Lilly Open Innovation Drug Discovery Program · 2017-06-27 · 2 4 6 8 10 12 14 s n l n way n t g t...

Company Confidential

2011© Eli Lilly and Company

ChemAxon UGM, Boston, Sep 25-26

Daniel H. Robertson, Sr. Dir, LRL IT Research

Lilly Open Innovation Drug

Discovery Program


2011 © Eli Lilly and Company

What is Open Innovation?

• Companies cannot afford to rely entirely on their

own research

• A paradigm that assumes that firms can and

should use external ideas as well as internal ideas

• Boundaries between firm and environment have

become more permeable



Our Underlying Philosophy

• Lilly’s number one priority is increasing the flow of innovative therapies that make a real difference for patients across multiple disease indications

• Partnering and collaborating is a part of our heritage and has been a key element of our strategy for more than a decade

• Successful partnerships are essential for Lilly’s ongoing pursuit of innovation

• We are committed to developing our current staff as well as scientific leaders for the future

Lilly Research Laboratories is exploring innovative approaches to improve success rates of future drug discovery

and development efforts



MW

Structural Complexity

specificity

therapeutic

protein

antibody

peptide

small peptide

natural product small

synthetic stapled

peptide

spiegelmer

ASO/siRNA

Small

Molecule

Accessible Target Space

Large

Molecule

bi-specific

antibody

Spectrum of Therapeutic Modality

Chemical Space



High Quality Molecules to Test

Clinical Hypotheses

Phenotypic Drug Discovery

Uncover/optimize

molecule signatures

Target Directed Screening Repurpose/modify

existing molecules

Fragment Approaches Molecules built

for purpose

Small Molecule Discovery Entry Points

Drug Discovery

discrete target

phenotype

Drug Discovery Strategies



Opportunity for Open Innovation

An Alternative Concept to Gathering

Chemical Diversity

Are we done with the compound collection?

• No, the compound collection needs to be dynamic and responsive to our

emerging areas of disease and target strategies

What challenges & barriers do we have to evolving our compound collection?

• Identification of new sources of compounds and maintenance of a large collection brings quality & financial challenges

Are there distinct sources of molecules available that we should consider (academia and small biotech)?

• We could engage external scientists to access their compounds and ideas in a collaborative framework to advance common interests



• Expand discovery organization through access to

external global scientific talent, assets and

resources.

• Unbiased partnerships with academics and small

biotechs.

• Explore alternative models for interaction and

value creation that leverage Lilly science.

• Incremental costs on top of existing internal

investments.

• Measurable return on investment.

Phenotypic Drug Discovery Initiative (PD2)

launched Sep 2009

Target Drug Discovery Initiative (TargetD2)

launched July 2011

Academia & Biotech

Open Innovation Drug Discovery

Scientific Initiatives



OIDD Design Challenges

Foundational

• Business model and universal MTA design

• Building trust

• IP ownership

• Biological data as up-front transactional currency

• Confidentiality of chemical structures

• Ability for academics to publish

• Compliance and consistency

Operational

• Website design and enablement within Lilly

• Managing multiple partnerships across the globe

• Compound logistics

• Timely data turnaround and communication

• Crisp internal decision-making

Organizational

• Demonstrating value to corporation

• Existing and expanding on incremental investment only

• Ensuring integration with internal portfolio:

• Avoiding conflict

• Reaching synergy



How Does Open Innovation Drug

Discovery Work?



• Hypotheses

• Compounds

• Web Interface

• Affiliation

• Informatics

• Communication

• Assays

• In Silico Models

• Evaluation and

Decision Making

Academia

&

Biotech

Open Innovation Architecture



Evolution of Available Assays




Security Structure



Governed through a universal MTA and affiliation process

To provide LRL with access to novel small-molecules that influence

biological targets or pathways of therapeutic area interest

openinnovation.lilly.com/dd


Program and Website

http://openinnovation.lilly.com/dd



Accessing the individual OIDD Account

Tour Inside the OIDD Website (1 of 5)

From the OIDD Training Guide (04-Sep-2012)



There are 4 important tabs to manage your compound submissions:

Manage Libraries: Maintain libraries of compounds (default view)

Track compounds: Overall view of user’s compounds

Ship Samples: Input shipping information (barcodes, weights, etc)

View Reports: Maintain all data reports associated with compounds

completed with biological screening

Managing the Individual OIDD Account





In the Track Compounds Tab

• You can track your compounds by the compound

ID, structure Name, current Stage, Status, stage

Outcome, etc.

• To filter, click on the drop down tab in the column,

go to “Filters” and choose the category you would

like to view.

Tracking Status of Compounds in the Individual OIDD Account





In the Ship Samples Tab

You can input shipping information (barcodes, sample amount, etc)

Shipping Samples from the Individual OIDD Account





In the View Reports Tab

You can view and download all data reports associated with

your compounds that have completed biological screening

Accessing Reports in the Individual OIDD Account





Open Innovation Current Global Network

280 Affiliations in 30 Countries: • 186 Research Universities

and Institutes

• 78 Small Biotechs

• 6 Collaborations

University

Research Institute

Small Biotech

Lilly Site



0

10 000

20 000

30 000

40 000

50 000

60 000Compounds Passed Informatics Filter (in silico)

Compounds Accepted for Biological Screening (in silico)

Compounds Received for Biological Screening 48,794

22,52

3 17,68

7

Cumulative Compound Metrics

0

200

400

600

800

1000

1200

1400

1600

1800

2000

0 0,05 0,1 0,15 0,2 0,25 0,3 0,35 0,4 0,46

Distance from Nearest Lilly Molecule

PD2 Compound Diversity Analysis

Num

ber

of C

om

pounds

Approx. 50% of

Compounds

Accepted for Screening Exclusion:

• Fail Med Chem Rules

• Insufficient Novelty

• Similar to Tested Compounds

• Similar to Controlled

..Substances

Filter

Compound Activity Evolution OIDD Compound Diversity Analysis



Chemical Diversity Metrics:

Analysis of Similarity Results

1

10

100

1000

10000

100000

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.43

Nu

mb

er o

f Mo

lecu

les

Distance

Chemical DiversityMolecular Distance for PD2 Fingerprints vs PubChem Structures

Many molecules are similar or

identical to those in PubChem, but a

large proportion are significantly

different (> 0.15)

Approximately one quarter of the

submitted structures (n=25.6K) are

significantly (> 0.15) different from

anything else in the OIDD2 collection.

Molecular Distance for OIDD Fingerprints vs PubChem Structures



OIDD Screening Metrics – August

2012 Analysis of Current Screening Module Results (15K submitted

cpds)

0

2

4

6

8

10

12

14

Anti-a

ngio

gene

sis

GLP

-1 S

ecre

tio

n

Kra

s/W

nt S

ynth

etic L

eth

al

Insu

lin S

ecre

tio

n

Wnt P

ath

way

ApoE

Secre

tio

n

GP

R119

R A

gon

ist

CG

RP

R A

nta

g

Apelin

R A

gon

ist

He

xo

kin

ase 2

In

h

mG

lu2 R

Anta

g

NP

T Inh

PD2

TargetD2

12,4

6,2

5,0

3,7 3,4

2,3 2,1

1,7

1,0 0,4

0,2 0,0

Primary Assay Module % Hit Rates

OIDD significantly complements

internal compound collection

with access to diverse,

biologically active molecules.



Characteristics of OIDD Collaborations

OIDD collaborations are flexible, can span the wide range of legal structures to match partner’s unique objectives

Opportunity for future revenue

Research funding

Publication opportunities

Opportunity to work with Lilly

Collaborations may be molecule-based or biology-based (TI/TV)

By design, collaborations are short duration, high/risk, relatively low cost to minimize overhead

Periodic progress evaluation, usually with 1-2 years of exclusivity for Lilly with a proviso to negotiate in good faith at the conclusion of that period

Managing expectations of up front value requires attention

We believe that this strategy will give us sufficient time to conduct research to determine whether the opportunity merits further investment



Demonstrating Internal Value:

OIDD Collaboration Opportunities

Anti-angiogenesis scaffold,

non-G2M, non-kinase MoA

(“right to evaluate” )

Diabetes scaffold, active in rat &

human islets

(2-yr postdoc support)

Anti-angiogenesis scaffold, good

LEAN, amenable to SAR

(fee-for-service only)



Opportunities from OIDD for Lilly

NCATS’ Pharmaceutical Collection of more than 3,800 approved and

investigational medicines will be screened in Lilly’s PD2 assays. Data

could provide new insights into biological pathways of approved or

potential medicines and will be made publicly available.



What Next?

• Short term:

• SAR and SPR models & other scientific tools available online

• Improved reporting tools

• Acceptance of plated samples

• Logistics improvements (voice of the customer)

• Expansion into new chemical types (large molecules)

• Profiling of reference standards and probe molecules

• Mid & long term:

• Reference collection for assay validation

• New target/assay ideas

• OIDD community of practice

Lilly Open Innovation Drug Discovery Program · 2017-06-27 · 2 4 6 8 10 12 14 s n l n way n t g t...

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