Launching Clinical Trials Small Company vs Large Company

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

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 Pervasis Therapeutics, Inc. Confidential Information

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

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 Pervasis Therapeutics, Inc. Confidential Information

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

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 Pervasis Therapeutics, Inc. Confidential Information

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 Pervasis Therapeutics, Inc. Confidential Information

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 Pervasis Therapeutics, Inc. Confidential Information

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 Pervasis Therapeutics, Inc. Confidential Information

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 Pervasis Therapeutics, Inc. Confidential Information

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 Pervasis Therapeutics, Inc. Confidential Information

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 Pervasis Therapeutics, Inc. Confidential Information

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

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 Pervasis Therapeutics, Inc. Confidential Information

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

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 Pervasis Therapeutics, Inc. Confidential Information

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 Pervasis Therapeutics, Inc. Confidential Information

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) Pervasis Therapeutics, Inc. Confidential Information

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 Pervasis Therapeutics, Inc. Confidential Information

Thank you! Further questions: Laurie Ridener lridener@pervasistx. com 617. 871. 1211 Pervasis Therapeutics, Inc. Confidential Information