Open Science accelerating drug discovery. Dr Wen Hwa Lee Director, Patient & Disease Foundations Strategic Alliances SGC, University of Oxford

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1 Open Science accelerating drug discovery Dr Wen Hwa Lee Director, Patient & Disease Foundations Strategic Alliances SGC, University of Oxford

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4 The (un)targeted cancer kinome. Fedorov O, Müller S, Knapp S. Nat Chem Biol Mar;6(3): Too many roads not taken. Edwards AM, Isserlin R, Bader GD, Frye SV, Willson TM, Yu FH. Nature Feb 10;470(7333):

5 Open Science can reduce duplication, improve efficiency and accelerate discoveries CREATIVE COMMONS PROPRIETARY Public-Private Partnership Public Domain Commercial Tools & Basic Knowledge NOVEL Proteins only! Structure Chemistry Antibodies Screening Cell Assays Discovery and Exploration No patent No restriction on use Open access to tools and data. Target identification & validation Drug Discovery and Development Facilitated by access to increased amount of information in the public domain - (re)screening - Lead Optimisation - Pharmacology - Metabolism - Pharmacokinetics - Toxicology - Chemical development - Clinical development Edwards, Bountra, Kerr, Willson Open access chemical and clinical probes to support drug discovery. Nat Chem Biol 2009 wenhwa.lee@thesgc.org

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7 SGC at a glance Operations started in June 2004 Government agencies, Wellcome Trust, charities & leading pharma companies +300-strong team in Oxford, Toronto, Stockholm, Campinas, Chapel Hill & Frankfurt (plus extended network) Open Access Policy: - Promptly placing results, reagents and know-how in the public domain - SGC scientists never file patents

8 Bromodomains: Open Access probe drives discovery of an entire new target class 2 Years and 8 months 6 Months 11 Months 1 Month 6 Months 3 Months July 2009 Jan 2010 Dec 2010 Jan 2011 July 2011 Oct 2011 Mar 2012 GSK informs SGC about Mitsubishi compound Oxford and Harvard start collaboration GSK carries out first in man (for open access - discovered indication!) Co -publication of JQ1 probe (SGC; cancer) and I-BET probe (GSK; inflammation) JQ1 distributed to 100+ labs Brd4 linked to AML (Nature) MM (Cell) Booming interest in Academia and Industry Pfizer BET probe announced Filippakopoulos et al, Nature 2010 (Dec)

9 Patients and Disease Organisations Sharp focus on specific disease areas Primary objective: discover/ improve therapies Sophisticated strategies Novel targets Excellent network of Clinicians Disease experts Participatory and Open Access to patients

10 Much more than just data and trials remove hurdles to their widespread use CHDI recognizes that the discovery of treatments for HD is dependent on the research scientists unobstructed access to quality-controlled and reliable research tools.

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12 Fibrodysplasia Ossificans Progressiva (FOP): From gene to clinical candidate % activity Gene Apr 2006 Gene causing FOP was discovered Mechanism 3 years 3 years 2 years Apr Structure solved; mutations mapped Pre-clinical New tool compounds & animal models Clinical candidate 2015 Clinical study being designed 6 years Tool compounds Potent and selective Kinase gain of function Alex N Bullock

13 I M a PATIENT

14 I MPATIENT Open access enabling early-stage drug discovery by patient & disease foundations

15 I MPATIENT programme partnerships I MPATIENT Nature Medicine 5 June 2014 Huntington s Disease + Role of epigenetic regulation in HD Novel proteins and strategies identified by CHDI network (eg. clearance, DNA repair, autophagy, energetics)

16 Real-time open lab notebook I MPATIENT Huntington s Disease + Real-time open notebook

17 Tapping into disease experts and patients

18 Open sharing and caring for each other

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20 Science knows no country, because knowledge belongs to humanity, and is the torch that illuminates the world. Louis Pasteur Definition of Open Science in 1800s

21 I MPATIENT calls for speed-dating!

22 Acknowledgements Aled Edwards Chas Bountra Cheryl Arrowsmith Michael Sundstrom Opher Gileadi Tim Willson Stefan Knapp Alex Bullock Paul Brennan Takis Prinos Arij Al Chawaf Amy Donner Rachel Harding Roslin Adamson Sergio Bartual Andrew Lewis Jenny Ward Mizio Matteucci FOP Friends CHDI Myeloma UK Brain Tumour Charity Chris Bedford-Gay Richard Simcox Leticia Toledo-Sherman Eric Low Lindsay Perera Simon Ridley Sarah Lindsell Erica Moyes David Jenkinson SGC Oxford SGC Toronto SGC UNICAMP SGC UNC SGC Stockholm SGC Frankfurt SGC Board SGC + ULTRA PIs ABOUT THE SGC The SGC is an international public-private partnership (UK charity number ) that aims to carry out basic science of relevance to drug discovery, placing all information, reagents and know-how into the public domain without restriction.

23 Contact Wen Hwa Lee, PhD Director Disease Foundations Network, Strategic Alliances Structural Genomics Consortium ABOUT THE SGC The SGC is an international public-private partnership (UK charity number ) that aims to carry out basic science of relevance to drug discovery, placing all information, reagents and know-how into the public domain without restriction.

24 I MPATIENT programme partnerships Stone-Man Syndrome + I MPATIENT Ultra-rare disease No treatment SGC co-dev. compounds. assays & models Multiple Myeloma + Brain Tumour Charity + Huntington s Disease + Relapses Need to identify novel targets for new treatments Myeloma UK already established Translational Research Programme & Clinical Trials Network Novel tissue platform and follow-up med chem to generate open clinical compounds for DIPG Role of epigenetic regulation in HD Novel proteins and strategies identified by CHDI network (eg. clearance, DNA repair, autophagy, energetics)

25 ZMPSTE24 and Progeria Liz Carpenter