Open Source Pharma: Game changing for innovative medicine
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The document discusses the European Lead Factory project, which aims to establish an open source pharma industry for developing drugs for neglected diseases. It outlines the collaborative drug discovery process, including crowdsourcing chemical compounds and biological targets, screening compounds through a shared library, and making qualified hit lists available to partners. The goal is to generate value from publicly funded initiatives through this large-scale open innovation experiment.
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Open Source Pharma: Game changing for innovative medicine
- 1. 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
- 2. 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
- 3. Drug Research Value Chain 3 Compound Value TargetTarget Hit finding Hit finding Hit to lead Hit to lead Lead series Lead series Phase I & II Phase I & II Phase II & registrate Phase II & registrate Sales €€Sales €€ Years 3 5 6 8 11 13 25
- 4. Collaborative Drug Discovery 4 Molecular Targets 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
- 5. A Large-Scale Controlled Experiment 5 Shared Use of Compound Collections Shared Use of Compound Collections Crowd- Sourcing Innovation from Biology & Chemistry Crowd- Sourcing Innovation from Biology & Chemistry Partnering of Public Target Programmes Partnering of Public Target Programmes Value Generation from Publicly- funded Initiative Value Generation from Publicly- funded Initiative
- 6. A Large-Scale Controlled Experiment 6 Shared Use of Compound Collections Crowd- Sourcing Innovation from Biology & Chemistry Crowd- Sourcing Innovation from Biology & Chemistry Partnering of Public Target Programmes Partnering of Public Target Programmes Value Generation from Publicly- funded Initiative Value Generation from Publicly- funded Initiative
- 7. 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. A Large-Scale Controlled Experiment 8 Shared Use of Compound Collections Shared Use of Compound Collections Crowd-Crowd- Sourcing Innovation from Biology & Chemistry Partnering of Public Target Programmes Partnering of Public Target Programmes Value Generation from Publicly- funded Initiative Value Generation from Publicly- funded Initiative
- 9. Join us! • Novelty (target or assay approach) • Top scientific quality • Defined molecular target • HTS compatible assay • Novelty • Drug-like • Diversity potential • Synthetic tractability • Innovation Target Proposals Library Proposals 9
- 10. List of hit structures = Flying start Potential partnerships €€€ and Opportunity to translate an idea into a chemical library 10 Target Proposals Library Proposals What you can get!
- 11. 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 European Screening Centre Execution
- 13. 13 shape flatness 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
- 14. Library Proposal Criteria 14 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. 15
- 17. Chemistry contributor’s… 17 Rights Compensation -fixed Monetary Rewards- € 500 € 2 000 € 5 000 Obligations Access Rights to Consortium Participants - Exclusive & Royalty Free
- 18. 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 >50 cmpdsDirect production
- 20. 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
- 21. Target assay owner’s… 21 Compensation to EU Lead Factory - for Direct Exploitation only - Option for EFPIA to 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
- 22. 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 Committee Target Programme Owner & Programme Office
- 24. Execution Target Programme 24 Confidential Programme Team Preliminary Hit List Qualified Hit List Hit Validation Functional assay Hit Expansion Crystallography Improved Hit List Compound clearance Programme Plan European Screening Centre
- 25. Deliverables Target Programme 25 Hit Statistics Qualified Hit List with associated biological data Preliminary Hit List (Compound sample or synthetic procedure) Assay Miniaturization
- 26. 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
- 27. What happens after QHL delivery? 27 17-7- Qualified Hit List 3-year exclusivity period (Research or Direct Exploitation) Milestone Payments First option to EFPIA partners
- 28. A Large-Scale Controlled Experiment 28 Shared Use of Compound Collections Shared Use of Compound Collections Crowd- Sourcing Innovation from Biology & Chemistry Crowd- Sourcing Innovation from Biology & Chemistry Partnering of Public Target Programmes Value Generation from Publicly- funded Initiative Value Generation from Publicly- funded Initiative
- 30. A Large-Scale Controlled Experiment 30 Shared Use of Compound Collections Shared Use of Compound Collections Crowd- Sourcing Innovation from Biology & Chemistry Crowd- Sourcing Innovation from Biology & Chemistry Partnering of Public Target Programmes Partnering of Public Target Programmes ValueValue Generation from Publicly- funded Initiative
- 31. 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
- 32. Ready for Value Generation 32
- 33. Made Possible by 33 EU Lead Factory combines innovation of Academia, agility of SMEs, and experience of Pharma and funding from
- 34. 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
Hinweis der Redaktion
- The disclaimer included in the exit slide, so this slide might be omitted.
- The ultimate goal European lead factory is to produce top-quality starting points for hit-to-lead/lead optimisation drug discovery programmes. ELF’s role is to help bridging the value gap in early drug discovery, i.e. enable the identification of high value, high quality hits that can be develop into drug lead compounds.
- The EU Lead Factory is the first pharmaceutical and life sciences partnership of its kind. Seven big pharma sharing proprietary compounds library ideas are crowdsourced in order to expand the JECL with top quality compounds biological target assays are crowdsourced targets will be screened to no upfront cost at the industry standard European Screening Centre against JECL It has been designed to create unrivalled opportunities for the discovery of new drug lead molecules.
- This slide reoccurs and can be used as an outline of the talk.
- 7 big pharma companies have joint forces and are sharing compounds not only with each other, but are also letting European researchers screen their targets through the EU Lead Factory.
- Participate ipv contribute
- The title can be adjusted depending on the audience. Your Reward! What’s in it for you! Get the reward!
- General outline for both Target owners and chemistry contributors. Terms of use website = You agree with the website storing your contact details etc. Submission agreement = Online submission of your proposal for review: You retain ownership of your proposal and only grant a license to the consortium for facilitating selection. You keep ownership of the idea and therefore are allowed to publish or pursue any activity you want. Access agreement = freedom to operate (submitter) and to evaluate (ELF) and confidentiality of proposal Form of Accession = Acceptance of all relevant clauses of the project agreement (requirement for participation, Not negotiable!)
- ELF aims to provide better compounds than the average screening library, i.e. incorporating more diverse hetero frameworks and more sp3 hybridized carbons (avoiding flatland). HFW, Lipkus et al : http://pubs.acs.org/doi/pdf/10.1021/jo8001276 Flatland, Walters et al:
- The molecule in the corner is an example of what would not fit in JECL. Molecular properties – the drug-relevant molecular properties with preferred clogP &lt; 4 Structural features – structural features that may constitute a liability in screening compounds Novelty – novelty of the proposed compounds by comparison with a reference set of commercially-available and patented compounds Diversity potential – value of the proposed approach for the synthesis of ideally more than 500 final compounds Synthetic tractability – the likely synthetic accessibility by consortium partners of the compound based on the precedent provided Innovative library design – the rationale that has been used for the design of the compound
- Proposals are submitted online via the EU Lead Factory website: www.EuropeanLeadFactory.eu
- Instant feed-back on your proposal in the for-purpose designed ELF submission tool
- N.B. This is only valid for accepted proposals and after the access agreement is signed. Phase 1. Online submission of your proposal for review: You retain ownership of your proposal and only grant a license to the consortium for facilitating selection. You keep ownership of the idea and therefore are allowed to publish or pursue any activity you want. Phase 2. If your proposal is accepted, you sign the accession agreement giving the consortium exclusive rights on you proposal and any compounds/derivatives generated with the proposal in exchange for a monetary reward.
- Criteria for €5,000 reward: Scaffold synthesis validated on a multi-gram scale AND With full experimental details and spectra for all intermediates provided for the validated synthesis AND With a physical sample of &gt;2 g (&gt;90% purity) of the key intermediate provided to the consortium immediately prior to diversification with AND With evidence of identify and purity provided for any derivatives that have been prepared from the key intermediate
- A balance weighing over in the advantage of the target owner. cf Back-up slides
- To secure high quality, ethically correct and efficient selection and execution of Target Programmes many committees and boards have been installed. Independent, external advisors are appointed in these committees. The European Screening Centre (logos to the left) uses services from other EU sponsored consortia, e.g. OpenPhacts.
- Programme Owner is part of the Programme Team Particularly interesting/promising target programmes can be offered med chem services within ELF, resulting in an Improved hit list (IHL), if resources allow.
- These numbers will change as of 21 May (Screening Selection Committee meeting)
- Patent Milestones Three Options (selected at Programme start):(a) € 50,000 to be paid within 45 day after receipt of invoice(b) € 75,000 to be paid within 2 years after achievement of the Milestone(c) 10 % of Compensations received by Programme Owner for Target Programme Clinical Milestones for a product containing a QHL Compound or M-Derivative First IND Approval€ 250,000 Start* Phase II€ 750,000(*dosing of 5th patient) Start* Phase III€ 2,500,000 Diagnostic Milestones for a product containing a QHL Compound or M-Derivative first market launch in the US, EU, China, Brazil, India or Japan€ 250,000 Change of Control upon licensing or transfer of a Target Programme to a Third Party (a) before IND approval€ 250,000 (b) after IND approval€ 1,000,000
- cf Back-up slide Dissemination: Publication Approval Publishing key results of target and scaffold programmes is encouraged in order to share the generated knowledge and further advertise the EU Lead Factory concept. However, it requires adherence to the consortium’s publication approval process, which aims to balance the interests of all participants.
- The European Lead Factory differs from the numerous academic initiatives in this field by emphasizing the aspect of value generation from the Lead Factory activities. Publications alone are not viewed as enough success. More tangible value is seen in down-stream alliances formed to progress the screening results along the pharmaceutical value chain, license agreements around generated intellectual property or the generation of spin-outs based on assets generated by external contributors and the European Lead Factory.