Why There Needs to be Open Data for Ultra-Rare and Rare Disease

Drug Discovery  

Sean Ekins1, Alex M. Clark2, Jill Wood3,4, Lori Sames5,6 and Allison Moore7

1Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay Varina, NC27526, USA.

2Molecular Materials Informatics, 1900 St. Jacques #302, Montreal, Quebec, Canada H3J 2S1

3Jonah's Just Begun, P.O. Box 150057, Brooklyn, NY 11215, USA.

4Phoenix Nest, P.O. BOX 150057, Brooklyn NY 11215, USA.

5Hannah's Hope Fund, P.O. Box 130, Rexford, NY 12148, USA.

6BioGAN Therapeutics, P.O. Box 130, Rexford, NY 12148, USA.

7Hereditary Neuropathy Foundation, 432 Park Avenue South – 4th floor,New York, NY 10016, USA.

• Very few researchers chasing >7000 diseases

• NIH $3.5bn in rare diseases - orphan drugs $749M 11.4% budget in 2011 numbers

• Relatively easy to treat. At the forefront of gene therapy resurgence

• Only miniscule clinical trials possible

Rare disease biology not well knownAffects 10s- 1000s per disease Treatments need to be expensive $1M/yr pp

The Problem/ Opportunity

Examples of Rare Diseases

This is Jonah

• Parents founded • He needs a cure for Sanfilippo syndrome

(MPS IIIC) • Collaborates with global groups• Researchers just developed a KO mouse

funded by Sanfilippo foundations globally• Searching for small molecule therapy,

study animal models (Dr. Alexey Pshezhetsky, University of Montreal)

• Working on gene therapy (Dr. Brian Bigger, University of Manchester)

• Natural History Study (Dr. Paul Levy, Montefiore)

• Started registry

This is Hannah

• Parents founded • She needs a cure for Giant Axonal

Neuropathy• Searching for small molecule

therapy (funded postdoc with Dr. Jim Inglese, NIH)

• Funded gene therapy - entering clinical trial (Dr. Steven Gray, UNC)

• Funded - Natural history study (Dr. Douglas Sproule, Columbia)

• Started Registry - GRIN

The Rare Disease Parent Odyssey

• Diagnosis of child• Try to find out about disease – papers behind paywall• Try to connect with scientists • Form not-for-profit• Raise funds• Fund Scientific research on disease• Advocate for support from NIH, FDA etc• Start a company• Try to find a cure before its too late

Wood J et al., Drug Disc Today, 18: 1043–1051, 2013

Let me repeat….A Parent/ Patient Advocate with no Ph.D. can do all this

• Start a foundation• Raise funds• Become an expert on their/childs disease• Set up a scientific advisory board• Fund scientific projects• Submit NIH grants• Start a company• Leverage social media, traditional media

Abigail Alliance for Better Access to Developmental DrugsAddi & Cassi FundAmerican Behcet's Disease AssociationAmschwand Sarcoma Cancer Foundation BDSRA (Batten Disease Support and Research Association)Beyond Batten Disease FoundationBlake’s Purpose Foundation Breakthrough Cancer Coalition Canadian PKU & Allied DisordersCenter for Orphan Disease Research and Therapy, University of PennsylvaniaChildren’s Cardiomyopathy FoundationCooley's Anemia FoundationDani’s Foundation Drew’s Hope Research Foundation EveryLife Foundation for Rare DiseasesGIST Cancer Awareness FoundationHannah's Hope Fund Hope4Bridget FoundationHypertrophic Cardiomyopathy Association - HCMAI Have IIH ISRMD (International Society for Mannosidosis and Related Diseases)Jacob’s Cure Jain FoundationJonah's Just Begun-Foundation to Cure Sanfilippo Inc.Kids V CancerKurt+Peter FoundationLGMD2I Research FundLymphangiomatosis & Gorham's Disease Alliance MAGIC FoundationManton Center for Orphan Disease ResearchMarbleRoadMary Payton's Miracle Foundation Midwest Asian Health Association (MAHA)

MPD SupportNational Gaucher FoundationNational MPS SocietyNational Organization Against Rare Cancers National PKU AllianceNational Tay-Sachs & Allied Diseases AssociationNew Hope Research Foundation NextGEN Policy Noah's Hope - Batten disease research fundOur Promise to Nicholas Foundation Oxalosis and Hyperoxaluria FoundationPartnership for Cures Periodic Paralysis AssociationRARE ProjectRyan Foundation for MPS Children Sanfilippo Foundation for ChildrenSarcoma Foundation of AmericaSolving Kids' Cancer Taylor's Tale: Fighting Batten Disease Team Sanfilippo FoundationThe Alliance Against Alveolar Soft Part SarcomaThe Life Raft Group The NOMID AllianceThe Transverse Myelitis AssociationThe XLH Network, Inc.United Pompe Foundation

Many of these groups are doing R&D on a shoestring how can we help? How do they fund it?

Just some of the many rare disease groups

Crowdfunding Science

Huffington Post The O’Neills raised > $1M through crowdfunding to datehttp://www.curesff.org/www.SavingEliza.comFunding gene therapy for Sanfilippo A

Jonny Lee Miller raised >$177,526 for Sanfilippo C on Crowdrise

Crowdfunding Rare Disease Science

Disruption needed• #1: NIH and other international scientific

funding bodies should mandate …open accessibility for all data generated by publicly funded research.

• #2: Reboot the pharmaceutical industry by extending the notion of ‘‘precompetitive’’ collaboration to encompass later stages of research to allow PPPs to flourish.

• #3: FDA takes a proactive role in making relevant clinical data available that will help all drug developers (as well as NCATS) to bridge the valley of death and remove a bottleneck.

• #4: Companies listen to the patients as they generate data on social media, mine it for indications and off target effects. Companies and funding bodies will find the innovators to exploit this information and use collaborative tools to share data

Rare disease foundations publishing their ideas and recommendations

• New ways to do research

• Sharing data openly

Examples of Open Science and Tools to Share Openly

Linked Open data cloud 2011 (Wikipedia)

Insert disease of choice here

Learning from OSDD TB and Malaria efforts

Open Source Drug Discovery (OSDD) is the concept of drug discovery where all data and ideas are shared in real time, and anyone may participate at any level.

This prior disclosure means that there will be no patents and that any technology is both academically and commercially exploitable by whoever wishes to do so.

Openness..can be confusing

• Open Access versus Free Access• Open Data versus free to download• Open Source and all of its “licenses”

Barriers

• Priority• Ownership of data• IP, patenting, How people make money• Ethical• Personal privacy• Publishing, rewards and promotions – kudos• Publishing open access has cost involved..

Benefits

• Other families and scientists can find your data• Minimize repetition• Lower costs of research, increase efficiency• Analogy to Linux – open source can be

commercial success• Some open scientists are notable

A Mobile App for Open Drug Discovery

A flipboard for science #ODDT

iOS only

Embraced by rare disease advocates

Getting people to share data openly is a challenge

NIH SBIR reviewers want closed systems to preserve IP

Developed with Alex Clark

Open Drug Discovery Teams – brings data from Twitter and the internet together

Ekins et al., Mol Informatics, 31: 585-597, 2012

http://goo.gl/r9NP7p

Uses of ODDT for Sanfilippo syndrome http://goo.gl/Zlpmyc

What is needed?

• “Helpers” to take the weight off the parent/patient• How to manage the complex data?• How to make sense of the literature?• How to foster collaboration?• How to leverage what is learnt from other diseases?• How scientists find funding or projects to work on?• How parents find scientists to solve their problems?• How to accelerate the process of discovery?• Find patients for registries and clinical studies

Support human Champions with software and systems

• Parents need expert advice• Drug Discovery advice• Preclinical advice• Awareness of research outside of their

disease

This could be you here

A mashup of..

• Crowdfunding• Crowdsourcing• Open Innovation• Open Source• Open Science• Precompetitive Initiative• Open Collaboration

Start a companyEnables you to apply for SBIR /STTR grants

Fund research – help academics and commercialize their work

Then use NIH TRND and NCATS programs

Getting the word out there – publish in open journals

Study using patient fibroblasts and plasma showed TGF-B1 elevatedPublished in closed journal

Knowns drugs that down regulate it not tested

Losartan, statins, puromycin, rimonabant, Aliskiren

http://goo.gl/Y2iBBF

Helping the researchers to help the patients

Finding Promiscuous Old Drugs for New Uses

everolimus

5-fluorouracil

ceftriaxone

Could In silico / in vitro repositioning find leads-drugs quicker?

One family found another family with a child with the disease by reading a blog

Increasing awareness – rare diseases go mainstream

..So lets make rare disease data open

PAPER ID: 22104 “Collaborative sharing of molecules and data in the mobile age” (final paper number: 43)DIVISION: COMP; DAY & TIME OF PRESENTATION: August 10, 2014 from 4:45 pm to 5:15 pmLOCATION: Moscone Center, West Bldg., Room: 2005 PAPER ID: 22094 “Expanding the metabolite mimic approach to identify hits for Mycobacterium tuberculosis ” (final paper number: 78)DIVISION: COMP: DAY & TIME OF PRESENTATION: August 11, 2014 from 9:00 am to 9:30 amLOCATION: Moscone Center, West Bldg., Room: 2005 PAPER ID: 22120 “Why there needs to be open data for ultrarare and rare disease drug discovery” (final paper number: 48)DIVISION: CINF:SESSION DAY & TIME OF PRESENTATION: August 11, 2014 from 10:50 am to 11:20 amLOCATION: Palace Hotel, Room: Marina PAPER ID: 22183 “Progress in computational toxicology” (final paper number: 125)DIVISION: TOXI: DAY & TIME OF PRESENTATION: August 12, 2014 from 6:30 pm to 10:30 pmLOCATION: Moscone Center, North Bldg. , Room: 134 PAPER ID: 22091 “Examples of how to inspire the next generation to pursue computational chemistry/cheminformatics” (final paper number: 100)DIVISION: CINF: Division of Chemical Information DAY & TIME OF PRESENTATION: August 13, 2014 from 8:25 am to 8:50 amLOCATION: Palace Hotel, Room: Presidio PAPER ID: 22176 “Applying computational models for transporters to predict toxicity” (final paper number: 132)DIVISION: TOXI: DAY & TIME OF PRESENTATION: August 13, 2014 from 9:45 am to 10:05 amLOCATION: InterContinental San Francisco, Room: Grand Ballroom A PAPER ID: 22186 “New target prediction and visualization tools incorporating open source molecular fingerprints for TB mobile version 2” (final paper number: 123)DIVISION: CINF: DAY & TIME OF PRESENTATION: August 13, 2014 from 1:35 pm to 2:05 pmLOCATION: Palace Hotel, Room: California Parlor

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We gratefully acknowledge all the scientists who have worked on the rare diseases described and shared their data

Lisa M. Jarvis for covering rare diseases at C&E News

Antony J. Williams for inspiring open research

Email: ekinssean@yahoo.com

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