Non For Profit Model for Rare Disease Therapy Development 11/15/2018

Rare Disease Therapy Development - Historically Therapy Development Process Historically big business Large investment Time to Trial 6 to 8 years Rare disease economically not attractive 11/15/2018

Typical Rare Disease “Proactive” Advocacy Groups Foster collaborations Liaisons between Basic Research and Biotech companies Deliver resources to fill funding gaps in the development process “Managing science” –resources/timeframes/direction/goals Therapy focus – move what is known today forward Political Involvement 11/15/2018

Standard Therapeutic Options Enzyme Therapy Gene Transfer Stem Cell Therapy Small Molecule Pharmaceuticals High Through-put Screening 11/15/2018

Therapy Development Process Proof of Concept Investigational New Drug Application (IND) Protocol Development Markers and Endpoints Toxicology Short Term Studies Long Term Studies Pharmacology Chemistry/Manufacturing Dosage and Delivery Studies 11/15/2018

Therapy Development Process (cont.) Institutional Review Board (IRB) Informed Consent Forms Approvals Recombinant Advisory Committee (RAC) Food and Drug Administration (FDA) Clinical Trial Initiation 11/15/2018

Rare Disease Therapy Development Process Commonality A B C Proof of Concept X X X IND X X X IRB X X X RAC X X X FDA X X X Clinical Trial Initiation X X X 11/15/2018

Rare Disease Synergies Regardless of the therapy we all face the same procedural development issues. Uniting empowers rare diseases What is good for one of us is good for all How do we leverage the commonality? 11/15/2018

Non-For-Profit Therapy Development Model Non-For-Profit foundation sponsors the therapy development Academic society is the Principle Investigator 11/15/2018

Non-For-Profit Therapy Development Model Benefits Goal is to develop therapies verses commercialization of a drug Quickly take proof of concept from the lab to the clinic NPF assume risk and responsibility Leveraging infrastructure and regulatory knowledge Provide data to companies for future clinical phases for long term solutions Funding sources: foundations, companies, or NIH Cost savings in therapy development for companies to prove concept before large scale investment Business issues not a concern to achieve the NFP goals regarding intellectual properties or patents 11/15/2018

Advancing Rare Diseases to the Clinic in a United Approach Rare diseases have a platform to move to a clinical program Together we have stronger voice to regulatory committees Quicker to clinic Develop NFP models for each type of therapy We all face the same issues 11/15/2018