our integrated global in-houseIMID capabilities in central laboratory services, market accessservices and HEOR strategies, andearly clinical services (includingbiomarkers) allow you to leverageour diverse strengths across allstages of your IMID clinical trials and optimize your drug development program.

Covance IMID drug development advantages:

Proven IMID clinical trial experience: Covance is the global leader withmore than 450 IMID studies involving over 150,000 patients since 2007.We have been involved with the development of 14 of 15 top IMID drugs.

High-quality data: Our laboratories in Geneva, Singapore, Shanghai,Tokyo, and Indianapolis deliver globally consistent data through unifiedequipment platforms and SOPs.

Global clinical trial sites: We have worked with more than 18,000 investigator sites in more than 75 countries, with access to many difficult-to-recruit populations.

Tightly controlled end-to-end sample management, with the ability toperform assay validations in-house:Our unique capabilities and dedicatedsupport for a variety of key IMID assays ensure consistent data.

Automated lab processes:We deliver maximum consistency and scalabilitywhile minimizing costs.

Global automated kit production:With the largest, highest capacity, mostautomated clinical trial kit production facility in the world, we can delivereconomy of scale and global consistency.

Expert scientific & medical consultation:Our experience provides youwith unique insights into study design and testing methodologies to assessyour drug's safety and efficacy.

Covance IMID drug development advantages:

Market access strategy: Our market access and global health economicsand outcomes research (GHEOR) teams provide comprehensive, targeted,and empirically guided strategies for bringing products to market.

Burden of illness: We can integrate our comprehensive retrospective and prospective burden of illness study services to ensure skilled projectmanagement for your site selection and maintenance.

Patient-reported outcomes (PROs): Our experience with several IMIDs and virtually all well-regarded PRO instruments across the IMIDspectrum enables us to capture the voice of the patient and minimize variability associated with the use of PRO instruments.

Health economic modeling: We offer development of cost-effectiveness and budget impact models, analysis of secondary databases to populatethese models, and integration with patient studies to understand the health outcomes that impact a disease state and related costs.

Value message development & dossiers: Covance provides empiricallybased, readily testable, and differentiating value messages, as well as dossiers (e.g., global value, AMCP) for global, regional, country-specific, or market-specific purposes.

Registration studies: Our clinical, operational, and GHEOR experts provide fast results on clinical, economic, and patient-reported outcomes,ensuring that registries are conducted seamlessly from design through implementation and support.

Covance IMID drug development advantages:

Recruitment:We offer a strong global Phase I presence with five clinical research units, a capacity of more than 350 beds, and the experience and ability to recruit patients with inflammation diseases.

Design and conduct of early unit-based IMID clinical studies:We can evaluate your product in a relevant patient population veryearly in your clinical development program.

Proof-of-concept (PoC) IMID studies: Our experience in smallerand scientifically focused multicenter PoC inflammation studieshelps drive your Phase IIb or III trial design.

Scientific insights: As your partner, our strong capabilities in inflammation biomarkers, translational medicine, and pharmacokinetic/pharmacodynamics (PK/PD) modeling, combined with our expertise in early clinical studies, enable you to create a successful Phase III trial.

Xcellerate®: optimizing your clinical trials

High-quality data—for betteranswers, soonerEnhance site selection, reduce waste, and improve ROIYou depend on high-quality, reproducible data to get the answers youneed early in the drug development process—so you can make the rightdecisions about what steps to take and what opportunities to pursue.

Xcellerate® is Covance’s unique, proprietary approach to forecasting, investigator and site selection, and clinical trial management. We willhelp you:

• Efficiently evaluate each potential study.

• Engage investigators likely to help you meet patient enrollment goals from the start.

• Obtain faster clinical outcomes, less waste, and more consistent and predictable on-budget studies.

As your IMID partner, we will also help you avoid scope creep and cost overruns while proactively preventing resource waste.

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The Covance Xcellerate®

platform harnesses the power of the industry’s largest clinicaltrial knowledge base, developedthrough our view into more than30 percent of all clinical trialsthrough our Central LaboratoryServices group.

The Covance clinical trial knowledge base—the industry'slargest—is the result of ourunique ability to index a largevolume of data in the publicspace and identify useful patterns/trends for our clients.

For you, the powerful combinationof our feasibility and site selectionprocesses, drug development expertise, and available investigatordata enhances your ability to select appropriate trial sites andplan and design IMID trialsbased on matched trial designand disease characteristics.

Our approach: aligned with your perspective and your needs

Your partner for a new IMID paradigmCreative, customized solutions to your IMID clinical trial needsAs your IMID drug development partner, our goal is to provide creative, customized solutions to your clinical trial needs.

You will benefit from our deep and broad expertise of IMIDs and related diseases. We are medically, scientifically, and operationally aligned with the new IMID paradigm and your drug development goals and requirements.

For more information, contact your account executive or visit us online at www.covance.com/inflammation.

© Copyright 2013, Covance Inc. BROCDS040-0513 TOC 01 02 03 04 05

Targeting IMIDs as a cohesive area

Faster decision- making and results

Increased clinical ROI Reduced risk Global

studies

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www.covance.com

Covance is an independent, publicly held company with headquarters in Princeton, New Jersey, USA.

Covance is the marketing name for Covance Inc. and its subsidiaries around the world.

IMID drug developers need a partner with a unique combination of area expertise, global clinical trial capabilities, and customer-focused service.

Covance perceives, operationalizes, and targets inflammation as a cohesive area—and our experts understand how to support your development of targeted mechanism-based treatments.

As your partner, Covance can enable faster decision-making, reduce the risk of errors and flawed data, and keep your clinical trial on time and on budget.

Covance can help you avoid scope creep and proactively ensure that your resources are used most cost-effectively.

IMID studies are associated with specific operational challenges (such as high placebo response rates and low enrollment and retention).

Covance understands how to reduce these risks and produce robust, high-quality data to support trial results and regulatory submissions.

Drug developers face significant challenges when conducting late-phase clinical studies.

Covance offers scalable, targeted, and cost-effective global reach and a network of global resources—so you can be assured of appropriate study participants, rapid enrollment, and consistent processes and high-quality data sets across global sites.