From   Chemistry       toDrug Candidates
Agenda  •   Introduction of Mercachem  •   Drug Discovery & trends  •   Development of services of Mercachem  •   Project ...
Facts and figures   Innovative Netherlands-based chemistry service provider in   discovery chemistry, medicinal chemistry ...
Facts and figures   4,000 m2 modern research facilities with 10 synthesis   laboratories (120 fume hoods)   Moved to a new...
Services   Exclusive   - Discovery chemistry services   - Medicinal chemistry services   - Process research & development ...
MarketsPharmaceuticals (~70%)Agrochemicals (~10 %)Animal Health (~5%)Flavors and fragrances (~5%)Speciality chemicals (~5%...
Drug Discovery Definition: process by which drugs are discovered and/or designed Process: • Identification & validation of...
Drug Discovery pipelineCosts (m$)(Out of pocket)Costs (m$)                  8(capitalized)
Drug Discovery pipeline   UMC                                UMC             Mercachem                                    ...
Trends in pharmaceutical research  Mergers and acquisitions at big pharma  (Organon, Schering-Plough, MSD)  R&D is moving ...
Outsourcing     Reasons:     •   Focus on primary activities     •   Expertise     •   New methodologies / technologies   ...
Development of ServicesPhase 0: Start   Start of Mercachem       •   Two founders with PhD in Organic Chemistry       •   ...
Development of ServicesPhase 1: discovery chemistry   Market trends (1996-2001):       •   Outsourcing of small parts of d...
Development of ServicesPhase 1: discovery chemistry   Discovery Chemistry Services:   Lab-scale synthesis of:      • Resea...
Drug Discovery pipeline       Discovery chemistry
Development of ServicesPhase 2: Process R&D services   Market trends (2002-2005):       •   Outsourcing of bigger parts of...
Development of ServicesPhase 2: Process R&D services   Process Research Services:       • Route development and route scou...
Drug Discovery pipeline       Discovery chemistry                         Process R&D
Development of ServicesPhase 3: Medicinal Chemistry services   Market trends (2006-2011):       •   Outsourcing of complet...
Development of ServicesPhase 3: Medicinal Chemistry services  Medicinal Chemistry Services:     •   Hit Finding , Hit opti...
Drug Discovery pipeline        Discovery chemistry                           Process R&D     Medicinal chemistry
Integrated services       Target             Assay         Hit            Lead         Preclinical      IND filing   Phase...
Mercachem’s strengths  Unprecedented knowledge solving synthetic challenges by  team of experienced chemists and knowledge...
Performance in 2010     Number of active customers      : > 60     Number of projects              : 205     Number of com...
Patents and publications  Patents and publications:  • WO2009007098 (Syngenta)  • WO2009003650 (Bayer CropScience)  • WO20...
Multidisciplinary Integration                                Partnerships:                                ZoBio Leiden    ...
Project Example:Reverse Transcriptase inhibitors Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI’s) anti HIV-drugs ...
Project Example:Reverse Transcriptase inhibitors Project Development & synthesis of 2nd generation DAPY compounds Results ...
Project Example:Dr. August Wolff – Mercachem collaboration in Medicinal chemistry   Dr. August Wolff Arzneimittel GmbH & C...
Project Example:PDE inhibitors for Neglected Tropical DiseasesProject T4-302:PDE inhibitors for Neglected Tropical Disease...
Project Example:PDE inhibitors for Neglected Tropical Diseases Project T4-302: PDE inhibitors for Neglected Tropical Disea...
Project Example:PDE inhibitors for Neglected Tropical DiseasesVolkskrant 13-09-2011
www.mercachem.com           Dr. Eelco Ebbers           eelco.ebbers@mercachem.com
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Mercachem - eelco ebbers 22092011

  1. 1. From Chemistry toDrug Candidates
  2. 2. Agenda • Introduction of Mercachem • Drug Discovery & trends • Development of services of Mercachem • Project examples 1
  3. 3. Facts and figures Innovative Netherlands-based chemistry service provider in discovery chemistry, medicinal chemistry and process research One of the leading CRO’s in Europe 110 employees (45% Ph.D. and 55% M.Sc./B.Sc.) Spin-out of University of Nijmegen Founded in 1997
  4. 4. Facts and figures 4,000 m2 modern research facilities with 10 synthesis laboratories (120 fume hoods) Moved to a new state-of-the-art laboratory facility in 2006 Located in Nijmegen (2 sites) Independent, privately owned
  5. 5. Services Exclusive - Discovery chemistry services - Medicinal chemistry services - Process research & development services to support research and development programs of companies and research institutes worldwide Regions: - Europe - US - Japan
  6. 6. MarketsPharmaceuticals (~70%)Agrochemicals (~10 %)Animal Health (~5%)Flavors and fragrances (~5%)Speciality chemicals (~5%)• cosmetics• monomers• diagnosticsResearch organizations (~5%)
  7. 7. Drug Discovery Definition: process by which drugs are discovered and/or designed Process: • Identification & validation of target & candidates • Synthesis, optimization & characterization • Screening and assays for therapeutic efficacy • Drug development • Clinical trials Despite advances in technology and understanding of biology drug discovery is still: • Lengthy, expensive, difficult, and inefficient process • Low rate of new therapeutic discovery Currently: Research and development cost of each NME: ~ US$1.8 billion
  8. 8. Drug Discovery pipelineCosts (m$)(Out of pocket)Costs (m$) 8(capitalized)
  9. 9. Drug Discovery pipeline UMC UMC Mercachem Synthon Former Organon
  10. 10. Trends in pharmaceutical research Mergers and acquisitions at big pharma (Organon, Schering-Plough, MSD) R&D is moving from big to medium to small specialized companies Outsourcing of R&D is increasing - Total value: 15-24 billion$ - Increase: 10-20% per year Increasing parts of drug discovery are being outsourced Virtual pharma Open innovation 10
  11. 11. Outsourcing Reasons: • Focus on primary activities • Expertise • New methodologies / technologies • Cost effective • Fasten product development (time to market) • Capacity & Quality 11
  12. 12. Development of ServicesPhase 0: Start Start of Mercachem • Two founders with PhD in Organic Chemistry • Market trend for outsourcing and specialized companies • Market niche for chemistry outsourcing • Business plan, financing • Start (1997) Characteristics: • Independent • Professional • Pragmatic • Product & services according to market needs • Compete on quality and innovation 12
  13. 13. Development of ServicesPhase 1: discovery chemistry Market trends (1996-2001): • Outsourcing of small parts of drug discovery • Outsourcing of non-IP projects • Limited outsourcing of biology • Pharma company in charge & initiates projects 13
  14. 14. Development of ServicesPhase 1: discovery chemistry Discovery Chemistry Services: Lab-scale synthesis of: • Research compounds • Scaffolds and building blocks • Reference compounds and metabolites • Synthesis of compound libraries • Development of novel chemistries Project Goals: • Preparation of (new) molecules for testing • Method of preparation is not important 14
  15. 15. Drug Discovery pipeline Discovery chemistry
  16. 16. Development of ServicesPhase 2: Process R&D services Market trends (2002-2005): • Outsourcing of bigger parts of drug discovery • Outsourcing of more IP sensitive projects • Increasing outsourcing of biology • Pharma company in charge & initiates projects • Upcoming competition from low-cost countries • Decreasing nr of new drugs entering the market • Patent cliffs • Mergers & acquisitions (M&A) • Increasing need for innovation 16
  17. 17. Development of ServicesPhase 2: Process R&D services Process Research Services: • Route development and route scouting • Process optimization and catalyst screening • Scale-up and small bulk supply (~1 kg, non-GMP) Project Goals: • Candidate or lead molecule is known • Development and optimization of method of preparation • Method development & Scale-up for material supply regarding clinical studies (GMP) 17
  18. 18. Drug Discovery pipeline Discovery chemistry Process R&D
  19. 19. Development of ServicesPhase 3: Medicinal Chemistry services Market trends (2006-2011): • Outsourcing of complete drug discovery projects • Outsourcing of IP sensitive projects • Both pharma company and CRO in charge • Both pharma company and CRO initiates projects • Increasing competition from low-cost countries • Increasing M&A 19
  20. 20. Development of ServicesPhase 3: Medicinal Chemistry services Medicinal Chemistry Services: • Hit Finding , Hit optimization • Hit-to-Lead • Lead Optimization • ADME Project Goals: • Design of molecules based on target information • Preparation and optimization of molecules with the right properties • Screening compounds against their properties • Combination of chemistry and biology 20
  21. 21. Drug Discovery pipeline Discovery chemistry Process R&D Medicinal chemistry
  22. 22. Integrated services Target Assay Hit Lead Preclinical IND filing Phase 1 identification development finding optimization development • Discovery Chemistry • Process chemistry • Medicinal Chemistry Skilled chemists Knowledge management Facilities/Equipment
  23. 23. Mercachem’s strengths Unprecedented knowledge solving synthetic challenges by team of experienced chemists and knowledge management Creative and independent thinking complimentary to customer knowhow Strong communication skills and proactive attitude when project requires Reliability reaching success with respect to quality and time High impact and high productivity due to combination of creativity, proactivity and effective infrastructure
  24. 24. Performance in 2010 Number of active customers : > 60 Number of projects : 205 Number of compounds synthesized : ~ 4,500 Delivery rate : 98%
  25. 25. Patents and publications Patents and publications: • WO2009007098 (Syngenta) • WO2009003650 (Bayer CropScience) • WO2005019208 (Grünenthal) • WO2004016581, WO2004074266 and WO2005028479 (Janssen) • WO2003171374 (Johnson & Johnson) • Synth. Comm., 2011, 41, 3246 (Janssen) • Biorg. Med. Chem. Lett., 2010, 20, 4350 (MSD Newhouse) • Eur. J. Org. Chem, 2010, 15, 2852 (Janssen) • Tet. Lett., 2010, 51, 543 (Janssen) • Synth. Comm., 2006, 36, 365 (Esperion) • Biorg. Med. Chem., 2005, 13, 223 (Esperion)
  26. 26. Multidisciplinary Integration Partnerships: ZoBio Leiden FBLG, NMR, Biacore Proqinase Freiburg Cancer pharmacology Vichem Budapest Kinase Inhibitor Library Life Science Park Oss Screening Facilities (HTS, uHTS) 100.000 Library 28
  27. 27. Project Example:Reverse Transcriptase inhibitors Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI’s) anti HIV-drugs Collaboration between Janssen Research Foundation and Mercachem In silico design New molecules designed by molecular modeling. X-ray crystallography of HIV reversed transcriptase complexed with key analogues Result: DAPY (DiArylPYrimidine) compounds
  28. 28. Project Example:Reverse Transcriptase inhibitors Project Development & synthesis of 2nd generation DAPY compounds Results • 2 years of synthesis with a team of 3 chemists • 280 compounds synthesized • Several patents and publications (novel routes & compounds) References 1. R. Leenders et al. Tetrahedron Lett. 2010, 51, 543 (patent: U.S. 7276510, 2007) 2. R. Leenders et al. Synth. Comm. 2010, accepted for publication (patent: WO 2005/028479) 3. R. Leenders et al. Eur. J. Org. Chem. 2010, 2852 (patent: WO2004/074266) 4. P. Janssen et al. J. Med. Chem. 2005, 48, 1901 (review)
  29. 29. Project Example:Dr. August Wolff – Mercachem collaboration in Medicinal chemistry Dr. August Wolff Arzneimittel GmbH & Co. KG and Mercachem BV start two drug development collaborations Bielefeld, Germany & Nijmegen, the Netherlands – August 26, 2010. Dr. August Wolff GmbH & Co. KG Arzneimittel and Mercachem have started two multi-year drug development collaborations. Dr. August Wolff GmbH & Co. KG Arzneimittel have licensed a number of patents from universities that cover novel classes of molecules with potential use in dermatology. Mercachem is responsible for medicinal chemistry and project management with the goal to further improve the properties of these molecules and to develop them into clinical candidates.
  30. 30. Project Example:PDE inhibitors for Neglected Tropical DiseasesProject T4-302:PDE inhibitors for Neglected Tropical DiseasesFocus: African Sleeping SicknessParasitic Disease (Trypanosome brucei)100% fatal if untreated50 million people at riskPresent Medication: A disgrace of modern pharmaceutical sciences old and toxic (~10% patients die from side effects), painful, resistanceAim of T4-302:A PDE (PhosphoDiEsterase) inhibitor as novel and well toleratedmedication for the African sleeping sickness Lead compound PDE
  31. 31. Project Example:PDE inhibitors for Neglected Tropical Diseases Project T4-302: PDE inhibitors for Neglected Tropical Diseases Mercachem: • participates in TIPharma (Top Institute Pharma) • project management, synthesis, SAR, medicinal chemistry PARTNERS IN CONSORTIUM • Mercachem, Nijmegen NL • Nycomed Pharma, Zurich CH • Top Institute Pharma • Vrije Universiteit, Amsterdam NL • University of Berne, CH • IOTA pharmaceuticals, Cambridge UK • Drugs for Neglected Disease initiative, Geneva CH • Koninklijk instituut van de Tropen, Amsterdam NL
  32. 32. Project Example:PDE inhibitors for Neglected Tropical DiseasesVolkskrant 13-09-2011
  33. 33. www.mercachem.com Dr. Eelco Ebbers eelco.ebbers@mercachem.com

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