Open Source Pharma: Game changing for innovative medicine
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Transcript of Open Source Pharma: Game changing for innovative medicine
Game Changing for Innovative Medicine
Dr. Dimitrios Tzalis, Taros Chemicals
Towards a New Open Source Pharma Industry for the Global Poor, Sfondrata 16-18 July 2014
Disclaimer
2
Dear Reader,
Only the official and formally signed contractual documents in
relation to the EU Lead Factory (the Project Agreement, Grant
Agreement, the Description of Work, and Third Party Access
Agreements) have a binding value in relation to the subject
matter covered in these slides.
Any information contained in these slides is not binding upon
the parties and can in no event be used to interpret or
complement the formally signed contractual documents
referred to above.
The EU Lead Factory Team
Drug Research Value Chain
3
CompoundValue
TargetTargetHit
findingHit
findingHit to lead
Hit to lead
Lead seriesLead
seriesPhase I &
IIPhase I &
II
Phase II &
registrate
Phase II &
registrateSales €€Sales €€
Years 3 5 6 8 11 13 25
Collaborative Drug Discovery
4
MolecularTargets
European
Screening
Centre
EFPIA contribution(>300.000 cpds)
Public contribution(up to 200.000 cpds)
Joint
European
Compound
Library
Compounds
uHTS
Compound logistics
Hit triage
Medicinal Chemistry
A Large-Scale Controlled Experiment
5
Shared Use of
Compound Collections
Shared Use of
Compound Collections
Crowd-SourcingInnovation
from Biology & Chemistry
Crowd-SourcingInnovation
from Biology & Chemistry
Partneringof Public Target
Programmes
Partneringof Public Target
Programmes
Value Generation from Publicly-
funded Initiative
Value Generation from Publicly-
funded Initiative
A Large-Scale Controlled Experiment
6
Shared Use of
Compound Collections
Crowd-SourcingInnovation
from Biology & Chemistry
Crowd-SourcingInnovation
from Biology & Chemistry
Partneringof Public Target
Programmes
Partneringof Public Target
Programmes
Value Generation from Publicly-
funded Initiative
Value Generation from Publicly-
funded Initiative
Building the JECL
7
Joint
European
Compound
Library
January 2013 January 2014June 2013
EFPIA Library:
326,486 Compounds
Public Library:
6,347 Compounds
August 2013
plated and delivered to 8 Screening Centres
A Large-Scale Controlled Experiment
8
Shared Use of
Compound Collections
Shared Use of
Compound Collections
Crowd-Crowd-SourcingInnovation
from Biology & Chemistry
Partneringof Public Target
Programmes
Partneringof Public Target
Programmes
Value Generation from Publicly-
funded Initiative
Value Generation from Publicly-
funded Initiative
Join us!
• Novelty (target or assay approach)
• Top scientific quality
• Defined molecular target
• HTS compatible assay
• Novelty
• Drug-like
• Diversity potential
• Synthetic tractability
• Innovation
TargetProposals
LibraryProposals
9
List of hit structures
=
Flying start
Potential partnerships
€€€
and
Opportunity to translate an idea into a chemical library
10
TargetProposals
LibraryProposals
What you can get!
Accession process
11
Agree to "Website Terms of Use"
Electronic signature
"Access Agreement"
Selection Committee
Signing
"Form of Accession"
Target/Library
Design
Proposal
Selected
Proposal
Joint
European
Compound
Library
EuropeanScreeningCentre
Execution
Crowdsourcing Chemical Scaffolds
13
sh
ap
e
flatn
ess
Fsp3
clogP
flatland
MW
Vertex team , J. Med. Chem., 54 ,6405–6416 (2011)
Fsp3 and clogP/MW diverged over the last 20 years!
Medicinal chemists create less three-dimensionality
Pronounced tendency for compounds from flatland
� Reliance on “easy chemistry“, Pd-couplings, etc.
~ 420.000 compounds
5% of HFW‘s are found in 75% of compounds!
CAS team, J. Org. Chem. 73, 4443-4451 (2008)
5% / 75%
plot percentage of HFW‘s on x-axis (most=left, least=right)
plot percentage of compounds that contain HFW on y axis
~ 25.000.000 organic compounds~ 2.600.000 HeteroFrameWorks
Library Proposal Criteria
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Criteria
Novelty
Diversity potential
ideally, potential to yield
>500 final compounds
Structural features
Innovative library
design
Synthetic tractability
Molecular properties
scored for drug-likeness
with preferred clogP < 4
Proposals of highest degree of technical maturity will be prioritised
15
Instant Feed-Back
16
Chemistry contributor’s…
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Rights
Compensation-fixed Monetary Rewards-
€ 500
€ 2 000
€ 5 000
Obligations
Access Rights to Consortium Participants
- Exclusive & Royalty Free
Better Validation = Better Reward
• Validated library idea
• Well documented protocols
• 2 g of key intermediate
• Evidence that >50 compounds can be prepared
•
Joint
European
Compound
Library 5,000 €+ appl VAT
>50cmpdsDirect production
Crowdsourcing Biological Targets
Target Proposal Criteria
• Value determined by
– Scientific quality
– Innovation potential of target
or
new chemistry associated with target
– Disease relevance
– Diversity of portfolio
• Technical feasibility of the assay
• Transfer to HTS in 3-4 months
• Different from EU Lead Factory targets
20
No phenotypic assays
Target assay owner’s…
21
Compensationto EU Lead Factory
- for Direct Exploitation only -
Option for EFPIAto license Target Programme for
Direct Exploitation
Access Rights and
Dissemination(IMI‘s IP Policy)
Obligations
Access Rights and 3 Year
Exclusivity to Exploit
Qualified Hit List Results
Full Control of Target
Programme Progression
Rights
Screening of a unique
Compound Library at
Screening Facility
Submission(1-2 weeks)
Submission(1-2 weeks)
Review
(1-2 months)
Review
(1-2 months)
Acceptance(1 month)
Acceptance(1 month)
Review and Selection Process
22
• Prior commitments
• Technically not feasible (yet)
No
Conditional
Yes
• Further guidance on process
• Arrangement of Legal Forms
StartStart
Programme Office Screening Selection
CommitteeTarget Programme Owner
& Programme Office
Organisational Framework
Programme Team
Target Planning
Board
Screening Selection
Committee
23
Ethics Advisory
Board
Screening Review Board
Execution Target Programme
24
Confidential
Programme Team
Preliminary Hit List
Qualified Hit List
Hit Validation
Functional assay
Hit Expansion
Crystallography
ImprovedHit List
Compound clearance
ProgrammePlan
European Screening
Centre
Deliverables Target Programme
25
Hit Statistics
Qualified Hit Listwith associated
biological data
Preliminary Hit List
(Compound sample or
synthetic procedure)
AssayMiniaturization
Public Target Programmes Progress
26
Submitted
53
Accepted
19
Assay
development
19
uHTS
11
Hit
Follow-up
6
QHL
1
Molecular
Targets
15 May 2014
What happens after QHL delivery?
27
17-7-
Qualified
Hit List
3-year exclusivity period(Research or Direct Exploitation)
MilestonePayments
First option to
EFPIA partners
A Large-Scale Controlled Experiment
28
Shared Use of
Compound Collections
Shared Use of
Compound Collections
Crowd-SourcingInnovation
from Biology & Chemistry
Crowd-SourcingInnovation
from Biology & Chemistry
Partneringof Public Target
Programmes
Value Generation from Publicly-
funded Initiative
Value Generation from Publicly-
funded Initiative
Partnering Opportunity
29
A Large-Scale Controlled Experiment
30
Shared Use of
Compound Collections
Shared Use of
Compound Collections
Crowd-SourcingInnovation
from Biology & Chemistry
Crowd-SourcingInnovation
from Biology & Chemistry
Partneringof Public Target
Programmes
Partneringof Public Target
Programmes
Value Value Generation from Publicly-
funded Initiative
Publication Policy
Dissemination is encouraged! Standard Reviewing Period
Presentations
Scientific publications
Posters
Abstracts
• Clearance from the
European Lead Factory team
• IP Protection
• No confidential data
• Conflicting interests
31
Ready for Value Generation
32
Made Possible by
33
EU Lead Factory
combines
innovation of Academia,
agility of SMEs, and
experience of Pharma
and funding from
Taros Chemicals GmbH & Co KG 34
Cross Pollination in Open Innovation
• Improves creativity by putting together the best minds on one problem
• Innovation increases when scientist of different backgrounds interact w/o formal hierarchy
• Larger population of researchers with different view points than the “limited” staff resource in an single company or academic/research institutes
• Open Innovation requires a new form of Project Management and Coordination