Rare Disease Day 2014

Presentation To:The Jackson Laboratory

Chris HempelAddi & Cassi Fund

A Family’s Quest To Treat An Ultra Rare Disease

The Story of Addi & Cassi

Rare Disease Day 2014

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 (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

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

Cyclodextrin as a Drug

Rare Disease Day 2014

Twins Receiving IV Infusions

Rare Disease Day 2014

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

Rare Disease Day 2014

Before Ommaya Reservoir Surgery

Rare Disease Day 2014

After Surgical Complication

Rare Disease Day 2014

Thank You For The Opportunity To Speak To You Today