A Family’s Quest To Treat An Ultra Rare Disease

1. A Family’s Quest To Treat An Ultra Rare Disease The Story of Addi & Cassi The Jackson Laboratory Presentation To: Chris Hempel Addi & Cassi Fund

2. Rare Disease “Advocists” • Hugh & Chris Hempel from Reno, Nevada • 2004: blessed with identical twins, Addi and Cassi, six • high-tech folks from the Bay Area • no scientific background • 2005: medical odyssey with twins begins • 2007: twins diagnosed with Niemann Pick Type C, ultra rare and fatal genetic cholesterol condition • Condition called “Childhood Alzheimer’s” • Self described rare disease “advocists”: • advocate + activist

3. SOAR-NPC • Teamed up with 5 families, pooled financial resources • Created ‘Virtual BioTech’ • SOAR-NPC (Support Of Accelerated Research) for Niemann Pick Type C disease • Fund researchers willing to collaborate across labs and engage with families • Created ‘ASAP Program’ – As Safe As Possible • Hired PhD to help sift through medical data • Short term: Looking for FDA approved drugs off-label or OTC supplements, anything to treat children today • Longer term: new drug development

4. Cyclodextrin – Our Miracle? • Days after NPC diagnosis, promising sugar compound cyclodextrin (HPBCD) came to our attention • Cyclodextrin is key ingredient in Febreze® Fabric Spray, fat free butter, GRAS in Europe/Japan • Cyclodextrin extracts cholesterol from cell cultures • Promising neurological results in NPC mice • Told Cyclodextrin was “many years” from ever going into children – work in parallel? • Inserted ourselves directly into the scientific process despite resistance and lack of knowledge

5. Cyclodextrin as a Case Study • Goal: How do we conduct and fund N of 2 human study and safety trial without Pharma, BioTech, NIH or NPC Foundation support? • Lorenzo’s Oil – Happening to me 20 years later? • Doctor at Children’s Hospital Oakland willing to help – form unique partnership • No experience with FDA or drug development process • Wrote intravenous human protocol from scratch • Hired Contract Pharma PhD expert • Created and tested the compound • Hospital Pharmacist created solution

6. Cyclodextrin as a Drug

7. Twins Receiving IV Infusions

8. FDA IND Success To Date • Same safety rules apply to us as “traditional trials” • April 2009, FDA approved intravenous INDs • 16 months after initial NPC diagnosis • FDA helpful but process is cumbersome especially when running a sprint, not a marathon • April 2010 filed Orphan Drug Application with FDA, received designation in May 2010 • August 2010 filed intrathecal INDs, approved Sept. 2010 • 1st intrathecal infusion into twins’ CNS on Oct. 15, 2010 • 2013 Filed Ommaya Route of Administration IND • 2014 First Ommaya Delivery

9. Initial N=2 Study Results and Next Steps • N=2 Intravenous study results: • Improvements: ataxia, eye movements, swallowing • Twins continue to decline neurologically, BBB issues • Future plans: • Phase Itrial at NIH; N=9 underway • Phase II trial being considered now…

10. Running Trial on a Shoestring Budget • Cyclodextrin is relatively inexpensive, no patents = no venture capital • Insurance – another miracle! • Goodwill of doctors, scientists and laboratories doing work pro-bono • Personal checkbook • Johnson and Johnson’s role (Toxicity Data, PK) • Time as valuable as money: Full-time job for 3 years • How do I get this drug approved for a cheaply as possible? • FDA Grants, Orphan Drug Tax Credits

11. Additional Treatment Avenues • Personalized Medicine approach; individual genome • Could be first family ever created from induced pluripotent stem cells (iPS cells derived from skin) • MIT has differentiated iPS cells into neurons • National Chemical Genomics Center (NCGC) and MIT collaboration • Create neuron model to test all FDA approved drugs and other library of compounds • ‘Search and Rescue’ mouse model underway

12. iPS Derived Neurons - Cassi

13. Before Ommaya Reservoir Surgery

14. After Surgical Complication

15. Thank You For The Opportunity To Speak To You Today