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Final Agenda                         June 19-21, 2013 • The Revere Hotel • Boston, MA


Cambridge Healthtech Institute and Bio-IT World’s Thirteenth Annual


Structure-Based
Drug Design
Genome to Drug Lead
with Big Data Approach




Keynote Presentation:
Drugging the Undruggable: Transforming
Nature’s α-Helix into Breakthrough Medicines
Tomi Sawyer, Ph.D., CSO, Aileron Therapeutics




 Corporate Sponsors:

                                                                     Register by March 22
                                                                     & save up to $350!


    Organized by:
    Cambridge Healthtech Institute                                    healthtech.com/SBD
Structure-Based
                        Drug Design

  Dear Colleague,

  Thank you for your continued interest and support                                                    Who You Will Meet
  regarding our Structure-Based Drug Design conference.                                                Titles:
                                                                                                        •	 Lab Head/Head
  The growing protein structure information has given structure-based methods a place of
                                                                                                        •	 Team Leader
  prominence in drug discovery. The current state of in silico technology for effectively using
                                                                                                        •	 Chief Scientific Officer
  biological big data for structure-based drug design is significantly limited by the lack of
                                                                                                        •	 Director
  a realistic environment for simulations and an absence of fully integrated infrastructure.
                                                                                                        •	 Research Scientist/Principal Scientist/
  Moreover, the emerging deluge of biological data of all kinds available to the field of                  Scientist
  biomedicine and the pharmaceutical industry represents a significant opportunity to                   •	 Senior Researcher/Researcher
  fundamentally change the process of disease target discovery and drug design.                         •	 Graduate Student
                                                                                                        •	 Professor
  Leveraging ever-increasing computing power and large-scale informatics framework that                 •	 PostDoc
  integrate functional, structural and expression information, we face ample opportunities to	
  fine-tune our protein-ligand modeling algorithm and modify the molecule to get the desired
  properties.                                                                                          Departments:
                                                                                                        •	 Biochemistry
  In silico approaches to rational structure-based drug discovery are leveraging big data               •	 Bioinformatics
  technology in the identification and optimization of lead compounds and the identification            •	 Chemical Biology
  and validation of drug targets, followed by the prediction of ligands for the target protein          •	 Chemistry
  from molecular modeling computation.                                                                  •	 Computational Biology
                                                                                                        •	 Computational Chemistry
  At CHI’s thirteenth annual Structure-Based Drug Design conference, you will hear about                •	 Discovery Chemistry
  developments in in silico technology, as well as experimental approaches useful for accurately        •	 Drug Discovery
  predicting and modeling the structures of proteins in structure-based drug design efforts.            •	 Informatics
  In addition, examples of successful applications of such technology approaches to                     •	 Lead Discovery
  genome-to-drug lead investigations will be addressed.                                                 •	 Medicinal Chemistry
                                                                                                        •	 Molecular Modeling
                                                                                                        •	 Scientific Computing
  Register by March 22 at the early rate and save up to $350 off                                        •	 Stuctural Biology
  your conference registration.                                                                         •	 Structural Chemistry
                                                                                                        •	 Structural Sciences


  Warmest regards,
                                                                                                       Co-Located Event:
                                                                                                       Eleventh Annual
  Ming Guo
                                                                                                       Next-Gen
  Conference Director
                                                                                                       Kinase Inhibitors:
  Cambridge Healthtech Institute             “Given both the overwhelming amount of available data
                                                                                                       Moving Towards a Successful Pipeline
                                             and the fact that traditional pharma approaches to
                                             innovation seem to have largely run out of steam, a bet   June 17-19
                                             on big data analytics might make a lot of sense now.”     healthtech.com/KIN
                                             - David Shaywitz, M.D., Ph.D., Physician, Scientist and    Best Value! Register for the
                                             Management Consultant                                      Structure-Based Drug Design
                                                                                                        and Kinase conferences at a
                                                                                                        special rate.



2 ••• healthtech.com/SBD
WEDNESDAY, JUNE 19                                                                               THURSDAY, JUNE 20

   STRUCTURE-BASED DRUG DESIGN FOR KINASE                                                        7:30 am Morning Coffee

1:15 pm Chairperson’s Opening Remarks                                                            8:30 Chairperson’s Remarks

1:20 Structure-Based Design of Potent and Selective inhibitors of PI3-Kinase Delta               »»
                                                                                                  KEYNOTE PRESENTATION:
Jeremy M. Murray, Ph.D., Scientist, Structural Biology, Genentech                                8:40 Drugging the Undruggable: Transforming Nature’s α-Helix into
Inhibition of PI3Kδ is considered to be an attractive mechanism for the treatment of
inflammatory diseases and leukocyte malignancies. Using a structure-based design
                                                                                                            Breakthrough Medicines
approach, we have identified a series of potent and selective inhibitors of PI3Kδ.                          Tomi Sawyer, Ph.D., CSO, Aileron Therapeutics
These inhibitors do not occupy the induced selectivity pocket between Trp760 and                               A major challenge of drug discovery has been to successfully
Met752 that is observed for other families of selective PI3Kδ inhibitors. Instead,                             modulate the biological properties of those therapeutic targets
the selectivity of the compounds for inhibition of PI3Kδ relative to other PI3K                                deemed “undruggable” as defined relative to small-molecules.
isoforms appears to be due primarily to the strong interactions these inhibitors                 However, recent advancements leveraging peptides and macrocycles are
are able to make with Trp760 in the PI3Kδ binding pocket. This talk will discuss                 expanding such drug space, especially for many intracellular protein–protein
the structural understanding of the selectivity of these inhibitors against other                interaction targets deemed “hot” drug-wise. Structural biology and computational
isoforms, pharmacokinetic properties and the ability of select compounds to inhibit              chemistry are key tools for such drug discovery. As a case study, advancements
the function of B-cells in vivo.                                                                 in stapled peptide technology to transform Nature’s α-helix into breakthrough
                                                                                                 medicines will be presented.

1:50 MD Simulations of Mutant and WT PI3Kα: Insights into the Mechanism
of Overactivation and Implications for Drug Design                                               9:10 A Beacon in the Dark: Structural Information in the Absence of Structure
Zoe Cournia, Ph.D., Investigator, Biomedical Research Foundation, Academy of Athens                         Edward R. Zartler, President and CSO, Quantum Tessera Consulting, LLC
                                                                                                               The current (and next) generation of drug targets are very difficult
PI 3 kinase alpha (PI3Kα) is one of the most frequently mutated proteins in human
                                                                                                               to ligand: membrane proteins, multimeric protein complexes,
cancers. Molecular dynamics simulations in aqueous solution performed for wild
                                                                                                               post-translationally modified proteins, protein-protein interactions.
type (WT) and H1047R mutant PI3Kα proteins, revealed different dynamical and
                                                                                                               Advances in structural biology have been made where we can obtain
structural features for the two proteins, which may lead to kinase overactivation in
                                                                                                 high resolution structural information for many of these targets. However, for a
the mutant variant. Binding site prediction and virtual screening further facilitated
                                                                                                 large swath of the current, and next-gen targets, we are simply working in the
the development of novel mutant-specific PI3Kα inhibitors that exploit the altered
                                                                                                 structural dark. Recent advances in NMR-based methods, coupled with novel ideas
conformation of the mutant with respect to the WT protein.
                                                                                                 in fragment-based hit generation, can now shine a light into this darkness, yielding
                                                                                                 crucial structural details to allow ligands to be rationally designed. We will discuss
2:20 Sponsored Presentation (Opportunity Available)                                              these advances and their application to drug discovery.

2:50 Refreshment Break in the Exhibit Hall with Poster Viewing                                                       FORCE FIELD CALCULATION
                           DRUG RESISTANCE                                                       9:40 Docking: Is It Possible to Know When It Works?
                                                                                                 Greg Warren, Ph.D., Senior Applications Scientist,
3:30 Sponsored Presentation (Opportunity Available)
                                                                                                 OpenEye Scientific Software, Inc.
                                                                                                 It is commonly held that the same, protein-centric approach, can be used
4:00 Towards a New Generation of Animicrobial Antifolates                                        successfully both to predict the bound conformation of a ligand in complex with a
           Dennis L. Wright, Ph.D., Professor of Pharmaceutical Sciences and                     given protein (pose prediction) and to rank molecules based on their probability of
           Chemistry, University of Connecticut                                                  being a binder to that protein (structure-based virtual screening). We will present
             We are using a structure-based design approach to develop potent                    tools in the OEDocking Suite that approach these two problems as issues of a
             and selective inhibitors of the enzyme dihydrofolate reductase (DHFR)               rather different nature. Successful results in virtual screening using the rigid protein
             from a variety of pathogenic organisms. Analysis of crystal structures              approximation in docking will be presented along with a flexible, ligand-centric
of trimethoprim-resistant and naturally-insensitive enzymes led to the design of a               approach to pose prediction that is much more reliable than traditional protein-
series of propargyl-linked antifolates characterized by high potency, good selectivity           centric posing tools. We also show that whether the problem is pose prediction or
over the human form of the enzyme and good anti-microbial activity.                              virtual screening, combining ligand and protein information in the same calculation
                                                                                                 produces better results.
4:30 Understanding Drug Mechanism of Action by Target Gene Overexpression
           Adam C. Palmer, Ph.D., Postdoctoral Fellow, Department of Systems                     10:10 Coffee Break in the Exhibit Hall with Poster Viewing
           Biology, Harvard Medical School
             The molecular targets of drugs can sometimes, but not always,                       10:40 Incorporating Ligand Polarisation in Binding Free Energy Calculations
             be identified amongst genes that confer drug resistance when                                    Jonathan W. Essex, Ph.D., Professor, Head, Computational Systems
             overexpressed. We quantitatively overexpressed genes encoding                                   Chemistry, Chairman, Institute for Complex Systems Simulation (ICSS),
known antibiotic targets and observed that drug resistance does not only increase;                           School of Chemistry, University of Southampton
it can remain unchanged, decrease, or even have a non-monotonic dependence on                                 While the methods underpinning the calculation of protein-ligand
target expression. These diverse effects are explained by simple models considering                           binding free energies are well understood, accurate calculations are
gene toxicity and drug-induction of harmful target-catalyzed reactions. The relation             still fundamentally limited by inadequate sampling of the protein-ligand complex,
between drug resistance and target expression may reveal unexpectedly complex                    and inaccurate modeling of the associated intermolecular interactions. To address
mechanisms of drug action.                                                                       the second issue, we have developed a simple and computationally inexpensive
                                                                                                 correction to the calculated free energies based on a hybrid quantum mechanics/
5:00 Close of the Day                                                                            molecular mechanics approach. In this presentation, the method will be described
                                                                                                 and its performance assessed in the calculation of small and drug-like molecules’
                                                                                                 free energies of hydration, and on the calculation of protein-ligand binding affinities
 Dinner Short Course (June 19, 6:00-8:00 pm)*                                                    in neuraminidase, CDK2 and COX2.
 Structure-Based Drug Design for Epigenetic Targets
 Johnathan R. Whetstine, Ph.D., Assistant Professor of Medicine, Harvard Medical School
 Philip Fallon, Ph.D., Senior Medicinal Chemist, Domainex Ltd.
                                                              *Separate registration required.




                                                                                                                                              healthtech.com/SBD ••• 3
11:10 Site Identification by Ligand Competitive Saturation (SILCS): Structure-           a significant portion of the total binding energy, and thus represent opportunities
             Based Free Energy Computational Approach for Ligand Discovery               for ligand design. Computing desolvation energetics typically requires lengthy
                                                                                         simulations, but this talk presents a fast and easy-to-use method (3D-RISM) which
             and Optimization                                                            computes desolvation energies in minutes, without using explicit simulations.
             Alexander D. MacKerell, Jr., Ph.D., Grollman-Glick Professor of             Application to ligand optimization is demonstrated using case studies.
             Pharmaceutical Sciences, Director, Computer-Aided Drug Design Center,
School of Pharmacy, University of Maryland                                               3:10 Refreshment Break in the Exhibit Hall with Poster Viewing
The Site Identification by Ligand Competitive Saturation (SILCS) method uses
explicit solvent all-atom molecular dynamics simulations to identify binding sites
                                                                                         3:40 Characterizing and Exploiting the Solvation of Protein Surfaces for
on proteins for functional group classes based on rigorous free energy criteria that
includes protein flexibility and fragment desolvation. Information from the SILCS        Applications in Drug Design and Discovery
approach, termed FragMaps, may be used for the identification of novel ligands           Tom Kurtzman Young, Ph.D., Assistant Professor, Department of Chemistry, Lehman
targeting protein, including de novo ligand design. In addition, the SILCS method        College, CUNY
may be combined with structural information on a ligand-protein complex to               The displacement of water from a binding site by a ligand is a principal, and often
facilitate modification of the ligand to improve its binding affinity.                   dominant, source of binding free energy. In recent years, a number of techniques
                                                                                         based on Inhomogeneous Solvation Theory have been developed that map out the
11:40 Blurring to Bring Binding Free Energies into Focus                                 solvation thermodynamics of protein binding sites (STOW, WaterMap, GIST). We
                                                                                         outline the physical basis of these mapping techniques and present some possible
            Kenneth M. Merz, Jr., University of Florida Research Foundation Professor,   applications in drug discovery and design.
            Edmund H. Prominski Professor of Chemistry, Department of Chemistry,
            Quantum Theory Project, University of Florida                                4:10 Mapping Protein Surfaces with MixMD to Identify New Binding Sites
              Docking calculations coupled with binding free energy estimates
              (scoring) are a mainstay of structure-based drug design. This talk                    Heather Carlson, Professor, Medicinal Chemistry, University of Michigan
addresses how to use ensemble principles to estimate and reduce uncertainty of                         Mixed-solvent molecular dynamics (MixMD) is an emerging technique in
computed binding free energies. We have developed methods to evaluate potential                        structure-based drug design (SBDD). The most significant benefits are the
function error and in this talk we will demonstrate how to use this knowledge to                       ability of a protein to adapt in the presence of a probe and the identification
improve the outcome of a docking and scoring exercise. This was accomplished via                       of binding sites where organic molecules specifically out-compete water.
the development of novel scoring approaches that employ statistical mechanical           Rather than ignoring the complicated role of water as most SBDD methods do, it is truly
principles and are coupled with error propagation. Importantly, our approach yields      embraced in MixMD. Blinded, experimental validation of the method will be presented.
free energies as well as estimates of the random and systematic errors in these
quantities, providing insight into the reliability of the computed free energies.        4:40 The Potency-Insolubility Conundrum in Drug Discovery: Mechanism and
                                                                                                    Solution for Hepatitis C Inhibitors
12:10 pm Luncheon Presentation (Opportunity Available)                                              Patrick R. Connelly, Ph.D., Principal Scientific Fellow, Vertex
or Lunch on Your Own                                                                                Pharmaceuticals, Inc.
                                                                                                         As compounds are optimized for greater potency during
                                      GPCR                                                               pharmaceutical discovery, their aqueous solubility often decreases,
                                                                                         making them less viable as orally-administered drugs. The potency-insolubility
1:30 Chairperson’s Remarks                                                               conundrum has prompted speculation, concern, and attempts to taxonomize
                                                                                         the problem or overcome it technologically. However, a fundamental molecular
                                                                                         connection between binding potency and aqueous insolubility has yet to be
1:40 An Automated Pipeline for the Modeling and Simulation of GPCRs:
                                                                                         elucidated. By examination of the structural and thermodynamic properties
           Applications to Structure-Based Drug Design                                   of telaprevir, a sparingly soluble inhibitor of the NS3 protease of the Hepatitis
           Hugo Gutierrez-de-Teran, Ph.D., Parga Pondal Research Fellow,                 C virus, it is revealed that potency and insolubility share a common origin. A
           Bioinformatics, Public Galician Foundation of Genomic Medicine                design strategy based on supramolecular graph set considerations provides a
             The recent advances in membrane protein crystallography have                generalizable solution to the conundrum.
             provided extremely valuable structural information of the superfamily
of G-protein-coupled receptors (GPCRs). Recently, we have developed GPCR-                5:10 Welcome Reception in the Exhibit Hall with Poster Viewing
ModSim (http://gpcr.usc.es), a web-based, automated pipeline to generate high-
quality 3D models of the remaining GPCRs and to perform molecular dynamics
(MD) simulations with an explicit representation of the cellular membrane,               6:30 End of Day
structural water, cholesterol or lipid molecules. With this computational tool,
research groups without prior experience in computational chemistry can set up           FRIDAY, JUNE 21
ambitious projects on SBDD in GPCRs in a systematic and comprehensive way.

                                                                                         7:30 am Breakfast Roundtable Discussions
2:10 How Drugs Bind and Control Their Targets: Characterizing GPCR
           Signaling through Long-Timescale Simulation                                                   FRAGMENT-BASED DRUG DESIGN
           Ron O. Dror, Senior Research Scientist, D. E. Shaw Research
              One-third of drugs act by binding to G protein–coupled receptors           8:30 Chairperson’s Remarks
              (GPCRs) and either triggering or preventing receptor activation, but the
              process by which they do so has proven difficult to characterize either    8:40 Case Histories of Recent Fragment-Based Drug Discovery Projects
experimentally or computationally. Anton, a special-purpose machine that we
designed to accelerate molecular dynamics simulations by orders of magnitude,                       Christopher W. Murray, Ph.D., Vice President, Discovery Technology, Astex
has enabled simulations in which drugs spontaneously associate with GPCRs                           Pharmaceuticals
to achieve bound conformations that match crystal structures almost perfectly.                         Here we describe some case histories of applying fragment-based
Anton simulations have also captured transitions of a GPCR between its active and                      drug discovery to challenging drug targets. This will include the design
inactive states, allowing us to characterize the mechanism of receptor activation.                     of protein-protein interaction inhibitors of IAP family proteins and the
Our results suggest opportunities for the design of drugs that achieve greater           design of allosteric inhibitors of full-length NS3 proteins from the Hepatitis C Virus.
specificity and control receptor signaling more precisely.                               The presentation will discuss the difficulties associated with applying fragment-
                                                                                         based drug discovery to challenging target classes and will discuss ways in which
                                                                                         these can be mitigated.
          WATER & SOLVATION IN DRUG DESIGN
2:40 Exploiting Solvent Effects in Drug Design and Optimization
                                                                        Sponsored by     9:10 Computational Protein Mapping to Drive the Development of Fragment
Chris Williams, Ph.D., Principal Scientist, Chemical Computing Group                     Hits into Leads
Upon ligand binding, solvent molecules around the binding pocket                         Sandor Vajda, Ph.D., Professor of Biomedical Engineering and Chemistry, Director,
and the ligand become displaced or rearranged. These desolvation energies can be         Biomolecular Engineering Research Center, Boston University

                                                                                                                                         healthtech.com/SBD ••• 4
Fragment-based drug design (FBDD) starts with finding fragment-sized compounds        A promising way to interfere with biological processes is through the control of
that are highly ligand efficient and can serve as a core moiety for developing        protein-protein interactions by means of small molecules. Recent advances in the
high-affinity leads. Although the core-bound structure of a protein facilitates the   understanding of the energetics and dynamics of protein-binding interfaces open
construction of leads, effective design is far from straightforward. We show that     up a way to apply rational design approaches for finding protein-protein interaction
protein mapping, a computational method developed to find binding hot spots,          modulators (PPIM). Here, we successfully identify small-molecule inhibitors of the
provides information that complements the fragment screening results and can          dimer to tetramer transition of the NHR2 domain within the RUNX1/ETO fusion
drive the evolution of core fragments into larger leads with a minimal loss or, in    protein, a novel target for the treatment of acute myeloid leukemia.
some cases, even a gain in ligand efficiency.
                                                                                      2:30 Structure-Based Guided Development of Focused Chemical Library
9:40 Determination of Binding Poses, Kinetics and Energetics in Fragment-             Dedicated to Orthosteric Modulation of Protein-Protein Interactions
           Based Design                                                                           Xavier Morelli, Ph.D., Group Leader, Cancer Research Center of Marseille,
           Gianni De Fabritiis, Ph.D., Computational Biophysics Laboratory (GRIB-                 CNRS
           IMIM), Universitat Pompeu Fabra, Barcelona Biomedical Research Park                     This talk will address some challenging issues: biological and
           (PRBB)                                                                                  chemical spaces of PPI with known orthosteric inhibitors, ligandability
                                                                                                   assessment of protein-protein interactions, design and validation of
                                                                                      chemical libraries dedicated to PPIs.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
                                                                                      3:00 Refreshment Break
10:40 The Tip of the Iceberg and the Chemical Universe: Fuzzy Hit Finding
            Under Synthetic Feasibility Conditions                                                          EPIGENETIC TARGETING
            Carsten Detering, Ph.D., CEO, BioSolveIT, Inc.
              We have come up with a method that addresses the problem of
                                                                                      3:15 Design and Develop Bromodomain Inhibitor for Cancer Therapy
              crowded patent space. It captures existing available chemistry in a                Jun Qi, Ph.D., Senior Research Scientist, Medical Oncology, Dana-Farber
              company and thus allows the researcher to fuzzily search in a larger               Cancer Institute
portion of the chemical universe available to him/her. Results are returned with                    In cancer, epigenetic proteins are promising and intensely studied
their underlying chemical synthesis, which renders retro-synthesis unnecessary.                     targets for therapeutic drug discovery. Among the chromatin-
Time saved can be invested in other Medicinal Chemistry efforts. The talk will                      modifying enzymes, so-called epigenetic “writers” “readers” and
                                                                                                                                                       ,
highlight the method as well as several application examples.                         “erasers” chromatin-binding modules or epigenetic “readers” have received
                                                                                               ,
                                                                                      comparatively little attention perhaps owing to perceptions regarding the difficulty
                                                                                      of targeting protein-protein interactions. Motivated by this challenge, we have
11:10 Advances in Predicting Protein-Protein Binding                  Sponsored by
                                                                                      developed first-in-class, drug-like inhibitors of “bromodomain and extraterminal
           Affinity and Protein Stability                                             domain” epigenetic readers (BETs) for mechanistic study and therapeutic
           Woody Sherman, Ph.D., Vice President, Applications                         application in cancer. We are continuously integrating the transcriptional
           Science, Schrodinger, Inc.                                                 consequences of BETi with changes in the epigenomic landscapes of cancer cells
                                                                                      to elucidate the mechanisms underlying response to BETi using chemical and
                                                                                      genetic perturbations.
11:40 Sponsored Presentation (Opportunity Available)
                                                                                      3:45 The Impact of Structural Data on Epigenetic Probe Discovery for the
12:10 pm Luncheon Presentation (Opportunity Available)                                Public Domain
or Lunch on Your Own                                                                             Dafydd Owen, Ph.D., Associate Research Fellow, Biotherapeutics
                                                                                                 Worldwide R&D, Pfizer Worldwide Medicinal Chemistry
               PROTEIN-PROTEIN INTERACTION                                                          Research into the role of epigenetics in disease could be significantly
                                                                                                    accelerated if cell-active chemical probes for such targets were
1:25 Chairperson’s Remarks                                                                          available to the research community, through a collaborative, open-
                                                                                      innovation model. Pfizer is a member of a public-private partnership led by the
1:30 How Does a Small-Molecule Inhibitor Bind at the Protein-Protein                  Structural Genomics Consortium (SGC) to help identify a suite of high-quality
                                                                                      chemical probes for epigenetic targets. This partnership is unique in that it brings
          Interface of Interleukin 2?                                                 the medicinal chemistry expertise within industry together with biological expertise
          Yibing Shan, Senior Scientist, DE Shaw Research                             in academia to drive basic research in an emerging area of important biology of
                                                                                      potential relevance to many diseases. The impact of structural biology on probe
                                                                                      discovery will be presented.

2:00 From Determinants of RUNX1/ETO Tetramerization to Small-Molecule                 4:15      Closing Remarks
           Protein-Protein Interaction Inhibitors Targeting Acute Myeloid
           Leukemia                                                                   4:30      End of Conference
           Holger Gohlke, Ph. D., Professor, Institute of Pharmaceutical and
           Medicinal Chemistry, Heinrich-Heine-University, Düsseldorf


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Invitation-Only VIP Dinner/Hospitality Suite                                Benefits of working with CHI for your lead
Sponsors will hand-pick their top prospects from the conference             generation needs:
pre-registration list for an evening of networking at the hotel or at a      •	 Your campaign will receive targeted promotion to CHI’s unparalleled
choice local venue. CHI will extend invitations and deliver prospects.          database of over 800,000 individuals, all of which are involved in
Evening will be customized according to sponsor’s objectives (i.e.              all sectors of the life sciences – lists can be segmented based on
purely social, focus group, reception style, or plated dinner with              geography, research area, title and industry
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Focus Groups                                                                    campaigns to expand awareness and bolster leads
CHI can help you organize and execute a focus group on site. This
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User Group Meeting
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Co-locate your user group with the Structure-Based Drug Design
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                                                                                                                     healthtech.com/SBD ••• 6
Hotel & Travel
Information                                                                                                  Past Attendee
                                                                                                             Testimonials:
                                                                                                             “The selection of speakers and
Conference Venue and Hotel:
                                                                                                             presentations strongly demonstrated

The Revere Hotel
                                                                                                             the expansive breadth and impact of
                                                                                                             structure-based drug design.”
                                                                                                             - Director of Bioinformatics,
200 Stuart Street, Boston, MA 02116                                                                          ActivX Biosciences
Tel: (617) 482-1800
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Discounted Room Rate: $249 s/d                                                                               - Team Leader, Molecular Modelling,
Discounted Reservation Cut-off Date: May 17, 2013                                                            CNRS-ICSN

Please visit our website to make your reservations                                                           “Good-quality up-to-date presentations
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sleeping accommodations. You will need to identify                                                           conference.”
yourself as a Cambridge Healthtech Institute                                                                 - CSO, De Novo Pharmaceuticals Ltd.
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room rate with the host hotel. Reservations made                                                             “Some discussions inspired new ideas I am
after the cut-off date or after the group room block                                                         going to try.”
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Rooms are limited, so please book early.                                                                     “Thanks to the organizers, it’s a very
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                                                                                                              - Senior Research Fellow, Molsys, Merck

                                                                                                             “Some important principles were
                                                                                                             highlighted with regard to the computational
                                                                                                             problem of describing ligand binding and
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                                                                                                                  healthtech.com/SBD ••• 7
Cambridge Healthtech Institute and Bio-IT World’s Thirteenth Annual
                                                                                                                                                            June 19-21, 2013

  Structure-Based
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CHI's Structure-Based Drug Design Conference - June 19-21, 2013, Boston, MA

  • 1. Final Agenda June 19-21, 2013 • The Revere Hotel • Boston, MA Cambridge Healthtech Institute and Bio-IT World’s Thirteenth Annual Structure-Based Drug Design Genome to Drug Lead with Big Data Approach Keynote Presentation: Drugging the Undruggable: Transforming Nature’s α-Helix into Breakthrough Medicines Tomi Sawyer, Ph.D., CSO, Aileron Therapeutics Corporate Sponsors: Register by March 22 & save up to $350! Organized by: Cambridge Healthtech Institute healthtech.com/SBD
  • 2. Structure-Based Drug Design Dear Colleague, Thank you for your continued interest and support Who You Will Meet regarding our Structure-Based Drug Design conference. Titles: • Lab Head/Head The growing protein structure information has given structure-based methods a place of • Team Leader prominence in drug discovery. The current state of in silico technology for effectively using • Chief Scientific Officer biological big data for structure-based drug design is significantly limited by the lack of • Director a realistic environment for simulations and an absence of fully integrated infrastructure. • Research Scientist/Principal Scientist/ Moreover, the emerging deluge of biological data of all kinds available to the field of Scientist biomedicine and the pharmaceutical industry represents a significant opportunity to • Senior Researcher/Researcher fundamentally change the process of disease target discovery and drug design. • Graduate Student • Professor Leveraging ever-increasing computing power and large-scale informatics framework that • PostDoc integrate functional, structural and expression information, we face ample opportunities to fine-tune our protein-ligand modeling algorithm and modify the molecule to get the desired properties. Departments: • Biochemistry In silico approaches to rational structure-based drug discovery are leveraging big data • Bioinformatics technology in the identification and optimization of lead compounds and the identification • Chemical Biology and validation of drug targets, followed by the prediction of ligands for the target protein • Chemistry from molecular modeling computation. • Computational Biology • Computational Chemistry At CHI’s thirteenth annual Structure-Based Drug Design conference, you will hear about • Discovery Chemistry developments in in silico technology, as well as experimental approaches useful for accurately • Drug Discovery predicting and modeling the structures of proteins in structure-based drug design efforts. • Informatics In addition, examples of successful applications of such technology approaches to • Lead Discovery genome-to-drug lead investigations will be addressed. • Medicinal Chemistry • Molecular Modeling • Scientific Computing Register by March 22 at the early rate and save up to $350 off • Stuctural Biology your conference registration. • Structural Chemistry • Structural Sciences Warmest regards, Co-Located Event: Eleventh Annual Ming Guo Next-Gen Conference Director Kinase Inhibitors: Cambridge Healthtech Institute “Given both the overwhelming amount of available data Moving Towards a Successful Pipeline and the fact that traditional pharma approaches to innovation seem to have largely run out of steam, a bet June 17-19 on big data analytics might make a lot of sense now.” healthtech.com/KIN - David Shaywitz, M.D., Ph.D., Physician, Scientist and Best Value! Register for the Management Consultant Structure-Based Drug Design and Kinase conferences at a special rate. 2 ••• healthtech.com/SBD
  • 3. WEDNESDAY, JUNE 19 THURSDAY, JUNE 20 STRUCTURE-BASED DRUG DESIGN FOR KINASE 7:30 am Morning Coffee 1:15 pm Chairperson’s Opening Remarks 8:30 Chairperson’s Remarks 1:20 Structure-Based Design of Potent and Selective inhibitors of PI3-Kinase Delta »» KEYNOTE PRESENTATION: Jeremy M. Murray, Ph.D., Scientist, Structural Biology, Genentech 8:40 Drugging the Undruggable: Transforming Nature’s α-Helix into Inhibition of PI3Kδ is considered to be an attractive mechanism for the treatment of inflammatory diseases and leukocyte malignancies. Using a structure-based design Breakthrough Medicines approach, we have identified a series of potent and selective inhibitors of PI3Kδ. Tomi Sawyer, Ph.D., CSO, Aileron Therapeutics These inhibitors do not occupy the induced selectivity pocket between Trp760 and A major challenge of drug discovery has been to successfully Met752 that is observed for other families of selective PI3Kδ inhibitors. Instead, modulate the biological properties of those therapeutic targets the selectivity of the compounds for inhibition of PI3Kδ relative to other PI3K deemed “undruggable” as defined relative to small-molecules. isoforms appears to be due primarily to the strong interactions these inhibitors However, recent advancements leveraging peptides and macrocycles are are able to make with Trp760 in the PI3Kδ binding pocket. This talk will discuss expanding such drug space, especially for many intracellular protein–protein the structural understanding of the selectivity of these inhibitors against other interaction targets deemed “hot” drug-wise. Structural biology and computational isoforms, pharmacokinetic properties and the ability of select compounds to inhibit chemistry are key tools for such drug discovery. As a case study, advancements the function of B-cells in vivo. in stapled peptide technology to transform Nature’s α-helix into breakthrough medicines will be presented. 1:50 MD Simulations of Mutant and WT PI3Kα: Insights into the Mechanism of Overactivation and Implications for Drug Design 9:10 A Beacon in the Dark: Structural Information in the Absence of Structure Zoe Cournia, Ph.D., Investigator, Biomedical Research Foundation, Academy of Athens Edward R. Zartler, President and CSO, Quantum Tessera Consulting, LLC The current (and next) generation of drug targets are very difficult PI 3 kinase alpha (PI3Kα) is one of the most frequently mutated proteins in human to ligand: membrane proteins, multimeric protein complexes, cancers. Molecular dynamics simulations in aqueous solution performed for wild post-translationally modified proteins, protein-protein interactions. type (WT) and H1047R mutant PI3Kα proteins, revealed different dynamical and Advances in structural biology have been made where we can obtain structural features for the two proteins, which may lead to kinase overactivation in high resolution structural information for many of these targets. However, for a the mutant variant. Binding site prediction and virtual screening further facilitated large swath of the current, and next-gen targets, we are simply working in the the development of novel mutant-specific PI3Kα inhibitors that exploit the altered structural dark. Recent advances in NMR-based methods, coupled with novel ideas conformation of the mutant with respect to the WT protein. in fragment-based hit generation, can now shine a light into this darkness, yielding crucial structural details to allow ligands to be rationally designed. We will discuss 2:20 Sponsored Presentation (Opportunity Available) these advances and their application to drug discovery. 2:50 Refreshment Break in the Exhibit Hall with Poster Viewing FORCE FIELD CALCULATION DRUG RESISTANCE 9:40 Docking: Is It Possible to Know When It Works? Greg Warren, Ph.D., Senior Applications Scientist, 3:30 Sponsored Presentation (Opportunity Available) OpenEye Scientific Software, Inc. It is commonly held that the same, protein-centric approach, can be used 4:00 Towards a New Generation of Animicrobial Antifolates successfully both to predict the bound conformation of a ligand in complex with a Dennis L. Wright, Ph.D., Professor of Pharmaceutical Sciences and given protein (pose prediction) and to rank molecules based on their probability of Chemistry, University of Connecticut being a binder to that protein (structure-based virtual screening). We will present We are using a structure-based design approach to develop potent tools in the OEDocking Suite that approach these two problems as issues of a and selective inhibitors of the enzyme dihydrofolate reductase (DHFR) rather different nature. Successful results in virtual screening using the rigid protein from a variety of pathogenic organisms. Analysis of crystal structures approximation in docking will be presented along with a flexible, ligand-centric of trimethoprim-resistant and naturally-insensitive enzymes led to the design of a approach to pose prediction that is much more reliable than traditional protein- series of propargyl-linked antifolates characterized by high potency, good selectivity centric posing tools. We also show that whether the problem is pose prediction or over the human form of the enzyme and good anti-microbial activity. virtual screening, combining ligand and protein information in the same calculation produces better results. 4:30 Understanding Drug Mechanism of Action by Target Gene Overexpression Adam C. Palmer, Ph.D., Postdoctoral Fellow, Department of Systems 10:10 Coffee Break in the Exhibit Hall with Poster Viewing Biology, Harvard Medical School The molecular targets of drugs can sometimes, but not always, 10:40 Incorporating Ligand Polarisation in Binding Free Energy Calculations be identified amongst genes that confer drug resistance when Jonathan W. Essex, Ph.D., Professor, Head, Computational Systems overexpressed. We quantitatively overexpressed genes encoding Chemistry, Chairman, Institute for Complex Systems Simulation (ICSS), known antibiotic targets and observed that drug resistance does not only increase; School of Chemistry, University of Southampton it can remain unchanged, decrease, or even have a non-monotonic dependence on While the methods underpinning the calculation of protein-ligand target expression. These diverse effects are explained by simple models considering binding free energies are well understood, accurate calculations are gene toxicity and drug-induction of harmful target-catalyzed reactions. The relation still fundamentally limited by inadequate sampling of the protein-ligand complex, between drug resistance and target expression may reveal unexpectedly complex and inaccurate modeling of the associated intermolecular interactions. To address mechanisms of drug action. the second issue, we have developed a simple and computationally inexpensive correction to the calculated free energies based on a hybrid quantum mechanics/ 5:00 Close of the Day molecular mechanics approach. In this presentation, the method will be described and its performance assessed in the calculation of small and drug-like molecules’ free energies of hydration, and on the calculation of protein-ligand binding affinities Dinner Short Course (June 19, 6:00-8:00 pm)* in neuraminidase, CDK2 and COX2. Structure-Based Drug Design for Epigenetic Targets Johnathan R. Whetstine, Ph.D., Assistant Professor of Medicine, Harvard Medical School Philip Fallon, Ph.D., Senior Medicinal Chemist, Domainex Ltd. *Separate registration required. healthtech.com/SBD ••• 3
  • 4. 11:10 Site Identification by Ligand Competitive Saturation (SILCS): Structure- a significant portion of the total binding energy, and thus represent opportunities Based Free Energy Computational Approach for Ligand Discovery for ligand design. Computing desolvation energetics typically requires lengthy simulations, but this talk presents a fast and easy-to-use method (3D-RISM) which and Optimization computes desolvation energies in minutes, without using explicit simulations. Alexander D. MacKerell, Jr., Ph.D., Grollman-Glick Professor of Application to ligand optimization is demonstrated using case studies. Pharmaceutical Sciences, Director, Computer-Aided Drug Design Center, School of Pharmacy, University of Maryland 3:10 Refreshment Break in the Exhibit Hall with Poster Viewing The Site Identification by Ligand Competitive Saturation (SILCS) method uses explicit solvent all-atom molecular dynamics simulations to identify binding sites 3:40 Characterizing and Exploiting the Solvation of Protein Surfaces for on proteins for functional group classes based on rigorous free energy criteria that includes protein flexibility and fragment desolvation. Information from the SILCS Applications in Drug Design and Discovery approach, termed FragMaps, may be used for the identification of novel ligands Tom Kurtzman Young, Ph.D., Assistant Professor, Department of Chemistry, Lehman targeting protein, including de novo ligand design. In addition, the SILCS method College, CUNY may be combined with structural information on a ligand-protein complex to The displacement of water from a binding site by a ligand is a principal, and often facilitate modification of the ligand to improve its binding affinity. dominant, source of binding free energy. In recent years, a number of techniques based on Inhomogeneous Solvation Theory have been developed that map out the 11:40 Blurring to Bring Binding Free Energies into Focus solvation thermodynamics of protein binding sites (STOW, WaterMap, GIST). We outline the physical basis of these mapping techniques and present some possible Kenneth M. Merz, Jr., University of Florida Research Foundation Professor, applications in drug discovery and design. Edmund H. Prominski Professor of Chemistry, Department of Chemistry, Quantum Theory Project, University of Florida 4:10 Mapping Protein Surfaces with MixMD to Identify New Binding Sites Docking calculations coupled with binding free energy estimates (scoring) are a mainstay of structure-based drug design. This talk Heather Carlson, Professor, Medicinal Chemistry, University of Michigan addresses how to use ensemble principles to estimate and reduce uncertainty of Mixed-solvent molecular dynamics (MixMD) is an emerging technique in computed binding free energies. We have developed methods to evaluate potential structure-based drug design (SBDD). The most significant benefits are the function error and in this talk we will demonstrate how to use this knowledge to ability of a protein to adapt in the presence of a probe and the identification improve the outcome of a docking and scoring exercise. This was accomplished via of binding sites where organic molecules specifically out-compete water. the development of novel scoring approaches that employ statistical mechanical Rather than ignoring the complicated role of water as most SBDD methods do, it is truly principles and are coupled with error propagation. Importantly, our approach yields embraced in MixMD. Blinded, experimental validation of the method will be presented. free energies as well as estimates of the random and systematic errors in these quantities, providing insight into the reliability of the computed free energies. 4:40 The Potency-Insolubility Conundrum in Drug Discovery: Mechanism and Solution for Hepatitis C Inhibitors 12:10 pm Luncheon Presentation (Opportunity Available) Patrick R. Connelly, Ph.D., Principal Scientific Fellow, Vertex or Lunch on Your Own Pharmaceuticals, Inc. As compounds are optimized for greater potency during GPCR pharmaceutical discovery, their aqueous solubility often decreases, making them less viable as orally-administered drugs. The potency-insolubility 1:30 Chairperson’s Remarks conundrum has prompted speculation, concern, and attempts to taxonomize the problem or overcome it technologically. However, a fundamental molecular connection between binding potency and aqueous insolubility has yet to be 1:40 An Automated Pipeline for the Modeling and Simulation of GPCRs: elucidated. By examination of the structural and thermodynamic properties Applications to Structure-Based Drug Design of telaprevir, a sparingly soluble inhibitor of the NS3 protease of the Hepatitis Hugo Gutierrez-de-Teran, Ph.D., Parga Pondal Research Fellow, C virus, it is revealed that potency and insolubility share a common origin. A Bioinformatics, Public Galician Foundation of Genomic Medicine design strategy based on supramolecular graph set considerations provides a The recent advances in membrane protein crystallography have generalizable solution to the conundrum. provided extremely valuable structural information of the superfamily of G-protein-coupled receptors (GPCRs). Recently, we have developed GPCR- 5:10 Welcome Reception in the Exhibit Hall with Poster Viewing ModSim (http://gpcr.usc.es), a web-based, automated pipeline to generate high- quality 3D models of the remaining GPCRs and to perform molecular dynamics (MD) simulations with an explicit representation of the cellular membrane, 6:30 End of Day structural water, cholesterol or lipid molecules. With this computational tool, research groups without prior experience in computational chemistry can set up FRIDAY, JUNE 21 ambitious projects on SBDD in GPCRs in a systematic and comprehensive way. 7:30 am Breakfast Roundtable Discussions 2:10 How Drugs Bind and Control Their Targets: Characterizing GPCR Signaling through Long-Timescale Simulation FRAGMENT-BASED DRUG DESIGN Ron O. Dror, Senior Research Scientist, D. E. Shaw Research One-third of drugs act by binding to G protein–coupled receptors 8:30 Chairperson’s Remarks (GPCRs) and either triggering or preventing receptor activation, but the process by which they do so has proven difficult to characterize either 8:40 Case Histories of Recent Fragment-Based Drug Discovery Projects experimentally or computationally. Anton, a special-purpose machine that we designed to accelerate molecular dynamics simulations by orders of magnitude, Christopher W. Murray, Ph.D., Vice President, Discovery Technology, Astex has enabled simulations in which drugs spontaneously associate with GPCRs Pharmaceuticals to achieve bound conformations that match crystal structures almost perfectly. Here we describe some case histories of applying fragment-based Anton simulations have also captured transitions of a GPCR between its active and drug discovery to challenging drug targets. This will include the design inactive states, allowing us to characterize the mechanism of receptor activation. of protein-protein interaction inhibitors of IAP family proteins and the Our results suggest opportunities for the design of drugs that achieve greater design of allosteric inhibitors of full-length NS3 proteins from the Hepatitis C Virus. specificity and control receptor signaling more precisely. The presentation will discuss the difficulties associated with applying fragment- based drug discovery to challenging target classes and will discuss ways in which these can be mitigated. WATER & SOLVATION IN DRUG DESIGN 2:40 Exploiting Solvent Effects in Drug Design and Optimization Sponsored by 9:10 Computational Protein Mapping to Drive the Development of Fragment Chris Williams, Ph.D., Principal Scientist, Chemical Computing Group Hits into Leads Upon ligand binding, solvent molecules around the binding pocket Sandor Vajda, Ph.D., Professor of Biomedical Engineering and Chemistry, Director, and the ligand become displaced or rearranged. These desolvation energies can be Biomolecular Engineering Research Center, Boston University healthtech.com/SBD ••• 4
  • 5. Fragment-based drug design (FBDD) starts with finding fragment-sized compounds A promising way to interfere with biological processes is through the control of that are highly ligand efficient and can serve as a core moiety for developing protein-protein interactions by means of small molecules. Recent advances in the high-affinity leads. Although the core-bound structure of a protein facilitates the understanding of the energetics and dynamics of protein-binding interfaces open construction of leads, effective design is far from straightforward. We show that up a way to apply rational design approaches for finding protein-protein interaction protein mapping, a computational method developed to find binding hot spots, modulators (PPIM). Here, we successfully identify small-molecule inhibitors of the provides information that complements the fragment screening results and can dimer to tetramer transition of the NHR2 domain within the RUNX1/ETO fusion drive the evolution of core fragments into larger leads with a minimal loss or, in protein, a novel target for the treatment of acute myeloid leukemia. some cases, even a gain in ligand efficiency. 2:30 Structure-Based Guided Development of Focused Chemical Library 9:40 Determination of Binding Poses, Kinetics and Energetics in Fragment- Dedicated to Orthosteric Modulation of Protein-Protein Interactions Based Design Xavier Morelli, Ph.D., Group Leader, Cancer Research Center of Marseille, Gianni De Fabritiis, Ph.D., Computational Biophysics Laboratory (GRIB- CNRS IMIM), Universitat Pompeu Fabra, Barcelona Biomedical Research Park This talk will address some challenging issues: biological and (PRBB) chemical spaces of PPI with known orthosteric inhibitors, ligandability assessment of protein-protein interactions, design and validation of chemical libraries dedicated to PPIs. 10:10 Coffee Break in the Exhibit Hall with Poster Viewing 3:00 Refreshment Break 10:40 The Tip of the Iceberg and the Chemical Universe: Fuzzy Hit Finding Under Synthetic Feasibility Conditions EPIGENETIC TARGETING Carsten Detering, Ph.D., CEO, BioSolveIT, Inc. We have come up with a method that addresses the problem of 3:15 Design and Develop Bromodomain Inhibitor for Cancer Therapy crowded patent space. It captures existing available chemistry in a Jun Qi, Ph.D., Senior Research Scientist, Medical Oncology, Dana-Farber company and thus allows the researcher to fuzzily search in a larger Cancer Institute portion of the chemical universe available to him/her. Results are returned with In cancer, epigenetic proteins are promising and intensely studied their underlying chemical synthesis, which renders retro-synthesis unnecessary. targets for therapeutic drug discovery. Among the chromatin- Time saved can be invested in other Medicinal Chemistry efforts. The talk will modifying enzymes, so-called epigenetic “writers” “readers” and , highlight the method as well as several application examples. “erasers” chromatin-binding modules or epigenetic “readers” have received , comparatively little attention perhaps owing to perceptions regarding the difficulty of targeting protein-protein interactions. Motivated by this challenge, we have 11:10 Advances in Predicting Protein-Protein Binding Sponsored by developed first-in-class, drug-like inhibitors of “bromodomain and extraterminal Affinity and Protein Stability domain” epigenetic readers (BETs) for mechanistic study and therapeutic Woody Sherman, Ph.D., Vice President, Applications application in cancer. We are continuously integrating the transcriptional Science, Schrodinger, Inc. consequences of BETi with changes in the epigenomic landscapes of cancer cells to elucidate the mechanisms underlying response to BETi using chemical and genetic perturbations. 11:40 Sponsored Presentation (Opportunity Available) 3:45 The Impact of Structural Data on Epigenetic Probe Discovery for the 12:10 pm Luncheon Presentation (Opportunity Available) Public Domain or Lunch on Your Own Dafydd Owen, Ph.D., Associate Research Fellow, Biotherapeutics Worldwide R&D, Pfizer Worldwide Medicinal Chemistry PROTEIN-PROTEIN INTERACTION Research into the role of epigenetics in disease could be significantly accelerated if cell-active chemical probes for such targets were 1:25 Chairperson’s Remarks available to the research community, through a collaborative, open- innovation model. Pfizer is a member of a public-private partnership led by the 1:30 How Does a Small-Molecule Inhibitor Bind at the Protein-Protein Structural Genomics Consortium (SGC) to help identify a suite of high-quality chemical probes for epigenetic targets. This partnership is unique in that it brings Interface of Interleukin 2? the medicinal chemistry expertise within industry together with biological expertise Yibing Shan, Senior Scientist, DE Shaw Research in academia to drive basic research in an emerging area of important biology of potential relevance to many diseases. The impact of structural biology on probe discovery will be presented. 2:00 From Determinants of RUNX1/ETO Tetramerization to Small-Molecule 4:15 Closing Remarks Protein-Protein Interaction Inhibitors Targeting Acute Myeloid Leukemia 4:30 End of Conference Holger Gohlke, Ph. D., Professor, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-University, Düsseldorf Sponsoring Society: Media Partners: Media Sponsor: 5 ••• healthtech.com/SBD
  • 6. Sponsorship & Exhibit CHI offers comprehensive sponsorship packages which include presentation opportunities, exhibit space and branding, as well as the use of the pre- and post-show delegate list. Sponsorship allows you to achieve your objectives Information before, during, and long after the event. Any sponsorship can be customized to meet your company’s needs and budget. Signing on earlier will allow you to maximize exposure to hard-to-reach decision makers. Agenda Presentations Showcase your solutions to a guaranteed, highly-targeted audience. Package includes a 15- or 30-minute podium presentation within Looking for additional ways to the scientific agenda, exhibit space, on-site branding and access to cooperative marketing efforts by CHI. drive leads to your sales team? CHI can help with custom lead Breakfast & Luncheon Presentations Opportunities include a 30-minute podium presentation. Boxed lunches generation programs! are delivered into the main session room, which guarantees audience attendance and participation. A limited number of presentations are We offer clients numerous options for custom lead generation programs to available for sponsorship and they will sell out quickly. Sign on to address their marketing and sales needs. Some of our programs include: live secure your talk! webinars, white papers, market surveys, podcasts, and more! Invitation-Only VIP Dinner/Hospitality Suite Benefits of working with CHI for your lead Sponsors will hand-pick their top prospects from the conference generation needs: pre-registration list for an evening of networking at the hotel or at a • Your campaign will receive targeted promotion to CHI’s unparalleled choice local venue. CHI will extend invitations and deliver prospects. database of over 800,000 individuals, all of which are involved in Evening will be customized according to sponsor’s objectives (i.e. all sectors of the life sciences – lists can be segmented based on purely social, focus group, reception style, or plated dinner with geography, research area, title and industry specific conversation focus). • All custom lead generation programs are promoted through our experienced marketing team that will develop and drive targeted Focus Groups campaigns to expand awareness and bolster leads CHI can help you organize and execute a focus group on site. This • For our webinar programs, we offer assistance in procuring speakers for exclusive gathering can be useful to conduct market research, gain your web symposia through our extensive roster of industry recognized feedback on a new product idea, and gather marketing intelligence from speakers across multiple disciplines within life sciences, as well as industry experts on a specific topic. Please inquire for more details. provide an experienced moderator and dedicated operations team to coordinate all efforts User Group Meeting • If choosing a white paper program, we can offer editorial experience and Co-locate your user group with the Structure-Based Drug Design provide an industry-recognized author to write your white paper conference. CHI will help market the event, manage logistical operations, develop an agenda, and more. CHI can handle the entirety of the meeting, or aspects of your choice. Exhibit Information Exhibitors will enjoy facilitated networking opportunities with qualified decision-makers at the Structure-Based Drug Design conference, making it the perfect platform to launch a new product, collect feedback and For additional sponsorship & generate new leads. Exhibit space sells out quickly, so reserve yours today! exhibit information, please contact: Additional Promotional Opportunities Include: • Conference tote bags Jon Stroup • Badge lanyards • Tote bag inserts of company literature Manager, Business Development • Padfolios 781-972-5483 • Keynote chair drop of company literature • Session room chair drop of company literature jstroup@healthtech.com • Program guide sponsor • Poster abstract book sponsor healthtech.com/SBD ••• 6
  • 7. Hotel & Travel Information Past Attendee Testimonials: “The selection of speakers and Conference Venue and Hotel: presentations strongly demonstrated The Revere Hotel the expansive breadth and impact of structure-based drug design.” - Director of Bioinformatics, 200 Stuart Street, Boston, MA 02116 ActivX Biosciences Tel: (617) 482-1800 “Very, very interesting and useful.” Discounted Room Rate: $249 s/d - Team Leader, Molecular Modelling, Discounted Reservation Cut-off Date: May 17, 2013 CNRS-ICSN Please visit our website to make your reservations “Good-quality up-to-date presentations online, or call the hotel directly to reserve your made this a stimulating and informative sleeping accommodations. You will need to identify conference.” yourself as a Cambridge Healthtech Institute - CSO, De Novo Pharmaceuticals Ltd. conference attendee to receive the discounted room rate with the host hotel. Reservations made “Some discussions inspired new ideas I am after the cut-off date or after the group room block going to try.” has been filled (whichever comes first) will be - Senior Research Fellow, Merck accepted on a space-and-rate-availability basis. Rooms are limited, so please book early. “Thanks to the organizers, it’s a very exciting conference. It’s very interesting to listen to all the talks. Some discussions inspired new ideas that I’m going to try!” - Senior Research Fellow, Molsys, Merck “Some important principles were highlighted with regard to the computational problem of describing ligand binding and the computational problem of describing Flight Discounts: ligand binding and drug-likeliness; and the best thing was that the speakers could Special discounts have been established with demonstrate that working solutions are American Airlines. beginning to emerge.” Please use one of the following methods: - Computational Chemist, • Call American Airlines at 1-800-433-1790 and Bayer HealthCare use Conference code 4463BU “Some very important principles were • Go to www.aa.com/group and enter 4463BU in highlighted and the best thing was that the promotion discount box the speakers could demonstrate working • Contact our dedicated travel agent, solutions.” Rona Meizler at 1-617-559-3735 or - Computational Chemist, Bayer HealthCare rona.meizler@protravelinc.com “It was great – best conference I’ve been to.” Car Rental Discounts: - Scientist, Prothana, Inc. Special rental discounts have been established with “A useful meeting where I gained more Hertz for this conference. insights and ideas to apply in my own research.” • Go to www.hertz.com and use our Hertz - Chemistry Specialist, Convention number (CV): 04KL0003 Catholic University Leuven • Call Hertz at 1-800-654-3131 and use our Hertz Convention Number (CV):04KL0003 healthtech.com/SBD ••• 7
  • 8. Cambridge Healthtech Institute and Bio-IT World’s Thirteenth Annual June 19-21, 2013 Structure-Based The Revere Hotel Boston, MA Drug Design Pricing and Registration Information Receive a FREE eNewsletter by signing up DINNER SHORT COURSE at chimediagroup.com Academic, Government, June 19 • 6:00pm-8:00pm Commercial Hospital-affiliated The latest industry news, commentary and highlights from Bio-IT World Structure-Based Drug Design for Epigenetic Targets $495 $295 Innovative management in clinical trials Conference Pricing (Excludes short course) A series of diverse reports designed to Early Registration until March 22, 2013 $1745 $845 keep life science professionals informed of the salient trends in pharmaceutical Advance Registration until May 10, 2013 $1895 $925 technology, business, clinical development, and therapeutic disease markets. Registrations after May 10, 2013, and on-site $2095 $995 For a detailed list of reports, visit InsightPharmaReports.com, or contact Rose LaRaia, rlaraia@healthtech.com, +1-781-972-5444. Special Package Pricing (Includes access to Structure-Based Drug Design & Next-Gen Kinase Inhibitors, excludes short course) Barnett is a recognized leader in clinical Early Registration until March 22, 2013 $2995 $1495 education, training, and reference guides for life science professionals involved in Advance Registration until May 10, 2013 $3145 $1565 the drug development process. For more information, visit barnettinternational.com. Registrations after May 10, 2013, and on-site $3345 $1585 Conference Discounts Cambridge Healthtech Associates™ (CHA™) uses its collaborative model to Poster Submission-Discount ($50 Off) improve the speed and economics of life Poster abstracts are due by May 10, 2013. Once your registration has been fully processed, we will send an email containing a unique link sciences R&D, leveraging its consulting, allowing you to submit your poster abstract. If you do not receive your link within 5 business days, please contact jring@healthtech.com. technology evaluations and communities. Visit www.chacorporate.com. *CHI reserves the right to publish your poster title and abstract in various marketing materials and products. International Society for Computational Biology (ISCB) Member- Discount 10% Off Additional registration details Subject to verification. Each registration includes all conference REGISTER 3 - 4th IS FREE: Individuals must register for the same conference or conference combination and submit completed registration form together ­ sessions, posters and exhibits, food functions, and access to the conference for discount to apply. proceedings link. Additional discounts are available for multiple attendees from the same organization. For more information on group rates, contact Handicapped Equal Access: In accordance with the ADA, Cambridge Healthtech David Cunningham at +1-781-972-5472. Institute is pleased to arrange special accommodations for attendees with If you are unable to attend but would like to purchase the Structure-Based Drug Design CD for $350 (plus shipping), please visit www.healthtech.com/sbd. special needs. All requests for such Massachusetts delivery will include sales tax. assistance must be submitted in writing to CHI at least 30 days prior to the start of the meeting. Eleventh Annual To view our Substitutions/ BEST VALUE! CO-LOCATED Next-Gen June 17-19 Register for both conferences at a Cancellations Policy, go to http://www.healthtech.com/regdetails Video and or audio recording of any kind EVENT Kinase Inhibitors healthtech.com/KIN special rate. is prohibited onsite at all CHI events. Moving Towards a Successful Pipeline How to Register: healthtech.com/sbd Please use keycode SBD F reg@healthtech.com • P: 781.972.5400 or Toll-free in the U.S. 888.999.6288 when registering!