The Story of Addi & Cassi

Presentation To :

Rare Disease Day 2014

A Family’s Quest To Treat An Ultra Rare Disease

Chris Hempel Addi & Cassi Fund

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 Rare Disease Day 2014

SOAR-NPC

• • • • • • • Teamed up with 5 families, pooled financial resources Created ‘Virtual BioTech’ • SOAR-NPC ( S upport O f A ccelerated R esearch) 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 Rare Disease Day 2014

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 Rare Disease Day 2014

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 Rare Disease Day 2014

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Cyclodextrin as a Drug

Twins Receiving IV Infusions

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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 Rare Disease Day 2014

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 I trial at NIH; N=9 underway – Phase II trial being considered now… Rare Disease Day 2014

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 Rare Disease Day 2014

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 Rare Disease Day 2014

iPS Derived Neurons - Cassi

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Before Ommaya Reservoir Surgery

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After Surgical Complication

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Thank You For The Opportunity

To Speak To You Today

Rare Disease Day 2014