Everylife Foundation Annual Scientific Workshop

ANNUAL RARE DISEASE SCIENTIFIC WORKSHOP Improving the Clinical Development Process

Workshop 6: Rationalizing Safety Testing to Enable Clinical Studies & Approval in the US for Rare Disease Treatments

Hosted By: EveryLife Foundation for Rare Diseases Sofitel Hotel Washington, D.C. Lafayette Square September 16, 2014

AGENDA Workshop Overall Goal: The goal of workshop 6 is to continue the discussions from previous workshops concerning issues most relevant to the development process of innovative medicines to treat rare diseases. This workshop will focus on the regulatory aspects of safety requirements during the drug development process, and current trends, issues, and perspectives on safety and toxicology. The goal of the workshop is to ensure all stakeholders have a chance to discuss and comment on the important scientific elements regarding the toxicity and safety regulatory requirements. Morning Session REGISTRATIO 8:30 – 9:00 N AND AM BREAKFAST Introduction 9:00 AM Welcome Emil Kakkis, MD, PhD President & Founder, EveryLife Foundation for Rare Diseases President &CEO, Ultragenyx

Session A: Safety & Toxicology Perspectives from Health Authority Agencies

9:30 AM IND-Enabling Safety Studies in Rare Diseases Timothy McGovern, PhD ODE Associate Director for 1 September 16, 2014 EveryLife Foundation Annual Scientific Workshop Pharmacology /Toxicology Office of New Drugs, CDER, FDA Questions & 9:50 AM Discussion

10:00 AM An EU Regulatory View on Non-Clinical Support for First in Human Trials in Rare Disease David R. Jones Expert Scientific Assessor, Licensing Division, MHRA Questions & 10:20 AM Discussion

Safety Assessment for Rare and Orphan Diseases in 10:30 AM Clinical Trials Andrew Mulberg, MD, FAAP, CPI Division Deputy Director, Division of Gastroenterol ogy and Inborn Error Products ODE III,CDER, FDA Questions & 10:50 AM Discussion

Session A (cont)

11:00 – 11:15 AM BREAK

11:15 AM Immune Tolerance Induction in

2 September 16, 2014 EveryLife Foundation Annual Scientific Workshop Enzyme Replacement Therapy for Lysosomal Storage Diseases: Optimizing Therapeutic Outcome with Preventive Strategies Amy S. Rosenberg, MD Director, Division of Therapeutic Proteins, CDER, FDA Questions & 11:35 AM Discussion

11:45 AM An Introduction to Biosafe and Overview of Activities in the Rare Disease Area Timothy MacLachlan, PhD, DABT Chair, Biosafe Leadership Committee Executive Director, Preclinical Safety, Novartis Questions & 12:05 PM Discussion

12:15 – 1:00 PM LUNCH Afternoon Session

Session B: Case Studies in PreClinical Safety and Toxicology

1:00 PM Preclinical

3 September 16, 2014 EveryLife Foundation Annual Scientific Workshop Experience with rhASM for Neimann- Pick Disease Gerald Cox, MD Vice President, Clinical Development, Rare Disease Group, Genzyme Questions & 1:20 PM Discussion

1:30 PM Nonclinical Development of Enzyme Replacement Therapies for Severely Affected Patients of Orphan Diseases: Assessment of Animal Model and Normal Animal Toxicology Data Charles O’Neill, PhD Vice President, Pharmacologi cal Sciences, Biomarin Questions & 1:50 PM Discussion

2:00 – 2:15 PM BREAK

Session C: Safety and Toxicology Issues for Genetic Platform Technologies

2:15 PM OSWG’s Role in Shaping Nonclinical Regulatory Strategy in the Development of Oligonucleotide Therapeutics David Schubert, PhD Vice President, Regulatory & Quality, Stealth Peptides Questions & 2:35 PM Discussion

4 September 16, 2014 EveryLife Foundation Annual Scientific Workshop

Session C (cont)

Preclinical Safety Assessment of Phosphorodia midate Morpholino Oligomers 2:45 PM (PMO) Peter Sazani, PhD Executive Director, Medical Affairs, Sarepta Questions & 3:05 PM Discussion

Gene Therapy Vector Platforms share common safety and 3:15 PM efficacy issues when deployed across groups of similar orphan diseases James Wilson, MD, PhD Professor of Pathology and Laboratory Medicine Research Director, Center for Orphan Disease Research and Therapy

5 September 16, 2014 EveryLife Foundation Annual Scientific Workshop Director, Gene Therapy Program, University of Pennsylvania Questions & 3:35 PM Discussion

Summary and Final Discussion, Future Directions and Closing 3:45 PM Remarks Emil Kakkis, MD, PhD President & Founder, EveryLife Foundation for Rare Diseases President & CEO, Ultragenyx

End of 4:15 PM Workshop

Thank you to our Scientific Workshop Sponsors: