Why Are We Still Doing Industrial Age Drug Discovery For Neglected Diseases in The

Information Age?

Sean Ekins

CollaborationsIn Chemistry,Fuquay Varina, NC

Some Technologies change faster than we do

But Drug Discovery has not changed much in 40 years

Because change happens slowly

Drug discovery is a very slow race… that needs a kickstart

And of course no treatments for neglected diseases are blockbusters

Still valuing the 70’s BLOCKBUSTER model but its changing

Produce few of …

The Old School vs New Schoolscreening

• New School - Many hurdles before in vivo - lots of data Yet HTS started in the 1980’s!!

• Old school – go in vivo at outset – little data

• New database technologies work well for New school but ..Old School type data ?

Drug Discovery Archeology

• Still a heavy emphasis on “testing” “doing “ rather than ‘learning’

• Mining data and historic data will increase in value

• Data becomes a repurposing opportunity

• How do we position databases for this?

• What about neglected diseases?

Now neglected diseases has big data too

A computational window into data and models

Should there be more ?

But what about small data?

• In some cases its all we have• In vivo data is not high throughput

• Small data builds networks DATA

V

http://smalldatagroup.com/

Ponder et al., Pharm Res In Press 2013

Tested >300,000 molecules Tested ~2M>1500 active and non toxic Published 177

Big Data: Screening for New Tuberculosis Treatments

How many will become a new drug?How do we learn from this big data?

«Tuberculosis» 333 papers in PubMed«Malaria» 301 papers in PubMed

Small data: Mouse In vivo model data

Can combining Big and Small data (in vitro, in vivo) help us find better compounds, faster ?

Avoid testing as many molecules

Connecting data/tools like a TB Spider

In vitro data In vivo data

Target data

ADME/Tox data & Models

Drug-like scaffold creation

TB Prediction Tools TB Publications

Where are the New TB drugs to be found?

In vivo actives (yellow)

Optimal Human properties

Optimal Mouse properties

Optimal TB entry properties

Filling the toolbox

• Who has the data?• Who has the models?• Who has molecules?

Drug Discovery Toolbox

Hunting for the in vivo data

It’s out there.. be patient

30 years with little TB mouse in vivo data

TB

MoDELS RESIDE IN PAPERSNOT ACCESSIBLE…THIS IS UNDESIRABLE

Hunting High and Low for new molecules to test

We need to search sources..From the Oceans…

To the ground To the treesTo the air..And do it virtually

Time for the New New School

Models replace testingTesting = confirmingPredict in vivo and in vitro in parallelMULTIDIMENSIONALSave resources

TO BE CONTINUED…

Joel S. FreundlichAntony J. WilliamsAlex M. Clark