1. The Use of Scientific Advisory Boards An Invaluable Tool in Drug Development Dr Robert Miller Chief Medical Officer Fulcrum Pharma Developments 19 th Annual EuroMeeting, Vienna 2007

2. Why Appropriate advice is the key to successful drug development

3. Drug Development is: >Expensive >Time consuming >Highly Competitive >Resource Intensive >Rewarding >Dangerous >Frustrating

4. Milestone Phase 0 Entry into Man Phase II Phase III / Pre- Submission Lead Compound Selection Developmental Pathway and Related Activities Path Target pharmacology In-vitro models Drug substance manufacture and formulation Initial Target Profile Output Preliminary Product Development Plan Manufacturing plans Competitor analysis Clinical Development Plan/Regulatory Strategy Market review Peri-approval plan/Life cycle management Target Profile, Competitor analysis and Potential market Corporate needs Budgeting and timelines Toxicology DMPK Preclinical models for pharmacology Potential therapeutic targets Translational research and PD assays Drug scale up Regulatory considerations Product appraisal Target profile refinement Therapeutic targets Further preclinical studies Biomarkers/PD assays Factors for progress to Phase II Target profile refinement Initial therapeutic indications Phase II Clinical trial design Critical success factors for Phase III Phase III strategy Regulatory Strategy Business strategy/licensing Critical review of emerging data Phase III trial designs Regulatory issues for submission Launch strategy Peri-approval strategy Publication planning

5. Where is the Expertise > Pharmaceutical  Strategy  Trial Design  Logistics

6. Where is the Expertise > Physician  Contemporary knowledge  Competitor studies  Clinical relevance

7. Why External Advice >Contemporary “real life” information –By Indication –Medical Practise –Feasibility –Critical success factors >Geographical perspective >Competitor information >Potential investigator

8. What External Advice >One-on-one –“I know a few famous doctors – I’ll go and ask them” –“I can take the advice I like best” –“Its cheaper” >Advisory Boards –“Complicated” –“What if they don’t agree with my plan” –“Expensive”

9. “One-on-Ones” What if they provide different advice? Who do you believe?

10. Advisory Boards aka. Focus Groups, Steering Groups >Can provide all of the suggestions in one meeting >Can “argue” against one point of view not universally held or not in the interests of the sponsor >Speak through the moderator rather provide an oration >Are with their peers so less likely to act as “prima donnas” >Can provide a consensus if meeting properly handled

11. Consensus is Best

12. Advisory Boards >The Make-up –Multinational and Multidisciplinary Composition –Current Clinical Practices –Trial design, relevant outcomes, target populations –Awareness of Competition / Treatment Trends >The Conduct –Clear brief –Clear moderation and direction of the discussions –Consensus on path forward –Not a “rubber stamp” >Potential for Advisers to be product champions

13. Path Output Corporate needs Target pharmacology In-vitro models Drug substance manufacture and formulation Initial Target Profile Toxicology DMPK Preclinical models for pharmacology Potential therapeutic targets Translational research and PD assays Drug scale up Regulatory considerations Product appraisal Target profile refinement Therapeutic targets Further preclinical studies Biomarkers/PD assays Factors for progress to Phase II Target profile refinement Initial therapeutic indications Phase II Clinical trial design Critical success factors for Phase III Phase III strategy Regulatory Strategy Business strategy/licensing Critical review of emerging data Phase III trial designs Regulatory issues for submission Launch strategy Peri-approval strategy Publication planning Preliminary Product Development Plan Manufacturing plans Competitor analysis Clinical Development Plan/Regulatory Strategy Market review Peri-approval plan/Life cycle management Target Profile, Competitor analysis and Potential market Budgeting and timelines Milestone Phase 0 Entry into Man Phase II Phase III / Pre- Submission Lead Compound Selection Scientific AB Target pharmacology In-vitro models Toxicology DMPK Preclinical models for pharmacology Potential therapeutic targets Translational research and PD assays Scientific/Clinical AB Target profile refinement Initial therapeutic indications Therapeutic targets Further preclinical studies Biomarkers/PD assays Factors for progress to Phase II Clinical AB Phase II Clinical trial design Critical success factors for Phase III Phase III strategy Regulatory Strategy Business strategy/licensing Critical review of emerging data Phase III trial designs Regulatory issues for submission Peri-approval AB Launch strategy Peri-approval strategy Publication planning When and What Advisory Boards

14. Why Do Advisory Boards Work >They provide: –a forum for the discussing development –reality check for plans and potential studies >They can: –identify issues and provide solutions –validate the development programme –provide product championship >They are critical because……

15. Planning is the Key Not everyone has the same ideas!

16. Development Strategy Planning Target Profile/MIRS Ongoing clinical trial data Current Information

17. Target Profile >Label Claims: –Indications for use –Dosage, route and regimen –Efficacy and safety –Product quality –Risk:benefit >Marketing Profile: –Features and benefits –Comparison to alternative treatments –Pharmacoeconomics >Commercial Targets: –Time to market –Licensing plans –Financial –COG –NPV –Sales –Market share –Licensing value etc –Patent life

18. Tools - MIRS Designs/data Completed/ ongoing studies Publications Guidelines Precedents New Studies Refutation Scientific precedent Re-analysis Expert opinion Issues Challenges Risks Comparisons Conflicting Results Questions Claims Features and benefits Advantages Interpretations Conclusions Support Response/ Rationale IssuesMessages

19. Development Strategy Planning Advisory Board(s) Target Profile/MIRS Ongoing clinical trial data Current Information

20. Development Strategy Planning Advisory Board(s) Target Profile/MIRS Ongoing clinical trial data Gap Analysis Current Information Investigator input Strategy Plan Protocols

21. Life Cycle Planning Advisory Board(s) Target Profile/MIRS Ongoing clinical trial data Gap Analysis Current Information Investigator input Life-cycle team review Life Cycle Strategy Plan

22. Summary >Advisory Boards are an excellent way of gauging opinion >They avoid the difficulties of one-to-one meetings where individual experts' opinions differ >They allow a consensus approach to development >They can be tailored according to the stage of development, the nature of the product and the breadth of discussions required >Independent moderation of Boards is an excellent way of getting a unbiased advice >The use of these boards should be factored into developments plans whether they be early or life-cycle

23. Robert M Miller Fulcrum Pharma Developments Hemel Hempstead United Kingdom Tel: +44 870 710 4360 +1 919 226 1440 ext 325 e-mail: robert.miller@fulcrumpharma.com Contact