Lead OptimizationPharmacology and Toxicology

DISCOVERY AND TRANSLATIONAL SERVICES

Table of contents

04Experience that inspires innovation

Optimize your study investment

Accelerating candidate selection starts here

Increase your probability for technical success03

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Accelerating candidate selection starts hereEnhancing efficiency, minimizing costs—right from the start

Lead optimization (LO) is one of the most expensive and time-consuming stages of the drug development process. Multiple factors make it more challenging given the need to improve the probability of technical success:

• The number of LO programs running simultaneously

• The number of molecules within each of those programs

• The need for integrated safety and efficacy endpoints

• The need for reproducible, decision-driving data

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Industry-leadingtimelines and delivery metrics fortoxicology studies

Expertise andexperience toenable fasterdecision-making

Accelerating candidate

selection starts here

Optimized study design and interpretation

Acceleratingcandidateselectionstarts here

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Streamlined processes, expertise and capabilities help to advance your molecule.

Covance enables faster decision-making by providing robust data through our integrated capabilities and technologies• Imaging• Pathology• Models• Biomarkers• Genomics

We will assign a dedicated team of scientists to your project—each with more than a decade of pharmaceutical industry experience in your therapeutic area—to helpyou select the best candidate.

Covance delivers rapid results that save you time and money.

• Award to study start: 10 days• Study end to data transfer: 15 days• Timelines met >95%• Reduced cycle time for non-GLP toxicology(40 days per iterative study)

Optimize your study investmentThe right expertise and resources to maximize the value of your study

By optimizing your LO process you can:

• Resolve issues faster

• Spend less time pursuing unsuitable compounds

• Focus resources on most likely candidates

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Anticipating and solving scientific issues

Full range of LO toxicology and safety pharmacologyservices

Unique imagingcapabilities to investigate yourcompound

Optimizeyour studyinvestment

By partnering with Covance, youbenefit from the answers providedby our broad range of service linesand our ability to add multiple endpoints to your studies. i

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Pathology engagementthroughout your study

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Covance has broad experience in dealingproactively with issues that arise early in LO,and can help you understand and address potential issues of your target or class—leadingto successful candidate selection. We can also create effective solutions for any significantissues (e.g., clinical holds) that may occur laterin the development process.

• Studies in small and large animals:

- Repeat dose studies

- Dose range finding, escalation and pilot studies

- Toxicokinetic studies

• Surgery Team

- Infusion capabilities

- Specialized catheter placements

• In vitro and in vivo metabolism

• Non-GLP Genetic Toxicology

• Nonclinical strategies for understanding clinical convulsion and other CNS endpoints

• CNS Safety Pharmacology

• Reduce stress with remote bleeding technologies to evaluate endocrine function in conscious animals

• Evaluation of cardiovascular function inconscious/unrestrained animals (rat, mouse, canine, ferret, NHP)

• Optical: fluorescence and luminescence technologies

• Computed tomography (CT)

• Magnetic resonance imaging (MRI)

• Ultrasound

• Thermal imaging

• Quantitative nuclear magnetic resonance spectroscopy (qNMR)

• Laser Doppler imaging

• Immunohistochemistry, standard and near-infrared fluorescence microscopy

- specialized cryotomy- laser microdissection- unique bone histology

• Histology services

• Morphologic assessment

• Transmission Electron microscopy

• Whole slide digital imaging

• Clinical pathology

- Flow cytometry

- Immunoassays

- Phenotypic and functional assays

- Endocrinology laboratory

• Peer review and consulting services

Identify andsolve scientific

issues

Optimize Study

Design and Interpretation

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By integrating toxicology and in vivo pharmacologystudies into your LO project, Covance can help youidentify issues as early as possible.

Increase your probabilityfor technical successIntegrated capabilities,successful solutions

Increase yourprobabilityfor technicalsuccess

Effective LO reduces attrition

Expertise in yourtherapeuticarea

Enable Rapid

Decisions

Integrated Efficacy and

Safety

Improve Probability of Technical Success

Reproducible Data

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Our integrated safety and efficacy capabilities,

technologies, and expertise make us uniquely qualified to improve the

probability of technical success—and your ability to bring an important

new medicine to market.

Covance integrates our wide breadth and depth

of toxicology and pharmacology expertise and technologies to

add multiple endpoints and maximize the value of each study.

• Pharmacology• Biomarkers• Imaging

• Pathology• Models• Genomics

Covance's breadth of capabilities enables us to help you:

• Solve both proactive and reactive issues as quickly and early in the

development process as possible.

• Empower you to make rapid decisions on the molecule

you are evaluating.

Covance studies are conducted under our Good Research Practices (GRP)

quality system (Including SOPs, training, documentation, and archiving)

• Reduced costs

• Reliable, valid, reproducible data

• Ensured Quality

We have streamlined our processes to provide industry-leading

timelines—enabling you to move forward quickly with the molecule

that has the best chance for success.

Your project will be assigned to senior scientists with expertise

in your therapeutic area and a deep knowledge of

regulatory expectations.

To aid in the analysis of efficacy of yourcandidate, we offer model development and validation capabilities across a broadrange of TA’s. All of our pharmacology scientists have 10+ years experience in a pharmaceutical environment to help you with the design and interpretation of your study.

• Oncology• Neuroscience• Cardiovascular• Inflammation• Endocrine, diabetes, and obesity• Inflammation, renal, and bone• Vaccines and infectious diseases

AttritionWITHOUT

Lead Optimization

AttritionWITHLead

Optimization

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Data Source: KMR 2012

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Experience that inspires innovationCollaboration that optimizes your development

When you partner with Covance, you will work collaboratively with a dedicated team of experts assigned specifically to your project—sharing information, identifying and interpreting findings, and providing you with the critical information you need to move forward with a successful candidate while prioritizingyour LO pipeline. This strong and productive relationship will continue until our team enables you to achieve your goal: the selection of a successful candidate for further development.

We’re ready to help you succeedFor more information, contact your account executive or visit us online at www.covance.com/leadoptimization.

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Experiencethat inspiresinnovation

Dedicatedteam of scientists foryour study

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• Therapeutic area expertise for your target

• Single Pathologist, Senior Scientist, andStudy Director are assigned throughout your program

• ACVP-boarded, Ph.D. veterinary pathologistswith extensive pharmaceutical experience

• Pathology engagement throughout study

Continuity with GLP Scientists

• Study and target knowledge shared between LO and GLP staff

THE AMERICAS +1.888.COVANCE (+1-888-268-2623) +1-609.419.2240

EUROPE/AFRICA +800.2682.2682 +44.1423.500888

ASIA PACIFIC +800.6568.3000 +65.6.5677333

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.