Human clinical data is the critical proof for new medical treatments. The current pharma, venture capital and NIH funding environments make it more important than ever for capital efficient clinical trial design and funding. Here are some best practices in mapping new treatments to clinical applications to accelerate clinical trial data.

1. Driving AcceleratedClinical Data ZEN CHU Wyss Institute HarvardMedical School Office of Technology Development CIMIT Innovation Grand Rounds Mass General Hospital May 4, 2010 © zen@acmedx.com

2. Best Practices for Med TechAccelerated De-Risking Challenges Today Innovation Landscape & Risks Teams & Conflict of Interest Clinical Innovation Rules & Tradeoffs Panel Discussion Good Business IS Good Medicine © zen@acmedx.com

3. Challenges In Driving Clinical Data Clinical effectiveness is not enough Pharma & venture funding tight Publications & research polluted with noise High sensitivity to Conflict of Interest FDA reviews more conservative, higher hurdles Payers & Clinicians demand Evidence-Based Data Health reform & Comparative Effectiveness impact today More important than ever to match Focused solution to clinical champions © zen@acmedx.com

4. Disciplined IntentonRole & Therapy © zen@acmedx.com

5. Clinical Innovation LandscapeMatch Resources to Opportunity Size Big Opportunities Complex Solutions, Fragmented Services Philanthropy/NIH Basic Research Grants Unknown Mechanisms Large Established Companies Integrate Whole Solutions Humanitarian Exemption, Venture Philantropy Low Capital Required High Venture-Backed Companies Focused Teams to Prioritize & Execute Discrete Product Product-Line Extensions License or Product Acq Royalties $100MM $1B Market Size of Opportunity © zen@acmedx.com

6. Segment To FocusPatients, Disease State, Providers Philanthropy/NIH Basic Research Grants Unknown Mechanisms Big Opportunities Complex Solutions, Fragmented Services Unfocused & Requires Segmentation Gates Foundation Ischemic Stroke Cystic Fibrosis Off-Label Uses Low Capital Required High RNAi for AMD Stem Cells Aortic Abdominal Aneurysm Ortho Lumbar Disc Gastric Bypass $100MM $500MM Market Size of Opportunity © zen@acmedx.com

7. Value To Whom? © zen@acmedx.com

8. Current Healthcare Model Drives Interventions Michael Porter, Tiesberg © zen@acmedx.com

9. Disease SegmentationMap Unmet Clinical Needs To Development Path Disease Natural History & Diagnostics Comorbidities & Adjacencies Physician Referral Patterns Untreatable Patient Subsegments Humanitarian Exemption Focus Segments on High Impact & High Value © zen@acmedx.com

10. Market Analysis CriticalEnables Path To Clinical Efficacy Proven Clinical Adoption Drivers 1) Patient pain & outcomes 2) Therapeutic procedure time 3) System costs over entire disease cycle Comparative Effectiveness Will Impact Prioritization © zen@acmedx.com

11. Return On Investment Drivers Choose Clinical Endpoints with Fastest & Highest ROI Hospital stay Re-admission & revision Complications & errors Recurrence Early detection (prevention coming?) Key Players Patients, Payors, Physicians, Hospitals © zen@acmedx.com

12. Analysis Is ParamountEfficacy is NecessaryBut Insufficient ForTranslating to Widespread Practice © zen@acmedx.com

13. Time & Risks © zen@acmedx.com

14. Value Inflection PointsTime to Market & FDA Approvalbut alsoTime to First Human Data&Time to Clinical Adoption © zen@acmedx.com

15. Acquisition/IPO Exit Reimbursement Published clinical results Market Introduction Salesforce hired Europe & Japan distribution FDA Approval Manufacturing ramp Human pivotal study Corporate partnership First human data First Hiccup & Danger of Momentum Loss CEO hired Pilot manufacturing Patent grant First FDA meeting Regulatory opinions Money raised & team hired Animal testing Clinician feedback Patent disclosure Prototype/Reduction to Practice Market Analysis Idea COMPRESS TIME TO MARKET FASTER CURES & ROI Value Time Critical Milestones © zen@acmedx.com Accelerate Clinical ImpactTime is Life

16. Which Risks to Prioritize? Market Risk Reimbursement Physician & Patient Adoption Packaged Solutions Value Regulatory Risk Safety & Efficacy Management Risk Technology IP Risk Time © zen@acmedx.com

17. Investor Risk Priorities Market Risk Reimbursement Physician & Patient Adoption Packaged Solutions Largest Risks Must Be Addressed & De-Risked Up Front Before Funding Value Regulatory Risk Safety & Efficacy Investors & Companies Willing to Take These Risks Management Risk Technology IP Risk Time © zen@acmedx.com

18. Build Team To Execute Market Risk Reimbursement Physician & Patient Adoption Packaged Solutions 1) Plan in Reverse 2) Team Execution Value Regulatory Risk Safety & Efficacy Management Risk Technology Risk Time © zen@acmedx.com

19. Teams Drive Data Clinical & Business teams Focus & segment the opportunities Build teams to match opportunity type Complement inventors with team BUILD TEAMS THAT UNDERSTAND THE RISK / EXECUTION TRADEOFFS © zen@acmedx.com

20. Building Clinical Team WhileNavigating Conflict of Interests Transparency in relationships & publication Equity holders cannot drive clinical data Avoid equity & minimize cash consulting Find & Engage Clinical Champions Match patients to risk/benefit Negotiate IP rights up front CAPITAL EFFICIENT & CREDIBLE DATA © zen@acmedx.com

21. 7 Rules of Innovation Minimize Time To Demonstration Build Smallest Possible Team Develop Only Bare Minimum Iterate Frequently Before Mfg Controls Never Develop What Can Be Bought Insist on Highest Quality Workmanship Prove One Idea/Variable At A Time EMPHASIS ON SPEED & PROOF © zen@acmedx.com

22. Clinical Data TradeoffsImpact & Speed versus Cost BALANCE COSTS & RISKS © zen@acmedx.com

23. Time is Life © zen@acmedx.com

24. Incremental vs BreakthroughPlenty of Incremental Value, Different Strategy © zen@acmedx.com

25. Clinical InnovationCritical Success Factors Rigorous Analysis Focused Plan To Early Proof Credible & Creative Team Adapt With New Data Evidence-Based Business Desire to help patients © zen@acmedx.com

26. Innovation Grand Rounds Panel Discussion:Driving Clinical Proof ZEN CHU Wyss Institute Harvard Medical School Office of Technology Development HELEN COLQUHOUN, MD Founder & CEO, Pleiad Devices DAVID REED, MD, MBA Serial Medical Entrepreneur AARON SANDOSKI Managing Director, Norwich Ventures

27. GOOD BUSINESS ISGOOD MEDICINE Thank You!www.LinkedIn.com/in/zenven © zen@acmedx.com