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COVER CHI’s 13th Annual CONFERENCE AT-A-GLANCE PLENARY KEYNOTES SHORT COURSES AGENDA Plenary April 3-4 Conferences »» Protein-Protein Interactions Keynotes »» & Autoimmune Inhibitors Chemistry »» Inhibitor Chemistry Optimizing Small Molecules for Tomorrow's Therapeutics »» GPCR-Targeted »» Fragment-Based Drug Activity-Based April 2-6, 2018 | San Diego, CA | Hilton San Diego Bayfront Discovery Proteomics: April 4-5 Conferences Protein and »» Ubiquitin Proteasome System Ligand Discovery Inhibitors on a Global Scale CONFERENCE PROGRAMS »» Small Molecules for Cancer Benjamin F. Cravatt, Immunotherapy PhD, Professor and APRIL 3-4 APRIL 4-5 APRIL 6 Co-Chair, Department »» Macrocyclics & Constrained of Molecular Peptides Medicine, The Protein-Protein Ubiquitin Proteasome Biophysical Approaches »» Targeting Complex Scripps Research Membrane Proteins Institute Interactions System Inhibitors for Drug Discovery April 6 Symposia Lead Optimization »» Biophysical Approaches for Inflammation & Small Molecules for  Drug Discovery for Autoimmune Inhibitors Cancer Immunotherapy »» Lead Optimization for Drug & Safety Metabolism & Safety »» Blood-Brain Penetrant Targeting Ras Kinase Inhibitor  Macrocyclics & Blood-Brain Inhibitors and MYC for the Treatment of Chemistry Constrained Peptides Penetrant Inhibitors HOTEL & TRAVEL Cancer Stephen Fesik, SPONSORSHIP PhD, Professor GCPR-Targeted  Targeting Complex Plus Short Courses & EXHIBIT of , Drug Design Membrane Proteins on April 2 & April 4 Pharmacology, and REGISTRATION Chemistry, Orrin H. Ingram II Chair in Cancer Research, Fragment-Based  Click Here to register Online Vanderbilt University Drug Discovery DrugDiscoveryChemistry.com School of Medicine DrugDiscoveryChemistry.com

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COVER CONFERENCE AT-A-GLANCE CONFERENCE AT-A-GLANCE PLENARY KEYNOTES SHORT COURSES AGENDA Monday Tuesday Wednesday Thursday Friday April 3-4 Conferences APRIL 2 APRIL 3 APRIL 4 APRIL 5 APRIL 6 »» Protein-Protein Interactions »» Inflammation & Autoimmune Inhibitors BIOPHYSICAL PRE-CONFERENCE PROTEIN-PROTEIN DINNER SHORT COURSES* UBIQUITIN PROTEASOME » APPROACHES FOR » Kinase Inhibitor Chemistry SHORT COURSES* INTERACTIONS SYSTEM INHIBITORS »» GPCR-Targeted Drug Design DRUG DISCOVERY »» Fragment-Based Drug Discovery LEAD OPTIMIZATION INFLAMMATION & SMALL MOLECULES FOR April 4-5 Conferences FOR DRUG AUTOIMMUNE INHIBITORS CANCER IMMUNOTHERAPY »» Ubiquitin Proteasome System METABOLISM & SAFETY Inhibitors »» Small Molecules for Cancer Immunotherapy KINASE INHIBITOR MACROCYCLICS & BLOOD-BRAIN »» Macrocyclics & Constrained CHEMISTRY CONSTRAINED PEPTIDES PENETRANT INHIBITORS Peptides »» Targeting Complex Membrane Proteins *Separate registration is required April 6 Symposia GCPR-TARGETED TARGETING COMPLEX »» Biophysical Approaches for DRUG DESIGN MEMBRANE PROTEINS Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant FRAGMENT-BASED Inhibitors DRUG DISCOVERY TRACK-HOPPING Attendees at Drug Discovery Chemistry are HOTEL & TRAVEL encouraged to “track-hop” between concurrent : Though you register for a particular SPONSORSHIP sessions conference or symposium, in reality you gain access to all & EXHIBIT concurrent conferences or symposia. For the best value, REGISTRATION register for a Premium Package, and gain access to all 12 conferences/symposia, plus two short courses, over five days of programming that best fits your research needs. Click Here to register Online DrugDiscoveryChemistry.com

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COVER SPONSORS CONFERENCE AT-A-GLANCE PLENARY KEYNOTES PREMIER SPONSORS: SHORT COURSES AGENDA April 3-4 Conferences »» Protein-Protein Interactions »» Inflammation & Autoimmune Inhibitors »» Kinase Inhibitor Chemistry »» GPCR-Targeted Drug Design »» Fragment-Based Drug Discovery April 4-5 Conferences CORPORATE SPONSORS: »» Ubiquitin Proteasome System Inhibitors »» Small Molecules for Cancer Immunotherapy »» Macrocyclics & Constrained Peptides »» Targeting Complex Membrane Proteins April 6 Symposia »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant Inhibitors

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A Division of Cambridge Innovation Institute DrugDiscoveryChemistry.com • 3 Save up to $200! Register by February 23 PLENARY KEYNOTES COVER CONFERENCE AT-A-GLANCE PLENARY KEYNOTES April 3, 2018 | 4:40 pm April 5, 2018 | 8:55 am SHORT COURSES Activity-Based Proteomics: Protein and Targeting Ras and MYC for AGENDA Ligand Discovery on a Global Scale the Treatment of Cancer April 3-4 Conferences Benjamin F. Cravatt, PhD Stephen Fesik, PhD »» Protein-Protein Interactions Professor and Co-Chair, Department of Molecular Medicine, The Scripps Professor of Biochemistry, Pharmacology, and Chemistry, Orrin H. Ingram II »» Inflammation & Autoimmune Research Institute Chair in Cancer Research, Vanderbilt University School of Medicine Inhibitors »» Kinase Inhibitor Chemistry Dr. Cravatt is a Professor and Co-Chair of the Department of Dr. Fesik’s research focus is on cancer drug discovery using »» GPCR-Targeted Drug Design Molecular Medicine at The Scripps Research Institute. His fragment-based approaches and structure-based drug »» Fragment-Based Drug research group is interested in understanding the roles that design. Prior to joining Vanderbilt in May 2009, Dr. Fesik was Discovery enzymes play in physiological and pathological processes, the Divisional Vice President of Cancer Research at Abbott April 4-5 Conferences especially as pertains to the nervous system and cancer. Dr. (2000-2009) where he built a pipeline of compounds that »» Ubiquitin Proteasome System Inhibitors Cravatt obtained his undergraduate education at Stanford are showing promising anti-cancer activities in early stage »» Small Molecules for Cancer University, receiving a BS in the Biological Sciences and a BA clinical trials. While at Abbott, he also developed a few new Immunotherapy in History. He then received a PhD from The Scripps Research NMR methods, determined the three-dimensional structures »» Macrocyclics & Constrained Institute (TSRI) in 1996. Professor Cravatt joined the faculty at of several proteins and protein/ligand complexes, pioneered Peptides »» Targeting Complex TSRI in 1997. Dr. Cravatt is a co-founder and scientific advisor a method for drug discovery called SAR by NMR, and applied Membrane Proteins of Activx Biosciences, Abide Therapeutics, and Vividion this method to identify and optimize ligands for binding to April 6 Symposia Therapeutics. His honors include a Searle Scholar Award, the many protein drug targets. His research has also involved the »» Biophysical Approaches for Eli Lilly Award in Biological Chemistry, a Cope Scholar Award, use of siRNA for target identification and target validation. Drug Discovery the Protein Society Irving Sigal Young Investigator Award, Dr. Fesik has published more than 240 papers, trained »» Lead Optimization for Drug Metabolism & Safety the Tetrahedron Young Investigator Award in Bioorganic 38 postdoctoral fellows, has been a reviewer for several »» Blood-Brain Penetrant and , the ASBMB Merck Award, and government funding agencies and has served as a member Inhibitors memberships in the National Academy of Sciences and of the Editorial Boards of many peer-reviewed journals. He HOTEL & TRAVEL American Academy of Arts and Sciences. is currently a member of Aileron Therapeutics SAB and the Bruker Board of Directors. His three awards from Abbott SPONSORSHIP & EXHIBIT include Researcher of the Year Team Award (2008). He has also received the NIH Director's Pioneer Award (2010), and REGISTRATION honors from numerous academic societies, the most recent being the AACR Award for Outstanding Achievement in Click Here to register Online Chemistry in Cancer Research (2012). DrugDiscoveryChemistry.com

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* COVER Short Courses CONFERENCE AT-A-GLANCE Afternoon Short Courses SC4: Diversity-Oriented Platforms for SC7: Introduction to Targeted Covalent Inhibitors Ligand Discovery Instructor: Mark Schnute, PhD, Associate Research PLENARY KEYNOTES Monday, April 2, 2:00 - 5:00 pm Instructors: Sepideh Afshar, PhD, Principal Research Fellow, Biotherapeutics Chemistry & Immunoscience SHORT COURSES , Department of Protein Engineering, Eli Lilly Research, Pfizer Global R&D SC1: Ligand-Receptor Molecular Interactions and Company • Overview of covalent drugs, irreversible AGENDA and Drug Design Svetlana Belyanskaya, PhD, Encoded Library and reversible inhibitors including recent Instructor: Maricel Torrent, PhD, Senior Scientist, AbbVie Technologies, R&D Platform Technology & Science, clinical examples April 3-4 Conferences • Drug design principles generally applicable to all GSK Boston • Biochemical analysis of covalent inhibitors »» Protein-Protein Interactions medicinal chemistry programs Pros and cons of affinity based screening platforms in • Design considerations for targeted »» Inflammation & Autoimmune • Interpretation of atomic-level protein X-ray and drug discovery: covalent inhibitors Inhibitors modeled structures of binding model • Phage display • De-risking covalent inhibitors »» Kinase Inhibitor Chemistry • Understanding the relative amounts of potency gain • mRNA display SC8: Introduction to the Ubiquitin Proteasome System »» GPCR-Targeted Drug Design from different interactions • DNA-encoded libraries Instructor: Alexander Statsyuk, PhD, Assistant Professor, • Case studies illustrate all the design strategies »» Fragment-Based Drug Department of Pharmacological and Pharmaceutical Discovery SC2: Advancing Tools and Technology for Dinner Short Courses Sciences, University of Houston Fragment-Based Design • Mechanisms of E1, E2, E3, and DUB enzymes April 4-5 Conferences Instructors: Ben Davis, PhD, Research Fellow, Biology, Monday, April 2, 6:00 - 9:00 pm • Technologies available and experimental controls »» Ubiquitin Proteasome System Vernalis Research • Discovered inhibitors and emerging biology Inhibitors SC5: Immunology Basics for Chemists Daniel A. Erlanson, PhD, Co-Founder, Carmot Instructors: Songqing Na, PhD, Senior Scientist, »» Small Molecules for Cancer Therapeutics, Inc. & Autoimmunity Res-AME, Eli Lilly Dinner Short Courses Immunotherapy • Why fragments – pros and cons and Company »» Macrocyclics & Constrained • What makes a good fragment, and a good Thomas Sundberg, PhD, Senior Research Scientist I, Wednesday, April 4, 6:30 - 9:00 pm Peptides fragment library Center for Development of Therapeutics, Broad Institute SC9: Impact of Convergence of Immunotherapy and »» Targeting Complex • Finding, validating and characterizing low of MIT and Harvard Epigenetics on Drug Discovery Membrane Proteins affinity ligands • Review of immune system’s cellular players • The importance of using orthogonal Instructors: Katherine Chiappinelli, PhD, Assistant April 6 Symposia • Review of inflammatory process screening methods Professor, Department of Microbiology, Immunology, » • Autoimmune & inflammation-related diseases » Biophysical Approaches for • What to do with a fragment – growing, and Tropical Medicine, The George Washington Drug Discovery • Current treatment landscape and University Cancer Center linking, and more promising drug targets »» Lead Optimization for Drug Alejandro Villagra, PhD, Assistant Professor, Department SC3: Drug Metabolism and Its Impact on Decisions in • Principles in immune-oncology (e.g., Metabolism & Safety of Biochemistry and Molecular Medicine, School of Lead Discovery and checkpoint blockade) Medicine and Health Sciences, The George Washington »» Blood-Brain Penetrant Instructor: John C. L. Erve, PhD, DABT, Consultant, Jerve Inhibitors SC6: Introduction to Allosteric Modulators and Biased University Scientific Consulting, Inc. Ligands of GPCRs Wayne W. Hancock, MD, PhD, Professor of Pathology • Applying drug metabolism concepts to HOTEL & TRAVEL Instructor: Terry Kenakin, PhD, Professor, Department and Chief of Transplant Immunology, Children’s Hospital lead optimization of Pharmacology, University of North Carolina School of Philadelphia and University of Pennsylvania SPONSORSHIP • Impact of drug structures on of Medicine • Epigenetic pathways that intersect and interact with & EXHIBIT important PK parameters • Overview of allosteric modulators and pathway the immune system • Common assays for predicting clearance and biased ligands • Effect of epigenetic therapies on the tumor and REGISTRATION metabolism-based drug-drug interactions • Approaches for screening and validation host immune system • Growing application of in silico tools in • Fitting functional allosteric data to obtain allosteric • Exploiting immunoepigenetics to enhance the drug metabolism drug parameters efficacy of current drug treatments Click Here to register Online • Role of bioactivation in drug toxicity • Case studies highlighting promises and challenges DrugDiscoveryChemistry.com Short courses continued on next page...

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* COVER Short Courses CONFERENCE AT-A-GLANCE SC10: Enabling Macrocyclic Compounds for Drug SC11: Trends in Physical Properties of Drugs SC12: Covalent Fragments: Applications in Target- Discovery: Opportunities, Challenges and Strategies Instructors: Terry Stouch, PhD, President, R&D, Science Based and Phenotypic Screens PLENARY KEYNOTES Instructors: Eric Marsault, PhD, Professor, Medicinal for Solutions, LLC Instructor: Alexander Statsyuk, PhD, Assistant SHORT COURSES Chemistry and Pharmacology, University of Sherbrooke Robert Fraczkiewicz, PhD, Team Leader, Simulations Professor, Department of Pharmacological and Mark Peterson, PhD, COO, Cyclenium Pharma, Inc. Plus, Inc. Pharmaceutical Sciences, University of Houston AGENDA • Unique characteristics of macrocycles Max Totrov, PhD, Principal Scientist, MolSoft, LLC • Design principles of covalent fragment libraries, • Factors affecting cell permeability and PK/ • Properties important for enhanced efficacy, delivery, target-based and phenotypic screens using April 3-4 Conferences ADME properties and formulation covalent fragments »» Protein-Protein Interactions • Synthetic strategies for macrocyclic compound • pKa, tautomerism, crystallization, others • Strategies to grow fragments into drug leads, »» Inflammation & Autoimmune libraries & macrocyclization challenges • Computational prediction: What works and case studies Inhibitors • Drug discovery and development examples and - what doesn’t • Coupling covalent fragment growth with selectivity »» Kinase Inhibitor Chemistry future perspectives • Experimental best practices profiling in cells »» GPCR-Targeted Drug Design »» Fragment-Based Drug Discovery April 4-5 Conferences »» Ubiquitin Proteasome System Inhibitors »» Small Molecules for Cancer Immunotherapy PRESENT A POSTER »» Macrocyclics & Constrained AND Peptides SAVE $50! »» Targeting Complex Cambridge Healthtech Institute encourages attendees Membrane Proteins to gain further exposure by presenting their work in the poster sessions. To secure a poster board and inclusion April 6 Symposia Student Fellowships Now in the conference materials, your abstract must be »» Biophysical Approaches for Drug Discovery Available – New for 2018! submitted, approved and your registration paid in full by February 23, 2018. Reasons you should present »» Lead Optimization for Drug Full-time graduate students and Metabolism & Safety your research poster at this conference: »» Blood-Brain Penetrant PhD candidates presenting a poster • Your poster will be seen by our international delega- Inhibitors are now encouraged to apply for tion, representing leaders from top pharmaceutical, biotech, academic and government institutions HOTEL & TRAVEL a Student Fellowship. Spaces are • Receive $50 off your registration SPONSORSHIP limited! Please see website for details. • Your poster will be automatically entered into the & EXHIBIT main conference poster competition • Your poster abstract will be published in our REGISTRATION conference materials

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COVER CONFERENCE AT-A-GLANCE CONFERENCES & SYMPOSIA PLENARY KEYNOTES SHORT COURSES AGENDA CONFERENCES SYMPOSIA April 3-4 Conferences »» Protein-Protein Interactions APRIL 3-4 APRIL 4-5 APRIL 6 »» Inflammation & Autoimmune Inhibitors »» Kinase Inhibitor Chemistry »» GPCR-Targeted Drug Design Protein-Protein Ubiquitin Proteasome Biophysical Approaches »» Fragment-Based Drug Interactions System Inhibitors for Drug Discovery Discovery April 4-5 Conferences »» Ubiquitin Proteasome System Lead Optimization Inflammation & Small Molecules for  Inhibitors for Drug Metabolism »» Small Molecules for Cancer Autoimmune Inhibitors Cancer Immunotherapy Immunotherapy & Safety »» Macrocyclics & Constrained Peptides »» Targeting Complex Kinase Inhibitor  Macrocyclics & Blood-Brain Membrane Proteins Chemistry Constrained Peptides Penetrant Inhibitors April 6 Symposia »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug GCPR-Targeted Targeting Complex Metabolism & Safety Drug Design Membrane Proteins »» Blood-Brain Penetrant Inhibitors

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COVER Protein-Protein Interactions CONFERENCE Targeting PPIs for Therapeutic Interventions AT-A-GLANCE April 3-4, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES Tuesday, April 3 9:10 Presentation to be Announced Sponsored by protein-protein interaction to combat autoimmunity. AGENDA Artem Evdokimov, PhD, CSO, HarkerBIO We were able to validate and characterize these April 3-4 Conferences 7:00 am Registration and Morning Coffee inhibitors in a variety of biochemical as well as cell- »» Protein-Protein Interactions based assays. More importantly, we can provide ONCOLOGY PPI TARGETS 9:40 Coffee Break preclinical proof-of-concept in relevant mouse models. »» Inflammation & Autoimmune 10:05 Discovery of Potent and Selective Mcl- Inhibitors 8:00 Welcome Remarks 11:35 Luncheon Presentation: The Rational Design of 1 Inhibitors Using Fragment Merging and »» Kinase Inhibitor Chemistry Anjani Shah, PhD, Conference Director, Cambridge Small-Molecule Neuropilin-1 Antagonists Healthtech Institute Structure-Guided Design Trevor Perrior, PhD, Chief Scientific Officer, Domainex »» GPCR-Targeted Drug Design James (Chris) Tarr, PhD, Drug Discovery Scientist II, 8:05 Chairperson’s Opening Remarks Neuropilin-1 (NRP1) is a receptor for vascular »» Fragment-Based Drug Stephen Fesik Laboratory, Department of Biochemistry, Kevin Lumb, PhD, Director, Discovery Sciences, endothelial growth factor A165 (VEGF-A) and Discovery Vanderbilt University the neuronal guidance molecule semaphorin 3A Janssen R&D Mcl-1 is a member of the Bcl-2 family of proteins April 4-5 Conferences (SEMA3A), which plays a key role in vascular and 8:10 Enabling Fragment and Structure-Based responsible for the regulation of apoptosis and a »» Ubiquitin Proteasome System neuronal development. Molecules which antagonise Discovery for Challenging Targets (Bcl-2, Mcl-1) highly validated target for cancer therapy. Using Inhibitors the interaction of NRP-1 with its protein ligands may Roderick E. Hubbard, PhD, Professor, University of York fragment screening by NMR followed by lead be useful in a number of therapeutic settings, in »» Small Molecules for Cancer and Director, Vernalis optimization employing structure-based design particular for the treatment of certain types of cancer. Immunotherapy Working on unprecedented targets is tough. It can methods, we have developed selective, picomolar In collaboration with Ark Therapeutics and »» Macrocyclics & Constrained take some time to generate suitable protein, develop inhibitors of Mcl-1. These compounds act via at University College London we have designed the Peptides an that can be trusted, identify tool compounds the intrinsic apoptotic pathway, potently inhibit first small-molecule inhibitors of this protein-protein »» Targeting Complex and design optimised molecules in the absence of proliferation in cellular assays, and deliver efficacy in interaction and have shown that they display the Membrane Proteins structural information. I will describe our approaches xenograft tumor models. Efforts to develop a suitable expected pharmacological profile to establish fragment and structure-based discovery clinical candidate are underway. April 6 Symposia for such targets, using as examples the early work 12:20 pm Session Break » 10:35 Targeting Nuclear Lamins to Inhibit DNA Repair » Biophysical Approaches for on Bcl-2 and Mcl-1 with Servier that resulted in Drug Discovery Xiangshu Xiao, PhD, Associate Professor, Physiology and TARGETING VIRAL, compounds that are now in Phase I clinical trials. Pharmacology, Oregon Health & Science University »» Lead Optimization for Drug 8:40 Structure-Based Design of Novel Inhibitors of Targeting DNA repair pathways has been validated NEURODEGENERATION AND OTHER Metabolism & Safety the MCL-1’s Protein-Protein Interaction as a promising strategy to develop novel cancer PROTEIN COMPLEXES »» Blood-Brain Penetrant Xin Huang, PhD, Principal Scientist, Department of therapeutics. However, it has been very challenging to Inhibitors 1:15 Chairperson’s Remarks Molecular Engineering, Amgen target DNA repair proteins. We have discovered a novel Roderick E. Hubbard, PhD, Professor, University of York Mcl-1, a member of the Bcl-2 family, inhibits pro-death role of lamins in DNA repair and have developed the and Director, Vernalis HOTEL & TRAVEL components of the intrinsic apoptosis pathway and first-in-class small molecules to target lamins to inhibit 1:20 HBV Capsid Assembly Inhibitors SPONSORSHIP thus is a key survival factor in multiple myeloma and DNA repair. We will present our exciting discovery other malignancies. Although compelling, targeting in this space. Andrew Cole, PhD, Research Fellow, Medicinal & EXHIBIT Chemistry, Arbutus disruption of Mcl-1’s protein–protein interaction to 11:05 Combatting Cancer and Autoimmunity by REGISTRATION induce tumor cell death was previously thought to be The encapsidation of pregenomic RNA by dimeric Targeting Centrosomes and Specific Ubiquitin Ligases units of hepatitis B virus core protein is an essential “un-druggable” due to the high affinities of Mcl-1 to Kamyar Hadian, PhD, Principal Investigator & Head, the pro-apoptotic Bcl-2 proteins and lack of a small step in the viral life cycle of HBV, facilitating viral Assay Development and Screening Platform, Helmholtz genome relaxed circular DNA synthesis, infectious Click Here to register Online molecule binding pocket. We report here our structure- Zentrum Muenchen based drug design of novel inhibitors of the Mcl-1 that virion production and maintenance of a nuclear DrugDiscoveryChemistry.com This lecture will give insights into two studies that deal covalently closed circular DNA pool. Small molecules led to AMG 176, a potent, selective, and bioavailable with the discovery of small molecules that either target Mcl1 inhibitor in clinical development. that bind at the core protein dimer:dimer interface centrosomes for cancer therapy or an E2/E3 ligase have been shown to demonstrate antiviral activity in

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COVER vitro and in vivo, through interference with the HBV 2:50 Drug Leads Originating from the Public/Private 5:30 Welcome Reception in the Exhibit Hall with CONFERENCE capsid assembly process. Consortium: European Lead Factory Poster Viewing AT-A-GLANCE Dimitrios Tzalis, PhD, CEO, Taros Chemicals; Head of 6:30 End of Day 1:50 FEATURED PRESENTATION: Chemistry, European Lead Factory PLENARY KEYNOTES Assessing Mitochondrial Quality Control Highlights of the European Lead Factory (ELF) Wednesday, April 4 • a public-private partnership that provides researchers SHORT COURSES to Inform Discovery of Small Molecules Targeting the Keap1-NRF2 System in Europe a unique platform for translating innovative 7:30 am Continental Breakfast Breakout Discussions AGENDA Michelangelo Campanella, PhD, PharmD, Professor and biology and chemistry into high-quality starting points Unit Head, Mitochondrial and Pharmacology for drug discovery CANCER, EPIGENETICS AND PPIs April 3-4 Conferences Research Group RVC and University College London • 200.000 de novo synthesized compounds are 8:30 Chairperson’s Remarks »» Protein-Protein Interactions Consortium for Mitochondrial Research complimenting 300.000 compounds provided by Maurizio Pellecchia, PhD, Professor of Biomedical »» Inflammation & Autoimmune My talk will report upon Nrf2 inducers as participating pharmaceutical partners Sciences, University of California, Riverside (UCR) School Inhibitors pharmacological tolls in mitochondrial quality • So far resulted in >5.000 hit compounds with a of Medicine »» Kinase Inhibitor Chemistry control operated by targeted autophagy. It will defined biological activity from >90 successfully completed HTS and hit evaluation campaigns out of 8:35 Design of Allosteric K-Ras Inhibitors Targeting »» GPCR-Targeted Drug Design elaborate on the prominent biological activity in the Switch II Pocket cellular homeostasis of the non-covalent Keap1-Nrf2 which a significant number of targets are PPIs »» Fragment-Based Drug Juan J. Perez, PhD, Professor, Department of Chemical protein-protein interaction (PPI) inhibitor PMI, which is 3:20 Sponsored Presentation (Opportunity Available) Discovery Engineering, Universitat Politecnica de Catalunya, structurally distinct from the covalent Keap1 modifiers 3:35 Refreshment Break in the Exhibit Hall with Barcelona April 4-5 Conferences (e.g. sulforaphane) and amenable to therapeutic Poster Viewing K-Ras is an oncoprotein involved in numerous »» Ubiquitin Proteasome System exploitation. Contextually, a newly devised method cancers. Inhibition of K-Ras has been elusive for many Inhibitors for High Throughput Screening (HTS) for this specific 4:30 Plenary Session Welcome Remarks from Event Director years because it cannot be competitive, due to the »» Small Molecules for Cancer category of Keap1-Nrf2 inhibitors will be presented. Anjani Shah, PhD, Conference Director, Cambridge high affinity of the protein for GTP. Recently, small Immunotherapy Healthtech Institute molecule inhibitors targeting the G12C K-Ras mutant »» Macrocyclics & Constrained 2:20 Thermodynamics-driven Structure-Activity have been disclosed. These molecules produce their Peptides Relationship Studies: Breaking the Enthalpy-Entropy 4:35 Sponsored Plenary Keynote Introduction action binding irreversibly into the inducible switch II Compensation Saga Results in Novel and Potent IAP (Opportunity Available) »» Targeting Complex pocket. In the present communication, we describe and XIAP Antagonists Membrane Proteins a novel series of reversible switch II inhibitors with Maurizio Pellecchia, PhD, Professor of Biomedical 4:40 PLENARY KEYNOTE: Activity- nanomolar affinity. April 6 Symposia Sciences, University of California, Riverside (UCR) School Based Proteomics: Protein and Ligand » 9:05 NuRD Epigenetic Complex: An Emerging Target » Biophysical Approaches for of Medicine Discovery on a Global Scale Drug Discovery Using NMR and thermodynamic screening approaches for Cancer Chemo-Sensitization Benjamin F. Cravatt, PhD, Professor and Elmar Nurmammadov, PhD, MBA, Assistant Professor, »» Lead Optimization for Drug with focused positional scanning libraries (fPOS) Co-Chair, Department of Molecular Medicine, The Director of Drug Discovery, Translational Neurosciences Metabolism & Safety novel areas on the target surface can be identified Scripps Research Institute that can be further exploited to design more potent and Neurotherapeutics, John Wayne Cancer Institute »» Blood-Brain Penetrant To address uncharacterized proteins, we have NuRD complex plays a major role in the regulation of Inhibitors and selective ligands. I will report on our recent work introduced chemical proteomic technologies that targeting the BIR3 domains of IAP family proteins, and expression, chromatin organization, DNA damage globally profile the functional state of proteins in repair, and genomic stability. NuRD complex is also HOTEL & TRAVEL will illustrate that enthalpy-entropy compensation in native biological systems. Among these methods thermodynamics-driven structure activity relationships involved in acquired resistance to chemotherapies is activity-based protein profiling (ABPP), which in a number of cancers, including deadly brain SPONSORSHIP studies can be used to design both novel pan-active utilizes chemical probes to map activity states & EXHIBIT agents and novel XIAP selective compounds. cancers. Targeting RBBP4, an integral component of large numbers of proteins in parallel. I will of this complex, sensitizes resistant cancer cells REGISTRATION discuss the application of ABPP to discover and to chemotherapy. We developed an approach that functionally annotate proteins in mammalian enables inhibition of RBBP4 and leads to selective physiology and disease, and the generation and elimination of resistant cancer cells; this is a new implementation of advanced ABPP platforms for Click Here to register Online direction in targeting of chemo-resistant cancer cells. proteome-wide ligand discovery. DrugDiscoveryChemistry.com 9:35 Coffee Break in the Exhibit Hall with Poster Viewing

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COVER FRAGMENT-BASED APPROACHES TO CONFERENCE FIND PPI INHIBITORS AT-A-GLANCE 10:30 Fragment-Based Discovery of a Chemical Probe PLENARY KEYNOTES for the NSD3-PWWP-1 Domain Jark Böttcher, Principal Scientist, Medicinal Chemistry, SHORT COURSES Boehringer Ingelheim RCV GmbH & Co KG AGENDA We describe the fragment-based discovery of molecules binding to the proposed methyl-lysine April 3-4 Conferences binding site of the PWWP-1 domain of NSD3. »» Protein-Protein Interactions Supported by a virtual screening approach and »» Inflammation & Autoimmune subsequent structure-based optimization, the initial Inhibitors hits were optimized into a chemical probe with »» Kinase Inhibitor Chemistry confirmed binding in cellular assays. The probe and the related negative control can be used to explore the » » GPCR-Targeted Drug Design functions of the PWWP-1 domain. »» Fragment-Based Drug 11:00 Lead Generation without an X-Ray Crystal Discovery Structure: An NMR Method to Probe Protein- April 4-5 Conferences Ligand Complexes »» Ubiquitin Proteasome System Julien Orts, PhD, Professor, Laboratory of Physical Inhibitors Chemistry, Swiss Federal Institute of Technology ETH »» Small Molecules for Cancer My talk is about a NMR method to solve protein-ligand Immunotherapy complex structure. I will present two or three examples »» Macrocyclics & Constrained of this method applied to finding inhibitors against Peptides specific PPI targets. »» Targeting Complex 11:30 In silico Fragment Screening to Identify Membrane Proteins Cryptic Pockets and Allosteric Sites for PPI Inhibitor Development April 6 Symposia Ben Cossins, PhD, Principal Scientist, UCB Pharma » » Biophysical Approaches for Drug development is increasingly difficult and Drug Discovery expensive. Valuable targets are not always amenable »» Lead Optimization for Drug to modulation by small molecules and resources Metabolism & Safety are often directed towards seemingly intractable »» Blood-Brain Penetrant targets. We have been building and applying molecular Inhibitors dynamics based fragment screening and de novo design approaches to try and understand ligandability HOTEL & TRAVEL and functionability for protein-protein interaction targets. We believe this approach can steer us towards SPONSORSHIP hit compounds for tractable PPI targets. & EXHIBIT 12:00 pm End of Conference REGISTRATION

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COVER Inflammation & Autoimmune Inhibitors CONFERENCE Small-Molecule Approaches for Oral-Based Therapeutics AT-A-GLANCE April 3-4, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES 9:10 Sponsored Presentation (Opportunity Available) 11:05 Ozanimod (RPC1063), an oral S1P1 and S1P5 AGENDA Tuesday, April 3 9:40 Coffee Break modulator, in Relapsing Multiple Sclerosis April 3-4 Conferences 7:00 am Registration and Morning Coffee Kristen Taylor Meadows, PhD, Principal Scientist, Cell »» Protein-Protein Interactions TARGETING INTRACELLULAR and Molecular Biology, Celgene TARGETING INTRACELLULAR Ozanimod, a small molecule S1P1 and S1P5 agonist, »» Inflammation & Autoimmune AND GPCRs FOR AUTOIMMUNITY AND demonstrated positive Phase III efficacy with a Inhibitors KINASES FOR AUTOIMMUNITY AND INFLAMMATION good safety profile in Relapsing Multiple Sclerosis, »» Kinase Inhibitor Chemistry INFLAMMATION 10:05 Discovery of Potent and Selective Inhibitors of an autoimmune disorder targeting myelin within » » GPCR-Targeted Drug Design 8:00 Welcome Remarks Receptor-Interacting Protein Kinase 1 (RIPK1) with the central nervous system. Ozanimod’s primary »» Fragment-Based Drug Anjani Shah, PhD, Conference Director, Cambridge in vivo Activity mechanism of action is to retain lymphocytes in Discovery Healthtech Institute Snahel Patel, PhD, Senior Scientific Manager, Discovery secondary lymphoid tissue. This talk will present data identifying specific peripheral immune populations April 4-5 Conferences 8:05 Chairperson’s Opening Remarks Chemistry, Genentech, Inc. targeted by ozanimod in preclinical models of MS, and »» Ubiquitin Proteasome System John Robinson, PhD, Director, Medicinal Chemistry, Array Regulation of cell death signaling is critical for the investigate direct effects on resident cells within the Inhibitors Biopharma maintenance of homeostasis and prevention of disease. A caspase-independent regulated form of central nervous system. »» Small Molecules for Cancer 8:10 BTK for Lupus and Other Indications: Lead cell death called necroptosis is rapidly emerging 11:35 Luncheon Presentation (Sponsorship Immunotherapy Optimization of a Covalent Inhibitor Lesley M. Liu-Bujalski, PhD, Group Leader, Medicinal as an important mediator of a number of human Opportunity Available) or Enjoy Lunch on Your Own »» Macrocyclics & Constrained pathologies including inflammatory bowel disease Peptides Chemistry, EMD Serono Research and Development 12:20 pm Session Break Institute, Inc. and ischemia reperfusion organ injury. Activation of »» Targeting Complex Bruton’s tyrosine kinase (Btk) is a promising drug necroptotic signaling through TNF signaling or organ NEW INFLAMMATION AND Membrane Proteins injury leads to the activation of kinases RIPK1 and target for the treatment of autoimmune diseases AUTOIMMUNITY TARGETS April 6 Symposia such as systemic lupus erythematosus (SLE) RIPK3 and culminates in inflammatory cell death. Here »» Biophysical Approaches for and rheumatoid arthritis (RA). We set out to we present the interesting development of potent and 1:15 Chairperson’s Remarks Drug Discovery identify an orally bioavailable, highly selective BTK selective RIPK1 specific inhibitors that demonstrate Jennifer Venable, PhD, Scientific Director, Medicinal protection in a mouse systemic inflammatory Chemistry, J&J »» Lead Optimization for Drug inhibitor, that might be suitable for the treatment response syndrome (SIRS) model. Metabolism & Safety of chronic diseases. Using a combination of X-ray 1:20 NASH and Inflammation: Therapeutic »» Blood-Brain Penetrant crystallography, wild-type and mutant BTK functional 10:35 Discovery and Optimization of Spleen Tyrosine Opportunities in a Complex Disease Inhibitors assays, stability studies, and in vivo PK/PD models, Kinase Inhibitors for Immunological Diseases Simon Bailey, PhD, MBA, Senior Vice President, lead optimization efforts led to the identification Michael Hoemann, PhD, Senior Scientist, Department of Research, Intercept HOTEL & TRAVEL of evobrutinib. Chemistry, AbbVie, Inc. 1:50 Anti-Inflammatory Effects of Non-Bile Acid FXR 8:40 BTK Covalent Inhibitor for Rheumatoid Arthritis This talk will focus on the approach to designing and Agonists in Liver Disease SPONSORSHIP Matthew D. Linnik, PhD, Senior Research Fellow, optimizing a series of Spleen Tyrosine Kinase (Syk) Bryan Laffitte, PhD, Director, Discovery Pharmacology, & EXHIBIT Immunology, Lilly Biotechnology Center inhibitors. We will highlight the methods used to Institute of the Research Foundation enhance potency, overcome the challenge of off-target REGISTRATION I will present preclinical and clinical pharmacology 2:20 The Design of Mechanism-Based Amine Oxidase of our covalent inhibitor against BTK that has some kinase selectivity and optimization of PK properties to yield compounds with in vivo efficacy in the rat CIA Inhibitors for the Treatment of Inflammation cross reactivity to other Tec kinases. It is in Phase Jonathan Foot, PhD, Senior Research Scientist, Drug II for rheumatoid arthritis. In addition to covering model. In addition, the talk will highlight the use of Click Here to register Online in vitro assays to identify compounds with superior Discovery, Pharmaxis Ltd. the non-clinical and clinical pharmacology results, Amine oxidases are a family of enzymes that catalyze DrugDiscoveryChemistry.com cardiovascular safety profiles. my presentation will also address how to study the oxidation of a wide variety of endogenous amines and characterize covalent inhibitors, including such as collagen or dopamine. They play a key distinguishing between pharmaco-kinetics and role in oxidative stress, inflammation and protein target occupancy. cross-linking, and in the initiation and progression of

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LEAD MEDIA PARTNERS: COVER fibrosis and cancer. Herein we will present strategies 5:30 Welcome Reception in the Exhibit Hall with CONFERENCE and chemical routes to identify selective amine Poster Viewing AT-A-GLANCE oxidase inhibitors for the treatment of inflammation- 6:30 End of Day driven diseases. PLENARY KEYNOTES 2:50 Targeting Lipid Mediator, Hepoxilin, Wednesday, April 4 SHORT COURSES for Combatting Inflammation and Inflammatory Bowel Disease 7:30 am Continental Breakfast Breakout Discussions AGENDA Cecil Robert Pace-Asciak, PhD, Professor, Translational Medicine and Pharmacology, Hospital for Sick Children TARGETING THE IL17 PATHWAY VIA April 3-4 Conferences Research Institute ROR NUCLEAR HORMONE RECEPTORS »» Protein-Protein Interactions Findings related to inflammation will be presented for 8:30 Chairperson’s Remarks »» Inflammation & Autoimmune a family of small molecules, Hepoxilins (HX), originally Bryan Laffitte, PhD, Director, Discovery Pharmacology, Inhibitors isolated in my laboratory, and of structural analogs Genomics Institute of the Novartis Research Foundation »» Kinase Inhibitor Chemistry (PBTs) that antagonize HX actions in vivo. Results »» GPCR-Targeted Drug Design for lung fibrosis and inflammatory bowel disease and enhanced neutrophil migration will be presented and 8:35 FEATURED PRESENTATION: RORC2 »» Fragment-Based Drug stimulation of neutrophil extracellular trap formation Inverse Agonists – Finding Lipophilic Discovery (NETosis). Other promising biological actions will be Efficiency in a Hydrophobic Pocket April 4-5 Conferences discussed. It is hoped that interest in this area will Mark Schnute, PhD, Associate Research »» Ubiquitin Proteasome System allow clinical development. Fellow, Medicine Design, Inflammation & Immunology Inhibitors Research, Pfizer 3:20 Sponsored Presentation (Opportunity Available) Small molecule, inverse agonists of the nuclear »» Small Molecules for Cancer 3:35 Refreshment Break in the Exhibit Hall with hormone receptor RORC2 are potential therapies for Immunotherapy Poster Viewing several autoimmune diseases through their ability »» Macrocyclics & Constrained to inhibit pro-inflammatory cytokine production. This Peptides 4:30 Plenary Session Welcome Remarks from Event Director presentation will describe how we have used the »» Targeting Complex Anjani Shah, PhD, Conference Director, Cambridge key design strategies of optimization of lipophilic Membrane Proteins Healthtech Institute efficiency and understanding the interplay of April 6 Symposia structure, pharmacology and target residence time to 4:35Sponsored Plenary Keynote Introduction » advance a high-throughput screening hit into a highly » Biophysical Approaches for (Opportunity Available) Drug Discovery potent, selective and orally bioavailable preclinical MEDIA PARTNERS: development candidate. »» Lead Optimization for Drug 4:40 PLENARY KEYNOTE: Activity- Metabolism & Safety Based Proteomics: Protein and Ligand 9:05 Investigation of Thiazole Bis-Amides as RORγt »» Blood-Brain Penetrant Discovery on a Global Scale Inverse Agonists Inhibitors Benjamin F. Cravatt, PhD, Professor and Kelly McClure, Senior Scientist, Immunology Chemistry, Co-Chair, Department of Molecular Medicine, The Janssen Research & Development HOTEL & TRAVEL Scripps Research Institute The nuclear retinoic acid receptor- SPONSORSHIP To address uncharacterized proteins, we have related orphan receptor gt (RORgt) drives Th17 cell & EXHIBIT introduced chemical proteomic technologies that differentiation and expansion, and cytokine production. globally profile the functional state of proteins in Blocking the production of pro-inflammatory cytokines REGISTRATION native biological systems. Among these methods by RORgt modulation has the potential to be an is activity-based protein profiling (ABPP), which effective treatment for autoimmune diseases. A utilizes chemical probes to map activity states promising series of thiazole bis-amide RORgt inverse Click Here to register Online of large numbers of proteins in parallel. I will agonists has been identified and our optimization discuss the application of ABPP to discover and efforts will be discussed. DrugDiscoveryChemistry.com functionally annotate proteins in mammalian 9:35 Coffee Break in the Exhibit Hall with physiology and disease, and the generation and Poster Viewing implementation of advanced ABPP platforms for proteome-wide ligand discovery.

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COVER 10:30 Targeting RORγ 11:00 The Discovery of AZD0284, an Inverse TH17 cells, which are important drivers of chronic CONFERENCE Daniel J. Cua, PhD, Group Leader, IMR Pathway Biology, Agonist of Nuclear Receptor RORγt for the inflammation in autoimmune diseases such as AT-A-GLANCE Merck Research Laboratories, Palo Alto Treatment of Psoriasis psoriasis or ankylosing spondylitis. We describe I will present our work demonstrating that targeting Frank Narjes, PhD, Senior Principal Scientist, Medicinal the discovery of our clinical candidate AZD0284, a PLENARY KEYNOTES of RORγ restrains TCR gene rearrangement and limits Chemistry, IMED Respiratory, Inflammation & compound that combines good oral bioavailability with development of auto-reactive T cells. Autoimmunity, AstraZeneca potent suppression of IL-17 production in human TH17 SHORT COURSES Retinoic acid receptor-related orphan receptor cells, and is currently in Phase I clinical trials. AGENDA C2 (RORc2, RORγt, or NR1F3) is essential for the 11:30 Presentation to be Announced development and differentiation of IL-17 producing April 3-4 Conferences 12:00 pm End of Conference »» Protein-Protein Interactions »» Inflammation & Autoimmune Inhibitors »» Kinase Inhibitor Chemistry »» GPCR-Targeted Drug Design »» Fragment-Based Drug “It’s a fantastic conference. It’s a very comfortable Discovery April 4-5 Conferences environment, a very open environment. It’s a very »» Ubiquitin Proteasome System Inhibitors well-thought-out conference.” »» Small Molecules for Cancer Immunotherapy – SIDNEY T., PROFESSOR & DIRECTOR, STEVENS INSTITUTE OF TECHNOLOGY »» Macrocyclics & Constrained Peptides »» Targeting Complex Membrane Proteins April 6 Symposia »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant Inhibitors

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COVER Kinase Inhibitor Chemistry CONFERENCE Emerging Approaches for the Discovery and Design of Kinase Inhibitors AT-A-GLANCE April 3-4, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES 9:10 Sponsored Presentation (Opportunity Available) algorithm, we performed a comprehensive analysis on AGENDA Tuesday, April 3 9:40 Coffee Break our extensive kinase data set that has yielded findings April 3-4 Conferences 7:00 am Registration and Morning Coffee far beyond those in the current literature. Indeed, one 10:05 Target Residence Time-Guided Optimization of »» Protein-Protein Interactions can construct a mini-kinase panel of optimal size that OPTIMIZING NEXT-GENERATION TTK Kinase Inhibitors is very predictive when compared to the corresponding »» Inflammation & Autoimmune Guido J.R. Zaman, PhD, Managing Director & Head of full kinase panel. Comparing this mini-kinase panel to Inhibitors KINASE INHIBITORS Biology, Netherlands Translational Research Center random selection, we find an enrichment of 45.1%. »» Kinase Inhibitor Chemistry 8:00 Welcome Remarks B.V. (NTRC) 11:35 Luncheon Presentation (Sponsorship »» GPCR-Targeted Drug Design Kip Harry, Senior Director, Conferences, Cambridge We studied NTRC 0066-0, a selective inhibitor of TTK, Healthtech Institute together with eleven TTK inhibitors from different Opportunity Available) or Enjoy Lunch on Your Own »» Fragment-Based Drug chemical classes developed by others. Parallel 12:20 pm Session Break Discovery 8:05 Chairperson’s Opening Remarks Gerhard Mueller, PhD, CSO, Gotham Therapeutics testing showed that the cellular activity of the TTK April 4-5 Conferences inhibitors correlates with their binding affinity and, ADVANCES IN COVALENT INHIBITOR »» Ubiquitin Proteasome System more strongly, with target residence time. X-ray DEVELOPMENT Inhibitors 8:10 FEATURED PRESENTATION: structures revealed that the most potent inhibitors Selective Targeting of Kinase Catalytic 1:15 Chairperson’s Remarks »» Small Molecules for Cancer induce a unique structural conformation. Based on and Non-Catalytic Function Stefan Laufer, PhD, Chairman, Pharmaceutical & Immunotherapy this insight, new TTK inhibitors were developed with Stefan Knapp, PhD, Professor, Department longer target residence times and very potent anti- Medicinal Chemistry, Pharmacy & Biochemistry, »» Macrocyclics & Constrained of Pharmaceutical Chemistry, Goethe Institut, Frankfurt University of Tuebingen Peptides proliferative activity. Advances in kinase structural biology led to an 1:20 Highly Selective JAK3-Inhibitors with a Covalent- »» Targeting Complex 10:35 Comparison of Methods for Determination of excellent structural coverage of the human kinase Reversible Binding Mode Targeting a Nitrile-Induced Membrane Proteins family and provided insight into the remarkable domain Drug-Target Engagement in Live Cells Aleksandra Baranczak, PhD, Senior Scientist, Discovery Arginine Pocket April 6 Symposia plasticity of the catalytic domain. Our laboratory Chemistry and Technology, AbbVie Stefan Laufer, PhD, Chairman, Pharmaceutical & » contributed 75 of the currently ~200 known crystal » Biophysical Approaches for While the list of potential techniques that enable Medicinal Chemistry, Pharmacy & Biochemistry, Drug Discovery structures, enabling a family-wide structural analysis University of Tuebingen for rational design of inhibitors. In this talk I will studies of target engagement is continuously »» Lead Optimization for Drug JAK3 functions are restricted to immune cells, summarize strategies that led to the development of expanding, identification of the best method Metabolism & Safety to evaluate interactions between a ligand and suggesting it as a primary target. However, the high highly selective inhibitors. I will discuss the discovery degree of structural conservation makes isoform »» Blood-Brain Penetrant of novel inhibitor binding sites including allosteric sites its cellular binding partner(s) remains far from Inhibitors straightforward. We will discuss the applicability of selective targeting a challenging task. Here we present and the exploitation of unusual structural features for picomolar inhibitors with unprecedented selectivity for the design of highly selective kinase inhibitors. various methods for determining target engagement HOTEL & TRAVEL of reversible and irreversible inhibitors of soluble JAK3. Selectivity was achieved by concurrent covalent- and membrane kinases in live cells. The strengths reversible targeting of a JAK3-specific cysteine SPONSORSHIP 8:40 Structure-Based Design of Long Residence Time residue and a novel induced binding pocket yielding into Novel Kinase Inhibitors and limitations of all methods will be analyzed, as & EXHIBIT well as their adaptability to high-throughput format versatile tool compounds for the elucidation of JAK3 Gerhard Mueller, PhD, CSO, Gotham Therapeutics specific functions. REGISTRATION The presentation focuses on the engineering of assay development. binding kinetic signatures into “deep-pocket-directed” 11:05 Determination of a Focused Mini-Kinase Panel 1:50 The Meisenheimer Complex as a Novel Paradigm scaffolds for achieving high-efficacy kinase inhibitors. for Early Identification of Selective Kinase Inhibitors in Drug Discovery: Targeting PLK1 through a Novel Covalent Mechanism Click Here to register Online We will demonstrate that a thorough understanding Scott Bembenek, PhD, Principal Scientist, Computer- of the precise pharmacophoric requirements on Aided Drug Discovery, Janssen Research & Development Campbell McInnes, PhD, Professor, Drug Discovery and DrugDiscoveryChemistry.com the target’s binding site is essential to pre-engineer Currently, a rational, systematic, and unbiased method Biomedical Sciences, University of South Carolina the desired slow off-rates into new, thus literature- for choosing such a mini-kinase panel that reliably We will describe novel inhibitors of PLK1 kinase unprecedented scaffolds that qualify as privileged determines a compound’s kinase selectivity profile activity that inhibit through a unique covalent strategy. structures for the target family of kinases. does not exist. Using a novel in-house deconvolution The discovery and optimization of these inhibitors is described in addition to confirmation of their on-

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COVER target anti-tumor mode of action through selective 4:40 PLENARY KEYNOTE: Activity- throughput screening using a novel biochemical assay CONFERENCE PLK1 inhibition. Based Proteomics: Protein and Ligand platform resulted in the identification of multiple AT-A-GLANCE 2:20 Bruton’s Tyrosine Kinase (BTK) – Considerations Discovery on a Global Scale chemotypes that target distinct AMPK subunits. We for the Design and Profiling of Irreversible Benjamin F. Cravatt, PhD, Professor and have established the molecular mode of action of PLENARY KEYNOTES Covalent Inhibitors Co-Chair, Department of Molecular Medicine, The these isoform-selective activators through structural, Scripps Research Institute biophysical and kinetic studies. SHORT COURSES Michael Friedman, PhD, Principal Scientist, AbbVie Over the past few years, the interest in covalent To address uncharacterized proteins, we have 9:35 Coffee Break in the Exhibit Hall with AGENDA inhibitors has increased dramatically with a number introduced chemical proteomic technologies that Poster Viewing of entities entering the clinic and demonstrating globally profile the functional state of proteins in April 3-4 Conferences significant efficacy. We will describe our approach to native biological systems. Among these methods KINASE INHIBITORS FOR CNS AND »» Protein-Protein Interactions is activity-based protein profiling (ABPP), which identification of the targets appropriate for covalent NEURODEGENERATIVE DISORDERS »» Inflammation & Autoimmune inhibition. We will describe in detail design of BTK utilizes chemical probes to map activity states Inhibitors inhibitors with the focus on the ones with high in vivo of large numbers of proteins in parallel. I will 10:30 Optimization of Brain Penetrant ATM Kinase »» Kinase Inhibitor Chemistry clearance but durable efficacy. We will presentin vivo discuss the application of ABPP to discover and Inhibitors for the Treatment of Huntington’s Disease functionally annotate proteins in mammalian Leticia Toledo-Sherman, PhD, Director of Computer- » data including efficacy in the preclinical models. » GPCR-Targeted Drug Design physiology and disease, and the generation and Aided Drug Design and Medicinal Chemistry, Chemistry, »» Fragment-Based Drug implementation of advanced ABPP platforms for CHDI Foundation Discovery 2:50 FEATURED PRESENTATION: proteome-wide ligand discovery. The presentation will be centered on our efforts to Discovery of the Covalent FGFR1-4 April 4-5 Conferences attain potent, selective and brain penetrant ATM Inhibitor PRN1371 for the Treatment of »» Ubiquitin Proteasome System kinase inhibitors as proof-of-concept agents for HD. Solid Tumors 5:30 Welcome Reception in the Exhibit Hall with Inhibitors Poster Viewing Importantly we demonstrate strong in vitro-in vivo Michael Bradshaw, PhD, Associate Director, correlations and a robust PK/PD relationship that »» Small Molecules for Cancer Principia Biopharma 6:30 End of Day warrant further studies with these compounds. Immunotherapy We have developed a selective, irreversible covalent »» Macrocyclics & Constrained inhibitor of FGFR1-4, PRN1371, by targeting a Wednesday, April 4 11:00 A Journey in the Kinome: Sponsored by Peptides cysteine residue within the kinase domain. PRN1371 Approaches, Strategies 7:30 am Continental Breakfast Breakout Discussions and a Bit of Luck »» Targeting Complex demonstrates highly selective and long lasting Daniele Andreotti, Director, Membrane Proteins inhibition of FGFR which extends beyond drug clearance from circulation. Strong inhibition was also DESIGN AND DEVELOPMENT OF Head, Medicinal Chemistry 3; Drug Design and April 6 Symposia sustained toward clinically relevant FGFR mutations NOVEL ALLOSTERIC MODULATORS Discovery, Aptuit » » Biophysical Approaches for and translocations. In addition, durable tumor 11:30 Discovery of 7-Oxo-2,4,5,7-tetrahydro-6H- Drug Discovery 8:30 Chairperson’s Remarks regression was obtained in multiple rodent xenograft Ravi G. Kurumbail, PhD, Research Fellow and Structural pyrazolo[3,4-c]pyridine Derivatives as Potent, Orally »» Lead Optimization for Drug models and was sustained even using an intermittent Biology Laboratory Head, Pfizer Available, and Brain-Penetrating Receptor Interacting Metabolism & Safety dosing strategy that provided drug holidays. PRN1371 Protein 1 (RIP1) Kinase Inhibitors - Analysis of »» Blood-Brain Penetrant is currently in a Phase I clinical trial for the treatment 8:35 Fragment-Based Discovery of Structure-Kinetic Relationships Inhibitors of solid tumors. Inhibitors of ERK Kinase Masato Yoshikawa, PhD, Principal Scientist, CNS Drug Marc O’Reilly, PhD, Senior Director of Molecular Discovery Unit, Research, Takeda Pharmaceutical HOTEL & TRAVEL 3:20 Presentation to be Announced Sponsored by Sciences, Company Limited This work describes the discovery of highly selective, We will present a discovery of 7-oxo-2,4,5,7-tetrahydro- SPONSORSHIP orally bioavailable, allosteric/bitopic inhibitors of ERK 6H-pyrazolo[3,4-c]pyridine derivatives as a novel & EXHIBIT 3:35 Refreshment Break in the Exhibit kinase which show robust anti-tumor activity in a range chemical series of brain-penetrating RIP1 kinase Hall with Poster Viewing of animal models. REGISTRATION inhibitors. The optimization by utilizing SBDD approach 4:30 Plenary Session Welcome Remarks from 9:05 Isoform-Selective Activators of AMP-Activated led to the discovery of a highly potent, orally active, and Event Director Protein Kinase for Metabolic Diseases brain-penetrating RIP1 kinase inhibitor with excellent Anjani Shah, PhD, Conference Director, Cambridge Ravi G. Kurumbail, PhD, Research Fellow and Structural PK profiles. Our preclinical candidate significantly Click Here to register Online Healthtech Institute Biology Laboratory Head, Pfizer suppressed necroptotic cell death both in mouse and DrugDiscoveryChemistry.com 4:35 Sponsored Plenary Keynote Introduction AMP-activated protein kinase (AMPK) is a human cells. Oral administration of the candidate (10 (Opportunity Available) heterotrimeric protein kinase that maintains cellular mg/kg, bid) attenuated disease progression in the and whole-body energy homeostasis. We have been mouse EAE model of multiple sclerosis. seeking specific activators of AMPK for the treatment 12:00 pm End of Conference of cardiovascular and metabolic diseases. High-

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COVER GPCR-Targeted Drug Design CONFERENCE New Structural, Pharmacological and Biophysical Insights and Tools AT-A-GLANCE April 3-4, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES Tuesday, April 3 PAM-Agonists and Beta-PAMs) in calcium and IP1 liability targets. In addition to radioligand binding, we AGENDA assays to illustrate how quantitative comparisons established a FACS-based quantification of GPCR April 3-4 Conferences 7:00 am Registration and Morning Coffee to pharmacological models can both identify expression to benchmark target expression against »» Protein-Protein Interactions mechanisms of action and also convert descriptive physiological level in native cells. RECEPTOR CONFORMATIONAL findings to predict data for therapeutic systems. Using »» Inflammation & Autoimmune 12:20 pm Session Break these models optimally allows the identification of Inhibitors STATES AND BIASED LIGANDS consistent and simple scales of activity that can guide GPCRs IN CANCER AND »» Kinase Inhibitor Chemistry 8:00 Welcome Remarks medicinal chemistry. »» GPCR-Targeted Drug Design Anjani Shah, PhD, Conference Director,Cambridge OTHER DISEASES Healthtech Institute 10:35 A New Tool for GPCR Thermo-Stabilization »» Fragment-Based Drug Seva Katritch, PhD, Assistant Professor, The Bridge 1:15 Chairperson’s Remarks Discovery 8:05 Chairperson’s Opening Remarks Institute, University of Southern California JoAnn Trejo, PhD, MBA, Professor and Vice Chair, Andrew Alt, PhD, Associate Director, Biology, Arvinas Department of Pharmacology, Associate Dean for April 4-5 Conferences 11:05 GPCR Allosteric Coupling Investigated by NMR Health Sciences Faculty Affairs, University of California, »» Ubiquitin Proteasome System and X-Ray Diffraction San Diego Inhibitors 8:10 FEATURED PRESENTATION: Matthew Eddy, PhD, Postdoctoral Fellow, Laboratory of β-arrestin Desensitization Cycles and 1:20 GPCRs as Targets in Cancer »» Small Molecules for Cancer Raymond Stevens, University of Southern California and Biosensor Assays Paul A. Insel, MD, Distinguished Professor, Pharmacology Immunotherapy The Scripps Research Institute Martin Lohse, PhD, Chairman, Max Delbrück Drug binding in human GPCRs is allosterically and Medicine; Co-Director, Medical Scientist MD/PhD »» Macrocyclics & Constrained Center, Berlin, Germany Training Program, University of California, San Diego Peptides connected over 30 Å to the intracellular signaling Optical analyses are providing new aspects in the surface. Using advanced techniques for stable isotope Emerging data suggest that GPCRs contribute to »» Targeting Complex analysis of GPCRs. Most notably, their activation and labeling, we probe this allosteric network with NMR malignancy and certain GPCRs have higher expression Membrane Proteins signaling can be monitored in real time and in intact spectroscopy in solution for a native GPCR and variant in tumors compared to normal tissue. Using multiple April 6 Symposia cells by FRET microscopy. Motility and interactions with strikingly different signaling properties. X-ray approaches to assess GPCRs in human tumors, »» Biophysical Approaches for can be studied by single molecule microscopy. These crystal structures of the same variant reveal local cancer cells and cancer-associated fibroblasts (CAFs) Drug Discovery methods can also be used to investigate downstream conformational rearrangements in a known signaling- in the tumor microenvironment, we find that tumors, signaling and to discover bias in G-protein- vs. cancer cells and CAFs have higher expression of many »» Lead Optimization for Drug related structural motif. In parallel, NMR data uncover beta-arrestin-mediated signals. They have allowed GPCRs. Confirmatory, validation data exist for multiple Metabolism & Safety large signaling-related changes in conformational the discovery of multiple active states of beta- dynamics. Information from both techniques paired such GPCRs in pancreatic cancer, a highly lethal »» Blood-Brain Penetrant arrestins, suggesting that beta-arrestins undergo an cancer in need of new, effective therapies. Inhibitors together provides a comprehensive picture of changes activation/deactivation cycle. Differential effects of in structure and dynamics underpinning GPCR 1:50 Illuminating the Onco-GPCRome various ligands indicate that they may differ in their HOTEL & TRAVEL allosteric coupling. J. Silvio Gutkind, PhD, Professor, Department of physiological effects by selectively stimulating distinct Pharmacology; Associate Director of Basic Science, kinase pathways. 11:35 Luncheon Presentation: Sponsored by SPONSORSHIP Reaching beyond Moores Cancer Center, UCSD & EXHIBIT Developing Stable GPCR Cell Lines Recent large cancer sequencing initiatives 9:10 Sponsored Presentation (Opportunity Available) have revealed that more than 25% of all human REGISTRATION Lisa Minor, Scientific Consultant, Multispan, Inc. 9:40 Coffee Break Developing high quality assays is paramount for drug malignancies harbor mutations in G proteins and 10:05 GPCR-Targeted Lead Optimization: The discovery screening. Multispan devoted significant GPCRs, and that certain GPCR families are aberrantly Importance of the Assay in Fitting Data to Models effort in developing signaling and phenotypic assays expressed in multiple human neoplasia. We will Click Here to register Online Terry Kenakin, PhD, Professor, Department of using endogenous targets such as RXFP1 in THP-1, present new evidence supporting the potential clinical DrugDiscoveryChemistry.com Pharmacology, University of North Carolina School CGRP in SK-N-MC, AMPK in C2C12, and DNA-PK in benefit of targeting GPCRs, G proteins, and their of Medicine HELA cells. We also developed stable cell line assays regulated signaling circuitry for cancer prevention and I will compare the muscarinic receptor Gq protein for CGRP, AM, and Amylin by studying and overcoming treatment. How GPCRs modulation can be exploited activation profiles of five exemplar molecules (slow endogenous RAMP expression and designed a to increase the response to new immunotherapies binding agonists, partial agonists, inverse agonists, 32-GPCR panel comprising CNS and cardiovascular will be discussed.

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COVER 2:20 Anti-Leukemic Activity of Imipridone ONC212 via 4:40 PLENARY KEYNOTE: Activity- 8:35 Ubiquitin-Mediated Inflammatory CONFERENCE Selective Targeting of Orphan GPCR GPR132/G2A Based Proteomics: Protein and Ligand Signaling by GPCRs AT-A-GLANCE Varun Vijay Prabhu, PhD, Associate Director, Research Discovery on a Global Scale JoAnn Trejo, PhD, MBA, Professor and Vice Chair, and Development, Oncoceutics, Inc. Benjamin F. Cravatt, PhD, Professor and Department of Pharmacology, Associate Dean for PLENARY KEYNOTES Imipridones are a new class of anti-cancer small Co-Chair, Department of Molecular Medicine, The Health Sciences Faculty Affairs, University of California, molecules that share a unique tri-heterocyclic core Scripps Research Institute San Diego SHORT COURSES structure and selectively engage GPCRs. Experimental To address uncharacterized proteins, we have Ubiquitination of 40 mammalian GPCRs has been AGENDA GPCR profiling using the PathHunter® β-Arrestin introduced chemical proteomic technologies that reported, but despite the rich complexity of GPCR assay (DiscoverX) and multidose validation revealed globally profile the functional state of proteins in signaling, ubiquitination is attributed largely to GPCR April 3-4 Conferences that imipridone ONC212 selectively targets orphan native biological systems. Among these methods degradation. We discovered that ubiquitination of »» Protein-Protein Interactions GPCR GPR132/G2A at nanomolar concentrations. is activity-based protein profiling (ABPP), which GPCRs promotes p38 activation on endosomes via »» Inflammation & Autoimmune BIOSENS-ALL BRET assay (Domain) showed that utilizes chemical probes to map activity states recruitment of TAB2, which co-associates with TAB1 Inhibitors ONC212 promotes Gq family activation downstream of large numbers of proteins in parallel. I will that directly binds to p38a. TAB1-dependent p38 »» Kinase Inhibitor Chemistry of GPR132. ONC212 was non-toxic to normal cells at discuss the application of ABPP to discover and activation is critical for PAR1-mediated endothelial therapeutic concentrations and demonstrated robust functionally annotate proteins in mammalian inflammatory responses. The mechanisms by which » » GPCR-Targeted Drug Design in vivo safety/efficacy in leukemia xenograft models. physiology and disease, and the generation and GPCR-induced p38 endosomal inflammatory signaling »» Fragment-Based Drug 2:50 Therapeutic Promise of Allosteric Modulators of implementation of advanced ABPP platforms for is regulated is not known and will be discussed. Discovery Angiotensin II Receptor proteome-wide ligand discovery. 9:05 Exploration of Endosomal GPCR Signaling Using April 4-5 Conferences Sadashiva Karnik, PhD, Professor, Molecular Cardiology, Electron Microscopy »» Ubiquitin Proteasome System Lerner Research Institute, Cleveland Clinic 5:30 Welcome Reception in the Exhibit Hall with Alex Thomsen, PhD, Postdoctoral Fellow, Lefkowitz Lab, Inhibitors Novel allosteric modulators were discovered based Poster Viewing Department of Medicine, Duke University »» Small Molecules for Cancer on crystal structure and computer assisted drug 6:30 End of Day We recently demonstrated that a class of GPCRs Immunotherapy development. These novel molecules showed high promote endosomal signaling by forming »» Macrocyclics & Constrained specificity and efficacy in pharmacological and Wednesday, April 4 “megaplexes” composed of a single GPCR that Peptides signaling studies. In vivo evaluation in animal models interacts simultaneously with β-arrestin, which drives are in progress. This will be the first report of allosteric 7:30 am Continental Breakfast Breakout Discussions the receptor internalization, and , which »» Targeting Complex chemotypes for any angiotensin receptor. initiates signaling from internalized compartments. Membrane Proteins 3:20 Sponsored Presentation (Opportunity Available) ENDOSOMAL SIGNALING Now we are applying a variety of electron microscopy April 6 Symposia 8:30 Chairperson’s Remarks (EM) and computational methods to obtain high- »» Biophysical Approaches for 3:35 Refreshment Break in the Exhibit Hall with resolution structural information about the megaplex Poster Viewing Irina Kufareva, PhD, Project Scientist, Handel and Drug Discovery Abagyan Lab, The Skaggs School of Pharmacy and (cryo-EM), and to visualize GPCR signaling on the »» Lead Optimization for Drug 4:30 Plenary Session Welcome Remarks from Pharmaceutical Sciences, University of California, endosomal surface within living cells (cryo-electron Metabolism & Safety Event Director San Diego tomography, cryo-ET). »» Blood-Brain Penetrant Anjani Shah, PhD, Conference Director, Cambridge Inhibitors Healthtech Institute 4:35 Sponsored Plenary Keynote Introduction HOTEL & TRAVEL (Opportunity Available) “I met some of my best SPONSORSHIP & EXHIBIT collaborators here. This is a REGISTRATION good networking tool. I like

Click Here to register Online the meeting; it’s very good.” DrugDiscoveryChemistry.com – DONALD D., PROFESSOR, UCSD

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COVER 9:35 Coffee Break in the Exhibit Hall with to distinct and previously unknown allosteric sites. 11:30 Kinetic Drug Discovery for GPCRs CONFERENCE Poster Viewing These results illustrate the power of integrating Sam Hoare, PhD, Founder and Chief Scientist, AT-A-GLANCE stabilized GPCR technologies into established Pharmacology Data Analysis, Pharmechanics, LLC NEW GPCR SCREENING AND BINDING screening paradigms. Novel paradigms are needed for translating the raw PLENARY KEYNOTES ASSAYS AND TOOLS 11:00 Drug-Target Binding Kinetics - A data emerging from new molecular biosensor and reader technology-based assays into meaningful SHORT COURSES 10:30 Discovery of Small Molecule Protease- Case for GPCRs Laura Heitman, PhD, Associate Professor, Research pharmacological activity parameters that can be used Activated Receptor 2 (PAR2) Antagonists for structure-activity analysis. We have developed AGENDA Dean G. Brown, PhD, Director of External Chemistry, Division of Drug Discovery and Safety, LACDR, Leiden University a new kinetic data analysis framework that, using April 3-4 Conferences Hit Discovery, Discovery Sciences, IMED Biotech Unit, It is now emerging that determining drug target standard curve-fitting software, yields values of the »» Protein-Protein Interactions AstraZeneca rate of onset of the response, and the total signal We employed two screening strategies to identify binding kinetics, next to traditional potency measures, »» Inflammation & Autoimmune produced. Here we will show the resulting structure- antagonists at protease activated receptor (PAR2), may improve the success rate of a candidate drug Inhibitors moving through the clinical development. Our work activity kinetics for beta2 adrenoceptor signaling, and one being a DNA-encoded library screen on PAR2 for biased agonism at the D2 dopamine receptor. »» Kinase Inhibitor Chemistry and the second a fragment screen using a stabilized provides new insights in ligand-GPCR interactions »» GPCR-Targeted Drug Design PAR2 GPCR receptor. From these efforts, we identified and underlines the importance of measuring binding 12:00 pm End of Conference kinetics of both drug candidates and competing »» Fragment-Based Drug two lead series of compounds, each of which bind endogenous ligands. Discovery April 4-5 Conferences »» Ubiquitin Proteasome System Inhibitors »» Small Molecules for Cancer Immunotherapy »» Macrocyclics & Constrained Peptides “Up-to-date discussion on late breaking strategies »» Targeting Complex Membrane Proteins for novel kinase inhibitor design.” April 6 Symposia – ANN A., SENIOR SCIENTIST, PFIZER »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant Inhibitors

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COVER Fragment-Based Drug Discovery CONFERENCE Hits to Leads and Lessons Learned AT-A-GLANCE April 3-4, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES Tuesday, April 3 9:10 Fragment-Based Screening for Sponsored by 11:05 Nanoscale Encapsulation for Optimized NMR AGENDA Metallo-ß-lactamases Fragment Based Drug Discovery April 3-4 Conferences 7:00 am Registration and Morning Coffee Inhibitors: SPR and NMR Josh Wand, PhD, Professor, Biochemistry & , »» Protein-Protein Interactions Combined Approach University of Pennsylvania CHEMISTRY CHALLENGES FOR Silvia Davalli, Senior Manager, Head, NMR Spectroscopy; Encapsulation of single protein molecules in reverse »» Inflammation & Autoimmune Drug Design and Discovery, Aptuit micelles is a new and potentially transformative Inhibitors GROWING FRAGMENTS 9:40 Coffee Break technology. Encapsulation significantly enhances »» Kinase Inhibitor Chemistry 8:00 Welcome Remarks fragment based screening using NMR spectroscopy. Anjani Shah, PhD, Conference Director, Cambridge »» GPCR-Targeted Drug Design NOVEL SPR AND NMR The technology in the context of several examples Healthtech Institute will be described. »» Fragment-Based Drug APPLICATIONS TO FBDD Discovery 8:05 Chairperson’s Opening Remarks 11:35 Luncheon Presentation: Sponsored by Daniel A. Erlanson, PhD, Co-Founder, Carmot 10:05 Enabling Alternative Binding Sites with Novel April 4-5 Conferences A Complete Pipeline for Biophysics Therapeutics, Inc. Fragment Screening Approaches Using Surface »» Ubiquitin Proteasome System Based Drug Discovery Plasmon Resonance Inhibitors 8:10 Creation of a Novel Class of Potent and Selective Gregg Siegal, CEO, ZoBio MTH1 Inhibitors Using Fragment-Based Design Kevin M. O’Malley, PhD, Senior Research Investigator, ZoBio has built an integrated technology pipeline »» Small Molecules for Cancer Jenny Viklund, PhD, Director, Protein Science and Drug Lead Discovery, LDO, Bristol-Myers Squibb R&D that enables a wide array of targets for FBLD and Immunotherapy Design, Sprint Bioscience Surface Plasmon Resonance (SPR) is an industry maximizes the chance of successfully generating »» Macrocyclics & Constrained This presentation describes our fragment-based standard method for the identification and high quality leads. I’ll discuss all the key elements, Peptides approach to create potent and selective inhibitors of characterization of fragment hits. Its label free including: building a fragment library, using high »» Targeting Complex MTH1 that also have promising drug-like properties. detection using changes in mass make it ideal to throughput protein engineering to solve structure Membrane Proteins MTH1 is an enzyme involved in degradation of definitively confirm target engagement. Typical uses problems and better understand target biology, why have been to interrogate known binding/active sites. April 6 Symposia oxidized dGTP to prevent its incorporation into we use orthogonal fragment screening, and the Probing alternative sites can have the advantage of » DNA. Enzymes such as MTH which are involved in advantages of having both NMR and X-ray structural » Biophysical Approaches for providing novel chemotypes with different modes of Drug Discovery sanitization of the nucleotide pool have been shown to biology capabilities. be important for tumor cell survival. interaction with target. Here we describe methods of »» Lead Optimization for Drug probing alternate epitopes using conventional and 12:20 pm Session Break Metabolism & Safety 8:40 Fragment to Lead: SAR and Optimization emerging SPR approaches. of Novel Bromodomain Inhibitors with High FRAGMENT-ASSISTED DRUG »» Blood-Brain Penetrant 10:35 Using NMR-Based Activity Assays to Inhibitors fsp3 Character DISCOVERY Justin Dietrich, PhD, Senior Scientist III, Discovery Identify Fragment Leads Against Two Trichomonas Vaginalis Enzymes 1:15 Chairperson’s Remarks HOTEL & TRAVEL Chemistry and Technology, AbbVie, Inc. This presentation will cover a recent application of Brian Stockman, PhD, Associate Professor and Chair, Derek Cole, PhD, Director, Medicinal Chemistry, Takeda SPONSORSHIP AbbVie’s revamped fragment library featuring an Chemistry, Adelphi University & EXHIBIT example where a fragment with high fsp3 character Trichomonas vaginalis is classified as a neglected 1:20 FEATURED PRESENTATION: The was quickly advanced to lead with high BEI, LE, and parasitic by the CDC, with about 5% of Convoluted Journey of an ERK2 Fragment REGISTRATION LipE as well as good oral bioavailability. The unique clinical cases resistant to current treatments. Two Series (with an HTS Detour) properties associated with fragments with high essential nucleoside ribohydrolase enzymes from T. Huifen Chen, PhD, Senior Scientist, sp3 character and some lessons learned on the vaginalis were screened against a fragment library Department of Biophysics, Genentech Click Here to register Online efficiency of chemistry to iterate 3d fragment hits will using NMR-based activity assays. Distinct classes ERK1/2 represent an essential downstream node in of inhibitors with ligand efficiencies greater than 0.5 DrugDiscoveryChemistry.com also be discussed. the Ras/Raf/MEK/ERK (MAPK) signal transduction were identified. Fragment expansion experiments pathway, and have attracted significant interest as have further improved ligand efficiencies and provided potential anticancer targets. Both fragment and high- direction to ongoing medicinal chemistry efforts throughput screens were carried out in parallel to designed to discover nM inhibitors of these enzymes. discover novel ERK1/2 inhibitors. In this presentation,

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COVER I discuss the journey of a fragment-based series along 3:20 Present and Futuristic Sponsored by Wednesday, April 4 CONFERENCE with how learnings from the fragment series were Collaborative Drug Discovery AT-A-GLANCE incorporated into the HTS-derived series which led to a Informatics Innovations (CDD Vault 7:30 am Continental Breakfast Breakout Discussions clinical candidate GDC-0994. + Bioassay Express) PLENARY KEYNOTES Barry Bunin, CEO, Collaborative Drug Discovery, Inc. NON-NMR APPROACHES FOR FBDD 1:50 Fragment-Based Discovery of CDD Vault software, activity & registration, SHORT COURSES 8:30 Chairperson’s Remarks Inhibitors of ERK Kinase visualization, inventory, and ELN capabilities Ben Davis, PhD, Research Fellow, Biology, AGENDA Marc O’Reilly, PhD, Senior Director of Molecular all address today’s markets. For tomorrow’s Vernalis Research Sciences, Astex Pharmaceuticals research: open source descriptors and model April 3-4 Conferences This work describes the discovery of highly selective, sharing capabilities allow for platform-independent 8:35 Hot-Spotting with Thermal Scanning: A »» Protein-Protein Interactions orally bioavailable, allosteric/bitopic inhibitors of ERK collaborations. We’ve also developed BioAssay Ligand- and Structure-Independent Assessment of Target Ligandability »» Inflammation & Autoimmune kinase which show robust anti-tumour activity in a Express, human-readable assay text to computer- Fredrik Edfeldt, PhD, Associate Principal Scientist, Inhibitors range of animal models. readable format to augment bioassay needs. Biophysics, Discovery Sciences, AstraZeneca »» Kinase Inhibitor Chemistry 2:20 Discovery of a Ketohexokinase (KHK) Inhibitor 3:35 Refreshment Break in the Exhibit Hall with R&D, Sweden »» GPCR-Targeted Drug Design for the Treatment of NAFLD/NASH: Fragment-to- Poster Viewing Evaluating the ligandability of a protein is essential Candidate via Structure-Based Drug Design and »» Fragment-Based Drug 4:30 Plenary Session Welcome Remarks from when defining hit-finding strategies or to prioritize Parallel Chemistry Discovery Event Director amongst drug targets. We demonstrate that high- Kim Huard, PhD, Senior Principal Scientist, Medicine Anjani Shah, PhD, Conference Director, Cambridge throughput thermal scanning can be used as a simple April 4-5 Conferences Design, Pfizer, Inc. Healthtech Institute and generic biophysical fragment screening method »» Ubiquitin Proteasome System Identification of a selective ketohexokinase (KHK) for this purpose. We have applied the method to a Inhibitors inhibitor was sought to help elucidate the effect of 4:35 Sponsored Plenary Keynote Introduction (Opportunity Available) large set of proteins and show that the assessment is »» Small Molecules for Cancer KHK inhibition on metabolic disorders. In our efforts predictive for the success of HTS. We have also made Immunotherapy towards this goal, key structural features interacting use of urea and D2O to improve assay sensitivity. with KHK were discovered through fragment-based 4:40 PLENARY KEYNOTE: Activity- »» Macrocyclics & Constrained 9:05 Weak Affinity Chromatography (WAC): A Novel Peptides screening and used to mine our compound collection Based Proteomics: Protein and Ligand for attractive chemical starting points. This fragment- Discovery on a Global Scale Approach to Fragment-Based Drug Discovery »» Targeting Complex to-candidate story will present the fragment-based Benjamin F. Cravatt, PhD, Professor and Sten Ohlson, PhD, Professor, School of Biological Membrane Proteins screen triage, compound optimization via structure- Co-Chair, Department of Molecular Medicine, The Sciences, Nanyang Technological University April 6 Symposia based drug design (SBDD), in vivo target validation and Scripps Research Institute Weak Affinity Chromatography (WAC) is an established »» Biophysical Approaches for clinical candidate selection. To address uncharacterized proteins, we have analytical affinity technique for specific and gentle Drug Discovery introduced chemical proteomic technologies that separation and analysis of biomolecules. Since its 2:50 Identification of eFT508, an Oral, Potent and inception in 1990 it has among other applications »» Lead Optimization for Drug globally profile the functional state of proteins in Highly Selective Inhibitor of Mitogen-Activated been successfully used as an efficient tool in drug Metabolism & Safety native biological systems. Among these methods Protein Kinase Interacting Kinase (MNK) 1 and 2, discovery, mainly for fragment screening. WAC »» Blood-Brain Penetrant via a Disciplined, Iterative Structure-Based Drug is activity-based protein profiling (ABPP), which utilizes chemical probes to map activity states advantages include speed, high quality fragment Inhibitors Design Strategy affinity information, reliable fragment-to-target binding Paul Sprengeler, PhD, Research Fellow, Medicinal of large numbers of proteins in parallel. I will discuss the application of ABPP to discover and kinetics information and enabling use of a standard HOTEL & TRAVEL Chemistry, eFFECTOR Therapeutics, Inc. LC/MS platform. Examples will be given on screening eFT508, an exquisitely selective, potent dual MNK1/2 functionally annotate proteins in mammalian SPONSORSHIP physiology and disease, and the generation and of membrane proteins (aquaporins), proteases, inhibitor, was designed to assess the potential for kinases, coagulation proteins, chaperones and protein- & EXHIBIT control of oncogene signaling at the level of mRNA implementation of advanced ABPP platforms for proteome-wide ligand discovery. protein interaction (PPI). REGISTRATION translation. The crystal structure-guided design beginning with fragments and fragment-like molecules 9:35 Coffee Break in the Exhibit Hall with leverages stereoelectronic interactions unique to 5:30 Welcome Reception in the Exhibit Hall with Poster Viewing MNK. eFT508 has potent in vivo anti-tumor activity in Poster Viewing Click Here to register Online models of DLBCL and solid tumors and is currently 6:30 End of Day DrugDiscoveryChemistry.com being evaluated in Phase 2 clinical trials in solid tumors and lymphoma.

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COVER FRAGMENTS FOR PPIs 11:00 Lead Generation without an X-Ray Crystal to modulation by small molecules and resources Structure: An NMR Method to Probe Protein- are often directed towards seemingly intractable CONFERENCE 10:30 Fragment-Based Discovery of a Chemical Probe AT-A-GLANCE Ligand Complexes targets. We have been building and applying molecular for the NSD3-PWWP-1 Domain Julien Orts, PhD, Professor, Laboratory of Physical dynamics based fragment screening and de novo PLENARY KEYNOTES Jark Böttcher, Principal Scientist, Medicinal Chemistry, Chemistry, Swiss Federal Institute of Technology ETH design approaches to try and understand ligandability Boehringer Ingelheim RCV GmbH & Co KG My talk is about a NMR method to solve protein-ligand and functionability for protein-protein interaction SHORT COURSES We describe the fragment-based discovery of complex structure. I will present two or three examples targets. We believe this approach can steer us towards molecules binding to the proposed methyl-lysine of this method applied to finding inhibitors against hit compounds for tractable PPI targets. AGENDA binding site of the PWWP-1 domain of NSD3. specific PPI targets. 12:00 pm End of Conference April 3-4 Conferences Supported by a virtual screening approach and 11:30 In silico Fragment Screening to Identify »» Protein-Protein Interactions subsequent structure-based optimization, the initial hits were optimized into a chemical probe with Cryptic Pockets and Allosteric Sites for PPI »» Inflammation & Autoimmune confirmed binding in cellular assays. The probe and Inhibitor Development Inhibitors the related negative control can be used to explore the Ben Cossins, PhD, Principal Scientist, UCB Pharma »» Kinase Inhibitor Chemistry functions of the PWWP-1 domain. Drug development is increasingly difficult and »» GPCR-Targeted Drug Design expensive. Valuable targets are not always amenable »» Fragment-Based Drug Discovery April 4-5 Conferences »» Ubiquitin Proteasome System Inhibitors »» Small Molecules for Cancer Immunotherapy “I really like this conference. I always learn new, »» Macrocyclics & Constrained Peptides latest developments that are occurring in the field.” »» Targeting Complex Membrane Proteins – MICHAEL F., PRINCIPAL SCIENTIST, ABBVIE April 6 Symposia »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant Inhibitors

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COVER Ubiquitin Proteasome System Inhibitors CONFERENCE Discovery and Development of Small Molecules Targeting DUBs and Ligases AT-A-GLANCE April 4-5, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES Wednesday, April 4 will be discussed as well as a system to address the through the design of bifunctional, Proteolysis- AGENDA ‘PROTACability’ of particular E3 ligases. Targeting Chimera (PROTAC) molecules. Based upon April 3-4 Conferences 12:30 pm Registration 2:40 Covalent Inhibitors and Degraders of Challenging our new classes of highly potent small-molecule BET »» Protein-Protein Interactions 12:45 Dessert Break in the Exhibit Hall with Targets in Cancer inhibitors, we have designed and optimized highly potent and efficacious small-molecule degraders »» Inflammation & Autoimmune Poster Viewing Dennis Dobrovolsky, Research Scientist, Department of BET proteins. We have performed critical and Inhibitors of Biological Chemistry and Molecular Pharmacology, extensive evaluation of our BET degraders for their »» Kinase Inhibitor Chemistry HIJACKING THE UPS FOR TARGETED Harvard Medical School This presentation will discuss new pharmacological therapeutic potential and mechanism of action in » PROTEIN DEGRADATION » GPCR-Targeted Drug Design strategies towards targeting kinases and other models of acute leukemia and solid tumors. »» Fragment-Based Drug 1:30 Welcome Remarks targets. Small molecules capable of inducing protein 5:30 Breakout Discussions Discovery Kip Harry, Senior Director, Conferences, Cambridge degradation through the recruitment of E3 ligases Healthtech Institute 6:15 End of Day April 4-5 Conferences will be discussed with a focus on kinases. A general 6:30 Dinner Short Courses* »» Ubiquitin Proteasome System 1:35 Chairperson’s Opening Remarks approach for identifying the most easily degradable *Separate registration required; please see page 3 Inhibitors Alexander Statsyuk, PhD, Assistant Professor, kinase targets will be presented. Chemical design Department of Pharmacological and Pharmaceutical principles for developing degraders will be discussed. for details. »» Small Molecules for Cancer Sciences, University of Houston New approaches for developing covalent kinase Immunotherapy inhibitors will also be discussed. Thursday, April 5 »» Macrocyclics & Constrained 1:40 Targeted Protein Degradation via Redirecting the Peptides Action of CRL4 E3 Ligases 3:10 Sponsored Presentation (Opportunity Available) 8:00 am Breakfast Presentation: Sponsored by Brian Cathers, PhD, Executive Director, Co-Leader & Improvements in NMR Approaches to »» Targeting Complex 3:40 Refreshment Break in the Exhibit Hall with Head, Drug Discovery, Protein Homeostasis Thematic Fragment Based Screening Membrane Proteins Poster Viewing Center of Excellence, Celgene Donna Baldisseri, Senior Applications April 6 Symposia Distinct cereblon binding molecules evoke different 4:30 Targeted Protein Degradation by Scientist, Bruker BioSpin »» Biophysical Approaches for phenotypic responses yet bind the same target. Small Molecules FBDD is a powerful search engine for identification of Drug Discovery Solution of the ligand bound CRBN complex provides a Alessio Ciulli, PhD, Professor, Chemical & Structural fragments that bind to disease relevant target proteins Biology, School of Life Sciences, University of Dundee »» Lead Optimization for Drug rationale for distinguishing “gain of function” targeting ultimately leading to drug candidates. NMR-based The application of small molecules to induce Metabolism & Safety of key substrates including the transcription factors FBDD screening requires compound library validation, Aiolos and Ikaros, the protein kinase CK1α, or the selected protein degradation is emerging as a preparation of hundreds of samples per campaign, »» Blood-Brain Penetrant transformative new modality of chemical intervention Inhibitors translation termination factor GSPT1. Is it possible automated acquisition, processing of thousands of to harness the action of a single E3 ligase and direct in drug discovery. We have previously shown that spectra, and their analysis for binding assessment. linking a VHL ligand that we had discovered with a HOTEL & TRAVEL its actions toward new and different substrates? Are Here is described the streamlined solutions offered other ligases able to be co-opted in a similar fashion? pan-BET inhibitor creates highly selective PROTAC by Bruker, automating this pipeline to improve the molecule MZ1. MZ1 triggers preferential intracellular SPONSORSHIP 2:10 PROTACs: The Chemical Equivalent of CRISPR speed and productiveness of FBDD screening for the & EXHIBIT degradation of Brd4, leaving the homologous BET . Dan Bondeson, Research Scientist, Crews Lab, Yale members untouched, and exhibits greater anti- REGISTRATION University proliferative activity in leukemia cell lines than pan- 8:45 Plenary Session Welcome Remarks from Induced protein degradation offers several advantages BET inhibition. Event Director over traditional inhibition strategies and has emerged Anjani Shah, PhD, Conference Director, Cambridge recently as a potential therapeutic option. For the 5:00 Target Protein Degradation for New Therapeutics Healthtech Institute Click Here to register Online Shaomeng Wang, PhD, Warner-Lambert/Parke-Davis past 16 years, we have helped develop this fast 8:50 Plenary Keynote Introduction DrugDiscoveryChemistry.com Professor, Medicine; Professor, Medicine, Pharmacology growing field, shepherding our initial chemical biology Kevin Lustig, PhD, CEO, Scientist.com concept into a drug development strategy that is on and Medicinal Chemistry; Director, Center for the verge of clinical validation. PROTACs with high Therapeutics Innovation, University of Michigan target selectivity, potency, and oral bioavailability Recently, a new small-molecule approach has been employed to target degradation of BET proteins

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COVER 8:55 PLENARY KEYNOTE: Targeting high-throughput manner. We illustrate the efficacy of in reductionist xenograft models are salutary, the more CONFERENCE Ras and MYC for the Treatment of this technology by evaluating the activity of disease- relevant actions in syngeneic tumor models and in AT-A-GLANCE Cancer relevant DUBs, in analyzing DUB inhibitor selectivity, patients involve balancing the effects of DUB inhibitors Stephen Fesik, PhD, Professor of and in evaluating how compounds impact DUB activity. on the immune system with their effects on tumor PLENARY KEYNOTES Biochemistry, Pharmacology, and Chemistry, Orrin 11:45 Sponsored Presentation (Opportunity Available) cells, and these are not things that can be predicted by H. Ingram II Chair in Cancer Research, Vanderbilt their structures or staring at their ADME/tox profiles. SHORT COURSES 12:00 pm Mining the Deubiquitinase Family for Novel University School of Medicine 2:50 USP7-Specific Inhibitors Target and Two of the most important targets in cancer Drugs Utilizing FORMA’s Drug Discovery Engine AGENDA Stephanos Ioannidis, PhD, Head, Early Portfolio, FORMA Modify the Enzyme’s Active Site via Distinct are Ras and MYC. However, both of these highly Chemical Mechanisms April 3-4 Conferences Therapeutics validated cancer targets are thought to be Irina Bezsonova, PhD, Assistant Professor, Department »» Protein-Protein Interactions undruggable. In this presentation, I will discuss our The deubiquitinating enzymes (DUBs), by their reversal of the ubiquitination/polyubiquitination process, are of Molecular Biology and Biophysics, University of »» Inflammation & Autoimmune approaches for targeting both of these proteins key enzymes regulating protein homeostasis. As such, Connecticut Inhibitors directly and indirectly using fragment-based USP7 is a deubiquitinating enzyme that plays a methods and structure-based design. modulators of DUB function have the potential to be »» Kinase Inhibitor Chemistry important therapeutics in oncology, immunology, pivotal role in multiple oncogenic pathways and »» GPCR-Targeted Drug Design neurodegenerative and other medical disorders therefore is a desirable target for new anti-cancer 9:45 Coffee Break in the Exhibit Hall with therapies. However, the lack of structural information »» Fragment-Based Drug involving pathological or dysregulated proteins. Poster Viewing about the USP7-inhibitor interactions has been a Discovery FORMA Therapeutics deploys multiple drug discovery screening platforms to explore broad target families critical gap in the development of potent inhibitors. April 4-5 Conferences DESIGN AND DEVELOPMENT OF on scale. Panels of functional cellular and enzymatic USP7 is unique among USPs in that its active site »» Ubiquitin Proteasome System NOVEL DEUBIQUITINASE (DUB) assays, including related target family selectivity is catalytically incompetent, and is postulated to Inhibitors rearrange into a productive conformation only upon INHIBITORS screens, were established to mine the DUBome for »» Small Molecules for Cancer novel chemical matter. binding to ubiquitin. Immunotherapy 10:40 Chairperson’s Remarks 3:20 Evaluation and Characterization of Small Tauseef R. Butt, PhD, President and CEO, Progenra, Inc. 12:30 Luncheon Presentation (Sponsorship »» Macrocyclics & Constrained Opportunity Available) or Enjoy Lunch on Your Own Molecule Inhibitors of Deubiquitinating Enzyme Peptides 10:45 Small Molecule Ubiquitin Protease (USP7) USP14 as Potential Anti-Cancer Agents 1:30 Dessert Break in the Exhibit Hall »» Targeting Complex Inhibitors with Immune Cell-Based Anti-Tumor Stina Lundgren, PhD, Senior Research Scientist, with Poster Awards Membrane Proteins Activity Superior to That of Biologicals Medivir AB Tauseef R. Butt, PhD, President and CEO, Progenra, Inc. April 6 Symposia 3:50 Refreshment Break In immune competent animal models, USP7 inhibitors INSIGHTS INTO DEUBIQUITINASE » » Biophysical Approaches for are potent anti-tumor agents, not only blocking ENZYMES AND INHIBITORS Drug Discovery TARGETING THE PPIs OF E3 LIGASES tumor growth but also eliminating tumor metastasis. 2:15 Chairperson’s Remarks »» Lead Optimization for Drug 4:20 HECT E3 and RBR E3 Ligases as Drug Targets to These results constitute the first example of a small Zhihao Zhuang, PhD, Associate Professor, Department of Metabolism & Safety Treat Cancer and Neurodegenerative Diseases: Basic molecule single agent that works by targeting both the Chemistry & Biochemistry, University of Delaware »» Blood-Brain Penetrant tumor itself and the host immune system and also by Science and New Screening Technologies Inhibitors eliminating tumor metastasis. In animal models, the 2:20 DUB Inhibitors in Syngeneic Cancer Models and Alexander Statsyuk, PhD, Assistant Professor, USP7 inhibitor demonstrates activity that is superior to in Preclinical Studies Department of Pharmacological and Pharmaceutical HOTEL & TRAVEL that of PD1 and CTLA4 antibodies. Wayne W. Hancock, M.D., Ph.D., Professor, Pathology Sciences, University of Houston and Chief of Transplant Immunology, Children’s Hospital E3 ligases (>600 known) are the key mediators SPONSORSHIP 11:15 Developing a Quantitative Profiling Platform to of Philadelphia and University of Pennsylvania of protein degradation pathways, and E3 ligase & EXHIBIT Evaluate Endogenous Deubiquitinase Activity When it comes to trash talking about cells, there inhibitors or activators are promising drug leads. In Willem den Besten, PhD, Senior Scientific Researcher, are lots to gossip about and reasons to do so. I will addition, E3 ligases can be executors that mediate the REGISTRATION Genentech briefly review the key interactions between the trash degradation of PROTAC targets. In this presentation, Here we describe the development of an analysis collectors and the trash recyclers within cells, and how we specifically discuss emerging biochemical platform that combines DUB ABPs with chemical this has gone from esoterica to essential in the era of mechanisms and biological roles of HECT and RBR E3 Click Here to register Online multiplexing, targeted mass spectrometry, novel immune-oncology. DUBs help determine the outcomes ligases, their therapeutic potential to treat cancers and internal reaction standards, and a customized DrugDiscoveryChemistry.com of checkpoint blockade inhibition and are key to the neurodegenerative diseases, and current screening statistical analysis program. Our strategy allows functions of each of the main players in the immune technologies to discover initial drug leads for this us to quantitate changes in DUB activity across response to cancer. While the effects of DUB inhibitors class of drug targets. a theoretically unlimited number of samples in a

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COVER 4:50 Novel Spiro[3H-indole-3,2´-pyrrolidin]-2(1H)-one The compounds are highly selective and show are not fully understood. We found that EDD- CONFERENCE Compounds as Potent, Chemically Stable and Orally excellent in vivo efficacy in a SJSA-1 xenograft DYRK2-DDB1DCAF1 is present at the centrosome, AT-A-GLANCE Active Inhibitors of the MDM2-p53 Interaction model even when given as a single dose as an organelle crucial for cell division, and that its Andreas Gollner, PhD, Laboratory Head, Medicinal demonstrated for BI-0252. enzymatic activity is regulated by a novel centrosomal PLENARY KEYNOTES Chemistry, Boehringer Ingelheim 5:20 Cep78, a Novel Inhibitor of the HECT E3 Ubiquitin protein called Cep78 in human cells. By using a Novel, chemically stable spiro[3H-indole-3,2´- combination of biochemistry, molecular biology, and SHORT COURSES Ligase EDD-DYRK2-DDB1DCAF1 pyrrolidin]-2(1H)-one compounds that are not prone William Tsang, PhD, Research Unit Director, Cell Division cell biology, we dissected the mechanism by which AGENDA to epimerization as observed for other spiro-oxindole and Centrosome Biology, Montreal Clinical Research EDD-DYRK2-DDB1DCAF1 is inhibited by Cep78. MDM2-p53 inhibitors are presented. Structure-based Institute 5:50 End of Conference April 3-4 Conferences optimization inspired by natural product architectures EDD-DYRK2-DDB1DCAF1 is a multi-subunit HECT »» Protein-Protein Interactions led to complex-fused ring systems ideally suited to E3 ubiquitin ligase whose physiological functions »» Inflammation & Autoimmune interrupt the MDM2-p53 protein-protein interaction. Inhibitors »» Kinase Inhibitor Chemistry »» GPCR-Targeted Drug Design »» Fragment-Based Drug Discovery April 4-5 Conferences »» Ubiquitin Proteasome System Inhibitors “What I really like at this conference is that there »» Small Molecules for Cancer Immunotherapy are parallel sessions. There is always a presentation »» Macrocyclics & Constrained Peptides at any time of the day that I find interesting.” »» Targeting Complex Membrane Proteins – STEFAN J., PRODUCT MANAGER, BRUKER BIOSPIN April 6 Symposia »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant Inhibitors

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COVER Small Molecules for Cancer Immunotherapy CONFERENCE Discovery and Development of Immune-Modulatory Small Molecules AT-A-GLANCE April 4-5, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES Wednesday, April 4 2:40 FEATURED PRESENTATION: Small 6:30 Dinner Short Courses* AGENDA Molecule Antagonists Targeting PD-1/ *Separate registration required; please see page 3 April 3-4 Conferences 12:30 pm Registration PD-L1 and Other Immune Checkpoint for details. »» Protein-Protein Interactions 12:45 Dessert Break in the Exhibit Hall with Pathways Murali Ramachandra, PhD, CSO, Aurigene Discovery Thursday, April 5 »» Inflammation & Autoimmune Poster Viewing Technologies Limited Inhibitors 8:00 am Breakfast Presentation: Sponsored by SMALL MOLECULES TARGETING PD-1/ We are developing small molecule oral agents dually »» Kinase Inhibitor Chemistry targeting PD-L1 and another pathway to increase Improvements in NMR Approaches to »» GPCR-Targeted Drug Design PD-L1 AND IDO the response rate, and with a relatively shorter Fragment Based Screening Donna Baldisseri, Senior Applications Scientist, »» Fragment-Based Drug 1:30 Welcome Remarks pharmacokinetic exposure for better management of Bruker BioSpin Discovery Kip Harry, Senior Director, Conferences, Cambridge irAEs. We have identified candidates potently targeting Healthtech Institute PD-L1 and VISTA or PD-L1 and TIM-3 pathways along FBDD is a powerful search engine for identification of April 4-5 Conferences with desirable physico-chemical profile, exposure upon fragments that bind to disease relevant target proteins »» Ubiquitin Proteasome System 1:35 Chairperson’s Opening Remarks oral dosing and pharmacological properties. CA-170, ultimately leading to drug candidates. NMR-based Inhibitors Rogier C. Buijsman, PhD, Head, Chemistry, Netherlands FBDD screening requires compound library validation, Translational Research Center B.V. (NTRC) the first candidate from this approach dually targeting »» Small Molecules for Cancer PD-L1 and VISTA, is now undergoing clinical trials. preparation of hundreds of samples per campaign, Immunotherapy 1:40 Small-Molecule Inhibitors of PD-1/PD-L1 automated acquisition, processing of thousands of »» Macrocyclics & Constrained Alexander Dömling, PhD, Professor and Chair, 3:10 Sponsored Presentation (Opportunity Available) spectra, and their analysis for binding assessment. Peptides Department of Drug Design, University of Groningen Here is described the streamlined solutions offered My research group is leading in the synthesis of 3:40 Refreshment Break in the Exhibit Hall with by Bruker, automating this pipeline to improve the »» Targeting Complex macrocyclic compounds with non-peptidic character. Poster Viewing speed and productiveness of FBDD screening for the Membrane Proteins We have not only devised 12 novel convergent 4:30 Discovery of PF-06840003, a Novel IDO Inhibitor pharmaceutical industry. April 6 Symposia straightforward synthetic ways to assemble very for Cancer Immunotherapy 8:45 Plenary Session Welcome Remarks from » » Biophysical Approaches for large macrocyclic libraries but we also applied Stefano Crosignani, PhD, Director, Medicinal Chemistry, Event Director Drug Discovery them to antagonize protein-protein interactions iTeos Therapeutics Anjani Shah, PhD, Conference Director, Cambridge »» Lead Optimization for Drug such as PD1-PD-L1. Tumors use Indoleamine 2-3 dioxygenase to induce Healthtech Institute Metabolism & Safety 2:10 Tetraiodothyroacetic Acid (Tetrac), a Small an immunosuppressive environment by promoting immune tolerance, effector T cell anergy and enhanced 8:50 Plenary Keynote Introduction »» Blood-Brain Penetrant Molecule Thyroid Hormone Antagonist, Disables Kevin Lustig, PhD, CEO, Scientist.com Inhibitors Immune Checkpoint Defenses of Cancer Cells Treg function. We have identified and characterized a Paul Davis, MD, Professor, Department of Medicine, new, highly selective, orally bioavailable IDO-1 inhibitor, HOTEL & TRAVEL Pharmaceutical Research Institute, Albany PF-0684003. PF-0684003 reverses human T cell 8:55 PLENARY KEYNOTE: Targeting Medical College anergy in vitro. It shows a very favorable ADME profile Ras and MYC for the Treatment of SPONSORSHIP We have shown that the PD-1/PD-L1 immune leading to favorable predicted human pharmacokinetic Cancer & EXHIBIT checkpoint is regulated non-immunologically by properties. These studies highlight the strong Stephen Fesik, PhD, Professor of potential of PF-0684003 as a clinical candidate in Biochemistry, Pharmacology, and Chemistry, Orrin REGISTRATION thyroid hormone. A thyroid hormone antagonist, tetrac, acts as a hormone receptor on an integrin expressed immuno-oncology. H. Ingram II Chair in Cancer Research, Vanderbilt by cancer cells to downregulate expression of PD-L1 5:00 Talk Title to be Announced University School of Medicine and PD-1 . beta-Catenin activation mediates T Rogier C. Buijsman, PhD, Head, Chemistry, Netherlands Two of the most important targets in cancer Click Here to register Online cell exclusion from the cancer microenvironment and Translational Research Center B.V. (NTRC) are Ras and MYC. However, both of these highly DrugDiscoveryChemistry.com validated cancer targets are thought to be tetrac blocks catenin activation non-immunologically 5:30 Breakout Discussions by inducing expression of miR-21 and CBY1 (Chibby). undruggable. In this presentation, I will discuss our Thus, acting outside the traditional immune system 6:15 End of Day approaches for targeting both of these proteins and at the level of gene expression, tetrac disables directly and indirectly using fragment-based immune defenses of tumor cells. methods and structure-based design.

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COVER 9:45 Coffee Break in the Exhibit Hall with 12:00 pm A First-in-Class Selective Class IIa Histone 2:50 Leniolisib (CDZ173) - The Discovery of a New CONFERENCE Poster Viewing Deacetylase (HDAC) Inhibitor, TMP195 Generation of Selective PI3Kδ Inhibitors AT-A-GLANCE Michael Nolan, PhD, Director, GlaxoSmithKline Nicolas Soldermann, PhD, Senior Investigator and Group SMALL MOLECULES TARGETING THE We recently reported that a first-in-class selective Leader, Global Discovery Chemistry, Novartis Institutes PLENARY KEYNOTES TUMOR MICROENVIRONMENT class IIa HDAC inhibitor (TMP195) influenced for BioMedical Research human monocyte responses to colony stimulating The discovery and characterization of leniolisib SHORT COURSES 10:40 Chairperson’s Remarks factors CSF-1 and CSF-2 in vitro. Here, we utilize a (CDZ173), a potent and selective inhibitor of Suresh Kumar, PhD, Senior Director, Research and AGENDA macrophage-dependent autochthonous mouse model Phosphoinositide 3-kinase delta (PI3Kd) will be Development, Progenra of breast cancer to demonstrate that in vivo TMP195 presented. We report how innovative medicinal April 3-4 Conferences 10:45 Targeting Tumor Microenvironment with treatment alters the tumor microenvironment and chemistry efforts led to the identification of a »» Protein-Protein Interactions Deubiquitinase Inhibitors for Cancer Immunotherapy reduces tumor burden and pulmonary metastases novel and promising tetrahydro-pyrido-pyrimidine »» Inflammation & Autoimmune Suresh Kumar, PhD, Senior Director, Research and through macrophage modulation. TMP195 induces lead series that could be rapidly further optimized Inhibitors Development, Progenra recruitment and differentiation of highly phagocytic into a favorable physicochemical space and »» Kinase Inhibitor Chemistry Immune suppressive Tregs and MDSCs in the tumor and stimulatory macrophages within tumors. resulted in the identification of leniolisib, currently microenvironment correlate with poor prognosis. in clinical development as an anti-inflammatory »» GPCR-Targeted Drug Design 12:30 Luncheon Presentation (Sponsorship Suppression of Tregs or impairment of Treg function Opportunity Available) or Enjoy Lunch on Your Own therapeutic agent. »» Fragment-Based Drug is an attractive cancer immunotherapy approach. 3:20 Discovery of a PI3Kβ/δ Inhibitor for the Discovery Deubiquitinase USP7 is critical for Treg function by 1:30 Dessert Break in the Exhibit Hall with Poster Awards Treatment of PTEN-Deficient Tumors: Building PI3Kβ April 4-5 Conferences regulating Foxp3 and TIP60. Progenra has developed Potency in a PI3Kδ-Selective Template potent USP7 inhibitors that impair Treg functions »» Ubiquitin Proteasome System KINASE IMMUNOMODULATORS Stephane Perreault, PhD, Research Scientist II, Medicinal Inhibitors and are efficacious in various syngeneic solid tumor Chemistry, Gilead Sciences, Inc. models. USP7 inhibitors alone or in combination can 2:15 Chairperson’s Remarks »» Small Molecules for Cancer The design, optimization, and in vivo evaluation of improve the efficacy and expand the scope of cancer Donald Durden, MD, Professor, Department of Immunotherapy a novel series of PI3Kβ/δ inhibitors in which PI3Kβ immunotherapy. Pediatrics, University of California, San Diego; Director of potency was built in a PI3Kδ-selective template will »» Macrocyclics & Constrained Operations, SignalRx Pharmaceuticals Peptides 11:15 Inhibiting Treg Trafficking into the Tumor be presented. This work led to the discovery of a Microenvironment 2:20 Discovery of Scaffold/Platform for the highly selective PI3Kβ/δ inhibitor displaying excellent »» Targeting Complex David Wustrow, Vice President, Drug Discovery, FLX Development of nM Potent Triple Inhibitor of PI3K/ pharmacokinetic profile and efficacy in a human PTEN- Membrane Proteins Bio, Inc. BRD4/CDK4/6 (Kinase/Epigenetic) Inhibitor, SRX3177 deficient LNCaP prostate carcinoma xenograft tumor April 6 Symposia Recent longitudinal studies in patients receiving IO for Maximum Cancer Cell Synthetic Lethality, model. Phosphoinositide 3-kinase β (PI3Kβ) signaling »» Biophysical Approaches for agents demonstrate an influx of Treg in responding Safety and Efficacy is required to sustain cancer cell growth in which the Drug Discovery patients which may dampen optimal anti-tumor Donald Durden, MD, Professor, Department of tumor suppressor phosphatase and tensin homolog »» Lead Optimization for Drug responses. Understanding the mechanisms of Pediatrics, University of California, San Diego; Director of (PTEN) has been deactivated. Metabolism & Safety Treg recruitment into the TME thereby preventing Operations, SignalRx Pharmaceuticals 3:50 Refreshment Break »» Blood-Brain Penetrant their ability to induce immune tolerance. This talk A novel thienopyranone molecular scaffold has been Inhibitors will describe the discovery of the key mechanism developed in silico to selectively inhibit PI3 kinase NOVEL IMMUNOMODULATORY SMALL of such Treg recruitment as well as in vitro and in (PI3K) as well as two other targets, the bromodomain MOLECULES HOTEL & TRAVEL vivo validation of this small molecule approach to protein, BRD4 and CDK4/6. Molecular modeling selectively decreasing immune tolerance in the TME. studies employing crystal structure analysis and 4:20 Tumor Immune Modulation following SPONSORSHIP 3:20 Presentation to be Announced Sponsored by robust PI3K, BRD4 and CDK4/6 homology models have Intratumoral Therapy with Small Molecule & EXHIBIT been developed and will be presented to describe how TLR7/8 Ligands these single small molecules can bind to inhibit such David Ferguson, PhD, Professor, Medicinal Chemistry, REGISTRATION distinctly different proteins and their functions. As a University of Minnesota cancer therapeutic, this triple inhibition mechanism The basic structural features of small molecule ligands allows for a unique and powerful way to modulate that confer selectivity to Toll-like receptors 7 and 8 Click Here to register Online critical components of cancer cells. will be discussed in the context of immunomodulation DrugDiscoveryChemistry.com and the design of cancer vaccines. An SAR analysis will be presented to identify structural features that

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COVER confer selectivity to TLR7 and TLR8 and ligand specific blockade therapies. Anti-tumor activity of TLR7/8 Phase II clinical trials for advanced cancer. DRD2 is CONFERENCE activation of key cytokines in producing antigen ligands requires or is associated with the infiltration expressed by immune cells and ONC201 has shown AT-A-GLANCE specific cellular responses in model systems. Finally, of activated CD8 T cells, formation of lymphoid immunostimulatory effects in preclinical studies, in vivo data will be shown that demonstrate the aggregates, and expression of cytokines and including increased intratumoral NK cell infiltration in PLENARY KEYNOTES potential of TLR7/8 stimulation in designing advanced chemokines associated with Th1 immunity, CTL xenografts. In agreement with preclinical observations, vaccines for cancer treatment. activity, T cell chemotaxis, and type I IFN inducible increase in circulating and intratumoral NK cells, SHORT COURSES 4:50 Tumor Immune Modulation following gene expression. cytokines and effector molecules was observed in AGENDA Intratumoral Therapy with Small Molecule 5:20 The Imipridone ONC201, a Selective DRD2 prostate, endometrial, glioblastoma and mantle cell TLR7/8 Ligands Antagonist, Exerts Immunostimulatory Activity in lymphoma patients. April 3-4 Conferences John Vasilakos, PhD, Senior Research Immunologist and Advanced Cancer Patients 5:50 End of Conference »» Protein-Protein Interactions Business Director for TLR Agonists, TLR Department, Joshua Allen, PhD, Vice President, Research and »» Inflammation & Autoimmune Drug Delivery Systems Division, 3M Development, Oncoceutics Inhibitors TLR7/8 ligands exhibit anti-tumor activity when ONC201 is an orally active small molecule antagonist »» Kinase Inhibitor Chemistry injected into tumors, and synergize with checkpoint of the G protein-coupled receptor DRD2 currently in »» GPCR-Targeted Drug Design »» Fragment-Based Drug Discovery April 4-5 Conferences »» Ubiquitin Proteasome System Inhibitors »» Small Molecules for Cancer Immunotherapy “I get in three days an absolute high-level overview »» Macrocyclics & Constrained Peptides about what’s going on in my field.” »» Targeting Complex – STEFAN L., CHAIRMAN, PHARMACEUTICAL & MEDICINAL Membrane Proteins CHEMISTRY, UNIVERSITY OF TUEBINGEN April 6 Symposia »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant Inhibitors

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COVER Macrocyclics & Constrained Peptides CONFERENCE Cell-Penetrating ‘Bigger’ Molecules AT-A-GLANCE April 4-5, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES Wednesday, April 4 2:40 Lipophilic Permeability Efficiency (LPE) Enables 3:40 Refreshment Break in the Exhibit Hall with AGENDA the Identification and Quantification of Structural Poster Viewing April 3-4 Conferences 12:30 pm Registration Effects on Macrocycle Permeability 4:30 Property-Based Drug Design beyond Ro5 »» Protein-Protein Interactions 12:45 Dessert Break in the Exhibit Hall with Matthew R. Naylor, PhD, LIFA Postdoctoral Fellow, Eli - Lessons Learned from AbbVie’s Drugs and Lilly & Co. »» Inflammation & Autoimmune Poster Viewing Compound Collection Macrocycle scaffold structure determines the balance Inhibitors Phil Cox, PhD, Senior Principal Scientist, Chemistry between lipophilicity and aqueous solubility in the »» Kinase Inhibitor Chemistry DESIGN RULES FOR MACROCYCLES Group Leader, Discovery Chemistry and Technology, pursuit of bRo5 therapeutics capable of passive AbbVie, Inc. »» GPCR-Targeted Drug Design 1:30 Welcome Remarks cell permeability. Current techniques to identify Anjani Shah, PhD, Conference Director, Cambridge This presentation will focus on the lessons learned »» Fragment-Based Drug such structure are time-intensive (NMR analysis) or Healthtech Institute from an initiative to analyze AbbVie’s internal database Discovery challenging on large peptides (in silico prediction). of compounds beyond Ro5 (including macrocycles). 1:35 Chairperson’s Opening Remarks Combining a simple hydrocarbon lipophilicity April 4-5 Conferences Scott Lokey, PhD, Professor, Chemistry and measurement with a predictor of aqueous solubility, 5:00 Rationalizing the Passive Membrane »» Ubiquitin Proteasome System Biochemistry, University of California, Santa Cruz Lipophilic Permeability Efficiency (LPE) quantifies Permeability of Cyclic Peptides Inhibitors Sereina Riniker, PhD, Assistant Professor, Laboratory of 1:40 Lessons for the Design of Synthetic Macrocycles the intrinsic ability of diverse bRo5 scaffolds to hide »» Small Molecules for Cancer Physical Chemistry, ETH Zürich from Machine Learning backbone or sidechain polarity for cell permeability. Immunotherapy The hypothesis for the passive membrane permeability Adrian Whitty, PhD, Professor, Biochemistry, Boston 3:10 Conformational Sampling of Sponsored by of cyclic peptides involves the interconversion »» Macrocyclics & Constrained University Macrocycles in Solution Peptides between “open” conformations and “closed” 2:10 Physical Chemical Properties for Drug Design in Paul Hawkins, PhD, Head, Scientific conformations prior to the entering of the membrane. »» Targeting Complex Beyond Rule of Five Chemical Space Solutions, OpenEye Scientific Software Using kinetic models based on molecular dynamics Membrane Proteins Marina Shalaeva, PhD, Principal Scientist, Medicinal Some types of macrocyclic molecules have been (MD) simulations in polar and apolar environments, April 6 Symposia Design, Pfizer shown to be orally bioavailable ligands for targets a rationale for the “permeability cliff” presented by »» Biophysical Approaches for New concepts and methods are being developed such as GPCRs and protein-protein interfaces, which the natural product cyclosporine A and its synthetic Drug Discovery for evaluation and modulation of properties of Bro5 requires then to be able to permeate cell membranes derivative cyclosporine E as well as for a recently effectively. The means by which high molecular weight »» Lead Optimization for Drug compounds to achieve acceptable PK/PD in drug published series of cyclic decapeptides is provided. macrocycles are able to be membrane permeable Metabolism & Safety candidate. In particular, the PLRP-S method for 5:30 Breakout Discussions estimating lipophilicity and ionization in nonpolar has been the subject of some recent study, but no »» Blood-Brain Penetrant clear conclusions have yet been reached. In this 6:15 End of Day Inhibitors membrane-like environment is described. A fast chromatographic assay is used to asses lipophilicity- presentation we discuss how to model effectively the 6:30 Dinner Short Courses* conformational properties of macrocycles in different HOTEL & TRAVEL ionization patterns of lipophilic, low solubility Bro5 *Separate registration required; please see page 3 compounds in combination with pKa by MCE, while environments and how experimental data gathered for details. SPONSORSHIP EPSA and ElogD are used to drive passive permeability in solution, particularly from NMR, can be used to & EXHIBIT and drug efficiency (lipE). improve that sampling. REGISTRATION

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COVER Thursday, April 5 BEYOND NATURAL PEPTIDES AND that bind to CXCR7 and also incorporate an N-linked peptoid functionality in order to overcome the poor CONFERENCE AMINO ACIDS AT-A-GLANCE 8:00 am Breakfast Presentation: Sponsored by permeability associated with peptides. The peptoid Improvements in NMR Approaches to 10:40 Chairperson’s Remarks group also enabled us to explore side chain diversity PLENARY KEYNOTES Fragment Based Screening Maxwell D. Cummings, PhD, Senior Principal Scientist, well beyond that of natural amino acids. Donna Baldisseri, Senior Applications Scientist, , Discovery Sciences, SHORT COURSES 12:30 Luncheon Presentation: Sponsored by Bruker BioSpin Janssen R&D Evaluation of Free Energy Calculations AGENDA FBDD is a powerful search engine for identification of for the Prioritization of Macrocyclic fragments that bind to disease relevant target proteins 10:45 FEATURED PRESENTATION: The Cyclophilin Inhibitors April 3-4 Conferences ultimately leading to drug candidates. NMR-based RaPID Discovery of Bioactive Pseudo- Janet Paulsen, PhD, Senior Scientist, Applications »» Protein-Protein Interactions FBDD screening requires compound library validation, Natural Peptides Science, Schrödinger »» Inflammation & Autoimmune preparation of hundreds of samples per campaign, Hiroaki Suga, PhD, Professor, Department of Macrocycles are often used to drug difficult targets, Inhibitors automated acquisition, processing of thousands of Chemistry, School of Science, The University of Tokyo such as PPIs or balance desirable drug properties. »» Kinase Inhibitor Chemistry spectra, and their analysis for binding assessment. This lecture will describe the most recent development Synthesis of these molecules can require significant Here is described the streamlined solutions offered »» GPCR-Targeted Drug Design in the genetic code reprogramming technology that effort with no guarantee that the molecule will have by Bruker, automating this pipeline to improve the enables us to express pseudo-natural peptides. The improved properties or meet pro ject goals. Here, »» Fragment-Based Drug speed and productiveness of FBDD screening for the technology involves (1) efficient macrocyclization of I will present a blinded retrospective investigation, Discovery pharmaceutical industry. peptides, (2) incorporation of non-standard amino performed in collaboration with Gilead, targeting April 4-5 Conferences 8:45 Plenary Session Welcome Remarks from acids, such as N-methyl amino acids, (3) reliable cyclophilin for Hepatitis C. FEP+ successfully »» Ubiquitin Proteasome System Event Director synthesis of libraries with the complexity of more predicted relative binding free energies, rank-ordered Inhibitors Anjani Shah, PhD, Conference Director, Cambridge than a trillion members, (4) rapid discovery of potent compounds and explained non-intuitive SAR for a »» Small Molecules for Cancer Healthtech Institute bioactive pseudo-natural peptides by the RaPID class of mini-sanglifehrins. Immunotherapy 8:50 Plenary Keynote Introduction system (or PDPS). 1:30 Dessert Break in the Exhibit Hall »» Macrocyclics & Constrained Kevin Lustig, PhD, CEO, Scientist.com with Poster Awards Peptides 11:15 Lead Optimization of Natural-Product Derived NaV1.7 Inhibitory Disulfide-Rich Peptides »» Targeting Complex CYCLIC PEPTIDES: DRUG 8:55 PLENARY KEYNOTE: Targeting Kaustav Biswas, PhD, Principal Scientist, Hybrid Modality Membrane Proteins Ras and MYC for the Treatment of Engineering, Amgen, Inc. DEVELOPMENT CHALLENGES April 6 Symposia Cancer My talk details Amgen’s program directed at inhibition 2:15 Chairperson’s Remarks »» Biophysical Approaches for Stephen Fesik, PhD, Professor of of the voltage-gated sodium channel NaV1.7 for pain Adrian Whitty, PhD, Professor, Biochemistry, Boston Drug Discovery Biochemistry, Pharmacology, and Chemistry, Orrin and itch using hits from a venom screen. We identified University H. Ingram II Chair in Cancer Research, Vanderbilt »» Lead Optimization for Drug novel toxin peptides from tarantula venom which have University School of Medicine 2:20 Cell Penetration Profiling for Biotherapeutics Metabolism & Safety disulfide-rich folded motifs. Using a combination of Two of the most important targets in cancer Joshua Kritzer, PhD, Associate Professor, Chemistry, »» Blood-Brain Penetrant positional scanning and peptide-ion channel molecular Tufts University are Ras and MYC. However, both of these highly docking studies, we will discuss the discovery of Inhibitors validated cancer targets are thought to be Several classes of biomolecules have emerged as synthetic analogues with activity in ex vivo and in vivo exciting potential therapies, but their development undruggable. In this presentation, I will discuss our behavioral NaV1.7-dependent models. HOTEL & TRAVEL approaches for targeting both of these proteins has been impeded by imprecise measurements of directly and indirectly using fragment-based 11:45 Sponsored Presentation (Opportunity Available) intracellular delivery. The Kritzer lab has devised a SPONSORSHIP new method for quantitating cell penetration, the & EXHIBIT methods and structure-based design. 12:00 pm Discovery of Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid ChloroAlkane Penetration Assay (CAPA). CAPA is REGISTRATION CXCR7 Modulators inexpensive and high-throughput, and it can quantitate 9:45 Coffee Break in the Exhibit Hall with penetration to individual cellular compartments. Poster Viewing Elnaz Menhaji-Klotz, PhD, Senior Principal Scientist, Internal Medicine Chemistry, Pfizer We are using CAPA to comprehensively profile cell penetration for diverse biomolecules and drug Click Here to register Online While several small molecules have been identified that modulate the activity of CXCR7, an attractive drug delivery systems. DrugDiscoveryChemistry.com target for a variety of disease indications, peptidic 2:50 Achieving Passive Permeability and Oral macrocycles may provide additional advantages in Bioavailability in Synthetic Cyclic Peptides terms of potency, selectivity, and reduced off-target Scott Lokey, PhD, Professor, Chemistry and activity. We report on a series of peptidic macrocycles Biochemistry, University of California, Santa Cruz

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COVER 3:20 Polar Hinges as Functionalized Conformational 4:20 Cyclotide Antagonists of the HDM2-HDMX RING- 5:20 Chemo-enzymatic Synthesis of Highly CONFERENCE Constraints in (Bi)Cyclic Peptides Mediated E3 Ligase Constrained Multicyclic Peptides AT-A-GLANCE Robert Liskamp, PhD, Chair of Chemical Biology and Julio Camarero, PhD, Professor, Pharmacology and Marcel Schmidt, Industrial PhD Candidate, Van’t Hoff Medicinal Chemistry, Chemistry, University of Glasgow Pharmaceutical Sciences, University of Southern Institute of Molecular Sciences, University of Amsterdam PLENARY KEYNOTES We wish to devise (cyclic) peptides and California The increasing number of macrocyclic peptides peptidomimetics as protein-protein interactions (PPI) The cyclotide scaffold has a tremendous potential currently being investigated as prospective SHORT COURSES inhibitors. Polar hinges have been developed for for the development of therapeutic leads based on therapeutics requires efficient, cost-effective routes AGENDA cyclization of peptides leading to bicyclic peptides their extraordinary stability and potential for grafting for their synthesis. We have developed a flexible and and cyclized peptides with improved solubility applications. We will show an example, where a large broadly applicable chemo-enzymatic strategy that April 3-4 Conferences and biological activity. Increasingly, we note that a cyclotide-based genetically encoded library was enables the efficient, scalable assembly of (multi) »» Protein-Protein Interactions good aqueous solubility of peptides is an absolute used to screen for low nanomolar antagonists for cyclic peptide macrocycles. We successfully employed »» Inflammation & Autoimmune prerequisite not only to be able to handle and purify the Hdm2-HdmX RING-mediated E3 ligase activity. omniligase-1-catalyzed peptide backbone cyclization Inhibitors our target peptides but it is also crucial for biological We will also present different strategies to improve for the synthesis of a plethora of peptides, ranging »» Kinase Inhibitor Chemistry activity characterization. the cellular uptake and pharmacokinetic profiles of from naturally occurring multicyclic peptides (e.g. bioactive cyclotides. cyclotide MCoTI-II) to multicyclic peptides containing »» GPCR-Targeted Drug Design 3:50 Refreshment Break 4:50 Constrained Oligomers Targeting the Ubiquitin- non-natural scaffolds with bifunctional biological »» Fragment-Based Drug Proteasome Pathway activity (e.g. tri- and tetracycles). Discovery Thomas Kodadek, PhD, Professor of Chemistry; 5:50 End of Conference April 4-5 Conferences Associate Dean of Graduate and Post-Doctoral Studies, »» Ubiquitin Proteasome System The Scripps Research Institute Inhibitors »» Small Molecules for Cancer Immunotherapy »» Macrocyclics & Constrained Peptides »» Targeting Complex Membrane Proteins April 6 Symposia »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant Inhibitors

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COVER Targeting Complex Membrane Proteins CONFERENCE Biophysical Techniques, Structure-Based Drug Design and Other Advances AT-A-GLANCE April 4-5, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES Wednesday, April 4 2:10 The Shifting Landscape of Structure-Based transporters themselves offer allosteric sites which AGENDA Drug Design through Developments in Cryo are shown to enrich drug discovery opportunities. April 3-4 Conferences 12:30 pm Registration Electron Microscopy 5:00 Signaling Bias across Receptor Classes »» Protein-Protein Interactions 12:45 Dessert Break in the Exhibit Hall with Stephen Muench, PhD, Assistant Professor, Department Brian J. Arey, PhD, Director, Mechanistic Pharmacology, of Membrane Biology, School of Biomedical Sciences, »» Inflammation & Autoimmune Poster Viewing Leads Discovery and Optimization, Bristol-Myers University of Leeds Inhibitors Squibb Co. Membrane proteins represent over 30% of the »» Kinase Inhibitor Chemistry STRUCTURE-BASED DESIGN FOR Signaling bias, or functional selectivity, of GPCRs genome and make up ~60% of therapeutic targets. is now a well-accepted phenomenon. With growing » COMPLEX MEMBRANE PROTEINS » GPCR-Targeted Drug Design However, despite their importance, our structural and access to crystal structures of GPCRs in liganded »» Fragment-Based Drug 1:30 Welcome Remarks biochemical understanding is still lacking. This talk will and un-liganded states, we have begun to get a Discovery Anjani Shah, PhD, Conference Director, Cambridge detail how new developments in electron microscopy clearer picture of the conformational rearrangements Healthtech Institute and extraction methodologies have opened up new April 4-5 Conferences that give rise to activation/selectivity in receptor opportunities for studying membrane proteins and »» Ubiquitin Proteasome System 1:35 Chairperson’s Opening Remarks signaling. However, understanding of signaling bias driving therapeutic design. In particular, it will discuss Inhibitors Sid Topiol, PhD, CSO, 3D-2drug, LLC; Professor and as it relates to other receptor classes has not been Director, Structural and Computational Drug Discovery, how we are now driving drug design through electron thoroughly addressed. This presentation will discuss »» Small Molecules for Cancer Stevens Institute of Technology microscopy on a range of membrane protein targets. commonalities that occur in activation of receptors Immunotherapy 2:40 Solute Carrier Transporters: An Emerging across receptor classes that suggest this phenomenon »» Macrocyclics & Constrained Drug Target Class is not restricted to GPCRs. Peptides 1:40 FEATURED PRESENTATION: Structure, Activation and Inhibition of Alan Wickenden, PhD, Scientific Director, Discovery 5:30 Breakout Discussions »» Targeting Complex Chemokine Receptors Sciences, Janssen Research & Development, LLC Membrane Proteins 6:15 End of Day Tracy M. Handel, Professor and Chair, 3:10 Sponsored Presentation (Opportunity Available) April 6 Symposia 6:30 Dinner Short Courses* Division of Pharmaceutical Sciences, Skaggs School 3:40 Refreshment Break in the Exhibit Hall with » *Separate registration required; please see page 3 » Biophysical Approaches for of Pharmacy and Pharmaceutical Sciences, School of Poster Viewing Drug Discovery Medicine, University of California, San Diego for details. »» Lead Optimization for Drug Chemokine receptors and their endogenous protein ALLOSTERIC MODULATION AND ligands are key to the etiology of many inflammatory Thursday, April 5 Metabolism & Safety BIASED SIGNALING: NOT JUST »» Blood-Brain Penetrant diseases. Preclinical studies have demonstrated the 8:00 am Breakfast Presentation: Sponsored by Inhibitors therapeutic potential of many chemokine receptors, FOR GPCRs? Improvements in NMR Approaches to yet successful drug discovery has been slow with only 4:30 Allosteric Modulation in and by Transporters Fragment Based Screening HOTEL & TRAVEL two FDA-approved small molecule drugs. Fortunately, of GPCR Ligands Donna Baldisseri, Senior Applications recent structural information should reverse this trend. Sid Topiol, PhD, CSO, 3D-2drug, LLC; Professor and Scientist, Bruker BioSpin SPONSORSHIP In this presentation, our current understanding of the Director, Structural and Computational Drug Discovery, FBDD is a powerful search engine for identification of & EXHIBIT structure and activation mechanisms of chemokine Stevens Institute of Technology fragments that bind to disease relevant target proteins receptors by chemokines, and strategies for receptor REGISTRATION Allosteric modulation of protein action has become ultimately leading to drug candidates. NMR-based inhibition with small molecules, will be summarized. increasingly more sought after as a means to achieve FBDD screening requires compound library validation, advantageous features such as ligand selectivity and preparation of hundreds of samples per campaign, tone. For endogenous amine GPCRs, these attributes automated acquisition, processing of thousands of Click Here to register Online are effectively achieved via independent proteins spectra, and their analysis for binding assessment. DrugDiscoveryChemistry.com such as the SERT transporter. Recent X-ray structural Here is described the streamlined solutions offered reports for dDAT and hSERT elucidate the structural by Bruker, automating this pipeline to improve the basis for drug binding at these targets. Further, the speed and productiveness of FBDD screening for the pharmaceutical industry.

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COVER 8:45 Plenary Session Welcome Remarks from 11:15 Discovery and Development of an 2:50 Nanodiscs for Biophysical Characterization of CONFERENCE Event Director NHE3 Inhibitor Membrane Proteins AT-A-GLANCE Anjani Shah, PhD, Conference Director, Cambridge Andrew King, PhD, Head, Biology and Ilia Denisov, PhD, Laboratory of Stephen Sligar, Healthtech Institute Pharmacology, Ardelyx Department of Biochemistry, University of Illinois at PLENARY KEYNOTES 8:50 Plenary Keynote Introduction 11:45 Sponsored Presentation (Opportunity Available) Urbana-Champaign Kevin Lustig, PhD, CEO, Scientist.com The Nanodisc platform has enjoyed wide applicability SHORT COURSES 12:00 pm Developing Novel Pain Drugs by Selectively as it provides a self-assembled system that Targeting Nav1.7 AGENDA renders typically insoluble yet biologically and 8:55 PLENARY KEYNOTE: Targeting David Hackos, PhD, Senior Scientist, Neuroscience, pharmacologically relevant membrane protein targets April 3-4 Conferences Ras and MYC for the Treatment of Genentech such as receptors, transporters, enzymes, and viral »» Protein-Protein Interactions Cancer Nav1.7 is a sodium ion channel that plays a role in antigens soluble in aqueous media. It has also Stephen Fesik, PhD, Professor of pain sensing. We and others have identified small »» Inflammation & Autoimmune provided a means for understanding the mechanism of Biochemistry, Pharmacology, and Chemistry, Orrin molecule compounds that bind to a novel site within Inhibitors cancer signaling complexes, such as KRas4b and its H. Ingram II Chair in Cancer Research, Vanderbilt the 4th voltage-sensing domain that lock the channel »» Kinase Inhibitor Chemistry effectors, which all form on a membrane surface. I will University School of Medicine into an inactivated state. We solved the structure of present our latest discoveries enabled by Nanodiscs. »» GPCR-Targeted Drug Design Two of the most important targets in cancer the binding site for this class of compounds (Ahuja 3:20 Using Label-Free Impedimetric Monitoring »» Fragment-Based Drug are Ras and MYC. However, both of these highly et al., Science 2015) which led to key insights into the to Profile the Pharmacology of Cell-Surface Discovery validated cancer targets are thought to be mechanism and the pharmacology of these selective undruggable. In this presentation, I will discuss our sodium channel inhibitors. Receptors in Vitro April 4-5 Conferences approaches for targeting both of these proteins Joachim Wegener, PhD, Professor, Division Cell- »» Ubiquitin Proteasome System 12:30 Luncheon Presentation (Sponsorship directly and indirectly using fragment-based Based Sensors, Fraunhofer Research Institution for Inhibitors Opportunity Available) or Enjoy Lunch on Your Own methods and structure-based design. Microsystems and Solid-State Technologies (EMFT), »» Small Molecules for Cancer 1:30 Dessert Break in the Exhibit Hall University of Regensburg Immunotherapy with Poster Awards This presentation will highlight several different 9:45 Coffee Break in the Exhibit Hall with approaches how non-invasive impedance »» Macrocyclics & Constrained Poster Viewing Peptides BIOPHYSICAL TOOLS FOR measurements can be used to characterize the pharmacology of GPCRs and other cell-surface »» Targeting Complex MEMBRANE PROTEINS NEW DRUG DISCOVERY APPROACHES receptors that can be switched from OFF to Membrane Proteins FOR ION CHANNEL AND 2:15 Chairperson’s Remarks ON states or changed in their activity by ligand Aaron Thompson, PhD, Scientist II, Department April 6 Symposia TRANSPORTERS binding. Impedance approaches are especially »» Biophysical Approaches for of Structural Biology, Dart Neuroscience; former suited for difficult-to-purify proteins because they Drug Discovery 10:40 Chairperson’s Remarks Postdoctoral Fellow of Ray Stevens Laboratory can be analyzed label-free in their native state Alan Wickenden, PhD, Scientific Director, Discovery »» Lead Optimization for Drug 2:20 Biophysical Characterization of GPCRs with in the membrane of living cells at endogenous Sciences, Janssen Research & Development, LLC Metabolism & Safety Crystallization-Enhancing Modifications expression levels. The non-invasive nature of the »» Blood-Brain Penetrant 10:45 Structural Insights from the Co-Crystal of the Matthew Eddy, PhD, Postdoctoral Fellow, Laboratory of measurement allows following the cell response Inhibitors Glycine Receptor Ion Channel Bound to Its Modulator Raymond Stevens, University of Southern California and to receptor activation and the intracellular signal Xin Huang, PhD, Principal Scientist, Department of The Scripps Research Institute amplification in real time. HOTEL & TRAVEL Molecular Engineering, Amgen We present two studies where biophysical techniques 3:50 Refreshment Break Glycine receptors (GlyRs) mediate inhibitory provide new insight into structure-function SPONSORSHIP neurotransmission in the central nervous system. relationships of human GPCRs and their implications CANCER-RELATED & EXHIBIT Selective activation of GlyRs has been hypothesized for drug discovery. First, NMR studies of a GPCR as an alternative approach to treat neuropathic pain. fusion protein used for X-ray crystallography document MEMBRANE TARGETS REGISTRATION Here we present crystal structures of GlyRa3 with how the fusion protein affects the signaling-related 4:20 Structure-Based Drug Design for Cancer-Related both positive and negative modulators. Our structures conformational equilibrium, highlighting potential Membrane Proteins provide new insights into molecular recognition of instances where drug-ligand interactions can be Avner Schlessinger, PhD, Assistant Professor, Click Here to register Online these modulators and their modulation mechanisms. affected. Second, NMR, X-ray diffraction, and other Pharmalogical Sciences, Mount Sinai School of Medicine DrugDiscoveryChemistry.com These results also offer promise of rational structure- biophysical methods are applied to GPCR variants with Solute carrier (SLC) transporters play a major role based design of new classes of GlyR modulators. mutations in a known allosteric center, and we explore in mediating nutrient delivery in reprogrammed the potential utility of these variants to accelerate cancer metabolism networks. We use computational GPCR drug discovery. methods including homology modeling and virtual screening, which are followed by experimental

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COVER testing, to discover novel small molecule ligands a drug discovery assay for identification of inhibitory modulate transcription of genes for cytokines and CONFERENCE for cancer-related transporters. Our results provide compounds that change the phosphorylation status of chemokines. T4 and tetrac also regulate expression AT-A-GLANCE useful tool compounds to characterize the role of the human Epidermal Growth Factor Receptor (EGFR) of the PD-L1 gene--thus modifying the inflammatory SLC transporters in cancer, as well as a framework in the context of living cells and in the low nanomolar process and angiogenesis. PLENARY KEYNOTES for developing efficacious lead compounds against range, an advance which may open up a whole new 5:50 End of Conference emerging drug targets. approach to drug development and lead to more SHORT COURSES 4:50 Applying Mammalian Membrane Two-Hybrid effective treatments for lung cancer patients. AGENDA (MaMTH) Assay Identifies Novel Cancer Targets 5:20 Thyroid Hormone Analogues as Angiogenic & Therapeutics Agents via the Integrin Receptor April 3-4 Conferences Igor Stagljar, PhD, Professor, Department of Molecular Paul Davis, MD, Professor, Department of Medicine, »» Protein-Protein Interactions Genetics, Department of Biochemistry, University Pharmaceutical Research Institute, Albany »» Inflammation & Autoimmune of Toronto Medical College Inhibitors I will demonstrate how the Mammalian Membrane Acting via a specific integrin receptor on tumor cells, »» Kinase Inhibitor Chemistry Two-Hybrid (MaMTH) assay can efficiently be used as thyroid hormone (T4) and its antagonist (tetrac), »» GPCR-Targeted Drug Design »» Fragment-Based Drug Discovery April 4-5 Conferences »» Ubiquitin Proteasome System Inhibitors »» Small Molecules for Cancer Immunotherapy »» Macrocyclics & Constrained Peptides »» Targeting Complex Membrane Proteins April 6 Symposia »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant Inhibitors

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COVER Biophysical Approaches for Drug Discovery CONFERENCE New Methods for Medicinal Chemists AT-A-GLANCE April 6, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES Friday, April 6 10:00 Identifying and Testing the Optimal Conditions 12:00 pm Session Break AGENDA for Kinetic Fragment-based Screening; a Novel TR- April 3-4 Conferences 7:25 am Registration and Morning Coffee FRET Based Approach ORTHOGONAL BIOPHYSICAL »» Protein-Protein Interactions David Sykes, MS, Experimental Officer, Laboratory of APPROACHES EMERGING TOOLS FOR DRUG Dmitry Veprintsev, Molecular and Cellular Pharmacology, »» Inflammation & Autoimmune University of Nottingham 1:00 Chairperson’s Remarks Inhibitors DISCOVERY – BIOPHYSICAL Developing new approaches for studying drug-receptor Phillip Schwartz, PhD, Senior Scientist, Structural Biology »» Kinase Inhibitor Chemistry AND BEYOND kinetics is key to improving screening efficiency. I and Biophysics, Takeda California »» GPCR-Targeted Drug Design 7:55 Welcome and Opening Remarks will describe a novel TR-FRET based competition- 1:05 Novel Approaches in Using NMR and SPR for »» Fragment-Based Drug Anjani Shah, PhD, Conference Director, Cambridge association kinetic binding approach testing the Fragment Hit Identification and Validation Discovery Healthtech Institute kinetics of a commercially available library of ~1400 Anil Padyana, PhD, Associate Director, Structural Biology Chris Smith, PhD, Director, Medicinal Chemistry, COI low molecular weight fragments at the dopamine D2 and Biophysics, Department of Biochemistry, Agios April 4-5 Conferences Pharmaceuticals receptor, a prototypical GPCR. A range of off-rates Pharmaceuticals »» Ubiquitin Proteasome System were obtained including examples with surprisingly Inhibitors 1:35 A Systematic Approach for Prosecuting 8:00 FEATURED PRESENTATION: Development of slow off-rates. This approach offers the potential to Fragment Hits in the Absence of »» Small Molecules for Cancer Cryo-Electron Microscopy for Pharmaceutical Drug discover chemical starting points for the development Structural Information Immunotherapy Design: From Implementation to Optimization of kinetically optimized medicines. Bradley Doak, PhD, Research Fellow, Medicinal »» Macrocyclics & Constrained Christopher Arthur, PhD, Principal Scientist Specialist, 10:30 Second-Harmonic Generation for Chemistry, Monash University Peptides Structural Biology, Genentech Conformation-Selective Drug Discovery: Developing fragment hits into lead-like structures can »» Targeting Complex 8:30 Application of Encoded Library Technology to PPI Case Studies be difficult, especially when no structural information Membrane Proteins Lead Generation at GSK Joshua Salafsky, PhD, Founder & CSO, Biodesy, Inc. is available. We aim to standardize the evaluation April 6 Symposia Svetlana Belyanskaya, PhD, Encoded Library I will review the state of the art in SHG technology and development of these fragment hits, with or »» Biophysical Approaches for Technologies, R&D Platform Technology & Science, with a number of case studies. In particular, I will without structural information, through exploration Drug Discovery GSK Boston discuss the sensitivity of SHG to subtle but biologically of vectors around the fragment. Here we present important allosteric conformational changes case studies that used chemoinformatic tools for »» Lead Optimization for Drug Affinity-based screening of DNA-encoded chemical that occur in protein-protein interactions. Various finding purchasable analogues as well as designing Metabolism & Safety libraries is routinely employed within GSK for lead generation. The platform has evolved over its approaches for setting up a protein-protein assay standardized libraries of reagents to explore and »» Blood-Brain Penetrant screen will be discussed as well. validate vectors for expansion. Inhibitors application to a quantitative on-DNA binding assay of billions of compounds simultaneously. A case study 11:00 Measure What Matters, When It Matters 2:05 Takeda’s Tool Kit of Biophysical Methods HOTEL & TRAVEL will be presented to illustrate the process of selection Delphine Collin, PhD, Vice President, Discovery and Pedro Serrano, PhD, Principal Scientist, Structural design and execution including the high throughput Biophysics, HarkerBIO, LLC Biology and Biophysics, Takeda SD SPONSORSHIP chemistry and hit confirmation using affinity selection By changing their conformation, proteins can carry 2:35 Networking and Discussion Session & EXHIBIT mass spectrometry used to follow up screens. out their functions and modulate the functions 3:05 Refreshment Break 9:00 Coffee Break of other molecules. As structure based drug REGISTRATION discovery’s appreciation of proteins as dynamic, 9:30 Native Mass Spectrometry and Collision-Induced flexible molecules grows, so does the importance of ADDRESSING CHALLENGING TARGETS Unfolding for Drug Discovery and Development probing conformational changes to the unliganded WITH BIOPHYSICAL APPROACHES Click Here to register Online Brandon T. Ruotolo, PhD, Associate Professor, form of a protein. Triaging our toolbox of orthogonal Department of Chemistry, University of Michigan 3:35 Coupling Biophysical Approaches with Molecular DrugDiscoveryChemistry.com techniques, including second harmonic generation Simulations to Optimize Compounds for Challenging measurements, we can investigate and measure Disease Targets protein structural motion. Woody Sherman, PhD, CSO, Silicon Therapeutics 11:15 Luncheon Presentation (Opportunity Available) We describe our drug discovery projects that combine or Enjoy Lunch on Your Own experimental and simulation methods to develop novel

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COVER medicines for diseases with targets that are currently demonstrating a scalable method for the successful entity. LC-MS offers the ability to detect and quantify CONFERENCE considered challenging. Our INSITE computational development of SPR assays for a wide range of wild- biomarkers with both specificity at single nodes AT-A-GLANCE platform accurately treats the underlying physics of type GPCRs. The SPR assays can be exploited for and comprehensive coverage of large, chemically molecular recognition (i.e. protein dynamics, water fragment screening and kinetic characterization to diverse networks, empowering not only SAR-based PLENARY KEYNOTES thermodynamics, and quantum mechanical effects) discover novel ligands. generation but also unknown and integrates with experimental techniques such pathway explorations. Case studies on both topics SHORT COURSES 4:35 Liquid Chromatography- Mass Spectrometry as X-ray crystallography, NMR, ITC, and second (LC-MS)-Based Metabolomics in Pharmacological will be presented. AGENDA harmonic generation. Lead Generation: From a Single Metabolic Node to 5:05 End of Conference 4:05 Characterization of Wild Type GPCRs Using Network Analysis April 3-4 Conferences Surface Plasmon Resonance Gang Xing, PhD, Principal Scientist, Internal Medicine »» Protein-Protein Interactions Iva Navratilova, PhD, Staff Scientist, Department of Research Unit, Pfizer Worldwide Research & »» Inflammation & Autoimmune Molecular Biology, University of Dundee Development, Pfizer, Inc. Inhibitors Expressing, purifying and analysing membrane The study of metabolic disease is complicated by »» Kinase Inhibitor Chemistry proteins using SPR is routinely challenging. In this sophisticated pathway networks contributing both »» GPCR-Targeted Drug Design presentation, we will present our latest results catabolically and anabolically to a single molecular »» Fragment-Based Drug Discovery April 4-5 Conferences »» Ubiquitin Proteasome System Inhibitors »» Small Molecules for Cancer Immunotherapy »» Macrocyclics & Constrained “There’s lots of interesting talks, but from quite Peptides »» Targeting Complex a diverse set of people, which makes for an Membrane Proteins April 6 Symposia interesting meeting” »» Biophysical Approaches for – BEN D., RESEARCH FELLOW, VERNALIS RESEARCH Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant Inhibitors

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COVER Lead Optimization for Drug Metabolism & Safety CONFERENCE Tools and Strategies for Incorporating Safety into Drug Design AT-A-GLANCE April 6, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES Friday, April 6 IMPACT OF DRUG TRANSPORT AND 11:00 Elucidating Mechanism-of-Toxicity Sponsored by AGENDA of FAAH Inhibitors via CLEARANCE April 3-4 Conferences 7:25 am Registration and Morning Coffee Proteome-Screening »» Protein-Protein Interactions 9:30 Detection and Assessment of Reactive Drug Steven Molinski, PhD, Senior Solutions UNDERSTANDING DRUG METABOLISM Metabolites in Drug-Mediated Hepatotoxicity Scientist, Cyclica Inc. »» Inflammation & Autoimmune Mark Grillo, PhD, Staff Scientist, Drug Metabolism & Cyclica has developed a protein structure-based Inhibitors AND DRUG-DRUG INTERACTIONS , MyoKardia, Inc. and AI-augmented drug discovery platform (Ligand »» Kinase Inhibitor Chemistry 7:55 Welcome and Opening Remarks A number of toxic drugs undergo bioactivation to Express) that provides a unique panoramic view of »» GPCR-Targeted Drug Design Tanuja Koppal, PhD, Conference Director, Cambridge chemically-reactive metabolites that bind covalently small-molecules in development, by identifying on-/ Healthtech Institute »» Fragment-Based Drug to endogenous macromolecules, proteins, DNA off-targets that may be expected as well as those John C. L. Erve, PhD, DABT, Consultant, Jerve Scientific Discovery leading to organ toxicity and carcinogenesis. Current that are unanticipated. Accordingly, Ligand Express Consulting, Inc. experimental techniques used to detect and assess can augment R&D programs by elucidating MoA of April 4-5 Conferences the potential liabilities of reactive metabolites and small molecules. »» Ubiquitin Proteasome System 8:00 FEATURED PRESENTATION: Addressing how information from mechanistic in vitro studies can Inhibitors 11:15 Luncheon Presentation (Opportunity Available) Biotransformation Issues in Early Discovery be employed to redesign candidate drugs leading to or Enjoy Lunch on Your Own »» Small Molecules for Cancer Deepak Dalvie, PhD, Senior Director, DMPK, Celgene blocked or minimized bioactivation and decreased Immunotherapy Drug metabolism plays an important role in the toxification will be discussed. 12:00 pm Session Break »» Macrocyclics & Constrained discovery and development of a drug candidate. 10:00 Application of Drug Transporters in CASE STUDIES: STRATEGIES FOR Peptides Addressing metabolism issues early on can result Drug Discovery »» Targeting Complex in candidates with less metabolism as well as Caroline Lee, PhD, Executive Director, Ardea Biosciences OPTIMIZING DMPK PROPERTIES Membrane Proteins bioactivation liabilities. Strategies and examples Inc., a member of the AstraZeneca Group 1:00 Chairperson’s Remarks of role of metabolism in early discovery will be April 6 Symposia Transporters play a key role in the disposition of Mark Grillo, PhD, Staff Scientist, Drug Metabolism & discussed in this talk. »» Biophysical Approaches for drugs. Transporters contribute to drug efficacy, drug Pharmacokinetics, MyoKardia, Inc. Drug Discovery interactions and may limit desired drug exposure. 1:05 Use of Integrated DMPK Approaches to Facilitate 8:30 Principles of Metabolite Identification by Mass The rationale and identification of the transporters »» Lead Optimization for Drug Design of Brain Penetrant Kinase Inhibitors Spectrometry for Drug Discovery and Development to implement in drug discovery will be discussed as Metabolism & Safety John C. L. Erve, PhD, DABT, Consultant, Jerve Scientific Xingrong Liu, PhD, Principal Scientist, Drug Metabolism well as the difficulties that may be encountered in and Pharmacokinetics, Genentech, Inc. »» Blood-Brain Penetrant Consulting, Inc. translating in vitro data to clinical outcome. Inhibitors Metabolite identification (Met ID) studies are an 1:35 A Proposed ADME Optimization Workflow for important component for both drug discovery and drug 10:30 Addressing the Challenges of Low Clearance Covalent Inhibitors HOTEL & TRAVEL development efforts. Mass spectrometry, particularly and Intracellular Free Drug Concentration Mehran Moghaddam, PhD, MBA, Founder and CEO, high mass accuracy techniques, is the primary tool Li Di, PhD, Research Fellow, Pharmacokinetics, Dynamics OROX Biosciences SPONSORSHIP for Met ID studies. Chemists often rely on internal or and Metabolism, Pfizer Inc. With the renewed interest in covalent inhibitors & EXHIBIT external scientists to perform metabolite identification Low clearance compounds continue to increase comes the responsibility to advance only compounds in drug discovery and lack of low clearance tools REGISTRATION and characterization but will benefit by understanding with drug-like properties in discovery programs. The how it is done. This talk will cover strategies used can lead to over-prediction of clearance, dose and traditional small molecule reversible drug discovery to identify drug metabolites allowing chemists to under-prediction of half-life. Intracellular free drug workflow includes target identification and validation, better understand the strengths and limitations of concentration is most relevant for development of lead identification, lead optimization and profiling Click Here to register Online these studies. PK/PD relationships and prediction of drug-drug and optimizing for ADME properties are paramount DrugDiscoveryChemistry.com interactions. This presentation will discuss approaches 9:00 Coffee Break in obtaining acceptable efficacy and safety. This to address these challenges and their applications in presentation will contrast the ADME workflow for drug discovery. discovery of covalent verses reversible inhibitors.

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COVER 2:05 Predicting Human PK and Exposure in Discovery how they were used at AbbVie to successfully address tissue samples. The accuracy and throughput is well CONFERENCE to Inform Lead Optimization and Candidate Selection a significant FmCYP3A4 and time-dependent inhibition suited to quantify and rank effects and toxicity of drug AT-A-GLANCE Natalie Hosea, PhD, DMPK San Diego Site Head, Takeda liability in a Spleen Tyrosine Kinase (SYK) program. metabolites, chemical libraries and lead candidates. Prediction of human pharmacokinetics and drug- 3:05 Refreshment Break Data generated will be useful for the analysis of drug PLENARY KEYNOTES related exposure underpins early decision-making effects on human vs. animal tissue, target organs and in drug discovery. More specifically, early human NEW ASSAYS FOR ADMET drug-drug interactions. SHORT COURSES predictions enable identification of key liabilities for PREDICTIONS AND EARLY DOSING 4:35 In vitro Tools for Successful Prediction of Human AGENDA focused optimization strategies as well as enabling Hepatic Clearance assessment of early safety information when coupled 3:35 Kriging - A New Approach for Building ADMET Jasleen Sodhi, Graduate Student, Laboratory of April 3-4 Conferences with pharmacology information. In this section, Prediction Models Dr. Leslie Benet, Pharmaceutical Sciences and »» Protein-Protein Interactions case studies on the application of predictions to Istvan Enyedy, PhD, Principal Scientist, Medicinal Pharmacogenomics Program, Department of »» Inflammation & Autoimmune optimization strategies and compound advancement Chemistry, Biogen Bioengineering and Therapeutic Sciences, University of Inhibitors will be discussed. Kriging is using the correlation of the distance between California, San Francisco »» Kinase Inhibitor Chemistry Continued on next page... molecules with the difference between their activity/ Accurate prediction of human pharmacokinetic ADMET properties for in silico predictions. We have »» GPCR-Targeted Drug Design 2:35 Co-Presentation: Strategies and Application of properties is critically important in drug discovery. CYP Inhibition and Phenotyping Assays to Optimize considered this algorithm since it allows us to easily Of particular importance is the prediction of hepatic »» Fragment-Based Drug SYK Inhibitor Drug-Drug Interaction Risk Profiles build, evaluate, and maintain models and has a report clearance, which largely determines drug exposure Discovery David M. Stresser, PhD, Principal Research Scientist, format that allows users to judge the accuracy of the and contributes to projections of dose, drug half-life April 4-5 Conferences AbbVie, Inc. predictions. The performance of eighteen models and and bioavailability. This talk will cover common in vitro »» Ubiquitin Proteasome System Michael Hoemann, PhD, Senior Scientist, Department of how training sets impact it will be presented. techniques used to predict hepatic clearance of new Inhibitors Chemistry, AbbVie, Inc. 4:05 Sensitive in vitro Screening for Structure/Tissue chemical entities and the fundamentals of in vitro to in »» Small Molecules for Cancer Cytochrome P450 interaction liabilities receive higher Toxicity Assessment with Rapid-Turnaround Time vivo extrapolation (IVIVE) of drug clearance. Immunotherapy scrutiny in therapeutic areas requiring low tolerance Ian Sweet, PhD, Associate Professor, Department of 5:05 End of Conference »» Macrocyclics & Constrained for drug-drug interactions. In these competitive market Medicine, University of Washington Peptides areas, rapid access to robust CYP metabolism and I will present sensitive technology we have developed inhibition data is crucial to a program’s success. We that continuously measures time courses of »» Targeting Complex Membrane Proteins April 6 Symposia »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug “Great opportunity to share and discuss cutting- Metabolism & Safety »» Blood-Brain Penetrant edge approaches/aspects in drug discovery.” Inhibitors – FABRIZIO G., PRINCIPAL SCIENTIST, ASTRAZENECA HOTEL & TRAVEL SPONSORSHIP & EXHIBIT will review early ‘perpetrator’ and ‘victim’ assays and pharmacologically relevant drug effects on solid REGISTRATION

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COVER Blood-Brain Penetrant Inhibitors CONFERENCE Tools, Strategies, and Design of Brain Penetrant Inhibitors AT-A-GLANCE April 6, 2018 | Hilton San Diego Bayfront | San Diego, CA PLENARY KEYNOTES SHORT COURSES Friday, April 6 DISCOVERY AND DEVELOPMENT OF MSC2120352 binds in the ATP-binding pocket of AGENDA the kinase: the QCA amide group forms bidentate BRAIN PENETRANT INHIBITORS FOR April 3-4 Conferences 7:25 am Registration and Morning Coffee interactions with the hinge region (Glu173-Leu175); »» Protein-Protein Interactions CANCER (CONT.) the electron-rich π system of the benzyl binds in the DISCOVERY AND DEVELOPMENT G-loop, utilizing noncovalent cation-π interactions with »» Inflammation & Autoimmune 9:30 Small Molecule Kinase Inhibitors for Brain the catalytic lysine-123. Inhibitors OF BRAIN PENETRANT INHIBITORS Cancer: Limitations, Challenges and Opportunities »» Kinase Inhibitor Chemistry FOR CANCER Timothy P. Heffron, PhD, Senior Scientist, Discovery 11:00 Sponsored Presentation (Opportunity Available) Chemistry, Genentech, Inc. »» GPCR-Targeted Drug Design 7:55 Welcome and Opening Remarks 11:15 Luncheon Presentation (Opportunity Available) Drug discovery aimed at treating neurological cancers or Enjoy Lunch on Your Own »» Fragment-Based Drug Kip Harry, Senior Director, Conferences, Cambridge must also consider the presence of the blood-brain Discovery Healthtech Institute barrier (BBB). High expression of transporters at 12:00 pm Session Break William F. Elmquist, PharmD, PhD, Professor and Head, April 4-5 Conferences the BBB limits most kinase inhibitors from freely Department of Pharmaceutics; Director, Brain Barriers BRAIN PENETRANT INHIBITORS FOR »» Ubiquitin Proteasome System reaching CNS malignancies within the brain.This Research Center, University of Minnesota Inhibitors talk will discuss the unmet need for neuro-oncology NEURODEGENERATIVE DISEASE AND 8:00 Brain Tumor Interactions: A Complex, Dynamic treatments, the significant opportunities that remain »» Small Molecules for Cancer PSYCHIATRIC DISORDER System Influencing Efficacy and Resistance for new kinase inhibitors in this space and the unique Immunotherapy William F. Elmquist, PharmD, PhD, Professor and Head, challenges and considerations for brain penetrant 1:00 Chairperson’s Remarks »» Macrocyclics & Constrained Department of Pharmaceutics; Director, Brain Barriers kinase inhibitor programs. Zoran Rankovic, Director, CBT Chemistry Centers, St. Peptides Jude Children’s Research Hospital Research Center, University of Minnesota 10:00 Discovery and Synthesis of the Macrocyclic »» Targeting Complex This talk will focus on the issues surrounding effective EML4-ALK Inhibitor, Lorlatinib (PF-06463922) 1:05 Art and Science of CNS Drug Design Membrane Proteins drug delivery to the invasive cells in brain tumors, Paul Richardson, PhD, Director, Process and Analytical Zoran Rankovic, Director, CBT Chemistry Centers, St. April 6 Symposia both primary and metastatic. While molecularly Technologies, Oncology Medicinal Chemistry, Pfizer Jude Children’s Research Hospital »» Biophysical Approaches for targeted anti-cancer agents have impressive inhibitory This talk will center on the design of PF-06463922, This presentation focuses on the interplay between Drug Discovery action against signaling pathways that drive tumor focusing on the optimization of the properties to the physicochemical and CNS pharmacokinetic growth, they have been ineffective in treating brain parameters, and medicinal chemistry strategies »» Lead Optimization for Drug achieve brain penetration. In addition, the synthesis tumors. The mechanisms responsible for this failure towards molecules with optimal brain exposure. Metabolism & Safety of PF-06463922 will be discussed with the key must be explored before progress can be made, step herein being the ring closure to form the final Since the challenge of CNS drug discovery could »» Blood-Brain Penetrant and inadequate drug delivery across an intact BBB be effectively addressed only with an in-depth Inhibitors 12-membered macrocycle. The development, is one critical factor for primary tumors and micro- optimization and subsequent scale-up of a novel understanding of the structure-brain exposure metastases in the brain. relationships built on reliable and meaningful HOTEL & TRAVEL direct arylation route to achieve this will be presented, 8:30 Roche Delivery Platforms for Biotherapeutics to leading to a sequence that is three steps shorter and pharmacokinetic data, the importance of modern CNS SPONSORSHIP Treat Brain Tumors is expected to provide a higher overall throughput of pharmacokinetic concepts including the “free drug” & EXHIBIT Eduard Urich, PhD, Pre-Clinical Project Leader and the desired API. hypothesis are also discussed. Senior Scientist, Roche Pharmaceutical Research and 1:35 Yeast-Based Phenotypic Screening to Identify REGISTRATION 10:30 Structure-Based Optimization of a Potent, Early Development, NORD Discovery & Translational Selective and CNS Penetrable p70S6K/AKT Inhibitor Brain Penetrant Inhibitors Area, Roche M2698 for the Treatment of Tumors with PAM Matt Lucas, PhD, Director, Medicinal Chemistry, I will describe an overview of our recent novel antibody Pathway Genomic Alterations Yumanity Therapeutics Click Here to register Online engineering platforms, including our Brain Shuttle Igor Mochalkin, PhD, Associate Director, Medicinal Phenotypic screening has undergone a revival in the DrugDiscoveryChemistry.com technology that utilizes receptor-mediated transcytosis Chemistry & Lead Optimization, EMD Serono, Inc. last decade. In this presentation, I will share some of to cross an intact BBB. Experimental data will illustrate Herein, we present the successful optimization of our learnings from Yumanity’s phenotypic screening the absolute requirement to cross the BBB to remove the quinazoline-8-carboxamide (QCA) series of dual platform to bias towards the identification of scaffolds tumor cells within the brain parenchyma. p70S6K/Akt inhibitors. The initial lead MSC2120352 that are brain penetrant with potential utility to treat 9:00 Coffee Break was identified in a focused, kinase library screen. protein misfolding diseases.

A Division of Cambridge Innovation Institute DrugDiscoveryChemistry.com • 38 Save up to $200! Register by February 23 Blood-Brain Penetrant Inhibitors | April 6, 2018

COVER 2:05 Rational Design of Exquisitely Selective BRAIN PENETRANT INHIBITORS FOR discovery in general and CNS in particular will be Inhibitors of the GSK3 Kinase Isoforms for the discussed together with contemporary understanding CONFERENCE NEURODEGENERATIVE DISEASE AND AT-A-GLANCE Treatment of Psychiatric and Neurological Disorders of drug discovery and medicinal chemistry scholarship, Florence Wagner, PhD, Senior Group Leader, Medicinal PSYCHIATRIC DISORDER (CONT.) translatability and project execution for this target PLENARY KEYNOTES Chemistry, Stanley Center for Psychiatric Research, The 3:35 Lead Optimization of Pyrazole Inhibitors of Dual class. Our strategy and search for novel kinase Broad Institute inhibitors will be illustrated with examples from two SHORT COURSES Leucine Zipper Kinase (DLK, MAP3K12) We report the discovery of the first isoform selective Snahel Patel, Senior Scientific Manager, Discovery active programs including LRRK2. AGENDA inhibitors of GSK3β or GSK3β. Exploiting a single Chemistry, Genentech, Inc. 4:35 A Human-Analog Platform for the Study amino acid difference within the ATP binding domain, Neurodegenerative diseases such as Alzheimer’s and of Drug Effects on the CNS and PNS across the April 3-4 Conferences we have developed novel, potent, brain penetrant Parkinson’s represent significant unmet medical needs Blood-Brain Barrier »» Protein-Protein Interactions inhibitors with unprecedented kinome selectivity. with no therapies able to slow the course of disease. James J. Hickman, PhD, Professor, Nanoscience »» Inflammation & Autoimmune These isoform selective inhibitors of GSK3β or GSK3β Dual Leucine Zipper Kinase (DLK) is a neuronal Technology, Chemistry, Biomolecular Science, University Inhibitors successfully decouple effects on β-catenin, and specific upstream regulator of the JNK pathway of Central Florida »» Kinase Inhibitor Chemistry therefore mitigate oncogenic concerns. that was recently identified as a central regulator of In this system, the BBB consists of human stem »» GPCR-Targeted Drug Design 2:35 Networking and Discussion Session degeneration in multiple contexts. We have progressed cell-derived endothelial cells and astrocytes on lead optimization of a pyrazole scaffold towards a opposing sides of a thin carbon-based membrane. »» Fragment-Based Drug 3:05 Refreshment Break desirable profile for a small molecule therapeutic and The neuronal cultures represent the central nervous Discovery demonstrating activity in neurodegeneration models. system with hippocampal neurons or the peripheral April 4-5 Conferences 4:05 Strategy and Tactics for the Discovery of Kinase nervous system with motoneurons. The setup allows »» Ubiquitin Proteasome System Inhibitors: A Lundbeck Perspective for the continuous monitoring of the trans-endothelial Inhibitors Klaus Baek Simonsen, PhD, Vice President, Discovery electrical resistance as well as the recording of »» Small Molecules for Cancer Chemistry, DMPK and Molecular Screening, Lundbeck neuronal activity in response to compounds or Immunotherapy This talk will highlight our drug discovery philosophy compound combinations. »» Macrocyclics & Constrained and strategies towards the discovery of new CNS 5:05 End of Conference Peptides drugs for kinases. The various challenges within drug »» Targeting Complex Membrane Proteins April 6 Symposia »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant Inhibitors Hotel & Travel Information HOTEL & TRAVEL Conference Venue & Hotel: Discounted Room Rate: $265 s/d SPONSORSHIP Hilton San Diego Bayfront Discounted Cut-off Date: & EXHIBIT One Park Blvd. February 26, 2018 San Diego, CA 92101 For more reservation information: REGISTRATION Phone: 619-564-3333 Visit the Hotel & Travel page of DrugDiscoveryChemistry.com Click Here to register Online DrugDiscoveryChemistry.com

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COVER Sponsorship and Exhibit Opportunities CONFERENCE AT-A-GLANCE CHI offers comprehensive sponsorship packages which include presentation PLENARY KEYNOTES opportunities, exhibit space, branding and networking with specific prospects. Sponsorship allow you to achieve objectives before, during, and long after the SHORT COURSES event. Any sponsorship can be customized to meet your company’s needs and AGENDA budget. Signing on early will allow you to maximize your exposure to qualified April 3-4 Conferences »» Protein-Protein Interactions decision-makers. »» Inflammation & Autoimmune Sponsored Presentations – Available within the Main Agenda! Inhibitors Showcase your solutions to a guaranteed, targeted audience. Package includes a 15- or »» Kinase Inhibitor Chemistry 30-minute podium presentation within the scientific agenda, exhibit space, on-site branding, »» GPCR-Targeted Drug Design access to cooperative marketing efforts by CHI, and more. Additional Opportunities Available »» Fragment-Based Drug Discovery Luncheon Presentations for Sponsorship Include: • Plenary Keynote Introduction April 4-5 Conferences Opportunity includes a 30-minute podium presentation. Boxed lunches are delivered into »» Ubiquitin Proteasome System the main session room, which guarantees audience attendance and participation. A limited • Poster Awards Inhibitors number of presentations are available for sponsorship and they will sell out quickly. Sign on • Welcome Reception Sponsor »» Small Molecules for Cancer early to secure your talk! • Conference Tote Bags Immunotherapy • Badge Lanyards SOLD! »» Macrocyclics & Constrained Invitation-Only VIP Dinner/Hospitality Suite • Hotel Room Keys Peptides Sponsors will select their top prospects from the conference pre-registration list for an • Padfolios »» Targeting Complex evening of networking at the hotel or choice local venue. CHI will extend the invitations and Membrane Proteins • Program Guide Advertisements deliver prospects, helping you to make the most out of this invaluable opportunity. Evening • ...and more! April 6 Symposia will be customized according to sponsor’s objectives (i.e.: purely social, focus group, recep- » » Biophysical Approaches for tion style, or plated dinner with specific conversation focus). Drug Discovery »» Lead Optimization for Drug One-on-One Meetings Metabolism & Safety Select your top prospects from the pre-conference registration list. »» Blood-Brain Penetrant CHI will reach out to your prospects and arrange the meeting for you. Inhibitors A minimum number of meetings will be guaranteed, depending on For more information, please contact: HOTEL & TRAVEL your marketing objectives and needs. A very limited number of these packages will be sold. Carolyn Benton | Business Development Manager SPONSORSHIP [email protected] | 781-972-5412 & EXHIBIT EXHIBIT REGISTRATION Exhibitors will enjoy facilitated networking opportunities with 750+ qualified delegates, making it the perfect Click Here to register Online opportunity to launch a new product, collect feedback, and generate new leads DrugDiscoveryChemistry.com from around the globe. Get noticed as a leader in the industry with an 8’ x 20’ exhibit space. Exhibit space sells quickly, so reserve yours today!

A Division of Cambridge Innovation Institute DrugDiscoveryChemistry.com • 40 Save up to $200! Register by February 23 2017 Attendee Demographics

COVER 39% Scientist/Technologist CONFERENCE 39% Scientist/Technologist AT-A-GLANCE 29%29% Executive/Director Executive/Director 12%12% Sales Sales & Marketing & Marketing PLENARY KEYNOTES   10%10% Professor Professor 69% United States SHORT COURSES 6% Manager 4%6% Assistant Manager 15% Europe AGENDA 69% United States 4% Assistant 15%13% Europe Asia April 3-4 Conferences 13%3% AsiaRest of World »» Protein-Protein Interactions  3% Rest of World »» Inflammation & Autoimmune Inhibitors US BREAKDOWN »» Kinase Inhibitor Chemistry 48%48% West West Coast Coast »» GPCR-Targeted Drug Design 41%41% East East Coast Coast 11% Midwest »» Fragment-Based Drug 11% Midwest Discovery April 4-5 Conferences »» Ubiquitin Proteasome System 73% Biotech & Pharma Inhibitors 73% Biotech & Pharma »» Small Molecules for Cancer 19%19% Academic Academic & Government & Government Immunotherapy   4%4% Press, Press, Services, Services, & Societies & Societies »» Macrocyclics & Constrained 3%3% Healthcare Healthcare Peptides 1% Financials »» Targeting Complex 1% Financial Membrane Proteins April 6 Symposia »» Biophysical Approaches for Drug Discovery »» Lead Optimization for Drug Metabolism & Safety »» Blood-Brain Penetrant Current Sponsors & Exhibitors as of November 17, 2017 Inhibitors • Acrotein • BioSolveIT • Creoptix • Kalexsyn Inc. • Piramal • Simulations HOTEL & TRAVEL ChemBio Inc. • Biotage • Cresset • Key Organics Pharmasolutions Plus, Inc. SPONSORSHIP • Analyticon • Prestwick Chemical • Southwest & EXHIBIT • Bruker BioSpin • Frontier Scientific • LabNetwork Discovery LLC Corporation • Promega Research Institute REGISTRATION • GE Healthcare • Liverpool • Anton Paar USA Corporation • SpiroChem AG • Chemspace • HarkerBio ChiroChem Ltd. • Aptuit Inc • Chiral Technologies • Multispan, Inc. • Reaction Biology • Synthonix Click Here to register Online • Icagen Corporation DrugDiscoveryChemistry.com • Bio-Logic • Cisbio • OpenEye Scientific • WAC™ – Weak • IntelliSyn • Richman Chemical Affinity • Biodesy • Collaborative Drug • Optibrium Ltd. • JEOL USA, Inc. • Sai Life Sciences Chromatography • Biosensing Discovery, Inc. • Pharmablock Instrument • Jubilant Biosys Ltd • Scientist.com • ZoBio

A Division of Cambridge Innovation Institute DrugDiscoveryChemistry.com • 41 Save up to $200! Register by February 23 Drug Discovery Chemistry PRICING & REGISTRATION INFORMATION April 2-6, 2018 | Hilton San Diego Bayfront | San Diego, CA

CONFERENCE DISCOUNTS Premium Conference Pricing, *Best Value* (Includes access to two conferences, two short courses, and one symposium) Poster Submission – Discount ($50 Off): COVER Commercial Academic, Government, Hospital Affiliated Poster abstracts are due by February 23, 2018. Once your registration has been CONFERENCE Advance Rate until February 23 $3249 $2099 fully processed, we will send an email AT-A-GLANCE Registrations after February 23 $3349 $2199 containing a unique link allowing you to submit your poster abstract. If you do PLENARY KEYNOTES not receive your link within 5 business Standard Conference Pricing (Includes access to two conferences, excludes short courses and symposia) days, please contact jring@healthtech. SHORT COURSES Advance Rate until February 23 $2449 $1199 com. *CHI reserves the right to publish your poster title and abstract in various AGENDA Registrations after February 23 $2649 $1299 marketing materials and products. April 3-4 Conferences Register 3 – 4th Is Free: Individuals Basic Conference Pricing (Includes access to one conference, excludes short courses and symposia) »» Protein-Protein Interactions must register for the same conference or conference combination and submit »» Inflammation & Autoimmune Advance Rate until February 23 $1849 $999 completed registration form together for Inhibitors Registrations after February 23 $1949 $1099 discount to apply. »» Kinase Inhibitor Chemistry Alumni Discount: Cambridge Healthtech Institute (CHI) appreciates your »» GPCR-Targeted Drug Design Short Course Pricing (April 2 & 4) past participation at Drug Discovery »» Fragment-Based Drug 1 Short Course $699 $399 Chemistry. As a result of the great loyalty Discovery you have shown us, we are pleased to 2 Short Courses $999 $699 extend to you the exclusive opportunity April 4-5 Conferences 3 Short Courses $1199 $799 to save an additional 20% off the »» Ubiquitin Proteasome System registration rate. Inhibitors Symposium Pricing (April 6) Group Discounts: Discounts are available for multiple attendees from the same »» Small Molecules for Cancer 1 Symposium $999 $599 Immunotherapy organization. For more information on PROGRAM SELECTIONS group rates contact Elizabeth Lemelin at »» Macrocyclics & Constrained 781-972-5488. Peptides Afternoon Short Courses Concurrent Conferences Concurrent Conferences Concurrent Symposia ADDITIONAL REGISTRATION DETAILS »» Targeting Complex (April 2) (April 3-4) (April 4-5) (April 6) Each registration includes all conference Membrane Proteins SC1: Ligand-Receptor Molecular sessions, posters and exhibits, food April 6 Symposia Interactions and Drug Design C6: Ubiquitin Proteasome System S1: Biophysical Approaches for Drug functions, and access to the conference C1: Protein-Protein Interactions proceedings link. Handicapped »» Biophysical Approaches for SC2: Advancing Tools and Inhibitors Discovery Technology for Fragment-Based Equal Access: In accordance with Drug Discovery the ADA, Cambridge Healthtech Design C2: Inflammation & Autoimmune C7: Small Molecules for Cancer S2: Lead Optimization for Drug Institute is pleased to arrange special »» Lead Optimization for Drug SC3: Drug Metabolism and Its Impact Inhibitors Immunotherapy Metabolism & Safety accommodations for attendees with Metabolism & Safety on Decisions in Lead Discovery and special needs. All requests for such » Drug Development C8: Macrocyclics & Constrained » Blood-Brain Penetrant C3: Kinase Inhibitor Chemistry S3: Blood-Brain Penetrant Inhibitors assistance must be submitted in Inhibitors SC4: Diversity-Oriented Platforms for Peptides writing to CHI at least 30 days prior to Ligand Discovery the start of the meeting. To view our C9: Targeting Complex Membrane HOTEL & TRAVEL Dinner Short Courses C4: GPCR-Targeted Drug Design Substitutions/ Cancellations Policy, go to (April 2) Proteins healthtech.com/regdetails Video and or SPONSORSHIP SC5: Immunology Basics for audio recording of any kind is prohibited Chemists onsite at all CHI events. & EXHIBIT C5: Fragment-Based Drug Discovery SC6: Introduction to Allosteric If you are unable to attend but REGISTRATION Modulators and Biased Ligands of would like to purchase the Drug GPCRs Dinner Short Courses (April 4) Discovery Chemistry CD for $750 SC9: Impact of Convergence of Immunology & Epigenetics in Drug Discovery SC7: Introduction to Targeted (plus shipping), please visit Click Here to register Online Covalent Inhibitors SC10: Enabling Macrocyclic Compounds for Drug Discovery: Opportunities, DrugDiscoveryChemistry.com. SC8: Introduction to the Ubiquitin Challenges & Strategies Massachusetts delivery will include DrugDiscoveryChemistry.com Proteasome System SC11: Trends in Physical Properties of Drugs sales tax. SC12: Covalent Fragments: Applications in Target-Based and Phenotypic Screens

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