Zen Chu's new presentation on the economic playbook for healthcare investment

1. The New Playbook for Healthcare Innovation CIMIT Innovation Grand Rounds Massachusetts General Hospital ZEN CHU Accelerated Medical Ventures ELAZER EDELMAN, MD, PhD MIT / HST / Harvard Medical School / Highland Capital MICHAEL GREELEY Flybridge Capital Partners MARSHA MOSES, PhD Children's Hospital Boston, Harvard Medical School JOE SMITH, MD, PhD VP, Emerging Technologies, Johnson & Johnson COSAT

6. Incremental vs Breakthrough Plenty of Incremental Value, Different Strategy © zen@acmedx.com METRIC INCREMENTAL BREAKTHROUGH Funding $$ $$$$$$ Market Size Varies depending on funding needed >$100MM 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

7. Value Built Far Past Invention Value Time Critical 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 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 © zen@acmedx.com

9. “ 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

10. Physician Roles on Team Value Time 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 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 Conflicts of Interest Critical Milestones © zen@acmedx.com

11. Accelerate Clinical Impact Time is Life Value 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 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 Critical Milestones COMPRESS TIME TO MARKET FASTER CURES © zen@acmedx.com

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

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

14. Prioritize & Translate Innovation Value Time Market Risk Reimbursement Physician & Patient Adoption Packaged Solutions Regulatory Risk Safety & Efficacy Management Risk Technology Risk 2) Team Execution 1) Plan in Reverse © zen@acmedx.com

17. Backup Information © zen@acmedx.com

18. 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 Hospital Sales Cycle Disincentives to change SALES Focused physician popul. Existing distribution Learning curves Entrenched behavior