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


Crowd-SourcingInnovation

from Biology & Chemistry



Partneringof Public Target

Programmes


Programmes

Value Generation from Publicly-

funded Initiative


funded Initiative


6

Shared Use of







Programmes


Programmes


funded Initiative


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


8

Shared Use of


Shared Use of


Crowd-Crowd-SourcingInnovation



Programmes


Programmes


funded Initiative


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

Instant Feed-Back

16

Chemistry contributor’s…

17

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

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• 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


28

Shared Use of


Shared Use of







Programmes


funded Initiative


funded Initiative

Partnering Opportunity

29


30

Shared Use of


Shared Use of







Programmes


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

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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

Open Source Pharma: Game changing for innovative medicine

Science

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