Open Source Pharma: Game changing for innovative medicine

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Presentation given by Dimitrios Tzalis, of the European Lead Factory, at the Open Source Pharma Conference at Rockefeller Foundation Bellagio Center, July 2014. Dimitrios Tzalis Bio: http://www.opensourcepharma.net/participants/dimitrios-tzalis Conference Agenda (See Day 1, Session 2): http://www.opensourcepharma.net/agenda.html

Transcript of 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 12. Crowdsourcing Chemical Scaffolds 13. 13 shape flatness Fsp3 clogP flatland MW Vertex team , J. Med. Chem., 54 ,64056416 (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 HFWs are found in 75% of compounds! CAS team, J. Org. Chem. 73, 4443-4451 (2008) 5% / 75% plot percentage of HFWs 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 16. Instant Feed-Back 16 17. Chemistry contributors 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 19. Crowdsourcing Biological Targets 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 owners 21 Compensation to EU Lead Factory - for Direct Exploitation only - Option for EFPIA to license Target Programme for Direct Exploitation Access Rights and Dissemination (IMIs 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 23. Organisational Framework Programme Team Target Planning Board Screening Selection Committee 23 Ethics Advisory Board Screening Review Board 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 29. Partnering Opportunity 29 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