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Mission Statement Orphan diseases represent a collection of disorders that afflict <200,000 individuals for any single disease type, and yet, as there are ~7,000 orphan diseases, in aggregate over 25M US citizens suffer substantial morbidity and mortality. Despite this burden, research in most orphan diseases has lagged far behind other major areas due to a combination of technological and funding limitations. The mission of the Penn Center for Orphan Disease Research and Therapy is to facilitate and expedite the development of novel therapies for orphan disorders/diseases. The Center will achieve this mission through innovation of therapeutic strategies and translation of these into the clinic, building on partnerships among investigators, academic institutions, industry, and funding agencies.

Opportunity There are major opportunities for developing therapies for rare diseases.  Industry interest in rare diseases has never been higher. Many industry programs are focused on developing small molecule and biological therapeutics targeting rare diseases. - Orphan Disease Act - Gateway to other indications  Gene Therapy is positioned to transform the treatment of many rare diseases.

Center Membership  To date, the Center has 229 full members and 91 associate members.  184 members at Penn/CHOP  45 members from other institutions, including members from 6 foreign countries  The 91 associate members are primarily Penn/CHOP trainees  In aggregate, the membership studies >200 rare diseases.

Center Leadership  Director: H. Lee Sweeney, PhD Research Director: Jim Wilson, MD, PhD Clinical Director: To be named  Program Areas and Heads:  Metabolic Disorders - Jim Wilson, MD, PhD  Hematological Disorders – Kathy High, MD  Rare cardiovascular diseases – Dan Rader, MD  Ocular Disorders – Jean Bennett, MD, PhD  Neuromuscular Disorders – H. Lee Sweeney, PhD  Internal Advisory Board  Program Heads  Terry Fadem (Industry Advisor)  External Advisory Board  Industry, Advocacy, Government, and Academic Advisors

Major activities of the Center in progress: 1)Drug/small molecule screening I. Cell-Based Drug Screens with NCATS (agreement in place) a. Repurposing screens that the Center contracts to have performed b. NCATS/Center Co-development grant program Chemical library screens with subsequent drug development - costs of screen and development covered by NCATS (competitive application) - investigator costs covered by Center II. Assay development and preliminary approved library screens with Wistar small molecule screening facility Contract with Wistar Molecular Screening Facility to help design screens that can be used in HT format and carry out initial screens III. Small molecule screens for altering Protein-Protein interactions or modulating enzyme activity Agreement terms with X-Chem have been reached.  Call for small molecule screening proposals to be released on June 1, 2014

Major activities of the Center in progress: 2)Research grants programs a)MPS I therapeutic development grants b)Rare disease research and therapy development grants Co-funded by Advocacy groups, industry, and individuals. The grants will be solicited in multiple Rare Disease areas, driven by participation of Advocacy groups. Funding generated by the “Million Dollar Bike Ride”

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SPIN FACTOR FOR Hemophilia

Improving the Process of Rare Disease Treatment Development Emil D. Kakkis, M.D., Ph.D. Chief Executive Officer and President, Ultragenyx Pharmaceutical, Inc.

Progress Toward Molecular Based Therapies for Neuromuscular Disease Jerry R. Mendell, M.D. Director, Center for Gene Therapy The Research Institute at Nationwide Children’s Hospital

Development of a 2-hydroxypropyl- β-cyclodextrin therapeutic trial for Niemann-Pick disease, type C1 Forbes D. Porter M.D., Ph.D. Senior Investigator, Program Head and Clinical Director, NICHD, NIH

Development of a Novel RNAi Therapeutic, Patisiran, for the Treatment of TTRmediated Familial Amyloidotic Polyneuropathy (FAP) Akshay K. Vaishnaw, M.D., Ph.D. Executive Vice-President and Chief Medical Officer, Alnylam Pharmaceuticals, Inc.

Exploration of AAV-Mediated Gene therapies for Inherited Ocular Disorders Gwyneth Jane Farrar, Ph.D. Professor of Genetics Smurfit Institute of Genetics Trinity College, Dublin

Gene Therapy for Haemophilia B UCL/St Jude's Trial Update at 4 Years Edward G.D. Tuddenham, M.D. Emeritus Professor of Haemophilia, UCL Katherine Dormandy Haemophilia Centre Royal Free Hospital

Speakers: Emil D. Kakkis, M.D., Ph.D. Chief Executive Officer and President, Ultragenyx Pharmaceutical, Inc. Jerry R. Mendell, M.D. Director, Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital Forbes D. Porter M.D., Ph.D. Senior Investigator, Program Head and Clinical Director, NICHD, NIH Edward G.D. Tuddenham, M.D. Emeritus Professor of Haemophilia, UCL Katherine Dormandy Haemophilia Ctr., Royal Free Hospital Gwyneth Jane Farrar, Ph.D. Professor of Genetics, Smurfit Institute of Genetics, Trinity College, Dublin Ireland Akshay K. Vaishnaw, M.D., Ph.D. Executive Vice-President and Chief Medical Officer, Alnylam Pharmaceuticals, Inc. Registration & Membership Info: or There is no cost to join or attend the symposium. Join us as we explore: “Emerging Therapies For Rare Diseases” Symposium includes: Breakfast, Lunch Poster Session Afternoon Reception