The document discusses high-impact medical innovation and the role of physician innovators. It covers topics such as identifying unmet clinical needs, building effective teams, navigating regulatory and reimbursement challenges, and techniques for generating new innovation opportunities.

1. High-Impact & High Value Medical Innovation Zen Chu CIMIT Forum Harvard Medical School Beth Israel Deaconess Medical Center © zen@acmedx.com

4. High Impact Innovation © zen@acmedx.com

7. Physician’s View of Value © zen@acmedx.com Time Market Introduction FDA Approval Patent grant First in Man Animal testing Patent disclosure Prototype/Reduction to Practice Idea Milestones Value Conflicts of Interest perceived & real Hand off to Licensing office

8. Investor’s View of Value © zen@acmedx.com Value Time Milestones 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 Management team hired Pilot manufacturing Patent grant First FDA meeting Regulatory opinions CEO hired Animal testing Clinician feedback Patent disclosure Prototype/Reduction to Practice Market Analysis Idea Anticipate Potential Exits

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

10. Which Risks to Prioritize? Value Time Market Risk Reimbursement Physician & Patient Adoption Packaged Solutions Regulatory Risk Safety & Efficacy Management Risk Technology Risk Largest Risks Must Be Addressed & De-Risked Up Front Before Funding Team, VCs & Partners Manage These Risks © zen@acmedx.com

12. “ Physicians and engineers often have no sense of the requirements to create a company…In a start up environment, more is not always better. Hiring the appropriate people at the right time can determine success or failure.” - Thomas Fogarty, MD – Founder & investor in over 30 medical companies Professor of Surgery, Stanford University © zen@acmedx.com

15. Development Best Practice © zen@acmedx.com Value Time Milestones Acquisition/IPO Exit Published clinical results Market Introduction Salesforce hired Europe & Japan distribution FDA Approval Manufacturing ramp Human pivotal study Corporate partnership First Hiccup & Momentum Loss Management team hired Pilot manufacturing Patent grant First FDA meeting Regulatory opinions CEO hired Animal testing Clinician feedback Patent disclosure Prototype/Reduction to Practice Market Analysis Idea 2) Hire team & Execute 1) Plan in Reverse

21. Incremental vs Breakthrough © zen@acmedx.com METRIC INCREMENTAL BREAKTHROUGH Funding $$ $$$$$$ Market Size Varies depending on funding needed >$500MM No current therapies Time Needed Adoption & Exit Shorter Match opportunity to strategy Longer Regulatory path dependent Value @ Exit Less More Major Risks Window of opportunity Execution quality & critical path Competition Technical/Clinical unknowns Market adoption hurdles Reimbursement Success Factors Focused execution Management experience Manufacturing economics Patents, Franchise Value Market adoption, Std of Care Investor expectations Patent Protection Less More Competition More Less

23. Time is Life © zen@acmedx.com ACCELERANT DECCELERANT REGULATORY Device 510(k) Predictive animal models New materials & claims Unclear endpoints CLINICAL Existing human data Reproducible published studies Non-superiority Entrenched behavior No practice benefit REIMBURSEMENT Existing Codes DRGs Private-pay, consumer Cost-Benefit Studies MARKET Reduce skills needed Physician buying power Unambiguous diagnostic Capital equipment purchase SALES Focused physician popul. Existing distribution Learning curves Entrenched behavior

24. Accelerants Amplify Clinical Impact & Return on Investment © zen@acmedx.com Value Cashflow Time Milestones $0 COMPRESS TIME TO MARKET FASTER CURES

27. © zen@acmedx.com Michael Porter, tiesberg Economics drive innovation to interventions

41. Identify Opportunity from Off-Label Usage © zen@acmedx.com

42. Conclusion It’s not brain surgery © zen@acmedx.com

46. Backup Materials

53. High Impact Clinical Innovation Course © zen@acmedx.com