1. Where is drug discovery going? Christopher A. Lipinski Scientific Advisor, Melior Discovery [email_address] DDND 2012 Lipinski keynote

4. Death Valley California DDND 2012 Lipinski keynote

5. Translational valley of death DDND 2012 Lipinski keynote "curing disease is a byproduct of the [NIH] system and not a goal," says FasterCures' Simon. Most scientists don't want to and don't have the skills to translate a discovery into a treatment; researchers at a dedicated center would try to do that full-time.

9. Bayer observation in NRDD DDND 2012 Lipinski keynote

13. Genomics financial madness DDND 2012 Lipinski keynote 1% success, NPV $34M, Decision Resources March 29, 2004

14. Target-based drug discovery: Slide thanks to Andrew Reaume, Melior Discovery DDND 2012 Lipinski keynote E1 E5 R2 R3 R4 R5 R6 R1 E2 E3 E4 E7 E6 DP 1 DP 2 D1 D2

15. … .the real picture R8 DP 5 Slide thanks to Andrew Reaume, Melior Discovery DDND 2012 Lipinski keynote E10 E9 E8 E1 E5 R2 R3 R4 R5 R6 R1 E2 E3 E4 E7 E6 DP 1 DP 2 R7 R9 R10 R11 R12 DP 3 DP 4 E7 E8 D1 D2

16. 50 years of medicinal chemistry DDND 2012 Lipinski keynote What Do Medicinal Chemists Actually Make? A 50-Year Retrospective Pat Walters et al. J Med Chem 2011

17. Attrition rates by phase The Productivity Crisis in Pharmaceutical R&D, Fabio Pammolli, Laura Magazzini and Massimo Riccaboni, Nature Reviews Drug Discovery 2011 (10) 428-438. DDND 2012 Lipinski keynote

18. Nanomolar is not necessary DDND 2012 Lipinski keynote Mean po dose is 47 mg Mean pXC 50 is 7.3 (IC 50 5 x 10 -8 ) Gleeson, M. Paul; Hersey, Anne; Montanari, Dino; Overington, John. Probing the links between in vitro potency, ADMET and physicochemical parameters. Nature Reviews Drug Discovery (2011), 10(3), 197-208.

19. Phenotypic screening advantage The majority of small-molecule first-in-class NMEs that were discovered between 1999 and 2008 were first discovered using phenotypic assays (FIG. 2): 28 of the first-in-class NMEs came from phenotypic screening approaches, compared with 17 from target-based approaches. How were new medicines discovered? David C. Swinney and Jason Anthony Nature Reviews Drug Discovery 2011 (10) 507-519. DDND 2012 Lipinski keynote

23. Do drug structure networks map on biology networks? DDND 2012 Lipinski keynote

24. Chemistry drug class network DDND 2012 Lipinski keynote