1 An Example of a Lean Startup: The Past, Present and Future of the Open Drug Discovery Teams Mobile App An Example of a Lean Startup: The Past, Present and Future of the Open Drug Discovery Teams Mobile App © Molecular Materials Informatics, Inc. and Collaborations in Chemistry April 2013 Sean Ekins 1, Alex M. Clark 2 1 Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay Varina, NC 27526, U.S.A. 2 Molecular Materials Informatics, 1900 St. Jacques #302, Montreal, Quebec, Canada H3J 2S1.

Timeline Feb 2012 – ODDT idea to prototype presented at Pistoia Alliance meeting in London April 2012 – App Launched and presented at Pistoia Alliance meeting in Boston July IndieGoGo Crowdfunding Aug ODDT paper published Oct Tweeted NCATS compound structures March 2013 – RSC Sponsors App

In the Beginning…The Past

When Given a New Challenge How do You Respond? Mid January 2012 Pistoia Alliance Ask for volunteers to present in a Dragon’s Den Scenario Feb 8 th at the RSC Ideas that will transform Pharma R&D in 2014 So my natural response was : “If I am going to take part I want to create something real”

Why it is time to transform R&D – This is just one disease! Tuberculosis Kills m/yr (~1 every 8 seconds) equivalent to malaria 1/3rd of worlds population infected!!!! Extensively drug resistant increasing incidence No new drugs in over 40 yrs Drug-drug interactions and Cc-morbidity with HIV Recent years have seen increased investment from Bill and Melinda Gates Foundation (BMGF) etc. But no impact on new clinical candidates except from pharma Pipeline is thin and weak No data sharing on the scale of malaria Open Source effort in India (OSDD) but no real international traction Disconnected efforts - CDD, Pharmas, Academia, NIH BMGF & NIH do not coordinate TB efforts, not mandating open data. – Result data hoarding – still not learning from failure – thousands of compounds screened and not accessible

Motivation Early 2012: Sean Ekins met Jill Wood at a rare disease conference Mother of a child suffering from Sanfillipo Syndrome -Incidence rate: 1 in ≫ 100,000 She had to become a scientist, doctor, entrepreneur and venture capitalist to accelerate a cure Finding information shouldn't be so hard... Jonah's Just Begun Phoenix Nest Biotech phoenixnestbiotech.com

The Problem Rare diseases? Neglected markets? Resources are extremely tight Cannot afford not to share research Drug discovery research is very asymmetric Diseases with many wealthy sufferers get most of the attention: great return on investment >7000 rare diseases

Inspiration There are many 1000s of diseases and few with cures Science Online 2012 on open notebooks and data overload Flipboard Could we create an app for science like Flipboard?

Why not create an app? Can we connect researchers and patients? Can we create Open Drug Discovery Teams How do we bring information on diseases to the people that need it Can we centralize the data that matters? Bring social media into rare diseases

What influenced design? Simple user friendly design concept Flipping through topics, big buttons, easy to see on phone and app Crowdsourcing – use feedback to vote on topics Why is there no Flipboard for Science?

So I started sketching on my iPad..

How would we go about finding these teams?

Can we create virtual teams of open researchers – we need a central hub to integrate open science data

Everything is on the cloud and the App becomes the glue for the team and projects

How the App should look – note the Flipboard inspiration

Sounding Boards are Very Important Antony J. Williams VP, Strategic development for ChemSpider at the Royal Society of Chemistry. Alex M. Clark is the founder of Molecular Materials Informatics, Inc. Alex said he could build the App

Within about 10 days Alex Created ODDT to present at the Pistoia meeting Focused on Tuberculosis, Malaria, HIV/AIDS, Huntington’s Disease, Sanfilippo Syndrome, and Green Chemistry as topics in version 1 We did not win the competition but had useful feedback – the need to articulate the value proposition

The Value Proposition The project is intended to bring together open data in a single aggregated collection, and then facilitate forming open research teams around this data Disseminate important information to a highly relevant target audience Network and discover other researchers with complementary interests, and opportunities to collaborate Team members will be able to borrow and reuse a growing collection of existing Open data. The community as a whole can debate, contest or endorse data based on its quality. The app could also be used as a type of “lab notebook” whereby individual researchers share links (URLs) to content and the app aggregates these.

Getting to the Alpha Version Added more topics – Chagas Disease, leishmaniasis Added voting Added Stats page Added datasheet viewing ….Find alpha testers

2012 ODDT Layout 9 Panels includes one on ODDT information Can use multiple Twitter accounts Here is my icon Stats summary About App

In the Beginning.. Summary App released on Appstore early April 2012 Ran an IndieGoGo crowdfunding experiment Presented at ACS, TriConf, Partnering for Cures in 2012 Several posters on slideshare and figshare Published a paper on ODDT Ekins S, Clark AM and Williams AJ, Open Drug Discovery Teams: A Chemistry Mobile App for Collaboration, Mol Informatics, 31: , ticles/PMC /pdf/minf pdf ticles/PMC /pdf/minf pdf

Drug Discovery Today, 18: , 2013 Disrupting Drug Discovery

Using ODDT in a Mobile App workflow Chem-Bio Informatics Journal, 13:

The Present

Rare and neglected disease and chemistry Topics – Keeps growing Tuberculosis, Malaria, Chagas disease, Leishmaniasis, HIV/AIDS, Huntingtons disease, Sanfilippo syndrome, Global Genes, Green Chemistry, Drug repurposing, Giant Axonal Neuropathy, Hunter syndrome, Real time chemistry, Hereditary Neuropathy Foundation, H5N1, Rare Disease report, Fibromuscular Dysplasia, iCancer ACS Chemical Information #tuberculosis #malaria #hivaids #huntingtons #sanfilipposyndrome #rarediseases #leishmaniasis #chagas #h5n1 #greenchemistry #hhf4gan #MPSII #huntersyndrome #hunterparents #realtimechem #HNF #raredr #fmdaware #icancer #ACSCINF

What can ODDT do? Collects Twitter feeds on hashtags for topics Collects RSS feeds on topics Allows you to see tweets of molecules and structure activity data If you contribute to a topic you are visible in the app It can track your contributions to topics All of the above happens in one App

2013 ODDT Layout

Tap on a panel and look at Incoming contents Click here to endorse or disapprove Click here to follow hyperlink

Browse through multiple pages of tweets

Endorse, Disapprove and Comment

Recent contents

Content

Tap on a link or image

Be able to download content

Look at your own and topic statistics Own statisticsTopic statistics

How to use the app Use it to publish links to your blogs on the topic Publish your chemistry, Structure activity data that could help others Use it to raise awareness of a new paper Parents / researchers can find out about the disease – what is current, what has published Use it to collaborate openly – an open labnotebook You can curate the data – vote on what matters to you Share the important findings Use it for inspiration that crosses diseases and topics Get rare and neglected disease researchers to use green chemistry.

What is needed Break down paywalls to papers – Neglected disease apps could increase visibility of older content to parent advocates and researchers Breaks down walls to data – Only recent data in PubChem etc..rediscovery of old drugs published previously for TB..(e.g. PNAS Gold et al.) Find sponsors who promote openness

Busting paywalls

Secure sharing

Problems can be opportunities Rare diseases have small research communities Less investment than Cancer, CV etc Published data inaccessible to parents But.. Apps existing for symptoms disease mgmt Tight knit communities Willing to collaborate Try different approaches Approaches generalizable, cheap, disruptive..

The Solution Schematic government pharma charity funding academics startups foundations literature blogs open science publication Twitter content aggregation research communities Open Drug Discovery Teams #hashtags RSS Feeds

Molecules ODDT is chemistry aware...opens up a world of possibilities... harvesting chemical data allows many possibilities

Chemistry ODDT understands links chemical data, and has special viewing, manipulation and collaboration features for molecules and reactions Other apps such as the Mobile Molecular DataSheet allow direct tweeting of chemical data with ODDT topic hash tags...

The Future

Future The App becomes a “notebook” for science Integrate other data sources PubMed, Google Scholar etc Add annotation around diseases Becomes a database of chemistry and biology data around the diseases that is open Link to tools that enable drug discovery by anyone Could we add docking and QSAR models etc. Rewards / badges

Logical next steps ODDT customizable by 7000 diseases Imagine each rare disease community as app – with access to private and public data (DDT) Make more data available as apps or publish in apps. Reuse data – mash up – find new ways to use- apps facilitate e.g. GSK just announced 200 TB cpds to be public - content could be pushed out in ODDT NCATS 58 molecules from Pharmas- no structures – published in ODDT Show examples of drug discovery by mobile device Show how hypothesis from one disease can apply elsewhere Demonstrate repurposing by app

Where to next ODDT is an experimental project Sponsorship: App is free, data is totally open Potentially valuable intellectual property Know of a rare or neglected disease with an online community? We can add a new topic Know anyone who is interested in sponsoring projects to increase awareness of rare or neglected diseases? Contact us!

Future Developments The Open Drug Discovery Teams project is currently a minimum viable product New developments are happening fast, e.g. - More topics - New data sources - Advanced cheminformatics Your feedback is welcome. Download the app, try it out, and get in touch!

Data to Appify? If you have Drug Discovery data or ideas that could be turned into an app please let us know Alex Clark has developed these other Apps

Availability Open Drug Discovery Teams (ODDT) is available free from the Apple iTunes AppStore

In the literature Ekins S, Clark AM and Williams AJ, Open Drug Discovery Teams: A Chemistry Mobile App for Collaboration, Mol Informatics, 31: , pdf pdf Clark AM, Williams AJ and Ekins S, Cheminformatics workflows using mobile apps, Chem-Bio Informatics Journal, 13: Ekins S, Clark AM and Williams AJ, Incorporating Green Chemistry Concepts into Mobile Applications and their potential uses, ACS Sustain Chem Eng, , Ekins S, Waller CL, Bradley MP, Clark AM and Williams AJ, Four disruptive strategies for removing drug discovery bottlenecks, Drug Discovery Today, 18: ,

52 © 2012 Molecular Materials Informatics, Inc. and Collaborations in Chemistry