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
Company Confidential
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
Company Confidential
2011 © Eli Lilly and Company
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
Company Confidential
2011 © Eli Lilly and Company
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
Company Confidential
2011 © Eli Lilly and Company
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
Company Confidential
2011 © Eli Lilly and Company
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
Company Confidential
2011 © Eli Lilly and Company
• 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
Company Confidential
2011 © Eli Lilly and Company
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
Company Confidential
2011 © Eli Lilly and Company
How Does Open Innovation Drug
Discovery Work?
Company Confidential
2011 © Eli Lilly and Company
• Hypotheses
• Compounds
• Web Interface
• Affiliation
• Informatics
• Communication
• Assays
• In Silico Models
• Evaluation and
Decision Making
Academia
&
Biotech
Open Innovation Architecture
Company Confidential
2011 © Eli Lilly and Company
Evolution of Available Assays
Company Confidential
2011 © Eli Lilly and Company
Open Innovation Drug Discovery
Security Structure
Company Confidential
2011 © Eli Lilly and Company
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
Open Innovation Drug Discovery
Program and Website
Company Confidential
2011 © Eli Lilly and Company
Accessing the individual OIDD Account
Tour Inside the OIDD Website (1 of 5)
From the OIDD Training Guide (04-Sep-2012)
Company Confidential
2011 © Eli Lilly and Company
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
Tour Inside the OIDD Website (2 of 5)
From the OIDD Training Guide (04-Sep-2012)
Company Confidential
2011 © Eli Lilly and Company
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
Tour Inside the OIDD Website (3 of 5)
From the OIDD Training Guide (04-Sep-2012)
Company Confidential
2011 © Eli Lilly and Company
In the Ship Samples Tab
You can input shipping information (barcodes, sample amount, etc)
Shipping Samples from the Individual OIDD Account
Tour Inside the OIDD Website (4 of 5)
From the OIDD Training Guide (04-Sep-2012)
Company Confidential
2011 © Eli Lilly and Company
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
Tour Inside the OIDD Website (5 of 5)
From the OIDD Training Guide (04-Sep-2012)
Company Confidential
2011 © Eli Lilly and Company
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
Company Confidential
2011 © Eli Lilly and Company
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
Company Confidential
2011 © Eli Lilly and Company
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
Company Confidential
2011 © Eli Lilly and Company
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.
Company Confidential
2011 © Eli Lilly and Company
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
Company Confidential
2011 © Eli Lilly and Company
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)
Company Confidential
2011 © Eli Lilly and Company
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.
Company Confidential
2011 © Eli Lilly and Company
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