Launching Clinical Trials: Small Company vs Large Company Environment

1. Launching Clinical Trials: Small Company vs Large Company Environment Laurie A. Ridener, RAC Senior Director, Clinical and Regulatory Affairs Pervasis Therapeutics, Inc. Cambridge MA

2. Background • Pervasis Therapeutics, Inc. • Combination Biologic / Device Product • 15 Employees • EMD Serono, Inc. • Recombinant Therapeutic Proteins, Novel Device Delivery Systems • 3,000 Employees WW • 700 in US (~125 in Clinical Affairs, 20 in Regulatory Affairs) • Biolink, Inc. • Hemodialysis Access Device • 30 Employees • Continuum Biomedical, Inc. • Medical / Dental Laser Systems • 75 Employees • Medical Device CRO • 5 years

3. Small Company University-based Research Laboratory Engineer Physician Entrepreneur Resources limited Timelines fixed Delays terminal Expert management Large Company Internal R & D Marketing Clinical Affairs Senior Management Business Development Resources available Timelines “extendable” Delays accommodated Management diffuse Clinical Development Program

4. Basic Documentation – All Companies • Approved IDE / IND • Protocol • Investigator’s Brochure/Instruction Manual • Informed Consent • Investigational Device / Product Supply • Investigators • Evaluated, Qualified, Initiated • Study Subjects • Data to Support Marketing Application

5. Full Service CRO SOP Development Protocol Development Site Monitoring Project Management Data Management Statistical Analysis Medical Writing Training Niche Service Providers / Independent Contractors Monitoring Statistical Analysis Project Management Medical Writing Vertical Integration Hire key personnel SOPs in place Launching a Clinical Trial: Small Company

6. Launching a Clinical Trial: Small Company • Full Service CRO • The bigger the better • Proven Track Record in managing clinical trials • All the resources within one organization • One check to write each month • High level of expertise of consultants • Too big to manage • Large team membership, often at many locations • Involved with too many clinical trials, no individualized attention • Procedural flexibility limited • Review / processing time extended • Contract negotiations / changes arduous • High turnover rate

7. Launching a Clinical Trial: Small Company • Niche Service Providers / Independent Contractors • Customer Oriented • Individualized service and contracts • Low overhead • Pay only for service actually needed • Lots of Moving Parts • Expertise not guaranteed • Project management becomes full time job • In-house leadership critical

8. Launching a Clinical Trial: Small Company • Vertical Integration • Robust Team Composition • Direct control / influence over study progress • Reaction time swift and nimble • SOPs need to be in place • Liability • Huge milestone, big commitment • Harder to exchange a bad hire • Office space a consideration

9. Launching a Clinical Trial: Small Company • Planning for a Smooth Launch • Investigator involvement in protocol development AND case report form content • Test drive CRFs with study coordinators • Know IRB meeting dates, assist investigators in preparing IRB application • Schedule Site Qualification visits parallel with IDE/IND preparation • Determine packaging and shipping requirements; confirm “ship to” addresses • Pre-assemble Study Notebooks

10. Launching a Clinical Trial: Small Company • Investigator Meeting • Generates enthusiasm and momentum • Chance to clarify end-points, data collection requirements • Present timeline and anticipated enrollment activity • Allows investigator concerns to be address with collegial support • Include Study Coordinator • cultivate a relationship of collaboration and teamwork • Include other direct participants • Radiologists, independent assessors, lab personnel • Schedule in conjunction with society meeting

11. Launching a Clinical Trial: Small Company • Intense pressure to enroll that first patient • Start contract / agreement / indemnification process early • Submit to IRBS concurrent with IDE/IND submission • Risk: FDA requires revisions, need to resubmit to IRB, additional cost • Benefit: study sites ready to enroll upon FDA green light • Be ready to turn around IRB requested changes to the consent document quickly • Case Report Forms printed or EDC built, tested, on-line • Collect Investigator regulatory documents early • CV, Financial Disclosure, copy of medical license, agreement

12. Launching a Clinical Trial: Small Company • Key Considerations for Success • Director/Senior level FTE • Strong leadership skills with extensive clinical trial expertise and project management oversight • Small company experience mandatory • Hands-on experience is equally important as project oversight • Consider a small to medium sized CRO to get the best of all possibilities • Full service • Personal attention • Flexibility and quick turnaround time on deliverables

13. Small Company University-based Research Laboratory Engineer Physician Entrepreneur Resources limited Timelines fixed Delays terminal Expert management Large Company Internal R & D Marketing Clinical Affairs Senior Management Business Development Resources available Timelines extendable Delays accommodated Management diffuse Clinical Development Program

14. Basic Documentation – All Companies • Approved IDE / IND • Protocol • Investigator’s Brochure/Instruction Manual • Informed Consent • Investigational Device / Product Supply • Investigators • Evaluated, Qualified, Initiated • Study Subjects • Data to Support Marketing Application

15. In-house capabilities SOP Development Protocol Development Site Monitoring Project Management Data Management Statistical Analysis Medical Writing Training Niche Service Providers / Independent Contractors Monitoring Statistical Analysis Project Management Medical Writing Vertical Integration Key personnel in place Launching a Clinical Trial: Large Company

16. Launching a Clinical Trial: Large Company • Firm commitment from Senior Management • Set priorities • Allocate resources • Strong leadership • Project Management • Diverse team members, multinational • Other priorities, not “customer” focused • Large number of clinical studies

17. Launching a Clinical Trial: Large Company • Weekly Cross Functional Team Meetings • Clinical Trial Leaders • Clinical Operations, Monitors • Manufacturing • Data Management • Biostats • Regulatory Affairs • Pharmacovigilance • Follow-up with Team Members between meetings • Assign and track action items, hold members accountable

18. Launching a Clinical Trial: Large Company • Planning for a Smooth Launch • Minimal Investigator involvement • Kick-off meeting still valuable • IRB applications prepared by site personnel • Site Qualification visits are scheduled as monitors are available • Shipping clinical trial materials (Supply Chain, outsource) • Study Notebooks (outsource)

19. Launching a Clinical Trial: Large Company • Key Considerations for Sucess • Senior level Clinical Trial Leader • Strong leadership skills with extensive clinical trial expertise and project management oversight • Budgeting expertise, knowing where to spend, where to save • Consider outsourcing when appropriate • Excellent interpersonal communication skills • Bi-directional • Different management styles for different personalities

20. Thank you! Further questions: Laurie Ridener lridener@pervasistx.com 617.871.1211