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Pharmaceutical Advisors

– Core staff with average 20 years industry experience

– Network of over 100 Advisors and growing– Covering every discipline for pharmaceutical

development and commercialization – Founded in 2001, currently more than 75 clients

• Small and mid-sized companies• Emerging pre-clinical and clinical stage

companies• Top 5 pharmaceutical companies• Suppliers to the Life Sciences

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The Issue We Address

Clinical ADME ToxChemistry

Process Development

Quality

Manufacturing

Clinical

Drug Substance

Drug Product

Drug Safety

Formulation

Project Management

Everyone can pull in the various experts needed …

Engineering

Regulatory

Marketing

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The Issue We Address

Clinical ADME ToxChemistryProcess

Development

Quality

Manufacturing

Clinical

Drug Substance

Drug Product

Drug Safety

Formulation

Project Management

Engineering

Regulatory

…linking broad and deep perspective early is key to anticipating issues, accelerating progress, managing risk and…

unlocking value!

Marketing

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Technology Platforms

Transaction Valuation and

Licensing

Advisors Industry Focus

Venture Capital

AnimalHealth

Suppliers to the Life Sciences

Medical Devices

Biotechnology

Pharmaceuticals

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Rapid, Interactive

Expert Panels

Rapid, Interactive

Expert Panels

PracticalQuality

Systems & Regulatory

PracticalQuality

Systems & Regulatory

Resolve Issues

Build SkillsChemistry,

Formulation Drug Delivery

Safety & Efficacy ADME

Resolve Issues

Build SkillsChemistry,

Formulation Drug Delivery

Safety & Efficacy ADME

Integrated Development

ViewLinking

CMC, Tox, Clinical

Integrated Development

ViewLinking

CMC, Tox, Clinical

Portfolio Decisions,

Due Diligence& Valuation

Portfolio Decisions,

Due Diligence& Valuation

Scale-up & Sourcing Decisions

Scale-up & Sourcing Decisions

Operational Input to

Capital Plans

Operational Input to

Capital Plans

Advisors Functional FocusIntegrating Research, Development Engineering and

Commercialization ExpertiseClick on Any Hexagon for ExamplesClick on Any Hexagon for Examples

Supporting Development, Operations, Strategy and Portfolio

Management

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What Do We Do Best?

ExpertContent

Efficient Process

ProfessionalManagement

What + How = Delivery Assurance

DeliveryAssurance

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Inverting the Consulting Model…

Proven DeliveryProven DeliveryInsight-DrivenInsight-Driven

Customized ResourcingCustomized ResourcingIntegrated, Experienced Functional PerspectiveIntegrated, Experienced Functional Perspective

Hands-On Problem-Solvers Hands-On Problem-Solvers Cost-effective, Flexible, IndependentCost-effective, Flexible, Independent

Industry ExpertsIndustry Experts

ExperiencedExperiencedConsultant Consultant ManagersManagers

Unique ClientUnique ClientSituationSituation

Unique ClientUnique ClientSituationSituation

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With Experienced Advisors…

• Associate Director, Venture Mgmt• Asst Director for Technical Affairs• Chief Executive Officer• Chief Operating Officer• Dept. Head of Pharmaceutical Engineering• Director of Fermentation and Biocatalysis

Development• Director of Formulation Development• Director of Pharmaceutics R&D• Director of Quality Control• Director of Sourcing & Planning of Chemical

Development• Director, Clinical Operations, Medical Affairs• Director, Experimental Pathology• Director, Global Medical Operations• Director, Planning and Business Support,

U.S. Medical and Regulatory Affairs• Director, Production of Therapeutic and

Diagnostic Proteins• Exec Director of Manufacturing

• Executive Vice President, Global Drug Safety, Metabolism and Safety Pharmacology

• Group Director of Clinical Research• Group Director of Process R&D• Group Director, Preclinical Safety Assessment• Manager of Organizational Effectiveness• Mgr, Radiopharmaceutical Manufacturing• President• President of Technical Operations• Senior Director Operations Planning -

Worldwide Pharmaceutical Group • Senior Director, North American Clinical

Affairs• Senior Manager, Clinical Research• Senior Vice-President and Chief Scientific

Officer• Senior Director of Process Chemistry• Senior VP of Pharmaceutical R&D• Senior VP, Global Drug Development• Vice President of Business Development• Vice President Information Technology• Vice President of Drug Development• Vice President of Process Development

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Who’ve Run Companies…• AAI, Inc.• American Cyanamid/Lederle

Labs• American Home Product• Amylin Pharmaceuticals• Applied Immune Services• Arthur D. Little• Astra Pharmaceuticals• Aventis• Axxima Pharmaceuticals AG• Baxter Healthcare Corp.• Benzon Pharmaceuticals• BioReliance Corporation• BMS• Boehringer Ingelheim• Boots Pharmaceuticals• Bristol-Myers Squibb• BSCI, Inc.• Cambrian Associates• Cambrex• Cancer Research Center• Cardinal Health• Centocor• Ciba-Geigy Corporation• Corixa• Coulter Pharmaceutical• Dentsply• Discovery Partners

• Millennium• Monsanto• Napp Researche Centre• National Cancer Institute• Neose• Norcliff-Thayer• Novartis• Ortho Biotech• PA Consulting Group• Pfizer• Pharmacia• Response Biomedical• Richardson-Vicks• Salmedix• Schering Corporation• Schering-Plough • Searle • Sepracor Inc.• Sigma-Aldrich Corporation• SmithKline Beecham• SUGEN• Tektagen• The Life Sciences Group• Upjohn Ltd.• US Environmental Protection

Agency• Wyeth-Ayerst

• Eli Lilly & Company• Environmental Toxicological,

Int’l• US FDA Center CBER & CDER• FEI Technologies• Fisons• Fluor Daniel• Genentech• Genovo• GSK• GX BioSystems• Hoechst Marion Roussel• Hybridon• ICI Pharmaceuticals • IMBIC• Immunex• Immunogenetics• Immunomedics • IMRE Corporation• Isolation Technologies• J&J• Knoll Pharmaceuticals,

Nottingham• Matthew Hall Engineering• Merck• Merck, Sharpe & Dohme • Mettler Toledo• MicroProbe Corporation

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With Broad Functional Expertise • Advisory Board s• Analytical Development• Analytical Methods

Development/Validation• Analytical Operations• Biologic Manufacturing• Bio-Pharmaceutical

Development• Bulk Active Ingredients• Bulk Clinical Supply Planning• Bulk Drug Substance• Bulk Manufacturing• Business Development • Capital Raising• Chemical Synthesis• Chemotherapeutic Agents• Clinical Pharmacology• Clinical Research• Clinical Supplies Mgmt &

Release• CMC of IND/NDAs• Commercial Product Profiling• Corporate Inventories• Cost Evaluation/Budget Prep

& Control• CRO, Supplier Auditing &

Mgmt• Diabetes & Metabolic

Diseases• Documentation• Drug Delivery Technology

• Manufacturing• Materials Resource Planning

New Bulk Substances• Novel Formulations• Oncology Clinical Research• Operations• Operations Research &

Management• Organizational Analysis• Parenteral/Oral Dosage Forms• Patents & Procedures• Performance Audits &

Validation• Pharmaceutical Formulation• Pharmaceutics Research• Pharmacodynamics• Pharmacokinetics• Phase III/Commercial Needs• Portfolio Management

Strategies (Evaluation)• Preformulation Studies• Preparative Chromatography• Process & Lab Automation• Process and/or Equipment

Validation• Process Development• Product Development• Product Launches• Product Licensing

• Drug Development Drug Interaction

• Drug Metabolism• Drug Product• Endocrinology & Metabolism• Engineering• Environmental Impact

Analysis• Expert Reports, Dossiers,

DMFs• Facility Design and/or

Operation• FDA Regulations & Inspections

(Technical Data Pkgs.)• Fermentation• Filling & Packaging Operations• Finance• Formulation Development• Good Clinical Practices• Hematology & Internal

Medicine• Immunochemistry Research• In Vitro Diagnostics• In-Process Control Activities• Intellectual Property

Management• Investments• Just-In-Time Methodologies• Laboratory Operations• Life-Cycle Strategy• Lipid Consultant• Long-Term Supply Agreements

• Project Implementation• Project Management

(Multi-national)• Purchasing• Quality Assurance• Quality Control• QC Strategies &

Assessment/QA• Quality Systems• R&D• Radiolabeled

Antibodies• Regulatory Affairs • Rx to OTC

Opportunities • Safety Evaluations• Sales and/or Marketing• Scale-Up from R&D to

Manufacturing• SOP Creation• Start-Ups• Supply Chain• Synthetic & Semi-

Synthetic Drug Candidates

• Target Identification• Technology Profile• Technology Transfer• Toxicology-Pathology• Transdermal

Technology

...That is Growing

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Our Strengths to Help You

• HOW we support our clients – Speed & flexibility– Content expertise & general management perspective– Business decisions & technical expertise

• Use our approach to solve problems and address issues– The RIGHT expertise based on client needs– We efficiently identify and involve what’s needed

• We effectively deploy and integrate the RIGHT resources– Insight about implications on other functions and processes– Multiple perspectives within a specialty where needed

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Some Relevant Case Studies

1. Support of Critical Manufacturing Issues for a Complex Biologic

2. High Powered Expert Panel on a Deal- Breaker Issue

3. Package/ Shipping Validation to Launch Key Products

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Recent Case Study (1)Support Critical Manufacturing Issues for a Complex

Biologic

The Issue• Our client is a small molecule drug discovery and development company that

acquired a commercially launched biologic pharmaceutical. Process variability in the fermentation of the drug was creating N-terminal variants, preventing the product from being manufactured reliably.

What We Did• Assembled a cross-functional team of Bio-Analytical, Fermentation, and Bio-

Manufacturing experts. We supported the client through the investigation, experimentation, and implementation phases of the project by:

– Assessing the process and existing data for root cause of process variability– Selecting and directing the outsourced supplier to identify weaknesses of the

existing process and analytical methods supporting the process– Identifying the most likely sources of variability– Establishing vendors for new analytical methods and fermentation development – Designing and executing an experimental protocol to definitively assign root

cause– Designing cost-effective scale-up plans to manufacture the revised process at

scale• Providing the client with:

– The root cause of variability in the face of a complex web of confounding factors– A cost-effective solution to product variability, avoiding product withdrawal

Protected a key source of revenue during a critical phase of growth for a young and growing Bio-Pharmaceutical Client

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The Team

• John Apathy, Trained in Biochemistry and Immunology. 20 years experience developing strategies and leading pharmaceutical product development teams within a major pharmaceutical company and as senior managing consultant with a major pharmaceutical consultancy.

• David Dodds, PhD, Former Director of Fermentation and Bio-catalysis Development with BMS

• Kent Iverson, formerly with Immunex and Coulter Pharmaceuticals, has led the Process Development and Materials Management departments of all products from pre-clinical development through commercialization.

• John McEntire, PhD Former Corporate Vice President of BioReliance, with expertise in biopharmaceutical development analytical and formulation.

• Tim Noonan, PhD. Trained as a medicinal chemist, and a former VP of manufacturing, Tim has broad manufacturing, operations and quality systems experience, was instrumental in the formation of a successful contract oligonucleotide manufacturing firm. Dr. Noonan also worked as a consultant to venture capital firms performing technology due diligence.

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Recent Case Study (2)High Powered Expert Panel on a Deal- Breaker Issue

The Issue• Our client identified a degredant as a known mutagen. The client needed to

understand the implications for development and the value of the compound for a partner meeting. They also needed the right regulatory strategy, as well as an understanding of the trade-offs between salt forms to pursue appropriate development programs.

What We Did• In less than 2 weeks assembled a team that addressed their issues

– 2 Gentox experts that wrote the ICH guidelines– 1 Gentox expert that convinced the FDA to act favorably with a similar

situation– CMC expertise with polymorph expertise– Pharmacology– Tox expertise in early and late development strategies

• Providing the client with:– Answers to the right questions to show their partner that they had control

and a plan– Awareness of questions they had not considered– Understanding of what was NOT an issue– Insight into the right development strategies to manage risk– Confidence that they had explored all the alternatives– One place to go for follow-up and coachingNo one got on a plane, stayed overnight, or was wined and dined

No one had to assemble and assimilate the input

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The Team• Jane S. Allen, Ph.D., D.A.B.T., former Director of Toxicology, GSK, RTP with expertise

in genetic toxicology. Member of US PhRMA committee that established the ICH genetic toxicology guidelines.

• Michael Berman, PhD, is a former biotech CEO with broad experience in pre-clinical development for Phase I studies with a focus on biologicals and peptides as well as small molecules. Dr. Berman has taken a number of novel biologicals into Phase I.

• Robert L. Brent, MD, Ph.D. Distinguished Professor of Pediatrics, Radiology and Pathology and Louis and Bess Stein Professor of Pediatrics, Jefferson Medical College, Philadelphia. Former advisor to Aventis for ARAVATM, with expertise in clinical medicine related to genetic toxicology.

• Charles E. Piper, PhD, former Executive Director, Clinical Research Strategic Partnering, Clinical Development, and former Executive Director, Product Safety Assessment, Preclinical Development, Searle. Member of US PhRMA committee that established the ICH genetic toxicology guidelines.

• Thomas Crawford, PhD, former Group Director of Process R&D with Pfizer where he was responsible for the development of chemical technology and the manufacture of supplies for drug candidates from nomination to transfer to Pfizer's Global Manufacturing Group.

• William D. Kerns DVM, MS, DACVP former Executive Vice President, Global Drug Safety, Metabolism and Safety Pharmacology, Eisai and SmithKlineBeecham.

• Guy Paulus, PhD. Served most recently as Senior Vice President Drug Safety Evaluation Pfizer Central Research Groton U.S.

• Robert Ronfeld, Ph.D. who led Pfizer’s Clinical Pharmacokinetics and Pharmacodynamics group with particular expertise in Drug Metabolism and Development Strategy.

• Richard S. Woodward, Ph.D. Biotechnology and pharmaceutical executive with multidisciplinary international experience. Formerly with Pharmacia, Ajinomoto USA, Inc. and Quality Biotech, Inc.

• Tim Noonan, PhD. Trained as a medicinal chemist, and a former VP of manufacturing, Tim has broad manufacturing, operations and quality systems experience, was instrumental in the formation of a successful contract oligonucleotide manufacturing firm. Dr. Noonan also worked as a consultant to venture capital firms performing technology due diligence.

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Recent Case Studies (3)Complex Package/ Shipping Validation to Launch Key

ProductsThe Issue• Our client is extending its growth strategy requiring an enhanced capability in packaging /

package design, logistics, shipping validation, quality, and management of vendors beyond current resources and internal capabilities.

What We Did• Assembled a cross-functional team of Logistics, Quality, Packaging and Manufacturing /

Operations experts. We are supporting the client through the investigation, planning & experimentation, and implementation phases of the project by helping to determine:

– when and how to utilize engineering resources from package design and testing firms vs. independent engineering resources,

– the cumulative effect of expected Time /Temp excursions in the context of stability / shelf life and possible variations in packaging and logistics

– where to utilize off-the-shelf secondary packaging solutions – where custom packaging solution are appropriate, trading off cost of manufacture and

design with logistics and other costs.– efficiencies anywhere in the distribution chain, based on decisions in packaging or other

areas– with complex, issues such as this, any key activities or decisions not assigned or staged.

• Providing the client with:– Roadmap for the packaging, shipping and shipping validation project, maintaining the

timeline– Key program management

Enabling progress in a critical area without the need to scale-up resources

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The Team

• John Apathy, Trained in Biochemistry and Immunology. 20 years experience developing strategies and leading pharmaceutical product development teams within a major pharmaceutical company and as senior managing consultant with a major pharmaceutical consultancy.

• William Gierke, former manager of Package Development with Eli Lilly and a member of the Drug & Pharmaceutical Packaging Committee

• Kent Iverson, former Vice President of Manufacturing & Process Development at Corixa, Coulter and Immunex. Kent has broad operational expertise and has implemented practical solutions to complex controlled temperature shipping issues for injectables and has developed successful supply plans for numerous 2-8C products.

• John Pock, former head of Performance Engineering & Worldwide Quality as well as manager of International Distribution at Eli Lilly.

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Other Recent Projects

• Rapid due diligence of compounds for critical decisions• Manufacturing and Outsourcing strategy including

determination of number of locations and in- source / outsource mix

• Integrated early and full drug development plans• Quality Systems planning and implementation for developing

company• cGMP Quality System Gap Analysis for an established company• Process development to address issues on a marketed product• Site Audits with regulatory and practical operations perspective• Manufacturing readiness assessment• Sourcing - identification of sources and review / selection• Candidate nomination process and portfolio review• Formulation and drug delivery choices• Market studies by simulating a pharma development group• Deal valuation support• cGMP Supplier Management

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Why do clients look to us?

• Trust and confidence that we will get it done• We apply world-class expertise that exactly meets the

need• Efficiency and effectiveness of our structured approach • Avoid time consuming management and coordination of

challenging resources and diverse inputs to complex issues

• Speed of results• Accountability at a single, rather than multiple points• We ensure a cross-functional and downstream view• Fixed predictable budget vs. multiple experts with “ the

meters running at different rates”

Delivery Assurance

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What is keeping you up at night?

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Practical Quality Systems& Regulatory Help

What we do and how it’s different:• Operations oriented Quality perspective, not just “ex-FDA…”• Practical approaches to regulatory compliance• Helps avoid costly reactive remedial consultants• Cost-effective, proactive compliance

Examples of recent projects:• Establishment of appropriate cGMP systems for a research

based company moving to commercial development• GAP Analysis and Action Plans following FDA Warning Letter• Vendor Audits that strengthen the vendor / client relationship• CGMP Gap Analysis and Action Plan• Pre-Approval Inspection Readiness Assessment

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Operational Input to Capital Plans

What we do and how it’s different:• Application of functional operations AND engineering expertise

to complement client resources• Helps client identify operational implications and issues with a

"downstream” perspective• Avoids costly change orders and “feature creep”, and supports

sound decisions, early in the process

Examples of recent projects:• Development of a URS ( User requirement Specification ) for

$200M Small and Large Molecule development facility• “Future Proofing” of current pharmaceutical process through

process and equipment reviews• Process Validation, Equipment Qualification and Operational

Efficiency input to design of new vessels for aseptic processing• Development of downstream processing technology

requirements to meet future development needs.

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Resolve Issues and Build Skills

What we do and how it’s different:• Focused and efficient application of functional expertise• Integrated development perspective• Multi-company perspectives• Access to the latest thinking• Integration of inputs without costly coordination

Examples of Recent Projects:• Expert oversight of challenging outsourced cytotoxic

fermentation• Dosage form strategy and action plan to obtain IP protection• Dosage form strategy to overcome half life deficiency• Micro Lab productivity analysis and recommendations to

improve efficiency and handle greater workload without adding staff

• Operational Cost Model for research stage company transitioning to a product stage company

• Informed Tox, CMC development and risk reduction plans to accelerate progressReturn / Next

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Rapid & Interactive Expert Panels

What we do and how it’ s different:• Expert teams, custom assembled to address critical issues• Focused assignments for panel members ensure efficient process• Individual and group discussions, across-functions and within

functions• Interactive panel discussions via telecon with the client• Real, actionable answers, action plans• Completed in 1-3 weeks

Examples of recent projects:• A rapid due diligence review of targets• Implications and path forward for gen- tox issue to support out-

license• Review and selection of appropriate animal models• Go / No-Go review of existing efficacy data• Manufacturability & scalability of synthetic routes

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Scale-up and Sourcing Decisions

What we do and how it’s different:• Capitalize on multiple advisors experience in development, sourcing, and

vendor management• Rapid identification of technical requirements, identification of possible

vendors, screening & qualification, support development of contracting, quality agreements etc.

• Drug Substance/API, Intermediates, Formulation, Drug Product, Fill-Finish

Examples of Recent Projects:• Identified and qualified sources for hard-to-locate emulsion capability in

Europe• Identified and qualified US sources of peptide manufacture for a

European company• API Development, Scale-Up and route filing strategy• Scalability / Manufacturability review• Vendor Management Strategy and Process for an emerging large Biotech• Identification and Qualification of Controlled Release Drug Product

manufacturers for an established Biotech

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Integrated Development View

The Core of Advisors’ Approach• Leverage understanding of the interrelationship

between CMC, Clinical and Safety development to create and protect value

• Multi-company and cross-functional perspectives• Insight-driven anticipation of Advisors Functional Focus

issues for improved risk management• Advisors who have been accountable for all aspects of

development• Application to specific issues and overall program

management

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Portfolio Decisions, Due Diligence and Valuation

What we do and how it’s different:• Concurrent technical and business perspective • Portfolio management decision experience across a wide

range of technologies and therapeutic areas• Rapid inclusion of focused subject matter expertise rather

than generalist research

Examples of recent projects:• Due Diligence of compounds in various therapeutic areas• Due Diligence of company business models• Valuation of compounds in support of out-licensing

decision• Assembly of a “ Virtual Pharmaceutical Company” team of

users to help a supplier understand the value of their technologies resulting in successful new business strategy

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