Final Weeks to Register EVENT 350+ 20 1 2 13 80+ 1,300+ FEATURES Speakers Conference Training Symposia Short Exhibiting Attendees Tracks Seminar Courses Companies Cover Conference At-A-Glance 16th Annual Sponsorship & Exhibit Short Courses Symposia The Industry’s Training Seminar Preeminent Event on Plenary Keynotes Novel Drug Targets Agenda Disc very »» Small Molecules for Cancer September 25-28, 2018 Immunotherapy on »» Autoimmune and Inflammation Sheraton Boston Drug Targets Boston, MA »» NK Cell-Based Cancer TARGET Immunotherapy »» Targeting Tumor Myeloid Cells »» Targeting the Ubiquitin- Proteasome System »» Kinase Inhibitor Discovery »» CNS and Neurodegenerative Targets »» GPCR-Based Drug Discovery »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 CONFERENCE TRACKS & SYMPOSIA »» Antibacterial Discovery and Development Immunotherapy Target-Based  Hot & Emerging Antibodies »» Targeting Gram-Negative Discovery & Validation Pathogens »» NASH and Fibrosis • Small Molecules for Cancer • Antivirals: Targeting HBV • Antibody Discovery Forum - »» Targeting the Microbiome Immunotherapy • Targeting the Ubiquitin- and Beyond Part 1 & Part 2 »» Antibody Discovery Forum - • Autoimmune and Inflammation Proteasome System • Targeting Autophagy • Antibodies Against Membrane Part 1 & Part 2 Drug Targets • Kinase Inhibitor Discovery • Antibacterial Discovery Protein Targets - Part 1 & Part 2 »» Antibodies Against Membrane • NK Cell-Based Cancer • CNS and Neurodegenerative and Development Protein Targets - Part 1 & Part 2 Immunotherapy Targets • Targeting Gram-Negative Hotel & Travel • Targeting Tumor Myeloid Cells • GPCR-Based Drug Discovery Pathogens • Constrained Peptides and • NASH and Fibrosis Registration Information Macrocyclics • Targeting the Microbiome Premier Sponsors: • Lead Generation Strategies Click Here to Register • Target Identification and DiscoveryOnTarget.com Validation - Part 1 & Part 2 DiscoveryonTARGET.com Final Agenda

A Division of Cambridge Innovation Institute Final Weeks 16th Annual to Register September 25-28, 2018 • Sheraton Boston • Boston, MA The Industry’s Preeminent Cover Disc veryonTARGET Event on Novel Drug Targets #BostonDOT18 Conference At-A-Glance ABOUT THE EVENT Cambridge Healthtech Institute’s 16th Annual Discovery on Target, “The Industry’s Preeminent Sponsorship & Exhibit Event on Novel Drug Targets,” will once again gather over 1,300 drug discovery professionals in Boston, MA, Short Courses this September 25-28, 2018. The event brings forth current and Symposia emerging “hot” targets, technologies and validation strategies for the Training Seminar development of novel small molecules and biologics. Plenary Keynotes Agenda CONFERENCE AT-A-GLANCE »» Small Molecules for Cancer CONFERENCE CHANNELS Immunotherapy Pre-Conference Symposia »» Autoimmune and Inflammation Drug Targets Immunotherapy Hot & Emerging Antivirals: Targeting »» NK Cell-Based Cancer Targeting Autophagy Regenerative Medicine TUESDAY HBV and Beyond Immunotherapy September 25 Target-Based  »» Targeting Tumor Myeloid Cells Antibodies Pre-Conference Short Courses Discovery & Validation »» Targeting the Ubiquitin- Proteasome System »» Kinase Inhibitor Discovery Immunotherapy Target-Based Discovery & Validation Hot & Emerging Antibodies Training Seminars »» CNS and Neurodegenerative Targets Small NK Targeting Target Antibodies CNS and Constrained Antibacteri- Antibody »» GPCR-Based Drug Discovery Molecules Cell-Based the Identifica- Against WEDNESDAY Neurode- Peptides al Discovery NASH and Discovery »» Constrained Peptides and for Cancer Cancer Ubiquitin- tion and Membrane September 26 generative and Mac­ and Devel- Fibrosis Forum Macrocyclics Immuno- Immuno- Proteasome Validation Protein TS1: Machine Targets rocyclics opment - PART 1 »» Lead Generation Strategies therapy therapy System - PART 1 Targets - PART 1 Learning »» Target Identification and for Effective Drug Validation - Part 1 & Part 2 Small NK Targeting Target Anti- Antibodies CNS and Constrained Antibody Discovery »» Antibacterial Discovery and Molecules Cell-Based the Identifica- bacterial NASH Against Decisions Neurode- Peptides Discovery Development for Cancer Cancer Ubiquitin- tion and Discovery and Membrane generative and Mac­ Forum »» Targeting Gram-Negative Immuno- Immuno- Proteasome Validation and Devel- Fibrosis Protein Targets rocyclics - PART 1 Pathogens therapy therapy System - PART 1 opment Targets - PART 1 »» NASH and Fibrosis »» Targeting the Microbiome Plenary Keynote Program THURSDAY »» Antibody Discovery Forum - September 27 Part 1 & Part 2 Autoim- Target Antibodies TS2: Targeting Targeting Targeting Antibody »» Antibodies Against Membrane mune and Kinase GPCR- Lead Identifica- Against Introduction Tumor Gram- the Discovery to Small Protein Targets - Part 1 & Part 2 Inflamma- Inhibitor Based Drug Generation tion and Membrane Myeloid Negative Microbi- Forum Molecule tion Drug Discovery Discovery Strategies Validation Protein Drug Dis- Cells Pathogens ome - PART 2 covery and Hotel & Travel Targets PART 2 Targets PART 2 - - Development

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Click Here to Register Autoim- Target Antibodies TS2: Targeting Targeting Targeting Antibody Introduction DiscoveryOnTarget.com mune and Kinase GPCR- Lead Identifica- Against FRIDAY Tumor Gram- the Discovery to Small Inflamma- Inhibitor Based Drug Generation tion and Membrane Molecule September 28 Myeloid Negative Microbi- Forum tion Drug Discovery Discovery Strategies Validation Protein Drug Dis- Cells Pathogens ome - PART 2 covery and Targets - PART 2 Targets - PART 2 Development

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Cover PREMIER SPONSORS Conference At-A-Glance Sponsorship & Exhibit Short Courses Symposia Training Seminar Plenary Keynotes CORPORATE SPONSORS Agenda »» Small Molecules for Cancer Immunotherapy »» Autoimmune and Inflammation Drug Targets »» NK Cell-Based Cancer Immunotherapy »» Targeting Tumor Myeloid Cells »» Targeting the Ubiquitin- Proteasome System »» Kinase Inhibitor Discovery »» CNS and Neurodegenerative Targets »» GPCR-Based Drug Discovery »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2 CORPORATE SUPPORT SPONSORS

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A Division of Cambridge Innovation Institute Sponsors & Exhibitors DiscoveryOnTarget.com • 3 Final Weeks to Register SPONSOR, EXHIBIT AND LEAD GEN OPPORTUNITIES Exhibit Information View Floorplan Comprehensive sponsorship packages allow you to achieve your objectives Cover before, during, and long after the event. Signing on earlier will allow you Conference Register as an Exhibitor At-A-Glance to maximize exposure to hard-to-reach decision-makers. Sponsorship & Exhibit Short Courses Podium Presentations—Available within Main Agenda! Symposia Showcase your solutions to a guaranteed, targeted audience through a 15- or 30-minute presentation during a specific conference program, breakfast, lunch, Training Seminar or separate from the main agenda within a pre-conference workshop. Package includes exhibit space, Looking for additional ways to Plenary Keynotes on-site branding, and access to cooperative marketing efforts by CHI. For the luncheon option, lunches are drive leads to your sales team? Agenda delivered to attendees who are already seated in the main session room. Presentations will sell out quickly, so sign on early to secure your talk! »» Small Molecules for Cancer CHI’s Lead Generation Programs will help you Immunotherapy One-on-One Meetings obtain more targeted, quality leads throughout »» Autoimmune and Inflammation Select your top prospects from the pre-conference registration list. CHI will reach out to your prospects the year. We will mine our database of Drug Targets and arrange the meeting for you. A minimum number of meetings will be guaranteed, depending on your 800,000+ life science professionals to your »» NK Cell-Based Cancer marketing objectives and needs. A very limited number of these packages will be sold. Immunotherapy specific needs. We guarantee a minimum of »» Targeting Tumor Myeloid Cells Invitation-Only VIP Dinner/Hospitality Suite 100 leads per program! Opportunities include: »» Targeting the Ubiquitin- Sponsors will select their top prospects from the conference pre-registration list for an evening of network- Proteasome System ing at the hotel or at a choice local venue. CHI will extend invitations and deliver prospects, helping you to • Live Webinars • Market Surveys »» Kinase Inhibitor Discovery make the most out of this invaluable opportunity. The evening will be customized according to sponsor’s • White Papers • Podcasts and More! »» CNS and Neurodegenerative objectives (i.e., Purely social, Focus group, Reception style, Plated dinner with specific conversation focus) Targets »» GPCR-Based Drug Discovery Additional branding & promotional opportunities include: »» Constrained Peptides and • Hotel Room Keys • Badge Lanyards • Padfolios For more information regarding exhibit Macrocyclics • Footprint Trails • Literature Distribution • Program Guide Advertisement and sponsorship, please contact: »» Lead Generation Strategies • Conference Tote Bags (Tote Bag Insert or Chair Drop) »» Target Identification and Rod Eymael Validation - Part 1 & Part 2 Business Development Manager »» Antibacterial Discovery and Development EXHIBIT 781.247.6286 »» Targeting Gram-Negative Exhibitors will enjoy facilitated [email protected] Pathogens networking opportunities with »» NASH and Fibrosis 1,300+ qualified delegates, making »» Targeting the Microbiome it the perfect platform to launch a »» Antibody Discovery Forum - new product, collect feedback, and Part 1 & Part 2 DELEGATE TITLE »» Antibodies Against Membrane generate new leads from around the world. Exhibit space sells out quickly, 36% Executive & Director Protein Targets - Part 1 & Part 2 31% Scientist/Technologist so reserve yours today! DELEGATE TITLE 13% Sales & Marketing Hotel & Travel COMPANY TYPE 2017 ATTENDEE DEMOGRAPHICS 9% Professor Registration Information LOCATION 8% Manager COMPANY TYPE 3% Assistant LOCATION Click Here to Register 72% Biotech & Commercial 79% DiscoveryOnTarget.com 14% Academic & Government11% 79% United States US BREAKDOWN 8% 2% 7% Healthcare United States 11% Europe 70% East Coast Europe 4% Service & Societies Asia 8% Rest of World Asia 19% West Coast 2% Financial 2% Rest of World 11% Midwest 36% Executive & Director 1% Press US BREAKDOWN 70% 31% Scientist/Technologist 72% 19% Biotech & Commercial 11% 13% Sales & Marketing 14% Academic & Government A Division of Cambridge Innovation Institute Sponsors & Exhibitors East Coast DiscoveryOnTarget.com • 9% Professor 4 7% Healthcare West Coast Midwest 8% Manager 4% Service & Societies 3% Assistant 2% Financial 1% Press SHORT COURSES* » September 25 & 27 Final Weeks to Register Our short courses are designed to be instructional, interactive and provide in-depth information on a specific topic. They allow for one-on-one interaction and provide a great way to explain more Cover technical aspects that would otherwise not be covered during our main presentations. Conference At-A-Glance Sponsorship & Exhibit Short Courses PRE-CONFERENCE SHORT COURSES what worked, what didn’t and what you need to assays to enable isolation of binding antibodies, Symposia consider when setting up low- and high-throughput including use of recombinant stable cell lines; 3) in | TUESDAY, SEPTEMBER 25 | screening experiments using 3D cell cultures in your vitro assays to measure functional activity of the Training Seminar 2:00 - 5:00 PM lab. The challenges working with 3D cell cultures, from antibody, including use of electrophysiology platforms Plenary Keynotes experimental design to data analysis will be discussed. and ion flux methods; and 4) review of promising Instructors: Madhu Lal-Nag, PhD, Group Leader, ligand-gated and voltage-gated ion channel targets Agenda SC1: INTRODUCTION TO GPCR- Trans-NIH RNAi Facility, National Center for Advancing and antibodies in development. Open discussion will »» Small Molecules for Cancer BASED DRUG DISCOVERY Translational Sciences, National Institutes of Health be actively encouraged. Immunotherapy This course will provide an understanding for some of Geoffrey Bartholomeusz, PhD, Associate Professor and Instructor: Trevor Wilkinson, PhD, Associate Director, »» Autoimmune and Inflammation the pharmacological complexities of G protein-coupled Director, Target Identification and Validation Program, Antibody Discovery and Protein Engineering, Drug Targets receptors (GPCRs) as well as for the tools used to Department of Experimental Therapeutics, Division of Medimmune Ltd., United Kingdom »» NK Cell-Based Cancer study them in a drug discovery setting. The course Cancer Medicine, The University of Texas MD Anderson Immunotherapy is well suited for biologists, pharmacologists and Cancer Center SC9: CNS TRANSLATIONAL »» Targeting Tumor Myeloid Cells medicinal chemists who have recently started working with GPCRs or for those who need a refresher on the STRATEGIES »» Targeting the Ubiquitin- PRE-CONFERENCE DINNER SHORT A greater understanding of CNS-related disease Proteasome System latest technological advances and newest paradigms. Instructor: Annette Gilchrist, PhD, Professor, COURSES | TUESDAY, SEPTEMBER 25 | biology and the emergence of new, improved targets »» Kinase Inhibitor Discovery Pharmacology, Midwestern University 6:00 - 8:30 PM and technologies has bought renewed interest in »» CNS and Neurodegenerative neuroscience. This short course describes the critical Targets SC2: DRUG METABOLISM AND ITS stages needed to translate an exciting CNS target into »» GPCR-Based Drug Discovery SC8: TARGETING OF ION CHANNELS an effective CNS therapy by addressing challenges »» Constrained Peptides and ROLE IN DISCOVERY AND DRUG WITH MONOCLONAL ANTIBODIES in biomarkers design and validation, modelling, Macrocyclics DEVELOPMENT Ion channels are important therapeutic targets imaging and methods to bridge the preclinical/clinical »» Lead Generation Strategies This short course will focus on concepts important for and currently represent the second largest target translation gap. »» Target Identification and those wanting to understand how drug metabolism is class addressed by therapeutic drugs. Significant Instructors: Chongzhao Ran, PhD., Assistant Professor Validation - Part 1 & Part 2 applied to drug discovery and development. Topics will opportunities exist for targeting ion channels with of Radiology, Massachusetts General Hospital, »» Antibacterial Discovery and include how drugs are metabolized, what enzymes are antibodies, but to date it has been challenging to Harvard Medical School Development involved, how drug metabolism concepts are applied discover therapeutic antibodies against them. This Changning Wang, PhD, Assistant Professor, »» Targeting Gram-Negative during lead optimization, how drug metabolites are course will examine emerging technologies and Radiology, Massachusetts General Hospital, Harvard Pathogens identified in preclinical studies and human clinical strategies for enabling the isolation of functional anti- Medical School »» NASH and Fibrosis trials, the role of bioactivation in drug toxicity and ion channel antibodies and highlight progress via case Vanita Chopra, PhD., Assistant Professor, Neurology, »» Targeting the Microbiome the growing application of in silico tools in drug studies. The topics to be covered include: 1) antibody Massachusetts General Hospital, Harvard »» Antibody Discovery Forum - metabolism. Those scientists involved in medicinal discovery, including methods to generate monoclonal Medical School chemistry, pharmacology and drug metabolism will antibodies and antigen preparation strategies; 2) Part 1 & Part 2 benefit from this overview. »» Antibodies Against Membrane Instructor: John C. L Erve, PhD, DABT, Consultant, Jerve Protein Targets - Part 1 & Part 2 Scientific Consulting, Inc. Hotel & Travel HOTEL & TRAVEL SC3: HOW TO BEST UTILIZE 3D Sheraton Boston Hotel Registration Information CELLS, SPHEROIDS, AND PDX 39 Dalton Street MODELS IN ONCOLOGY Boston, MA 02199 Click Here to Register The course will provide an overview of 3D cell culture T: 617-236-2000 DiscoveryOnTarget.com and spheroid models currently available and where Discounted Room Rate: $329 and how these models are being used, specifically for oncology research. The instructors will share Reservation Cutoff: August 29, 2018 their experiences on how they tested and evaluated For more information, visit DiscoveryOnTarget.com various cell culture reagents and growth matrices,

A Division of Cambridge Innovation Institute Short Courses urses | HOTEL & TRAVEL * Separate registration required DiscoveryOnTarget.com • 5 SHORT COURSES* » September 25 & 27 Final Weeks to Register

SC10: APPLICATIONS OF ARTIFICIAL design of these probes for preclinical and clinical SC15: INTRODUCTION TO TARGETED Cover studies will also be discussed. INTELLIGENCE AND MACHINE COVALENT INHIBITORS Conference Instructor: Alexander Statsyuk, PhD, Assistant Professor, LEARNING IN DRUG DISCOVERY AND Department of Pharmacological and Pharmaceutical Covalent inhibitors of kinases have re-emerged At-A-Glance as a drug design strategy due to more examples DEVELOPMENT Sciences, University of Houston Sponsorship & Exhibit of their safety and efficacy in patients. Covalent This course aims to educate a diverse group of DINNER SHORT COURSES | THURSDAY, inhibitors have the advantage of increased selectivity Short Courses scientists-chemists, biologists, toxicologists, and and longer action of duration but there are still those involved in translational and clinical research, Symposia SEPTEMBER 27 | 7:00 - 9:30 PM important issues about their design and application about the growing use and applications of AI and ML. that need to be better understood. This course will Training Seminar Talks start with explaining the basic terminology used SC13: GPCR STRUCTURE-BASED cover practical as well as theoretical issues that a and what it means, followed by discussions separating Plenary Keynotes DRUG DISCOVERY medicinal chemist needs to keep in mind in developing the hope from the hype. It goes into the caveats and covalent inhibitors. Agenda Recent breakthroughs in obtaining high-resolution limitations in AI and ML, while exploring ways in which Instructor: Mark Schnute, PhD, Associate Research »» Small Molecules for Cancer it can be successfully applied in the drug discovery structures of G protein-coupled receptors (GPCRs) by both X-ray crystallography and Cryo-EM, are rapidly Fellow, Medicine Design, Inflammation & Immunology Immunotherapy and development pipeline. There will be experts from impacting the pharmaceutical industry. This course Research, Pfizer, Inc. »» Autoimmune and Inflammation various areas presenting case studies on how they will review how GPCR structures elucidated to date Drug Targets have used AI/ML tools for lead optimization, target have informed our current understanding of GPCR SC16: IMMUNOLOGY BASICS »» NK Cell-Based Cancer discovery, visualizing and classifying large datasets, Immunology is a difficult subject to master, even for patient stratification and more. function. The course will also provide examples of Immunotherapy how GPCR structural information is being applied to immunologists. Newly discovered cell types and their »» Targeting Tumor Myeloid Cells Instructors: Arvind Rao, PhD, Associate Professor, associated function in human health and disease Department of Computational Medicine and guide rational approaches for GPCR drug discovery. »» Targeting the Ubiquitin- Another course focus is on new biophysical have been continuously revealed over the last decade. Proteasome System Bioinformatics, University of Michigan In this course immunologists (non-physicians) with Jin Yao, PhD, Scientific Investigator, Computational techniques that provide complementary information »» Kinase Inhibitor Discovery extensive experience in the biopharmaceutical drug Biology and Statistics, Target Sciences, GSK on GPCR dynamics and function. Recent examples of »» CNS and Neurodegenerative discovery and development will break it down for Anna Basile, PhD, Postdoctoral Research Scientist nuclear magnetic resonance (NMR) and the impact Targets you by filling the gaps that most chemists have. Department of Biomedical Informatics Columbia of other biophysical techniques on drug discovery »» GPCR-Based Drug Discovery It’s not a comprehensive course – but hopefully University will be shared. »» Constrained Peptides and Instructors: Matthew Eddy, PhD, Assistant Professor, better – a useful course. The focus will range from basic background biology and terminology that Macrocyclics SC11: MECHANISTIC Chemistry, University of Florida »» Lead Generation Strategies Huixian Wu, PhD, Principal Scientist, Structural and immunologists take for granted and then jump »» Target Identification and UNDERSTANDING OF Molecular Sciences, Discovery Sciences, Pfizer, to the biological underpinnings of the areas and targets a lot of medicinal chemists are developing Validation - Part 1 & Part 2 PHARMACOLOGICAL Inc. Groton compounds against. »» Antibacterial Discovery and PROBES FOR THE UBIQUITIN- Instructors: Songqing Na, PhD, Senior Scientist, Development SC14: ADVANCING TOOLS AND PROTEASOME SYSTEM Biotechnology & Autoimmunity Res-AME, Eli Lilly »» Targeting Gram-Negative This course is intended for the audience interested in TECHNOLOGIES FOR FRAGMENT- and Company Pathogens drug discovery programs aimed to develop PROTACs BASED DESIGN Thomas Sundberg, PhD, Senior Research Scientist I, »» NASH and Fibrosis (molecular degraders) and/or small molecule This course aims to introduce the fundamentals of Center for Development of Therapeutics, Broad Institute »» Targeting the Microbiome inhibitors targeting components of the ubiquitin- Fragment-Based Lead Discovery (FBLD) to attendees. of MIT and Harvard »» Antibody Discovery Forum - proteasome system (UPS). This course will cover basic The first section will focus on the concepts of using Part 1 & Part 2 mechanistic biochemistry of the ubiquitin-proteasome fragments for hit generation. Special emphasis will SC17: TECHNOLOGIES TO ASSESS »» Antibodies Against Membrane system, which includes E1, E2, E3, and deubiquitinating be placed on practical pitfalls and the many ways to PERMEABILITY AND EFFLUX IN Protein Targets - Part 1 & Part 2 enzymes, and their macromolecular architecture. advance fragments to leads and drugs. The second Subsequently, the course will transition into a general part of the course will discuss the variety of fragment GRAM-NEGATIVE BACTERIAL Hotel & Travel discussion of existing biochemical assays and screening methods and when they are best applied. PATHOGENS technologies to discover PROTACs and small molecule The composition of fragment libraries will also be Our lack of understanding of the molecular basis Registration Information inhibitors of E1, E2, E3, and deubiquitinating enzymes. discussed in detail. The attendees should come away for compound penetration into and efflux out of Finally, existing PROTACs and pharmacological probes from this course with a solid understanding of what gram-negative bacteria has been identified as a Click Here to Register targeting E1, E2, E3, and deubiquitinating enzymes, FBLD is and how to apply it. key bottleneck for the rational discovery of novel DiscoveryOnTarget.com their pharmacological properties, and basic control Instructors: Daniel A. Erlanson, PhD, Co-Founder, Carmot antibacterial compounds. A main driver of this experiments that need to be done to inform a better Therapeutics, Inc. knowledge gap is the historical lack of assays, Mary Harner, PhD, Research Investigator II, Mechanistic tools, and/or predictive models to provide medicinal Biochemistry, Bristol-Myers Squibb R&D chemists with structure-activity relationships that

A Division of Cambridge Innovation Institute Short Courses * Separate registration required DiscoveryOnTarget.com • 6 SHORT COURSES* » September 25 & 27 Final Weeks to Register

could guide optimization of whole cell penetration (and Cover efflux avoidance). However, there have been some Conference recent, promising advances in the field which set the At-A-Glance stage for future innovative approaches. Instructors: David Six, PhD, Investigator III, Infectious Sponsorship & Exhibit Diseases, Novartis Institutes for BioMedical Research Short Courses Ram Iyer, PhD, Principal Scientist (Bacteriology), Entasis Therapeutics, Inc. Symposia Training Seminar SC18: PRACTICAL PHENOTYPIC Plenary Keynotes SCREENING Phenotypic drug discovery is experiencing a Agenda Renaissance in the pharmaceutical industry, based »» Small Molecules for Cancer on its successful track record in delivering first-in- Immunotherapy class medicines. This approach offers the promise »» Autoimmune and Inflammation of delivering both novel targets and chemical Drug Targets matter modulating a disease phenotype of interest. »» NK Cell-Based Cancer Although phenotypic screening may appear at first Immunotherapy sight to be similar to target-based screening, there »» Targeting Tumor Myeloid Cells are some significant differences between the two »» Targeting the Ubiquitin- approaches. These need to be properly considered Proteasome System and addressed to ensure the greatest likelihood of success for phenotypic drug discovery programs. »» Kinase Inhibitor Discovery This presentation will cover a range of relevant topics »» CNS and Neurodegenerative with a goal of providing practical information to help Targets prosecute such programs more effectively. »» GPCR-Based Drug Discovery Instructor: Fabien Vincent, PhD, Associate Research »» Constrained Peptides and Fellow, Hit Discovery and Lead Profiling Group, Macrocyclics Pfizer, Inc. »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Short Courses * Separate registration required DiscoveryOnTarget.com • 7 SYMPOSIA » September 25 Final Weeks to Register Back by popular demand are focused, one-day pre-conference symposia, designed to highlight areas of discovery research currently capturing the interest of developers, and poised to grow in importance over the next few years. Pre-conference symposia complement topics covered during main conference meetings, and can be Cover combined to provide a robust and comprehensive four days of unique programing based on personal interest. Conference At-A-Glance Sponsorship & Exhibit Short Courses 2nd Annual | September 25 TARGETING THE RNA AND 10:15 Preclinical Antiviral Profile of the Novel HBV Symposia Core Inhibitor EP-027367 Antivirals: Targeting PROTEINS OF HEPATITIS B VIRUS Michael Vaine, PhD, Principal Scientist, Virology, Enanta Training Seminar HBV and Beyond 9:00 Welcome Remarks Pharmaceuticals Plenary Keynotes New Drug Development for Anjani Shah, PhD, Conference Director, Cambridge EP-027367 is a novel HBV inhibitor that modulates Healthtech Institute capsid assembly and other core protein functions. In Agenda Infectious Diseases vitro, it inhibits rcDNA production with low double digit »» Small Molecules for Cancer 9:05 Chairperson’s Opening Remarks Antiviral drug development is shifting its focus to David B. Smith, PhD, Vice President, Global Research and nanomolar activity, is active across HBV genotypes Immunotherapy hepatitis B virus (HBV) after the encouraging success Development Leader, Hepatitis, Alios BioPharma Inc., A-H, nucleos(t)ide resistant variants, and inhibits »» Autoimmune and Inflammation of developing direct-acting antivirals against the part of the Janssen Pharmaceutical Companies nascent cccDNA formation in infectable cell lines. In Drug Targets hepatitis C virus. Both viruses cause liver disease and a human liver, chimeric mouse model, EP-027367 can »» NK Cell-Based Cancer reduce circulating HBV titers by up to 3-logs with 28 represent major global health problems that can lead 9:15 KEYNOTE PRESENTATION: New Directions Immunotherapy to death from liver failure. Progress has been made days of treatment. »» Targeting Tumor Myeloid Cells towards a Functional Cure for Chronic in several HBV-specific approaches such as RNAi to Hepatitis B 10:45 Sponsored Presentation (Opportunity Available) »» Targeting the Ubiquitin- silence HBV gene production, or inhibitors of the virus’s Proteasome System Jan Martin Berke, PhD, Principal Scientist, 11:00 Networking Coffee Break with Poster Viewing capsid assembly, some of which are in early-stage Hepatitis Discovery, Janssen Research & »» Kinase Inhibitor Discovery clinical trials. Advances are also occurring in more Development, Beerse, Belgium »» CNS and Neurodegenerative DIRECT-ACTING broadly applicable antiviral approaches, especially While approximately 260 million individuals Targets ANTIVIRALS FOR HBV those that modulate the host immune system. Join this worldwide are chronically infected with the »» GPCR-Based Drug Discovery symposium to stay abreast of new drug development Hepatitis B virus, current regimens provide only 11:30 AB-452: A Selective Small-Molecule »» Constrained Peptides and in the HBV and broader infectious disease field and to a fraction of patients with functional cure, loss Destabilizer of HBV Viral RNA Macrocyclics share insights and strategies with fellow researchers. of S-antigen and suppression of the virus in Min Gao, PhD, Senior Scientist, Biology, Arbutus »» Lead Generation Strategies the absence of continued treatment. With the Biopharma, Inc. »» Target Identification and AB-452 is a potent HBV RNA destabilizer. It is RECOMMENDED ALL ACCESS goal of developing finite duration combination Validation - Part 1 & Part 2 regimens that deliver a higher rate of functional inactive against a panel of DNA and RNA viruses, »» Antibacterial Discovery and PACKAGE: Choose 2 Short Courses cure, multiple mechanism of action agents are demonstrating the specificity of AB-452. Since AB-452 Development or 1 Symposium and 2 Conferences/ currently in development. This presentation will promotes the degradation of HBV RNAs, especially sRNA and consequently, inhibits multiple stages »» Targeting Gram-Negative Training Seminars overview progress to date in this area. Pathogens of viral life cycle in vitro and in vivo, combination »» NASH and Fibrosis • September 25 Symposium: Antivirals: regimens containing AB-452 could not only further »» Targeting the Microbiome Targeting HBV and Beyond 9:45 Antiviral Activities of AB-506, a Next Generation inhibit HBV DNA replication and potentially increase »» Antibody Discovery Forum - • September 26-27 Conference: HBV Capsid Inhibitor, in Combination with AB-452, an the cure rate, but also provide an opportunity to HBV RNA Destabilizer, Nucleos(t)ide Analogs and the shorten the treatment duration. Part 1 & Part 2 NASH and Fibrosis RNAi Agent ARB-1467 »» Antibodies Against Membrane 12:00 pm Using siRNA to Target the • September 27-28 Conference: Autoimmune René Rijnbrand, PhD, Vice President, Biology, Arbutus Protein Targets - Part 1 & Part 2 and Inflammation Drug Targets HBV Transcriptome Biopharma Inc. James C. Hamilton, MD, MBA, Vice President Clinical Hotel & Travel Increasing HBV cure rates will require a combination Development, Arrowhead Pharmaceuticals Tuesday, September 25 regimen that blocks viral replication, reduce s antigen Hepatocyte targeted siRNA therapeutics can be used Registration Information levels, starve cccDNA formation and activate immune to silence HBV viral mRNA transcripts leading to 8:00 am Pre-Conference Symposia and Short responses to eliminate cccDNA. Capsid inhibitor AB- reduction in serum antigen levels and inhibition of Course Registration 506 in combination with RNA destabilizer AB-452, NAs viral replication. This mRNA silencing effect applies Click Here to Register or the RNAi agent ARB-1467 using HBV cell culture DiscoveryOnTarget.com 8:00 Morning Coffee to the entire viral transcriptome including transcripts and animal models showed additive to synergistic derived from integrated DNA and cccDNA which may antiviral activity. These data suggest that these agents be important in generating functional cures are mechanistically compatible and may be used for treatment in a combination regimen.

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Cover 12:30 HBV Ribonuclease H: Drug Discovery and 4:25 Closing Comments Tuesday, September 25 Target Validation 4:30 Close of Symposium Conference John Tavis, PhD, Professor of Molecular Virology, 8:00 am Pre-Conference Symposia and Short At-A-Glance Department of Molecular Microbiology and Immunology, 5:00 Pre-Conference Dinner Short Course Registration Course Registration Sponsorship & Exhibit St. Louis University School of Medicine 8:00 Morning Coffee HBV replication requires the viral ribonuclease H Click here for details on short courses offered. Short Courses (RNaseH), but no anti-RNaseH drugs exist. We 2nd Annual | September 25 UNDERSTANDING THE CELLULAR Symposia developed assays to measure RNaseH activity and identify HBV replication inhibitors. >100 inhibitors EFFECTS OF TARGETING Training Seminar Targeting Autophagy were found, the best having an EC50 of 110 nM and AUTOPHAGY Understanding and Modulating Plenary Keynotes a therapeutic index of 390. RNaseH inhibitors are 9:00 Welcome Remarks synergistic with nucleos(t)ide analogs, insensitive to Autophagy Pathways for Agenda Tanuja Koppal, PhD, Conference Director, Cambridge HBV’s genetic diversity, and can suppress HBV viremia Drug Discovery Healthtech Institute »» Small Molecules for Cancer in infected humanized mice, so the RNaseH is a Immunotherapy promising target for novel drug development. Autophagy has been shown to play a role in many 9:05 Chairperson’s Opening Remarks »» Autoimmune and Inflammation Jeff MacKeigan, PhD, Professor of Cancer Biology 1:00 Sponsored Presentation (Opportunity Available) diseases, such as cancer, autoimmune, CNS, Drug Targets metabolic and infectious disorders. However, targeting and Complex Diseases, College of Human Medicine, »» NK Cell-Based Cancer 1:00 Pre-Conference Short Course Registration autophagy is complex because there are different Michigan State University Immunotherapy Click here for details on short courses offered. types of autophagy and they all involve various cellular 9:15 Autophagy in Cancer: Known and Unique Targets »» Targeting Tumor Myeloid Cells 1:15 Enjoy Lunch on Your Own pathways that are not well understood. Many studies Jeff MacKeigan, PhD, Professor of Cancer Biology »» Targeting the Ubiquitin- have shown that autophagy can also have a binary and Complex Diseases, College of Human Medicine, Proteasome System STIMULATING HOST function, for instance, acting as a tumor suppressor Michigan State University »» Kinase Inhibitor Discovery RESPONSES AND TARGETING or a tumor enhancer in cancer. Despite such Our lab uses predictive computational modeling complexities, it is promising to see many preclinical and cell-based measurements to accurately model »» CNS and Neurodegenerative EMERGING VIRUSES Targets and clinical studies underway using already approved the autophagic process. We are now extending our »» GPCR-Based Drug Discovery 2:45 Chairperson’s Remarks autophagy drugs and novel inhibitors. Cambridge models to predict the therapeutic benefit of inhibiting »» Constrained Peptides and René Rijnbrand, PhD, Vice President, Biology, Arbutus Healthtech Institute’s symposium on Targeting autophagy in cancer. Our research suggests that Macrocyclics Biopharma Inc. Autophagy taps into the recent excitement in this targeting known and unique kinases in the autophagy »» Lead Generation Strategies 2:55 Achieving Functional Cure of Chronic HBV field by bringing together a group of experts who are pathway can uncover more selective and potent »» Target Identification and Infection with REP 2139-Based Combination Therapy uncovering new mechanisms and inhibitors to help small molecule inhibitors as compared to current drug discovery. lysomotropic agents. Validation - Part 1 & Part 2 Andrew Vaillant, PhD, CSO, Replicor, Inc. »» Antibacterial Discovery and HBsAg loss during treatment of chronic HBV infection 9:45 Downregulation of Autophagy by a Cancer- Development predicts functional remission persisting after the RECOMMENDED ALL ACCESS Specific Ubiquitin Ligase Targeting AMPK completion of therapy but is rarely achieved with Ryan Potts, PhD, Associate Member, Department »» Targeting Gram-Negative PACKAGE: Choose 2 Short Courses Pathogens approved therapies. REP 2139 uniquely allows of Cell and Molecular Biology, St. Jude Children’s »» NASH and Fibrosis HBsAg clearance in most patients, dramatically or 1 Symposium and 2 Conferences/ Research Hospital »» Targeting the Microbiome potentiating the ability of immunotherapy to restore Training Seminars AMP-activated protein kinase (AMPK) is a master »» Antibody Discovery Forum - host control of infection. Follow-up data from the sensor and regulator of cellular energy status. Upon latest clinical trials with REP 2139-based combination • September 25 Symposium: metabolic stress, AMPK suppresses anabolic and Part 1 & Part 2 therapy demonstrating the achievement of long Targeting Autophagy promotes catabolic processes, including autophagy, »» Antibodies Against Membrane term functional cure in HBV and HDV infection • September 25 Short Course 11: Mechanistic to regain energy homeostasis. Here, I will discuss a Protein Targets - Part 1 & Part 2 will be featured. Understanding of Pharmacological Probes for widespread mechanism to suppress AMPK through its Hotel & Travel 3:25 Targeting TLR7 for Emerging Infectious Diseases the Ubiquitin-Proteasome System ubiquitination and degradation by the cancer-specific James B. Whitney, PhD, Professor, Center for Virology • September 26-27 Conference: Targeting the MAGE-A3/6-TRIM28 ubiquitin ligase. Recent findings Registration Information and Vaccine Research, Harvard Medical School and Ubiquitin-Proteasome System on the regulation of MAGE-A3/6 protein stability under nutrient deprivation will also be discussed. Ragon Institute of MGH, MIT, and Harvard • September 27-28 Conference: Kinase Click Here to Register 3:55 Small Molecule Inhibitors of Flavivirus Entry Inhibitor Discovery 10:15 Targeting Autophagy in Colorectal Cancer Cells: DiscoveryOnTarget.com Inspired by the Humural Immune Response A Relevant Strategy? • September 27 Short Course 18: Practical Steve Jean, PhD, Assistant Professor, Department of Priscilla L. Yang, PhD, Professor, Department Phenotypic Screening of Microbiology and Immunobiology, Harvard Anatomy and Cell Biology, Université de Sherbrooke Medical School APC loss, and KRAS activation, two hallmarks of CRC, are linked to increased autophagic flux, suggesting a

A Division of Cambridge Innovation Institute Symposia DiscoveryOnTarget.com • 9 SYMPOSIA » September 25 Final Weeks to Register

Cover potential involvement of autophagy in CRC. Through in cells. Our findings indicate that autophagic activity in present our progress in applying phenotypic screening vivo approaches on CRC cell lines, we found that the malignant cells does not promote tumorigenesis in a paradigms to identify novel autophagy pathway nodes. Conference outcome of autophagy inhibition in a complex system cancer-cell intrinsic manner, but alters extrinsic host At-A-Glance is unpredictable. Hence, the relationship between responses to tumor growth. GOING BEYOND AUTOPHAGY autophagy inhibition and cancer driver/passenger Sponsorship & Exhibit mutations must be clarified before autophagy 1:00 Sponsored Presentation (Opportunity Available) 3:55 Regulation and Consequences of Autophagy Short Courses inhibition can be considered as a therapeutic 1:00 Pre-Conference Short Course Registration and Non-Canonical Autophagy Resembling LC3- avenue in CRC. Click here for details on short courses offered. Associated Phagocytosis or LAP Symposia Michael Overholtzer, PhD, Associate Member, 1:15 Enjoy Lunch on Your Own Training Seminar 10:45 Sponsored Presentation (Opportunity Available) Cell Biology Program, Memorial Sloan Kettering 11:00 Networking Coffee Break with Poster Viewing Cancer Center Plenary Keynotes EXPLORING TOOLS & ASSAYS Autophagy proteins have parallel functions in non- 11:30 Leveraging Autophagy’s Ability to Regulate Agenda TO PROBE AND QUANTIFY THE autophagic processes that involve LC3 lipidation. Notably, Apoptosis to Improve Cancer Therapy »» Small Molecules for Cancer AUTOPHAGY CASCADE LC3-Associated Phagocytosis or LAP was discovered Andrew Thorburn, DPhil, Chair, Department of as a parallel function of core autophagy proteins that Immunotherapy Pharmacology, University of Colorado, School 2:45 Chairperson’s Remarks lipidate LC3 onto phagosomes and other endocytic »» Autoimmune and Inflammation of Medicine Ian Ganley, PhD, Programme Leader, The MRC Protein membranes. Here I will discuss new data uncovering Drug Targets In this presentation, I will discuss how autophagy Phosphorylation and Ubiquitylation Unit, The Sir James regulation of LAP and the consequences of this process »» NK Cell-Based Cancer inhibition sensitizes tumor cells to undergo apoptosis Black Centre, School of Life Sciences, University that differ from macroautophagy. The engagement of Immunotherapy and necroptosis and how this can be leveraged to of Dundee LAP by lysosomotropic drugs, including chloroquine, will »» Targeting Tumor Myeloid Cells enhance the activity of other anti-cancer agents. 2:55 Illuminating Mitochondrial Autophagy in Vivo also be discussed. »» Targeting the Ubiquitin- 12:00 pm Regulation of Innate Immunity by Ian Ganley, PhD, Programme Leader, The MRC Protein Proteasome System 4:25 Roles for Autophagy Genes beyond Autophagy: Selective Autophagy Phosphorylation and Ubiquitylation Unit, The Sir James Control of Exosome Release and Exosome- »» Kinase Inhibitor Discovery Aditya Murthy, PhD, Scientist, Cancer Immunology, Black Centre, School of Life Sciences, University Mediated Metastasis »» CNS and Neurodegenerative Genentech, Inc. of Dundee Derrick Gibbings, PhD, Assistant Professor, Cellular and Targets Molecular mechanisms by which autophagy limits Mitophagy, the autophagy of mitochondria, is Molecular Medicine, University of Ottawa »» GPCR-Based Drug Discovery inflammation remain poorly understood. We have an essential quality control (QC) mechanism of Autophagy and autophagy-related genes (Atg) have »» Constrained Peptides and recently shown that loss of the autophagy gene pathophysiological relevance with strong links been attributed prominent roles in tumorigenesis, Macrocyclics Atg16L1 promotes interferon-mediated pathology to Parkinson’s disease, cancer and inflammatory tumor growth, and metastasis. Extracellular »» Lead Generation Strategies via accumulation of the signaling adaptor TRIF. disorders. However, if and how mitophagy proceeds vesicles called exosomes are also implicated in »» Target Identification and Multiplexed proteomics identified SQSTM1/p62 within specific cellular subtypesin vivo has remained cancer metastasis. Here, we demonstrate that Validation - Part 1 & Part 2 and Tax1BP1 as autophagy receptors for TRIF. unclear, largely due to a lack of tractable models. To exosome production is strongly reduced in cells »» Antibacterial Discovery and Human macrophages harboring the Crohn’s disease- address this, we developed “mito-QC”, a fluorescent lacking Atg5 and Atg16L1, but this is independent Development associated ATG16L1 variant (T300A) exhibited reporter mouse that allows the facile assessment of of Atg7 and canonical autophagy. These findings »» Targeting Gram-Negative elevated cytokine production upon TLR3/4 stimulation. mitophagy and mitochondrial architecture in vivo. uncover mechanisms controlling exosome release Pathogens These findings implicate selective autophagy as a key 3:25 Phenotypic Screening Paradigms for Autophagy and identify means by which autophagy-related »» NASH and Fibrosis immunoregulatory node in innate immunity. Pathway Regulators genes can contribute to metastasis in autophagy- »» Targeting the Microbiome 12:30 Extrinsic Roles of Tumor-Intrinsic Autophagy Philip A. Bergman, BS, Investigator III, Chemical Biology independent pathways. »» Antibody Discovery Forum - Christina H. Eng, PhD, Senior Principal Scientist, Pfizer and Therapeutics, Novartis Institutes for BioMedical 4:55 Closing Comments Part 1 & Part 2 Oncology R&D Research, Inc. Tanuja Koppal, PhD, Conference Director, Cambridge »» Antibodies Against Membrane The role of autophagy in cancer has been extensively To identify novel autophagy pathway nodes, we Healthtech Institute Protein Targets - Part 1 & Part 2 examined, yet the impact of autophagy inhibition established phenotypic pooled CRISPR screening on neoplastic disease varies greatly and depends paradigms and mapped regulators of autophagy cargo 5:00 Close of Symposium Hotel & Travel on a number of factors such as genetic context and and cargo receptors in mammalian cells. As proof of 5:00 Pre-Conference Dinner Short tumor landscape. Metabolic stress such as nutrient concept, we performed a genome-wide screen for the Course Registration Registration Information and oxygen limitation, oncogenic mutations, and autophagy cargo receptor p62 and validated mTOR Click here for details on short courses offered. chemotherapeutic treatment are all situations that signaling and the entire macroautophagy machinery Click Here to Register may fuel the dependence on autophagy in tumorigenic as key regulators of p62 turnover. Here, we will DiscoveryOnTarget.com

A Division of Cambridge Innovation Institute Symposia DiscoveryOnTarget.com • 10 TRAINING SEMINAR » September 27-28 Final Weeks to Register Cambridge Healthtech Institute Training Seminars offer real-life case studies, problems encountered and solutions applied, along with extensive coverage of the academic theory and background. Each Cover Training Seminar offers a mix of formal lecture and interactive discussions and activities to maximize By Cambridge Healthtech Institute the learning experience. These Training Seminars are led by experienced instructors who will focus on Conference content applicable to your current research and provide important guidance to those new to their fields. At-A-Glance Sponsorship & Exhibit Short Courses day 1: Thursday, September 27 | 12:20 pm - 7:00 pm Symposia day 2: Friday, September 28 | 7:30 am - 4:00 pm TRAINING SEMINAR INFORMATION Training Seminar Each CHI Training Seminar offers 1.5 days of instruction with start and stop Plenary Keynotes DAY 1 - THURSDAY 12:20 - 2:00 pm Plenary Keynote Program times for each day shown above and on the Event-at-a-Glance published in Agenda 2:00 - 2:45 pm Refreshment Break in the Exhibit Hall with Poster Viewing the onsite Program & Event Guide. Training Seminars will include morning »» Small Molecules for Cancer 3:00 - 7:00 pm Training Seminar 2 in Session and afternoon refreshment breaks, as applicable, and lunch will be provided Immunotherapy 7:00 pm Training Seminar 2 Close of Day to all registered attendees on the full day of the class. »» Autoimmune and Inflammation Each person registered specifically for the Training Seminar will be provided Drug Targets DAY 2 - FRIDAY »» NK Cell-Based Cancer 7:30 - 8:30 am Interactive Breakfast Breakout Discussion Groups with a hard copy handbook for the Seminar in which they are registered. A Immunotherapy 8:30 am - 4:00 pm Training Seminar 2 in Session limited number of additional handbooks will be available for other delegates »» Targeting Tumor Myeloid Cells 12:30 - 1:30 pm Lunch Provided who wish to attend the Seminar, but after these have been distributed, no 4:00 pm Training Seminar 2 Concludes »» Targeting the Ubiquitin- additional books will be available. Proteasome System Though CHI encourages track hopping between conference programs, we »» Kinase Inhibitor Discovery TS2: INTRODUCTION TO SMALL MOLECULE DRUG »» CNS and Neurodegenerative DISCOVERY AND DEVELOPMENT ask that Training Seminars not be disturbed once they have begun. In the Targets Instructor: H. James Harwood Jr., PhD, Founder and CEO, Delphi interest of maintaining the highest quality learning environment for Training »» GPCR-Based Drug Discovery BioMedical Consultants, LLC Seminar attendees, and because Seminars are conducted differently than This 1.5-day lecture-based interactive seminar focuses on strategies for »» Constrained Peptides and conference programming, we ask that attendees commit to attending identifying drug discovery targets, discovering and characterizing small Macrocyclics the entire program, and not engage in track hopping, as to not disturb the »» Lead Generation Strategies molecule hits, and developing structure-activity relationships to advance hands-on style instruction being offered to the other participants. »» Target Identification and hits through lead optimization, preclinical development, and clinical evaluation. Participants will learn the stages and processes required to advance programs Validation - Part 1 & Part 2 from idea to clinic, through examples and case studies. This seminar is intended for »» Antibacterial Discovery and scientists in either academia or industry who would like to become more familiar Development with small molecule drug discovery and development. »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis * For detailed agendas and further details, please visit the conference website »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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Cover Conference At-A-Glance Sponsorship & Exhibit Short Courses Symposia PLENARY KEYNOTE PROGRAM Thursday, September 27, 12:20 - 2:00 pm Training Seminar Plenary Keynotes The 2018 Plenary Keynote Program will Nathanael S. Gray, PhD, Professor of Biological Chemistry and Agenda provide a unified underlying theme on Molecular Pharmacology, Dana-Farber Cancer Institute »» Small Molecules for Cancer meeting the new challenges of novel drug Nathanael Gray spent his childhood in Zambia, Yemen, India and Immunotherapy Sudan before returning to the US to attend high school at Berkeley »» Autoimmune and Inflammation development. High in California. During his PhD at University of California at Drug Targets Berkeley, he discovered Purvalanol, one of the first selective inhibitors of cyclin- »» NK Cell-Based Cancer dependent kinases. After receiving the PhD in 1999, Dr. Gray moved to the Genomics Immunotherapy New Approaches to Challenging Targets in Cancer Institute of the Novartis Research Foundation in San Diego, where he was named »» Targeting Tumor Myeloid Cells The development of new anti-cancer therapies continues to be massively outpaced Director of Biological Chemistry in 2001. Dr. Gray’s research team was responsible »» Targeting the Ubiquitin- by the rapidly expanding knowledge into the biological mechanisms that underpin for the development of several clinical candidates, including BAF312 which is Proteasome System the development of cancer. One major obstacle is that many potentially interesting currently undergoing Phase III clinical trials for the treatment of Multiple Sclerosis. Dr. Gray joined the faculty of Harvard Medical School and the Dana-Farber Cancer »» Kinase Inhibitor Discovery targets are challenging to drug. This lecture will focus on strategies using covalent Institute in 2006 to continue his research using synthetic chemistry and functional »» CNS and Neurodegenerative inhibitors and small molecule degraders which hold the promise of making many small molecule discovery to modulate biological pathways important in cancer. His Targets previously challenging targets druggable. In particular, we will focus on the use of research group has been responsible for the discovery of novel inhibitors of wild- »» GPCR-Based Drug Discovery these approaches to target kinases and present some key advantages of small molecule degraders including potency, selectivity and abrogation of non-kinase type and mutant forms of EGFR (WZ4002), mTor (Torin1 and Torin 2), Bcr-Abl (GNF- »» Constrained Peptides and 2, GNF-5, HG-7-85-01), Mps1 (Mps1-IN-1 Mps1-IN-2), Erk5 (XMD8-92), b-Raf, LRRK2 Macrocyclics activity dependent functions. We will also describe efforts to target KRAS – a notorious and frequent oncogene that has been recalcitrant to small molecule (LRRK2-IN-1), Jnk1,2,3 (JNK-IN-7) and Ephrin kinases which have become widely »» Lead Generation Strategies used research tools and have inspired several drug discovery programs. »» Target Identification and approaches. Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative 2018 EVENT FEATURES Pathogens The 16th Annual Discovery on Target, “The Industry’s Preeminent Event on Novel Drug Targets,” will once again gather »» NASH and Fibrosis »» Targeting the Microbiome over 1,300 drug discovery professionals in Boston, MA, this September 25-28, 2018. The event brings forth current and »» Antibody Discovery Forum - emerging “hot” targets, technologies and validation strategies for the development of novel small molecules and biologics. Part 1 & Part 2 »» Antibodies Against Membrane • Over 350+ speakers presenting across 20 conference • Poster sessions featuring cutting-edge, Protein Targets - Part 1 & Part 2 tracks, 2 training seminars and 3 symposia ongoing research • 16 Short Courses to provide additional training • Student fellowships offering discounted registration for Hotel & Travel and education to brush up on your knowledge or young researchers looking to make a difference Registration Information expand your horizons • 1,300+ international delegates focusing on preclinical • Exhibit hall of 80+ companies with novel research and the challenges and opportunities in early Click Here to Register technologies and solutions drug discovery and development DiscoveryOnTarget.com • Plenary keynote program unified by an underlying • Sponsored talks by leading technology and service theme on meeting the new challenges of novel providers showcasing new offerings drug development • Dedicated poster viewing and interactive panel discussions for active networking A Division of Cambridge Innovation Institute Plenary Keynotes & Event Features DiscoveryOnTarget.com • 12 Final Weeks to Register CONFERENCE CHANNELS & SYMPOSIA Take advantage of Discovery on Target’s program channels to explore the 1.5-day main program conferences and pre-conference symposia that align with your research. Conference and Symposia details below. Also, supplement your education with short courses and training seminars. Click here for details on short courses offered and click here Cover for details on training seminars. As part of the (best value) All Access registration choose from 2 Short Courses or 1 Conference Symposium, and 2 Conferences/Training Seminars. At-A-Glance Sponsorship & Exhibit Short Courses Symposia September 25 Symposia ·· Antivirals: Targeting ·· Targeting Autophagy Training Seminar HBV and Beyond ·· Regenerative Medicine Plenary Keynotes Agenda »» Small Molecules for Cancer Immunotherapy »» Autoimmune and Inflammation Drug Targets September 26-28 »» NK Cell-Based Cancer Immunotherapy Immunotherapy ·· Small Molecules for Cancer Immunotherapy ·· Autoimmune and Inflammation Drug Targets »» Targeting Tumor Myeloid Cells ·· NK Cell-Based Cancer Immunotherapy ·· Targeting Tumor Myeloid Cells »» Targeting the Ubiquitin- Proteasome System »» Kinase Inhibitor Discovery »» CNS and Neurodegenerative Targets »» GPCR-Based Drug Discovery Target-Based Discovery & Validation September 26-28 »» Constrained Peptides and ·· Targeting the Ubiquitin-Proteasome System ·· Kinase Inhibitor Discovery Macrocyclics »» Lead Generation Strategies ·· CNS and Neurodegenerative Targets ·· GPCR-Based Drug Discovery »» Target Identification and ·· Constrained Peptides and Macrocyclics ·· Lead Generation Strategies Validation - Part 1 & Part 2 ·· Target Identification and Validation -PART 1 ·· Target Identification and Validation -PART 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis September 26-28 »» Targeting the Microbiome Hot & Emerging »» Antibody Discovery Forum - ·· Antibacterial Discovery and Development ·· Targeting Gram-Negative Pathogens Part 1 & Part 2 ·· NASH and Fibrosis ·· Targeting the Microbiome »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Agenda DiscoveryOnTarget.com • 13 IMMUNOTHERAPY Final Weeks to Register 2nd Annual | September 26-27 Small Molecules for Cancer Immunotherapy Cover Unraveling the Chemistry and Biology for Next-Generation Therapies Conference At-A-Glance Sponsorship & Exhibit

Short Courses First-generation cancer immunotherapy agents being developed or approved are engineered T cells targeting are immune potentiators and represent a new class of Symposia tumors or mostly antibody-based biologics that target the immune checkpoint cascade. The success of these orally bioavailable, small molecule immuno-oncology biologics in the clinic is now inspiring the discovery and development of small molecules that act on intracellular therapeutics. Increase in the endogenous metabolite, Training Seminar targets affecting immuno-modulatory pathways in cancer. Cambridge Healthtech Institute’s 2nd Annual Small guanosine, with PNP inhibition leads to activation of Plenary Keynotes Molecules for Cancer Immunotherapy conference brings together discovery chemists and biologists to talk TLR2, 4 and 7. Potential attributes for differentiation about these new intracellular oncology targets and immuno-modulatory small molecule inhibitors that are being of PNP inhibitor (NTR001) are: less adverse events Agenda developed to act alone or in combination with existing treatments. from targeted immune activation in tumor micro- »» Small Molecules for Cancer environment; human safety known and doses Immunotherapy 8:10 Beyond PD-1 Axis: The Next Generation Oral defined, and immune activation in clinical/preclinical »» Autoimmune and Inflammation RECOMMENDED ALL ACCESS Checkpoint Inhibitor Targeting the CD47/SIRPα studies confirmed. Drug Targets PACKAGE: Choose 2 Short Courses Pathway for Cancer Immunotherapy 9:40 Grand Opening Coffee Break in the Exhibit Hall » » NK Cell-Based Cancer or 1 Symposium and 2 Conferences/ Pottayil G. Sasikumar, PhD, Associate Research Director with Poster Viewing Immunotherapy and Head of the Peptide Chemistry group, Aurigene »» Targeting Tumor Myeloid Cells Training Seminars Discovery Technologies Limited 10:25 The Network-Driven Drug Discovery (NDD) »» Targeting the Ubiquitin- • September 25 Symposium: Encouraged by our success in discovering small Approach and Lead Generation: Novel Immune- Modulatory Small Molecules Case Study Proteasome System Targeting Autophagy molecule immune checkpoint inhibitors predominantly Sree Vadlamudi, PhD, Programme Manager, e »» Kinase Inhibitor Discovery impacting T cells, we are now focusing on next • September 25 Short Course 3: How to Therapeutics plc »» CNS and Neurodegenerative generation checkpoint inhibitors. In this presentation, Best Utilize 3D Cells, Spheroids, and PDX The majority of drug discovery approaches involve Targets we will discuss successful identification of oral Models in Oncology the search for a single binding target in a well- »» GPCR-Based Drug Discovery agents targeting the CD47/signal regulatory protein • September 26-27 Conference: Small Molecules alpha (SIRPα) axis, a critical regulator of myeloid characterized pathway. But while pathways are easy »» Constrained Peptides and for Cancer Immunotherapy to envisage, they do not reflect the complexity of Macrocyclics cell activation and a checkpoint for macrophage and dendritic-cell mediated phagocytosis and biological systems. A more realistic way to describe »» Lead Generation Strategies • September 27-28 Conference: Targeting Tumor Myeloid Cells antigen presentation. the underlying interactions which occur is as a »» Target Identification and network. We have implemented and validated a highly Validation - Part 1 & Part 2 • September 27 Short Course 16: 8:40 Small Molecule Immune Oncology Therapies productive NDD approach to identify NCEs in diverse »» Antibacterial Discovery and Immunology Basics from Ubiquitin Proteasome System areas of biology. We will describe a case study Development Suresh Kumar, PhD, Senior Director R&D, Progenra, Inc. highlighting the discovery and optimizationof small »» Targeting Gram-Negative Progenra is developing small molecule inhibitors molecules modulating tumor micro environment (TME) Pathogens Wednesday, September 26 targeting deubiquitinases and ubiquitin ligases that with a novel mechanism of action. promote tumor growth and immune evasion. The »» NASH and Fibrosis 7:00 am Registration Open and Morning Coffee deubiquitylase (DUB) USP7 stabilizes several pro- 10:55 Epigenetic Control of Immune Checkpoint »» Targeting the Microbiome tumorigenic proteins and plays an essential in Treg Inhibitor Responses »» Antibody Discovery Forum - UPDATE ON SMALL MOLECULES function by regulating post-translational modification Diana Hargreaves, PhD, Assistant Professor, Molecular Part 1 & Part 2 IN DEVELOPMENT FOR of Foxp3 and TIP60. Progenra has developed potent and Cell Biology, Salk Institute for Biological Sciences »» Antibodies Against Membrane Mutations in subunits of the SWI/SNF chromatin IMMUNOONCOLOGY USP7 inhibitors that exhibit direct anti-tumor activity Protein Targets - Part 1 & Part 2 in multiple xenograft tumor models. Most importantly, remodeling complex are known to potentiate 8:00 Welcome Remarks USP7 inhibitors also impair Treg functions and are responses to checkpoint therapies and are thus Hotel & Travel Tanuja Koppal, PhD, Conference Director, Cambridge efficacious in syngeneic solid tumor models. attractive targets for the development of small Healthtech Institute molecules for cancer therapy. Here we describe a key Registration Information 9:10 Purine Nucleoside Phosphorylase Inhibitors as 8:05 Chairperson’s Opening Remarks role for the SWI/SNF subunit ARID1A in controlling Novel, First-in-Class Small Molecule Immunotherapy chromatin accessibility and histone modifications at Paul Kassner, PhD, Vice President, Quantitative Biology, Shanta Bantia, PhD, President and CEO, Nitor Click Here to Register FLX Bio Inc. transcriptional enhancers and discuss our efforts to DiscoveryOnTarget.com Therapeutics identify novel SWI/SNF complex inhibitors. We have discovered, contrary to all previous literature, that purine nucleoside phosphorylase (PNP) inhibitors

A Division of Cambridge Innovation Institute Small Molecules for Cancer Immunotherapy DiscoveryOnTarget.com • 14 IMMUNOTHERAPY Final Weeks to Register

Cover 11:25 Development of CCR4 Antagonists for that detects amino-acid deprivation leading to T cell cytokines IFNγ and IL6. These insights have important Cancer Immunotherapy anergy and apoptosis. GCN2 inhibitors abrogated the ramifications for the therapeutic development of Conference Paul Kassner, PhD, Vice President, Quantitative Biology, suppressive function of MDSCs leading to restoration IDO1 inhibitors. At-A-Glance FLX Bio Inc. of proliferation and effector function of CD8 T cells. 4:35 Toll-Like Receptor 7 and 8 Agonists with Direct Regulatory T cells (Treg) suppress anti-tumor immunity Sponsorship & Exhibit 2:25 Discovery of Small Molecule AhR Antagonists to Inflammasome Activation in the tumor microenviroment (TME). CCR4 is highly Overcome Local Tumor Immunosuppression David Ferguson, PhD, Professor, Medicinal Chemistry, Short Courses expressed on Treg and responsible for recruitment University of Minnesota of Treg to the TME. FLX475 is a potent and selective Christoph Steeneck, PhD, Director Medicinal Chemistry, Symposia Phenex Pharmaceuticals AG The basic structural features of small molecule ligands CCR4 antagonist in Phase I clinical trials. The that confer selectivity to Toll-like receptors 7 and 8 Training Seminar The Aryl Hydrocarbon Receptor (AhR) is widely preclinical development, patient selection strategy and will be discussed in the context of immunomodulation biomarker plan for FLX475 will be discussed. known for mediating toxicity and tumor-promoting Plenary Keynotes activities of halogenated hydrocarbons and polycyclic and the design of cancer vaccines. An SAR analysis 11:55 PANEL DISCUSSION will be presented to identify structural features that Agenda aromatic hydrocarbons. However in recent years, confer selectivity to TLR7 and TLR8 and ligand specific »» Small Molecules for Cancer 12:25 pm Session Break ample evidence emerged that AhR activation causes immunosuppression and that AhR antagonism could activation of key cytokines in producing antigen- Immunotherapy 12:35 Luncheon Presentation (Sponsorship represent a treatment for cancer complementary specific cellular responses in model systems. Finally, »» Autoimmune and Inflammation Opportunity Available) or Enjoy Lunch on Your Own to checkpoint inhibitors. An overview on Phenex` in vivo data will be shown that demonstrates the Drug Targets 1:15 Refreshment Break in the Exhibit Hall with series of small molecule AhR antagonists and their potential of TLR7/8 stimulation in designing advanced »» NK Cell-Based Cancer Poster Viewing optimization will be given. The lead molecules show vaccines for cancer treatment. Immunotherapy high potency, favorable ADME/PK and in vivo efficacy. »» Targeting Tumor Myeloid Cells IMPACTING TLRs, CYTOKINES AND 2:55 Sponsored Presentation (Opportunity Available) 5:05 Interactive Breakout Discussion Groups »» Targeting the Ubiquitin- PRO-INFLAMMATORY PATHWAYS Join a breakout discussion group. These are informal, Proteasome System 3:25 Refreshment Break in the Exhibit Hall with Poster 1:50 Chairperson’s Remarks moderated discussions with brainstorming and »» Kinase Inhibitor Discovery Viewing and Poster Competition Winner Announced David Ferguson, PhD, Professor, Medicinal Chemistry, interactive problem solving, allowing participants »» CNS and Neurodegenerative University of Minnesota 4:05 IDO1 as a Promoter of Inflammatory from diverse backgrounds to exchange ideas and Targets Neovascularization experiences and develop future collaborations around »» GPCR-Based Drug Discovery 1:55 Targeting Myeloid Cell Suppressor Function Alexander J. Muller, PhD, Associate Professor, Lankenau a focused topic. Details on the topics and moderators »» Constrained Peptides and through Inhibition of GCN2 Institute for Medical Research are available on the conference website. Macrocyclics Buvana Ravishankar, PhD, Scientist, Discovery Biology, IDO1 is a tryptophan catabolizing enzyme implicated »» Lead Generation Strategies FLX Bio Inc. in maintaining pregnancy and tumoral immune Myeloid-derived suppressor cells (MDSC) are a major 6:05 Welcome Reception in the Exhibit Sponsored by »» Target Identification and escape. This may, however, be just one aspect component of the tumor microenvironment with Hall with Poster Viewing Validation - Part 1 & Part 2 of a multifaceted role for IDO1. Our studies have potent immune-suppressive activity. MDSC within 7:10 Close of Day »» Antibacterial Discovery and determined that, by triggering the integrated the tumor mediate local depletion of amino-acids Development stress response, IDO1 can support inflammatory that induce suppression of T cell proliferation and neovascularization through its positioning at the Thursday, September 27 »» Targeting Gram-Negative activation. GCN2 kinase is a stress response kinase Pathogens regulatory interface between the inflammatory 7:30 am Registration Open and Morning Coffee »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 Media Partners »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2 Official Publications Lead Sponsoring Publications Hotel & Travel

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A Division of Cambridge Innovation Institute Small Molecules for Cancer Immunotherapy DiscoveryOnTarget.com • 15 IMMUNOTHERAPY Final Weeks to Register

Cover EMERGING TARGETS AND 9:05 Discovery of Scaffold/Platform for the 10:50 PROTACS: The Chemical Equivalent of CRISPR Development of Dual Kinase/Epigenetic Inhibitors Shanique Alabi, Graduate Student, Laboratory of Dr. Conference COMBINATIONS FOR CANCER for the Activation of Innate and Adaptive Craig Crews, Department of Molecular, Cellular and At-A-Glance IMMUNOTHERAPY Antitumor Immunity Developmental Biology, Yale University Sponsorship & Exhibit 8:00 Chairperson’s Remarks Donald Durden, MD, PhD, Professor, Department of Induced protein degradation offers several advantages Pediatrics, University of California, San Diego; Director of over traditional inhibition strategies and has emerged Short Courses Amar Natarajan, PhD, Professor, Eppley Institute for Cancer Research, Fred and Pamela Buffett Cancer Operations, SignalRx Pharmaceuticals recently as a potential therapeutic option. For the Symposia Center, University of Nebraska Medical Center A novel thienopyranone molecular scaffold has been past 16 years, we have helped develop this fast- discovered to selectively inhibit PI3 kinase as well as growing field, shepherding our initial chemical biology Training Seminar 8:05 Exhausted CD8 Cells May Predict Response to the bromodomain protein BRD4. Molecular modeling concept into a drug development strategy that is on Plenary Keynotes Immune Checkpoint Inhibitors in Breast Cancer studies and a robust PI-3K and BRD4 BD1 homology the verge of clinical validation. PROTACs with high Pamela Munster, MD, Professor, Department of model has been developed and will be presented to target selectivity, potency, and oral bioavailability Agenda Medicine; Director, Early Phase Clinical Trials Unit, and describe how these single small molecules can bind will be discussed as well as a system to address the »» Small Molecules for Cancer Leader, Developmental Therapeutics Program, University to inhibit such distinctly different proteins and their ‘PROTACability’ of particular E3 ligases. Immunotherapy of California San Francisco functions. As a cancer therapeutic, this dual inhibition 11:20 Luncheon Presentation (Sponsorship »» Autoimmune and Inflammation Immune checkpoint inhibitors have limited efficacy mechanism allows for a unique and powerful way Opportunity Available) or Enjoy Lunch on Your Own Drug Targets in estrogen receptor (ER)+ breast cancer. Implicated to modulate critical components of cancer cells. »» NK Cell-Based Cancer factors include scarcity of tumor infiltrating Finally, other inhibitors developed in silico against 11:50 Conference Registration Open Immunotherapy lymphocytes (TILs), low PD-L1 expression, female other targeted kinases e.g. BTK in combination with »» Targeting Tumor Myeloid Cells gender and liver involvement. Evaluation of in vitro and PI3K-gamma and PI3K-delta will be presented as novel 12:20 pm Plenary Keynote Program »» Targeting the Ubiquitin- in vivo effects of epigenetic modulation with HDACi immuno-oncological agents. Click here for details. on Tregs, change in TIL composition and data from a Proteasome System clinical trial in patients with (ER)+ metastatic breast 9:35 Coffee Break in the Exhibit Hall with »» Kinase Inhibitor Discovery cancer suggests that HDACi induced Treg regulation Poster Viewing 2:00 Refreshment Break in the Exhibit Hall with »» CNS and Neurodegenerative and the presence of exhausted CD8+ cells in a small 10:20 Plate-Based Approach to Identify PROTACS Poster Viewing Targets subset of patients (ER)+ breast cancer patients were Molecules and Protein Degraders 2:45 Close of Conference »» GPCR-Based Drug Discovery predictive of response. Davide Gianni, PhD, Team Leader, Discovery Sciences, »» Constrained Peptides and AstraZeneca Macrocyclics 8:35 Chemical Genetic Screens Identify Kinase Inhibitor Combinations that Target Anti-Apoptotic PROTACS provide a new modality to drug previously »» Lead Generation Strategies Proteins for Cancer Therapy challenging targets and much evidence indicates »» Target Identification and Amar Natarajan, PhD, Professor, Eppley Institute for that protein degraders are a mode of inhibition that Validation - Part 1 & Part 2 Cancer Research, Fred and Pamela Buffett Cancer can be pursued post HTS. Western Blot is mostly »» Antibacterial Discovery and Center, University of Nebraska Medical Center used to characterize PROTACS molecules, but it has Development Systematic CRISPR studies defined signaling arms in a number of obvious limitations. The adoption of »» Targeting Gram-Negative the apoptosis network that can be targeted for cancer plate-based approaches is essential in PROTACS and Pathogens therapy. Using a pair of doxycycline (Dox)-inducible several options are available such as, antibody-based »» NASH and Fibrosis cell lines that specifically report on targeting either the and non-antibody based approaches. We will present »» Targeting the Microbiome Mcl-1 arm or the Bcl-2/Bcl-xL/Bcl-w arm we identified two case studies building plate-based, HTS-friendly »» Antibody Discovery Forum - unique combination of inhibitors that synergistically protein degradation assays potentially applicable for Part 1 & Part 2 induce apoptosis. Here we will present preclinical PROTACS identification campaigns. »» Antibodies Against Membrane studies that validate these combinations that can be Protein Targets - Part 1 & Part 2 rapidly translated to the clinics.

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A Division of Cambridge Innovation Institute Small Molecules for Cancer Immunotherapy DiscoveryOnTarget.com • 16 IMMUNOTHERAPY Final Weeks to Register 3rd Annual | September 27-28 Autoimmune and Inflammation Drug Targets Cover Towards Oral-Based Therapeutics Conference At-A-Glance Sponsorship & Exhibit

Short Courses This conference focuses on small molecule, peptide or macrocyclic-based agents that have the potential to 3:55 Identification of Two Novel Chemical Series for Symposia be developed into oral-based therapies for the treatment of autoimmune diseases and chronic inflammation the Irreversible Inhibition of Myeloperoxidase (MPO) disorders. The success of biologics for autoimmune diseases coupled with rapid advances in basic research Andrew W. Patterson, PhD, Senior Investigator I, Global Training Seminar has validated many immunology-relevant signaling pathways and uncovered new intracellular molecules to Discovery Chemistry, Novartis Institutes for Biomedical Plenary Keynotes target for potential new drug agents that can enter the cell. Discovering oral-based therapies, which offer patient Research, Inc. convenience is a high priority in the drug discovery industry because of the chronic nature of many autoimmune Agenda and inflammation conditions and the fact that their incidence is predicted ot steadily increase due to the growing 4:25 Refreshment Break in the Exhibit Hall with »» Small Molecules for Cancer aging population. Poster Viewing Immunotherapy 5:00 Role of STING in Innate Immunity and »» Autoimmune and Inflammation 2:50 Chairperson’s Opening Remarks Implications for Drug Discovery Drug Targets RECOMMENDED ALL ACCESS Shruti Sharma, PhD, Assistant Professor, Department of Shruti Sharma, PhD, Assistant Professor, Department of »» NK Cell-Based Cancer PACKAGE: Choose 2 Short Courses Immunology, Tufts Immunology, Tufts Immunotherapy or 1 Symposium and 2 Conferences/ 5:30 Inhibitor of NCK, a First-in-Class TCR Signaling »» Targeting Tumor Myeloid Cells 2:55 Discovery and Investigation of Selective Training Seminars Immunoproteasome Inhibitors Adaptor for Combatting Autoimmunity »» Targeting the Ubiquitin- Balbino Alarcon, PhD, Professor, Center for Molecular Proteasome System • September 25 Symposium: Antivirals: Michael Siu, PhD, Senior Scientist, Discovery Chemistry, Genentech, Inc. Biology Severo Ochoa, National Research Council of »» Kinase Inhibitor Discovery Targeting HBV and Beyond The importance of the immunoproteasome for Spain, Madrid »» CNS and Neurodegenerative • September 25 Short Course 11: Mechanistic immune cell function has led to efforts to selectively Antigen binding to the T cell receptor (TCR) triggers Targets Understanding of Pharmacological Probes for inhibit this target to deplete pathogenic immune cells the recruitment of the cytosolic adaptor protein Nck »» GPCR-Based Drug Discovery the Ubiquitin-Proteasome System for the potential treatment of autoimmune diseases. to a proline-rich sequence (PRS) in the cytoplasmic »» Constrained Peptides and • September 26-27 Conference: Herein, we describe the discovery of β5i (LMP7) tail of the TCR’s CD3ε subunit. We have generated an Macrocyclics NASH and Fibrosis selective inhibitors and their effects on immune cells. orally-available, inhibitor of the TCR-Nck interaction »» Lead Generation Strategies These inhibitors have provided new understanding of that selectively inhibits TCR-triggered T cell activation »» Target Identification and • September 27-28 Conference: Autoimmune at subnanomolar concentrations. The inhibitor is and Inflammation Drug Targets immunoproteasome inhibition that suggests selective Validation - Part 1 & Part 2 inhibition may have limited potential for immune not immunosuppressive and exerts a long-lasting »» Antibacterial Discovery and • September 27 Short Course 16: cell depletion. protective effect in several models of autoimmunity Development Immunology Basics even when the compound is no longer present. 3:25 The Anti-inflammatory Effect of SINE (Selective »» Targeting Gram-Negative Inhibitors of Nuclear Export) Compounds in the 6:00 Targeting the Keap1-NRF2 System to Pathogens Combat Inflammation Thursday, September 27 Context of IBD »» NASH and Fibrosis Douglas Widman, Phd, Research and Development Michelangelo Campanella, PhD, PharmD, Professor and »» Targeting the Microbiome 11:50 am Conference Registration Open Program Manager, Karyopharm Therapeutics, Inc. Unit Head, Mitochondrial Cell Biology and Pharma-cology »» Antibody Discovery Forum - Karyopharm Therapeutics has developed a class of Research Group RVC and University College London Part 1 & Part 2 Consortium for Mitochondrial Research 12:20 pm Plenary Keynote Program compounds known as Selective Inhibitors of Nuclear »» Antibodies Against Membrane My talk will report upon Nrf2 inducers as pharmacological Click here for details. Export (SINE), which reversibly bind to and inhibit the Protein Targets - Part 1 & Part 2 function of nuclear export protein, exportin-1 (XPO1). tolls in mitochondrial quality control operated by In murine DSS induced c olitis, longer, less inflamed targeted autophagy and its impact on autoimmunity and Hotel & Travel 2:00 Refreshment Break in the Exhibit Hall with colons and more normal stool consistency was inflammation. The presentation will also elaborate on the Poster Viewing observed in mice treated with SINE compound. SINE prominent biological activity in cellular homeostasis of Registration Information compounds demonstrate the ability to reduce chronic the non-covalent Keap1-Nrf2 protein-protein interaction NEW INTRACELLULAR DRUG inflammation by multiple mechanisms including (PPI) inhibitor PMI, which is structurally distinct from the covalent Keap1 modifiers (e.g., sulforaphane) and Click Here to Register TARGETS FOR INFLAMMATION inhibiting NF-kB activity even in presence of TNF-α. DiscoveryOnTarget.com amenable to therapeutic exploitation. 2:45 Welcome Remarks 6:30 Dinner Short Course Registration Anjani Shah, PhD, Conference Director, Cambridge Click here for details on short courses offered. Healthtech Institute 9:30 Close of Day

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Cover Friday, September 28 9:05 Reverse Translation for Therapeutic 2:00 FEATURED PRESENTATION: PTG-200, An Oral Development in the Human Microbiome Peptide Antagonist of the IL-23 Receptor, for the Conference 7:00 am Registration Open Ulrich Thienel, MD, PhD, CMO, Finch Therapeutics, Inc. Treatment of IBD At-A-Glance A major challenge in microbiome research is David Y. Liu, PhD, CSO, Protagonist Therapeutics Sponsorship & Exhibit 7:30 Interactive Breakfast Breakout interpreting correlations observed in human cohort studies or murine models. However, with the Short Courses Discussion Groups 2:30 Identification of a First-in-Class RIP1 Kinase Grab a cup of coffee and join a breakout discussion increasing abundance of clinical interventional data Inhibitor in Clinical Trials for Immuno-Inflammatory Symposia group. These are informal, moderated discussions from experience with fecal microbiota transplantation, Diseases via DNA-Encoded Libraries there is an opportunity to develop therapeutic insights Training Seminar with brainstorming and interactive problem solving, Philip A. Harris, PhD, Senior Director, Pattern Recognition allowing participants from diverse backgrounds directly from clinical observations. Finch Therapeutics Receptor DPU, GlaxoSmithKline Plenary Keynotes to exchange ideas and experiences and develop identifies microbial therapies by observing patterns of RIP1 kinase activity is a critical driver of cell death and microbial engraftment that drive clinical responses. Agenda future collaborations around a focused topic.Details pro-inflammatory cytokine production downstream of We plan to use the patterns to develop a new »» Small Molecules for Cancer on the topics and moderators are available on the multiple signaling pathways including TNFR1. Hence conference website. generation of rationally selected microbiota therapies RIP1 inhibitors have the potential to result in a broad Immunotherapy for Inflammatory Bowel Disease. therapeutic benefit in inflammatory diseases. This talk »» Autoimmune and Inflammation 9:35 NOD2, Innate Immunity and the Microbiome will describe the identification of a novel and selective Drug Targets THE MICROBIOME, AUTOIMMUNITY Klare Lazor, Graduate Student, Laboratory of Catherine RIP1 inhibitor series from a DNA-encoded library, »» NK Cell-Based Cancer AND INFLAMMATION Grimes, Department of Chemistry and Biochemistry, and the lead optimization leading to identification of Immunotherapy University of Delaware development candidate GSK2982772, now in Phase »» Targeting Tumor Myeloid Cells 8:30 Chairperson’s Remarks 10:05 Coffee Break in the Exhibit Hall with Poster IIa clinical evaluation in psoriasis, rheumatoid arthritis »» Targeting the Ubiquitin- Thomas Sundberg, PhD, Senior Research Scientist I, and ulcerative colitis patients. Proteasome System Center for Development of Therapeutics, Broad Institute Viewing and Poster Competition Winner Announced 3:00 Targeting TLRs in Fibrotic Disease »» Kinase Inhibitor Discovery of MIT and Harvard Glenda Trujillo, PhD, Principal Scientist, Translational »» CNS and Neurodegenerative INTRACELLULAR KINASE Research for Fibrosis Discovery Biology, Bristol-Myers Targets INHIBITORS FOR INFLAMMATION/ 8:35 KEYNOTE PRESENTATION: Bacterial Squibb Company »» GPCR-Based Drug Discovery Transformations in Autoimmune Drug AUTOIMMUNITY 3:30 Identification of Two Novel Chemical Series for »» Constrained Peptides and Metabolism 10:45 Considerations in the Generation of Covalent Macrocyclics Jason Michael Crawford, PhD, Maxine F. Singer the Irreversible Inhibition of Myeloperoxidase (MPO) BTK Inhibitors Andrew W. Patterson, PhD, Senior Investigator I, Global »» Lead Generation Strategies ’57 Ph.D. Associate Professor of Chemistry and Noel S. Wilson, PhD, Senior Scientist II, Discovery »» Target Identification and Associate Professor of Microbial Pathogenesis, Discovery Chemistry, Novartis Institutes for Biomedical Chemistry and Technology, AbbVie Research, Inc. Validation - Part 1 & Part 2 Yale University 11:15 Evobrutinib (BTK inhibitor) in Autoimmunity: MPO is a peroxidase present in phagocytic cells »» Antibacterial Discovery and Photorhabdus asymbiotica is a Preclinical Updates that participates in innate immune response, with a Development gammaproteobacterial pathogen that causes Andrew Bender, PhD, Senior Scientist, Discovery Biology, primary anti-microbial function of generating powerful »» Targeting Gram-Negative systemic and severe soft tissue infections in humans. During infection, it produces tapinarof, EMD Serono oxidants (i.e. HOCl). MPO activation is also associated Pathogens with generating oxidants within tissues. As such, »» NASH and Fibrosis an immunomodulatory drug developed to treat 11:45 Sponsored Presentation (Opportunity Available) psoriasis and atopic dermatitis. We show that plasma MPO levels have been linked to several chronic »» Targeting the Microbiome 12:15 pm Session Break inflammatory diseases including cardiovascular »» Antibody Discovery Forum - bacteria transform tapinarof into other novel metabolites that regulate arylhydrocarbon 12:25 Luncheon Presentation (Sponsorship disease. Here we describe two novel series of Part 1 & Part 2 receptor and Nrf2 antioxidant signaling, Opportunity Available) or Enjoy Lunch on Your Own irreversible, mechanism-based MPO inhibitors that »» Antibodies Against Membrane phenotypes responsible for tapinarof’s clinical 1:15 Refreshment Break in the Exhibit Hall with are orally bioavailable and active in vivo in a peritonitis Protein Targets - Part 1 & Part 2 efficacy. We also show that closely related Poster Viewing model of acute inflammation. Hotel & Travel dietary metabolites associated with “alternative” 4:00 Close of Conference IBD treatments undergo similar novel ORAL-BASED APPROACHES FOR Registration Information transformations. AUTOIMMUNITY 1:55 Chairperson’s Remarks Click Here to Register Songqing Na, PhD, Senior Scientist, Biotechnology & DiscoveryOnTarget.com Autoimmunity Res-AME, Eli Lilly and Company

A Division of Cambridge Innovation Institute Autoimmune and Inflamation Drug Targets DiscoveryOnTarget.com • 18 IMMUNOTHERAPY Final Weeks to Register 3rd Annual | September 26-27 NK Cell-Based Cancer Immunotherapy Cover Engineering Strategies and Clinical Evidence Conference At-A-Glance Sponsorship & Exhibit Short Courses

Symposia A growing number of studies into pathways elucidating NK cell biology, activating and suppressing NK cell banked, characterized and repeatedly applied to our Training Seminar function, the development of pharmacological and genetic methods to enhance NK cell anti-tumor immunity, stage-specific directed differentiation process to and the ability to expand NK cells ex vivo have set the stage for a new generation of cancer immunotherapies. As reproducibly and reliably generate NK cells. Preclinical Plenary Keynotes preclinical and clinical studies continue, there is a clear need to better understand the mechanisms underlying data highlight the therapeutic value of pluripotent- Agenda the regulation of NK cell phenotype and function within the tumor environment to accelerate the development of derived NK cells including anti-tumor capacity, »» Small Molecules for Cancer NK cell-targeting therapeutics. manufacturing reliability and preclinical efficacy. Immunotherapy 9:10 Inhibition of MICA and MICB Shedding by Tumor Cambridge Healthtech Institute’s 3rd Annual NK Cell-Based Cancer Immunotherapy conference will once »» Autoimmune and Inflammation Cells Elicits NK Cell-Mediated Tumor Immunity again convene immuno-oncology researchers, cancer immunotherapy developers, and technology providers to Drug Targets Kai W. Wucherpfennig, MD, PhD, Professor and Chair, discuss current challenges and opportunities - from discovery NK immuno-oncology to clinical studies, share »» NK Cell-Based Cancer Cancer Immunology and Virology, Dana-Farber Cancer latest technologies and development approaches, as well as to provide updates on preclinical, clinical, and Institute; Professor, Neurology and Microbiology/ Immunotherapy combination studies. »» Targeting Tumor Myeloid Cells Immunobiology, Harvard Medical School »» Targeting the Ubiquitin- We rationally designed antibodies targeting the Proteasome System RECOMMENDED ALL ACCESS 8:10 KEYNOTE PRESENTATION: MICA α3 domain, the site of proteolytic shedding, Novel Strategies to Produce Better and found that these antibodies prevent loss of »» Kinase Inhibitor Discovery PACKAGE: Choose 2 Short Courses NK Cells to Treat Cancer cell surface MICA/B by human cancer cells. These »» CNS and Neurodegenerative Jeffrey Miller, MD, Professor, Medicine, antibodies inhibit tumor growth in multiple fully Targets or 1 Symposium and 2 Conferences/ Division of Hematology, Oncology and immunocompetent mouse models and reduce human »» GPCR-Based Drug Discovery Training Seminars Transplantation, University of Minnesota melanoma metastases in a humanized mouse model. »» Constrained Peptides and • September 25 Symposium: We have developed a trispecific killer engagers Macrocyclics Targeting Autophagy 9:40 Grand Opening Coffee Break in the Exhibit Hall (TriKE) platform to make NK cells antigen with Poster Viewing »» Lead Generation Strategies • September 25 Short Course 3: How to specific and enrich for a unique population »» Target Identification and Best Utilize 3D Cells, Spheroids, and PDX of adaptive NK cells that kill better, mediate MODULATING NK CELLS FOR Validation - Part 1 & Part 2 Models in Oncology enhanced antibody-dependent cellular »» Antibacterial Discovery and HIGHER SPECIFICITY AND • September 26-27 Conference: NK Cell-Based cytotoxicity, can resist immune suppression Development Cancer Immunotherapy mechanisms and exhibit properties of POTENCY (CONT.) »» Targeting Gram-Negative immunologic memory. To overcome limitation of 10:25 NKTR-255: Accessing the Immunotherapeutic Pathogens • September 27-28 Conference: Targeting single cell infusions, a platform to deliver off-the- Tumor Myeloid Cells Potential of IL-15 for NK Cell Therapies »» NASH and Fibrosis shelf NK cells derived from clonal, genetically Saul Kivimae, PhD, In Vivo Pharmacology Function Lead, »» Targeting the Microbiome • September 27 Short Course 16: modified induced pluripotent stem cells (iPSC) Nektar Therapeutics »» Antibody Discovery Forum - Immunology Basics was developed. These strategies alone or in IL-15 has long been recognized for its potential as an Part 1 & Part 2 combination with checkpoint blockade are key immunotherapeutic agent. Exploiting this potential has to the future. »» Antibodies Against Membrane Wednesday, September 26 been challenging due to unfavorable pharmacokinetic Protein Targets - Part 1 & Part 2 properties. NKTR-255 is a novel polymer-conjugated 7:00 am Registration Open and Morning Coffee IL-15 that shows prolonged plasma exposure and IL-15 Hotel & Travel 8:40 Pluripotent Cell-Derived NK Cells as a Cornerstone Approach for Off-the-Shelf pathway activation while retaining high affinity IL-15Rα binding. NKTR-255 treatment expands and sustains Registration Information MODULATING NK CELLS FOR Cancer Immunotherapy HIGHER SPECIFICITY AND POTENCY Bahram (Bob) Valamehr, PhD, MBA, Vice President, activation of NK and CD8 memory T cell populations. High level of NK cell dependent anti-tumor efficacy is 8:00 Welcome Remarks Cancer Immunotherapy, Fate Therapeutics, Inc. Click Here to Register I will discuss our progress towards translating a demonstrated in NKTR-255 treated mouse models of DiscoveryOnTarget.com Ngoc Emily Le, PhD, Associate Producer, Cambridge tumor metastasis. Healthtech Institute unique and effective strategy to create a renewable source of “off-the-shelf” engineered NK cells derived 8:05 Chairperson’s Opening Remarks from a single-cell derived master pluripotent cell Bahram (Bob) Valamehr, PhD, MBA, Vice President, line. The derived master pluripotent cell line is Cancer Immunotherapy, Fate Therapeutics, Inc.

A Division of Cambridge Innovation Institute NK Cell-Based Cancer Immunotherapy DiscoveryOnTarget.com • 19 IMMUNOTHERAPY Final Weeks to Register

Cover 10:55 Engineering NK Cells for Enhanced Potency which showed the cells to be safe with some signs of NK cells in combination with other novel agents in and Persistence efficacy and an interesting manageable side effect. transplant and non-transplant settings. Conference James B. Trager, PhD, Senior Vice President, Research At-A-Glance 2:25 NK Cell Subsets and Their Plasticity – and Development, Nkarta Therapeutics Implications for Cell Therapy DISCOVERY PLATFORMS AND Sponsorship & Exhibit NK cells form a first line of defense against cancer, Karl-Johan Malmberg, MD, PhD, Professor, Cancer TECHNOLOGIES FOR NK CELLS and they can be effective mediators of cytotoxicity and Immunology, Institute for Cancer Research, Oslo Short Courses adaptive immunity. Efforts to maximize their potential 4:35 Dynamic Analysis of Human Natural Killer Cell University Hospital, Norway Response at Single-Cell Resolution Symposia as cancer therapeutics are hampered by difficulty in In this talk, I will discuss new insights into the expanding NK cells, relatively short in vivo persistence, Tania (Tali) Konry, PhD, Assistant Professor, Training Seminar underlying mechanisms behind the functional and the ability of tumor cells to evade NK recognition. We Pharmaceutical Sciences, Northeastern University diversification of human NK cells, including the We have developed a high throughput droplet based Plenary Keynotes will discuss recent progress in overcoming these barriers formation of a molecular memory, evidence for subset to successful therapeutic application of NK cells. microfluidic platform to investigate the key features Agenda plasticity and dynamic imprints caused by NK cell of NK cells associated with rapid, slow or inactive »» Small Molecules for Cancer 11:25 Engineered, Off-the-Shelf NK Cell Lines for responses to cytomegalovirus infection. In terms of tumor killing kinetics in NHL. We are working on Patient Specific Cancer Treatment clinical translation, we are currently exploring new Immunotherapy identifying NK cell heterogeneity and bio-functional Hans Klingemann, MD, PhD, Vice President, Research & strategies to selectively expand such “adaptive” NK »» Autoimmune and Inflammation characteristics to discover novel drug combinations Development, NantKwest, Inc. cells for cancer therapies. Drug Targets for NK cell dependent immunotherapy via an aNK and haNK have completed Phase I studies, taNK »» NK Cell-Based Cancer 2:55 Fuelling Robust Anti-Tumor NK Cell Responses integrated droplet platform. We identified significant (her-2 CAR) for glioma is currently accruing patients. David Finlay, Assistant Professor, School of variability in NK-lymphoma cell contact duration, Immunotherapy Further genetic modifications of the haNK platform »» Targeting Tumor Myeloid Cells Biochemistry and Immunology, School of Pharmacy and frequency, and subsequent cytolysis. We extended this include additional CARs as well as homing receptors Pharmaceutical Sciences, Trinity College Dublin, Ireland technique to characterize functional heterogeneity in »» Targeting the Ubiquitin- and molecules that can positively affect the tumor Proteasome System For robust anti-tumour functions NK cells increase the cytolysis of primary cells from b-NHL patients microenvironment. The off-the-shelf character of uptake of cellular fuels and the flux through metabolic »» Kinase Inhibitor Discovery these cells is reflected in the fact that they can be pathways. We have characterised these metabolic »» CNS and Neurodegenerative 5:05 Interactive Breakout Discussion Groups cryopreserved and irradiated in bulk and shipped to the responses in activated NK cells, discovered the Targets Join a breakout discussion group. These are informal, treatment site overnight. metabolic regulators involved and their importance »» GPCR-Based Drug Discovery moderated discussions with brainstorming and 11:55 PANEL DISCUSSION for NK cell effector function. NK cells have profound interactive problem solving, allowing participants »» Constrained Peptides and metabolic defects in various disease states where Macrocyclics 12:25 pm Session Break from diverse backgrounds to exchange ideas and NK cell functional responses are impaired. These experiences and develop future collaborations around »» Lead Generation Strategies 12:35 Luncheon Presentation (Sponsorship discoveries have important implications for NK cell »» Target Identification and Opportunity Available) or Enjoy Lunch on Your Own a focused topic. Details on the topics and moderators immunotherapies. are available on the conference website. Validation - Part 1 & Part 2 1:15 Refreshment Break in the Exhibit Hall with 3:25 Refreshment Break in the Exhibit Hall with Poster »» Antibacterial Discovery and Poster Viewing Viewing and Poster Competition Winner Announced Development 6:05 Welcome Reception in the Exhibit Sponsored by Hall with Poster Viewing »» Targeting Gram-Negative CLINICAL DEVELOPMENTS OF NK CLINICAL DEVELOPMENTS OF NK Pathogens CELL-BASED THERAPIES 7:10 Close of Day »» NASH and Fibrosis CELL-BASED THERAPIES (CONT.) »» Targeting the Microbiome 1:50 Chairperson’s Remarks 4:05 Harnessing NK Cell Memory for Thursday, September 27 »» Antibody Discovery Forum - Hans Klingemann, MD, PhD, Vice President, Research & Leukemia Immunotherapy Development, NantKwest, Inc. 7:30 am Registration Open and Morning Coffee Part 1 & Part 2 Rizwan Romee, MD, Member Faculty and Director, 1:55 Genetic Modification of NK Cells to Retarget Haploidentical Donor Transplant Program, Oncology/ »» Antibodies Against Membrane DISCOVERY PLATFORMS Protein Targets - Part 1 & Part 2 and Sustain Anti-Tumor Activity in Patients with BMT and Leukemia Program, Dana Farber Cancer Multiple Myeloma Institute, Harvard Medical School AND TECHNOLOGIES FOR NK Hotel & Travel Evren Alici, MD, PhD, Head, Gene and Cell Therapy Group, We identified human cytokine induced memory-like CELLS (CONT.) Division of Hematology, Medicine, Karolinska University cells induced by brief activation of conventional NK Registration Information Hospital, Sweden cells with IL-12 and IL-18. These memory-like NK 8:00 Chairperson’s Remarks In this talk, I will comparatively discuss various cells have enhanced anti-leukemia responses and Hans Klingemann, MD, PhD, Vice President, Research & Development, NantKwest, Inc. Click Here to Register strategies for NK cell gene modification, modulation we recently completed first-in-human Phase I clinical DiscoveryOnTarget.com of degranulation using small molecules, as well as trial of these memory-like NK cells in patients with 8:05 NK Cells and Glioblastoma decreasing NK cell time-to-next-kill via modulation of advanced AML/MDS with very promising safety Michael A. Caligiuri, MD, President and Physician-in- intracellular RNA sensing pathways. I will also discuss and efficacy signal. We are now working on several Chief, City of Hope National Medical Center results of a first-in-man autologous ex vivo expanded approaches to expand the use of these memory-like Glioblastoma remains an incurable malignancy, NK cell clinical trial in patients with multiple myeloma presenting as late-stage disease with a very poor

A Division of Cambridge Innovation Institute NK Cell-Based Cancer Immunotherapy DiscoveryOnTarget.com • 20 IMMUNOTHERAPY Final Weeks to Register

Cover overall survival. Oncolytic viral therapy is currently expressing iPSC-NK cells demonstrate improved being explored in clinical trials, but in some instances, anti-tumor activity in vitro and in vivo. We are now Conference natural killer (NK) cells present a barrier to effective translating these NK-CAR-iPSC-NK cells to produce At-A-Glance viral replication and tumor lysis. We have discovered a standardized, targeted “off the shelf” anti-cancer Sponsorship & Exhibit how NK cells “see” human herpes virus – a mechanism immunotherapy. we have named Fc bridged cellular cytotoxicity – and Short Courses 11:20 Luncheon Presentation (Sponsorship have therefore devised strategies to circumvent this Opportunity Available) or Enjoy Lunch on Your Own Symposia barrier for this deadly disease. 11:50 Conference Registration Open Training Seminar 8:35 New Insights into Requirements for Human NK Cell Development Plenary Keynotes Emily Mace, PhD, Assistant Professor, Pediatric 12:20 pm Plenary Keynote Program Click here for details. Agenda Immunology, American Society for Hematology Scholar, »» Small Molecules for Cancer Pediatrics, Columbia University Irving Medical Center In this talk, I will discuss recent developments in Immunotherapy 2:00 Refreshment Break in the Exhibit Hall with understanding the requirements for the differentiation »» Autoimmune and Inflammation Poster Viewing and expansion of functionally mature human NK cells Drug Targets from immature precursors. In particular, I will focus on 2:45 Close of Conference »» NK Cell-Based Cancer insights derived from in vitro differentiation systems Immunotherapy that hold promise for better understanding and »» Targeting Tumor Myeloid Cells improving the efficiency and specificity of clinically »» Targeting the Ubiquitin- relevant NK cell subsets. Proteasome System 9:05 Reports from Wednesday Evening »» Kinase Inhibitor Discovery Breakout Discussions »» CNS and Neurodegenerative Targets 9:35 Coffee Break in the Exhibit Hall with »» GPCR-Based Drug Discovery Poster Viewing »» Constrained Peptides and Macrocyclics DISCOVERY PLATFORMS AND »» Lead Generation Strategies TECHNOLOGIES FOR NK CELLS (CONT.) »» Target Identification and 10:20 Discovering Novel Therapeutic Antibody to Validation - Part 1 & Part 2 Modulate NK Cells for Cancer Immunotherapy »» Antibacterial Discovery and Zhengmao Ye, PhD, Biochemical and Cellular Development Pharmacology, Genentech »» Targeting Gram-Negative Natural Killer cell is a critical immune cell subset Pathogens mediating tumor killing. In this proposal, I plan to discuss »» NASH and Fibrosis a drug discovery project targeting a cell surface protein »» Targeting the Microbiome that mediates the suppression of NK and CD8+ T cell »» Antibody Discovery Forum - activity. I will discuss the functional assay development/ Part 1 & Part 2 antibody screening strategy for lead identification as well »» Antibodies Against Membrane as pharmacological characterization of the lead molecule Protein Targets - Part 1 & Part 2 and its MOA elucidation. 10:50 Engineering Human Pluripotent Stem Cells Hotel & Travel to Produce NK Cells with Improved Targeted Anti- Cancer Activity Registration Information Dan Kaufman, MD, PhD, Professor, Director of Cell Therapy Program, University of California, San Diego Click Here to Register Our studies have designed novel chimeric antigen DiscoveryOnTarget.com receptors optimized to enhance NK cell-mediated anti-tumor activity. We use human induced pluripotent stem cells (iPSCs) as a platform to express these NK-CARs and can efficiently produce iPSC-derived NK cells with stable CAR expression. NK-CAR-

A Division of Cambridge Innovation Institute NK Cell-Based Cancer Immunotherapy DiscoveryOnTarget.com • 21 IMMUNOTHERAPY Final Weeks to Register 2nd Annual | September 27-28 Targeting Tumor Myeloid Cells Cover Successful Strategies and Clinical Advancement Conference At-A-Glance Sponsorship & Exhibit

Short Courses Recently, our understanding of the Tumor Microenvironment (TME) has shed light onto the importance of 3:25 Chemotherapy-Induced Metastasis: Mechanisms Symposia tumor-infiltrating myeloid cells, such as tumor-associated neutrophils (TANs), myeloid-derived suppressor and Translational Opportunities cells (MDSCs), tumor-associated macrophages (TAMs), and tumor-associated dendritic cells (TADCs), as George S. Karagiannis, DVM, PhD, Anatomy and Training Seminar critical contributors to the suppression of innate and adaptive immune responses. Importantly, these cells Structural Biology, Albert Einstein College of Medicine Plenary Keynotes exist in various states within the TME, producing either immunosuppressive or immunostimulatory responses. Anatomy and Structural Biology Therapeutically targeting of tumor myeloid cells to eliminate or to convert them to their immunostimulatory state A better understanding of the mechanistic Agenda has emerged as a new and complementary strategy in the suite of cancer immunotherapy approaches. However, underpinnings of chemotherapy-induced metastasis »» Small Molecules for Cancer our understanding of tumor-resident myeloid cell phenotype and their possible divergent function in the tumor will allow us to better predict which patients are Immunotherapy microenvironment is still not elaborated. more likely to exhibit pro-metastatic responses to »» Autoimmune and Inflammation chemotherapy and will help develop new therapeutic Drug Targets Cambridge Healthtech Institute’s 2nd Annual Targeting Tumor Myeloid Cells conference will bring together strategies to neutralize chemotherapy-driven »» NK Cell-Based Cancer experts in the field to examine their phenotypic complexity and possible functions in connection with the tumor prometastatic changes. Immunotherapy microenvironment. We will also discuss evidences for their contribution to cancer pathogenesis from new clinical 3:55 Talk Title to be Announced »» Targeting Tumor Myeloid Cells studies along with regulation mechanisms of myeloid cells by tumors. Kipp Weiskopf, MD, PhD, Resident Physician, Internal »» Targeting the Ubiquitin- Medicine, Brigham and Women’s Hospital Proteasome System TUMOR MICROENVIRONMENT AND 4:25 Refreshment Break in the Exhibit Hall with »» Kinase Inhibitor Discovery RECOMMENDED ALL ACCESS Poster Viewing »» CNS and Neurodegenerative PACKAGE: Choose 2 Short Courses THE IMMUNE SYSTEM Targets or 1 Symposium and 2 Conferences/ 2:45 Welcome Remarks Ngoc Emily Le, PhD, Conference Producer, Cambridge TUMOR MICROENVIRONMENT AND »» GPCR-Based Drug Discovery Training Seminars »» Constrained Peptides and Healthtech Institute THE IMMUNE SYSTEM (CONT.) Macrocyclics • September 25 Symposium: 2:50 Chairperson’s Opening Remarks 5:00 Targeting the ATP: Adenosine Pathway in Cancer »» Lead Generation Strategies Targeting Autophagy Kipp Weiskopf, MD, PhD, Resident Physician, Internal Tim Sullivan, PhD, Vice President, Business »» Target Identification and • September 25 Short Course 3: How to Medicine, Brigham and Women’s Hospital Development, Arcus Biosciences, Inc. Validation - Part 1 & Part 2 Best Utilize 3D Cells, Spheroids, and PDX In many tumors, extracellular adenosine contributes »» Antibacterial Discovery and Models in Oncology 2:55 KEYNOTE PRESENTATION: to an immunosuppressed tumor micro-environment Development • September 26-27 Conference: NK Cell-Based Reprogramming Tumor (TME) via activation of the A2a receptor (A2aR), »» Targeting Gram-Negative Cancer Immunotherapy Microenvironment to Enhance expressed on lymphocytes, and the A2b receptor Pathogens Immunotherapy (A2bR), expressed on myeloid cells. AB928 is a novel • September 27-28 Conference: Targeting and selective dual A2aR/A2bR antagonist designed »» NASH and Fibrosis Tumor Myeloid Cells Dai Fukumura, MD, PhD, Deputy »» Targeting the Microbiome Director of Edwin L. Steele Laboratory and to potently block the immunosuppressive effects of »» Antibody Discovery Forum - • September 27 Short Course 16: Investigator, Massachusetts General Hospital; adenosine in the TME. Immunology Basics Part 1 & Part 2 Associate Professor, Harvard Medical School 5:30 Inhibition of STAT3 by Antisense Oligonucleotide »» Antibodies Against Membrane Immune checkpoint blocker immunotherapy has Treatment Decreases the Immune Suppressive Tumor Protein Targets - Part 1 & Part 2 Thursday, September 27 revolutionized oncology. However, its efficacy Microenvironment in Syngeneic Tumor Models is limited to small fraction of patients. Our Theresa Proia, PhD, Associate Principal Scientist, In Vivo Hotel & Travel 11:50 am Conference Registration Open laboratory has been dissecting the role of tumor Bioscience, Oncology IMED Biotech Unit, AstraZeneca microenvironment (TME) in tumor progression We explored the ability of a mouse STAT3 targeted Registration Information 12:20 pm Plenary Keynote Program and therapeutic response. We found that antisense oligonucleotide (ASO) to enhance the Click here for details. TME suppresses anti-tumor immunity via two antitumor activity of an anti-PD-L1 mAb in syngeneic Click Here to Register components – abnormal ECM and infiltrated murine tumor models. Our data indicate that DiscoveryOnTarget.com myeloid cells – resulting in hypoperfusion, inhibition of STAT3 has immunomodulatory activity, 2:00 Refreshment Break in the Exhibit Hall with hypoxia and immunosuppression. We specifically through reduction of suppressive CD163+ Poster Viewing developed strategies to reprogram immune cells and in combination with anti-PDL1, increased TME and enhance immunotherapy by targeting cytotoxic activity of CD8+ T cells in CT26 tumors, these mechanisms. leading to significant tumor growth inhibition. These

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Cover data demonstrate the opportunity to effectively are equipped with a broad functional repertoire that 11:15 The Development of ARRY382 combine STAT3 ASO with antibodies such as those promotes tumor growth by suppressing cytotoxic T John E. Robinson, PhD, Director, Array BioPharma, Inc. Conference targeting PD-L1 to enhance the activity of immune cell activity, stimulating neo-angiogenesis and tissue There is growing interest in the role of CSF1 in At-A-Glance checkpoint inhibitors. remodeling. There are several pharmacological cancer. CSF1 driven M2 macrophages mediate Sponsorship & Exhibit 6:00 Targeting Myeloid Cells in the Microenvironment approaches to therapeutically target tumor-associated immune suppression in the tumor microenvironment myeloid cells, each of which has unique advantages and therefore CSF1R inhibition provides a viable Short Courses David C. Linehan, MD, Seymour I. Schwartz Professor, Chairman, Surgery, University of Rochester Medical and challenges that need to be considered to achieve therapeutic strategy for augmenting established tumor Symposia Center Objective clinical benefit. immunotherapeutics such as anti-PD-1 and anti-CTLA4. ARRY-382 is a potent, selective CSF1R kinase inhibitor Training Seminar Targeting tumour-associated CXCR2+neutrophils 9:05 Targeting Tumor Infiltrating Myeloid Cells for (TAN) or tumour-associated CCR2+ macrophages Effective Immunotherapy that could have utility in immune-oncology. In a phase Plenary Keynotes (TAM) alone improves antitumour immunity in Alan Wang, PhD, Associate Professor, Cancer Biology, I study in cancer patients ARRY-382 induced a 28X increase in circulating CSF-1 while simultaneously Agenda preclinical models. However, a compensatory influx The University of Texas MD Anderson Cancer Center reducing non-classical (M2) macrophages by 96% from »» Small Molecules for Cancer of an alternative myeloid subset may result in a Both human cancers and mouse tumors are heavily persistent immunosuppressive TME and promote infiltrated with various types of myeloid cells. Their baseline. The design and discovery of ARRY-382 along Immunotherapy therapeutic resistance. Here, we show CCR2 and immune suppressive roles in GEM models, including with additional clinical results will be presented. »» Autoimmune and Inflammation CXCR2 combined blockade reduces total tumour- castration resistance prostate cancer, colon cancer, Drug Targets infiltrating myeloids, promoting a more robust pancreatic cancer and GBM will be discussed. Results EMERGING TECHNOLOGIES AND »» NK Cell-Based Cancer antitumour immune response in PDAC compared with on combinations of MDSCs targeting agents and MODEL ADVANCEMENT Immunotherapy either strategy alone. immune checkpoint blockade will be presented. »» Targeting Tumor Myeloid Cells 11:45 Chairperson’s Remarks »» Targeting the Ubiquitin- 6:30 Dinner Short Course Registration 9:35 Reprogramming Tumor-Associated Donald L. Durden, MD, PhD, Director, SignalRx Proteasome System Click here for details on short courses offered. Macrophages by Targeting PI3K- γ with IPI-549 Pharmaceuticals, Inc. Jeffery Kutok, MD, PhD, CSO, Infinity Pharmaceuticals »» Kinase Inhibitor Discovery 9:30 Close of Day 11:45 Macrophage Syk-PI3Kγ-HIF Axis Controls IPI-549 is a first-in-class, oral, selective PI3K-γ inhibitor »» CNS and Neurodegenerative Tumor Immune Suppression that in preclinical studies reprograms macrophages Targets Friday, September 28 Donald L. Durden, MD, PhD, Director, SignalRx from an immune-suppressive to an immune-activating »» GPCR-Based Drug Discovery Pharmaceuticals, Inc. 7:00 am Registration Open phenotype and can overcome resistance to checkpoint »» Constrained Peptides and inhibitors. We are conducting a Ph 1/1b study 12:15 pm Session Break Macrocyclics 7:30 Interactive Breakfast Breakout IPI-549-01 (NCT02637531) evaluating the safety, 12:25 Luncheon Presentation (Sponsorship »» Lead Generation Strategies tolerability, pharmacokinetics, pharmacodynamics, and Opportunity Available) or Enjoy Lunch on Your Own »» Target Identification and Discussion Groups Grab a cup of coffee and join a breakout discussion immunomodulatory activity of IPI-549 to determine its 1:15 Refreshment Break in the Exhibit Hall with Validation - Part 1 & Part 2 group. These are informal, moderated discussions recommended Phase II dose and preliminary efficacy, Poster Viewing »» Antibacterial Discovery and with brainstorming and interactive problem solving, as monotherapy and combined with nivolumab, in Development allowing participants from diverse backgrounds ~200 advanced solid tumor patients. EMERGING TECHNOLOGIES AND »» Targeting Gram-Negative to exchange ideas and experiences and develop 10:05 Coffee Break in the Exhibit Hall with Poster MODEL ADVANCEMENT (CONT.) Pathogens future collaborations around a focused topic. Details Viewing and Poster Competition Winner Announced »» NASH and Fibrosis 1:55 Chairperson’s Remarks on the topics and moderators are available on the 10:45 Blocking the CD47 “Do Not Eat” Signal with »» Targeting the Microbiome conference website. Donald L. Durden, MD, PhD, Director, SignalRx »» Antibody Discovery Forum - SIRPaFc Fusion Proteins Pharmaceuticals, Inc. Bob Uger, PhD, CSO, Trillium Therapeutics, Inc. Part 1 & Part 2 CD47 is an innate immune checkpoint that binds to 2:00 Cancer Immunotherapy Getting Brainy: »» Antibodies Against Membrane TARGETING MYELOID CELLS IN SIRPα and delivers a “do not eat” signal to suppress Visualizing the Distinctive CNS Metastatic Niche to Protein Targets - Part 1 & Part 2 CANCER – CLINICAL APPROACHES macrophage phagocytosis. Many tumors express Illuminate Therapeutic Resistance Bryan Ronain Smith, PhD, Associate Professor, Hotel & Travel 8:30 Chairperson’s Remarks high levels of CD47 to escape macrophage-mediated immune surveillance. Trillium Therapeutics is Instructor, Radiology and Molecular Imaging Program, Jeffery Kutok, MD, PhD, CSO, Infinity Pharmaceuticals Stanford University Registration Information developing SIRPaFc fusion proteins to block the 8:35 A Drug Development Perspective on Targeting CD47 “do not eat” signal. The preclinical rationale Current methods to examine the immunobiology of Tumor-Associated Myeloid Cells and emerging clinical data for this novel class metastases in the brain are constrained by tissue Click Here to Register Majety Meher Vinay Krishna Mohan, PhD, Principal of innate immune system checkpoint inhibitors processing methods that limit spatial data collection, DiscoveryOnTarget.com Scientist, Cancer Immunotherapy, Discovery Oncology, will be discussed. omit dynamic information, and cannot recapitulate the Pharma Research and Early Development (pRED), Roche heterogeneity of the tumor microenvironment. In the Innovation Center Munich current review, we describe how high-resolution, live Myeloid cells represent one of the most abundant imaging tools, particularly intravital microscopy (IVM), immune cell populations within the tumor stroma and are instrumental in answering these questions.

A Division of Cambridge Innovation Institute Targeting Tumor Myeloid Cells DiscoveryOnTarget.com • 23 IMMUNOTHERAPY Final Weeks to Register

Cover 2:30 Sialyl Tn: A Novel Therapeutic Target for Myeloid 3:00 TIM-3 Regulates CD103+ Dendritic Cell Function 3:30 Re-Programming Tumor Myeloid Compartment Derived Suppressor Cells and Response to Chemotherapy in Breast Cancer Karrie Wong, PhD, Investigator II, Exploratory Conference David A. Eavarone, PhD, Senior Scientist, Siamab Brian Ruffell, Assistant Member, Immunology, H. Lee Immuno-Oncology, Novartis Institutes for BioMedical At-A-Glance Therapeutics Moffitt Cancer Center and Research Institute Research, Inc. Sponsorship & Exhibit Tumor expression of the glycan Sialyl Tn (STn) is well Immunotherapeutic approaches are particularly Granulocyte-macrophage colony-stimulating factor established and can be leveraged for therapeutic lacking in breast cancer. Here we describe that TIM-3 (GM-CSF), a pleiotropic cytokine that modulates the Short Courses intervention. We have detected the presence of STn on expression by intratumoral CD103+ DCs regulates differentiation and maturation of innate immune cells, Symposia the surface of infiltrating myeloid derived suppressor chemokine expression during paclitaxel treatment, has a complex role in cancer immunotherapy. In the cells (MDSCs) in a panel of human tumor samples. with anti-TIM-3 antibody administration leading to tumor microenvironment, GM-CSF contributes to Training Seminar Data from in vivo tumor models links tumor and MDSC an immune-mediated response to chemotherapy immunosuppression in the tumor microenvironment Plenary Keynotes STn expression and supports the use of anti-STn in murine models. These findings expand upon the in a context dependent manner by inducing myeloid therapeutics for targeting MDSCs and reducing tumor potential targets of TIM-3 antibodies currently in suppressor cells and regulatory T cells. Using an in Agenda immune suppression. clinical trials and offer a rationale for combinatorial vitro assay and in vivo syngeneic tumor models, we »» Small Molecules for Cancer studies with chemotherapy. explored targets of GM-CSF mediated myeloid cell Immunotherapy immunosuppression. »» Autoimmune and Inflammation 4:00 Close of Conference Drug Targets »» NK Cell-Based Cancer Immunotherapy »» Targeting Tumor Myeloid Cells »» Targeting the Ubiquitin- Proteasome System »» Kinase Inhibitor Discovery »» CNS and Neurodegenerative Targets »» GPCR-Based Drug Discovery »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Targeting Tumor Myeloid Cells DiscoveryOnTarget.com • 24 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register 6th Annual | September 26-27 Targeting the Ubiquitin-Proteasome System Cover Small Molecules and Assays for Modulating DUBs, Ligases and More Conference At-A-Glance Sponsorship & Exhibit

Short Courses The ubiquitin-proteasome system (UPS) is a well-controlled, selective mechanism for intracellular protein interleukin (IL)-1β and IL-18. The deubiquitinase Symposia degradation and turnover. New understanding of the role and molecular mechanisms involved in the enzyme, STAM-binding protein (STAMBP) is necessary dysregulation of the UPS has led to its emergence as a key regulator of protein function and stability. Although for inflammasome activation and IL-1β secretion after Training Seminar implicated to play a role in cancer, CNS, infectious diseases and more, the multi-step processes involved, and the Toll-like receptor (TLR) agonism. A small-molecule Plenary Keynotes diversity of substrates, make it difficult to target the UPS. However, in recent years, the development of high- inhibitor of STAMBP suppresses IL-1β release after quality chemical probes and assay technologies has turned it into one of the most exciting targets for discovering TLR agonism in both cell and tissue models. These Agenda novel drugs. In the UPS, the ligases and deubiquitinases (DUBs) have recently attracted a lot of attention as findings describe a unique pathway of inflammasome »» Small Molecules for Cancer possible targets for clinical intervention. Cambridge Healthtech Institute’s Targeting the Ubiquitin-Proteasome regulation with the identification of STAMBP as a Immunotherapy System conference will bring together a diverse group of chemists and biologists to discuss the promise and potential therapeutic target. »» Autoimmune and Inflammation challenges in modulating the UPS. 9:40 Grand Opening Coffee Break in the Exhibit Hall Drug Targets with Poster Viewing »» NK Cell-Based Cancer RECOMMENDED ALL ACCESS 8:10 USP14: Mechanism, Specificity, and Inhibition 10:25 New Screening Technologies and Chemical Immunotherapy Daniel Finley, PhD, Professor, Department of Cell Biology, »» Targeting Tumor Myeloid Cells PACKAGE: Choose 2 Short Courses Probes Targeting the Ubiquitin System: Inhibitors, Harvard Medical School Activators, and Degraders »» Targeting the Ubiquitin- or 1 Symposium and 2 Conferences/ USP14, a proteasomal deubiquitinating enzyme, Proteasome System Alexander Statsyuk, PhD, Assistant Professor, can rapidly remove ubiquitin prior to substrate Department of Pharmacological and Pharmaceutical »» Kinase Inhibitor Discovery Training Seminars commitment to degradation, thus rescuing substrates Sciences, University of Houston »» CNS and Neurodegenerative • September 25 Symposium: from a fate of degradation. Accordingly, small- The Ubiquitin System has emerged as promising Targets Targeting Autophagy molecule USP14 inhibitors that we have identified system for drug discovery. Two major principles »» GPCR-Based Drug Discovery • September 25 Short Course 11: Mechanistic can stimulate the degradation of specific proteasome of targeting the ubiquitin system have emerged: »» Constrained Peptides and Understanding of Pharmacological Probes for targets. USP14 shows a novel principle of selectivity in direct targeting of the enzymes that control protein Macrocyclics the Ubiquitin-Proteasome System that it only deubiquitinates proteins carrying multiple ubiquitination, and hijacking E3 ligases to induce »» Lead Generation Strategies • September 26-27 Conference: Targeting the ubiquitin chains. USP14 is activated ~1000-fold by the protein degradation. In this lecture I will outline novel »» Target Identification and Ubiquitin-Proteasome System proteasome. We will discuss interesting new mutants screening tools and technologies to discover small Validation - Part 1 & Part 2 that prevent this activation. • September 27-28 Conference: Kinase molecule inhibitors/activators and hijackers for RBR/ »» Antibacterial Discovery and Inhibitor Discovery 8:40 Conformational Remodeling of USP7 Catalytic HECT E3 ligases. Development Domain to Promote Deubiquitinating Activity 10:55 A Targeted Quantitative Proteomic Assay for »» Targeting Gram-Negative • September 27 Short Course 18: Practical Ayşegül Özen, PhD, Scientist II, Blueprint Medicines Phenotypic Screening Parkinson’s Disease That Measures the Dynamics Pathogens USP7 catalytic domain (USP7cd) shows limited activity of Ubiquitin Events on Mitochondria and Their »» NASH and Fibrosis alone and is regulated by intramolecular domains. Modulation by Small Molecules » Structural features stabilizing the inactive state and » Targeting the Microbiome Wednesday, September 26 Alban Ordureau, PhD, Postdoctoral Fellow, Laboratory »» Antibody Discovery Forum - atomistic mechanism of activation remain unclear. By of Dr. Wade Harper, Department of Cell Biology, Harvard Part 1 & Part 2 7:00 am Registration Open and Morning Coffee comparative structural analyses, molecular dynamics Medical School »» Antibodies Against Membrane simulations, and in silico sequence re-engineering, The kinase PINK1 and Ub ligase Parkin, both mutated Protein Targets - Part 1 & Part 2 EMERGING ASSAYS & APPROACHES we identified key determinants of USP7cd activation, in Parkinson’s disease, promote mitochondrial outer engineered USP7cd for improved activity, and show TO STUDY AND MODULATE THE membrane ubiquitylation and mitophagy. We have Hotel & Travel that electrostatics in a distal loop and local packing in developed a quantitative proteomics approach that UBIQUITIN CASCADE the core together modulate USP7cd activation. allows the dynamics and site specificity of Parkin- Registration Information 8:00 Welcome Remarks 9:10 Targeting the Deubiquitinase STAMBP Inhibits dependent mitochondrial ubiquitylation to be assessed Tanuja Koppal, PhD, Conference Director, Cambridge Inflammasome Activity in model systems and ES cell-derived neurons. Click Here to Register Healthtech Institute Joseph S. Bednash, MD, Postdoctoral Scholar, Division We demonstrate that this approach can be used DiscoveryOnTarget.com 8:05 Chairperson’s Opening Remarks of Pulmonary and Critical Care Medicine, University of to monitor the activity of activators, inhibitors and Daniel Finley, PhD, Professor, Department of Cell Biology, Pittsburgh regulators of the pathway with precision. Harvard Medical School Inflammasomes regulate innate immune responses by facilitating maturation of inflammatory cytokines,

A Division of Cambridge Innovation Institute Targeting the Ubiquitin-Proteasome System DiscoveryOnTarget.com • 25 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover 11:25 Mass Spectrometry Analysis of Linkage- Consistent with this observation, depletion of Nrf1 developed potent and selective inhibitors of USP7 as a Specific Ubiquitin Sites in Response to enhances proteasome inhibitor-mediated apoptosis novel approach to cancer therapy. Conference Oxidative Stress in multiple cancer cells. In this presentation, I will At-A-Glance Gustavo M. Silva, PhD, Assistant Professor, Department describe a strategy to target the Nrf1 pathway 5:05 Interactive Breakout Discussion Groups Sponsorship & Exhibit of Biology, Duke University to potentiate the action of proteasome inhibitor Join a breakout discussion group. These are informal, Oxidative stress is a prevalent condition that can lead drugs in cancer. Short Courses moderated discussions with brainstorming and to cell death, causing a variety of human diseases. 2:25 Small Molecule Activation of interactive problem solving, allowing participants Symposia To combat the harmful effects of oxidative stress, Proteasome Activity from diverse backgrounds to exchange ideas and protein ubiquitination plays a significant role in Training Seminar Jetze Tepe, PhD, Associate Professor of Chemistry, experiences and develop future collaborations around regulating function, location, and fate of the proteome. Department of Chemistry, Michigan State University a focused topic. Details on the topics and moderators Plenary Keynotes Although the ubiquitin system is highly complex, here Intrinsically disordered proteins are important, low- are available on the conference website. we used mass spectrometry to tease out a distinct Agenda abundant signaling proteins targeted for degradation ubiquitin signal, revealing new pathways relevant for by the 20S proteasome. When over-expressed, »» Small Molecules for Cancer 6:05 Welcome Reception in the Exhibit Sponsored by stress response. these disordered proteins are directly implicated in Immunotherapy Hall with Poster Viewing 11:55 Drugging the Undruggable: Sponsored by many human diseases, including neurodegenerative »» Autoimmune and Inflammation Discovering Novel Drugs for the diseases and cancer. Our work demonstrates 7:10 Close of Day Drug Targets Ubiquitin-Proteasome System that small molecules can enhance the catalytic »» NK Cell-Based Cancer Peter Foote, PhD, Senior Scientist II, Research & degradation of intrinsically disordered proteins by the Thursday, September 27 Immunotherapy Development, LifeSensors 20S proteasome, which represents a new therapeutic 7:30 am Registration Open and Morning Coffee »» Targeting Tumor Myeloid Cells While ubiquitin regulates critical disease pathways, strategy to combat human diseases. »» Targeting the Ubiquitin- few FDA-approved drugs target the UPS, due to a 2:55 Sponsored Presentation (Opportunity Available) NEW PROBES AND INHIBITORS Proteasome System lack of physiological HTS tools and PD markers for »» Kinase Inhibitor Discovery cellular activity. We have developed assays enabled 3:25 Refreshment Break in the Exhibit Hall with Poster TARGETING DUBS AND LIGASES »» CNS and Neurodegenerative by Tandem Ubiquitin Binding Entities (TUBEs) to Viewing and Poster Competition Winner Announced 8:00 Chairperson’s Remarks Targets quantitate cellular substrate ubiquitylation and help 4:05 USP7 Inhibition Impairs FOXP3+ Treg Function Stephanos Ioannidis, Ph.D., Head, Early Portfolio, FORMA »» GPCR-Based Drug Discovery accelerate successful compounds to the clinic. and Promotes Antitumor Immunity Therapeutics »» Constrained Peptides and 12:10 Sponsored Presentation (Opportunity Available) Wayne W. Hancock, MD, PhD, Professor, Pathology and Macrocyclics Chief of Transplant Immunology, Children’s Hospital of »» Lead Generation Strategies 12:25 pm Session Break Philadelphia and University of Pennsylvania »» Target Identification and 12:35 Luncheon Presentation (Sponsorship FOXP3+ T-regulatory (Treg) cells are present in Validation - Part 1 & Part 2 Opportunity Available) or Enjoy Lunch on Your Own increased numbers and display significantly enhanced »» Antibacterial Discovery and 1:15 Refreshment Break in the Exhibit Hall with suppressive function compared to Tregs isolated Development Poster Viewing from adjacent lung, lymph node or blood of the »» Targeting Gram-Negative same individual, leading to potent suppression of Pathogens NOVEL STRATEGIES FOR TARGETING host anti-tumor immunity. USP7 inhibition is able Maximize your experience on- to preferentially impair FOXP3+ Treg function while »» NASH and Fibrosis USP7 AND PROTEASOME site at Discovery on Target 2018! »» Targeting the Microbiome maintaining host-anti-tumor immunity, leading to »» Antibody Discovery Forum - 1:50 Chairperson’s Remarks beneficial effects when used alone or in conjunction The Intro-Net offers you the opportunity with checkpoint blockade, vaccination or other Part 1 & Part 2 1:55 Targeting the Nrf1-mediated Proteasome to set up meetings with selected therapeutic approaches. »» Antibodies Against Membrane Recovery Pathway in Cancer attendees before, during and after this Protein Targets - Part 1 & Part 2 Senthil K. Radhakrishnan, PhD, Assistant Professor, 4:35 Potent and Selective USP7 Inhibitors Target conference, allowing you to connect Department of Pathology, Virginia Commonwealth Multiple Tumor Types through Diverse Mechanisms to the key people you want to meet. Hotel & Travel University Paul Kassner, PhD, Vice President, FLX Bio, Inc. Inhibition of cellular proteasome results in USP7 is a deubiquitinase with multiple downstream This online system was designed with Registration Information transcriptional upregulation of proteasome targets. Inhibitors of USP7 are expected to decrease your privacy in mind and is available subunit genes eventually leading to the recovery of function of oncogenes, increase tumor suppressor only to registered session attendees Click Here to Register proteasome activity. In mammalian cells, this recovery function, enhance immune function and sensitize of this event. Registered conference DiscoveryOnTarget.com pathway is mediated by the transcription factor Nrf1. tumor cells to DNA damaging agents. FLX Bio has attendees will receive more information on accessing the Intro-Net in the weeks leading up to the event.

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Cover 8:05 DUBing The Undruggable 9:05 Ubiquitination-Deubiquitination: A Friend and foe and non-antibody based approaches. We will present Stephanos Ioannidis, Ph.D., Head, Early Portfolio, FORMA in Cellular Homeostasis two case studies building plate-based, HTS-friendly Conference Therapeutics Sayantanee Niyogi, PhD, Scientist, Membrane Biology protein degradation assays potentially applicable for At-A-Glance FORMA Therapeutics deploys multiple drug discovery Section, National Institutes of Health (NIH) PROTACS identification campaigns. Sponsorship & Exhibit screening platforms to explore the DUB family We performed a screen knocking down about 100 10:50 PROTACS: The Chemical Equivalent of CRISPR (DUBome) and along with DUB scaffold repurposing, deubiquitinating enzymes to screen for DUBs that had Short Courses Shanique Alabi, Graduate Student, Laboratory of Dr. automated parallel synthesis, and computational an effect on traffic of proteins, upregulated during Craig Crews, Department of Molecular, Cellular and Symposia / crystallographic insights specific and selective Cancer. We identified two DUBs; USP3 and USP6 Developmental Biology, Yale University inhibitors within the DUBome have been identified. As that decreased the half-life of long-lived proteins Training Seminar Induced protein degradation offers several advantages part of a fully-integrated R&D strategy, DUB alliances routing them to degradation. We also discovered that over traditional inhibition strategies and has emerged Plenary Keynotes which include FORMA and key collaborative networks over-expression of USP6 could counter the effect recently as a potential therapeutic option. For the have been forged to assist in the interrogation of of an E3-Ligase MARCH8 induced degradation. This Agenda past 16 years, we have helped develop this fast- previous undruggable targets via specific DUB study demonstrates that cycles of ubiquitylation »» Small Molecules for Cancer growing field, shepherding our initial chemical biology inhibition. In this presentation FORMA’s novel and deubiquitylation can determine whether specific concept into a drug development strategy that is on Immunotherapy approach to DUBs and drugging the undruggable proteins are degraded or recycled. the verge of clinical validation. PROTACS with high »» Autoimmune and Inflammation will be described. 9:35 Coffee Break in the Exhibit Hall with target selectivity, potency, and oral bioavailability Drug Targets 8:35 Ubiquitin Code-Reading, Writing and Editing: Poster Viewing will be discussed as well as a system to address the »» NK Cell-Based Cancer Future of Breakthrough Therapies 10:20 Plate-Based Approach to Identify PROTACS ‘PROTACability’ of particular E3 ligases. Immunotherapy Tauseef R. Butt, PhD, President and CEO, Progenra, Inc. »» Targeting Tumor Myeloid Cells Molecules and Protein Degraders 11:20 Luncheon Presentation (Sponsorship We are currently developing small molecules that Davide Gianni, PhD, Team Leader, Discovery Sciences, Opportunity Available) or Enjoy Lunch on Your Own »» Targeting the Ubiquitin- inhibit the cancer-supporting DUBs and ubiquitin Proteasome System AstraZeneca 11:50 Conference Registration Open ligases. The DUB inhibitors are capable of both killing PROTACS provide a new modality to drug previously »» Kinase Inhibitor Discovery tumor cells directly and suppressing regulatory challenging targets and much evidence indicates »» CNS and Neurodegenerative T cells, thereby unleashing effector T cells, which that protein degraders are a mode of inhibition that 12:20 pm Plenary Keynote Program Targets identify and kill tumor cells. These results constitute can be pursued post HTS. Western Blot is mostly Click here for details. »» GPCR-Based Drug Discovery the first example of a small molecule single agent used to characterize PROTACS molecules, but it has »» Constrained Peptides and that works by targeting both the tumor itself and the a number of obvious limitations. The adoption of Macrocyclics tumor’s ability to escape surveillance and killing by the 2:00 Refreshment Break in the Exhibit Hall with plate-based approaches is essential in PROTACS and Poster Viewing »» Lead Generation Strategies host immune system and, in addition, by eliminating several options are available such as, antibody-based »» Target Identification and tumor metastasis. 2:45 Close of Conference Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Targeting the Ubiquitin-Proteasome System DiscoveryOnTarget.com • 27 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register 11th Annual | September 27-28 Kinase Inhibitor Discovery Cover Emerging Targets, Tools, and Development Strategies Conference At-A-Glance Sponsorship & Exhibit

Short Courses In 2017 we saw several kinase inhibitors approved by the FDA. Case studies of approved, clinically advanced or patients where encouraging early activity has Symposia promising inhibitors will be presented at this year’s Kinase Inhibitor Discovery conference at the Discovery on been observed. Target event in Boston. Special coverage will be given to work dedicated to binding kinetic studies with kinases Training Seminar 3:55 Sensors for Continuous Monitoring Sponsored by and other issues that remain a challenge, including selectivity. Attend to learn more. of Protein Kinase & Phosphatase Activity Plenary Keynotes Erik Schaefer, President, AssayQuant Agenda RECOMMENDED ALL ACCESS 2:50 Chairperson’s Opening Remarks Technologies »» Small Molecules for Cancer Campbell McInnes, PhD, Professor, Drug Discovery and AssayQuant® is combining chelation-enhanced PACKAGE: Choose 2 Short Courses Biomedical Sciences, University of South Carolina fluorescence, using the sulfonamido-oxine (Sox) Immunotherapy chromophore, with high-throughput peptide synthesis »» Autoimmune and Inflammation or 1 Symposium and 2 Conferences/ 2:55 Cancer Drug Resistance, Challenge and methods to identify optimized physiologically-based Drug Targets Training Seminars Opportunity – The Osimertinib Story substrates for measuring the activity of protein »» NK Cell-Based Cancer • September 25 Symposium: Stephen Fawell, PhD, Vice President, Head Oncology iScience, AstraZeneca kinases and phosphatases. The result is a simple yet Immunotherapy Targeting Autophagy powerful method that allows continuous, quantitative »» Targeting Tumor Myeloid Cells First line EGFR inhibitors like gefitinib are highly active • September 25 Short Course 1: Introduction to in EGFRmt NSCLC, however most patients eventually and homogenous detection of activity using »» Targeting the Ubiquitin- GPCR-Based Drug Discovery recombinant enzymes or crude cell or tissue lysates. Proteasome System relapse with drug resistant disease of which the • September 25 Short Course 10: Applications of majority are driven by a second T790M mutation. This approach provides a quantum improvement »» Kinase Inhibitor Discovery Artificial Intelligence and Machine Learning in Osimertinib, a potent and selective covalent inhibitor in assay performance and productivity needed to »» CNS and Neurodegenerative Drug Discovery and Development was specifically designed to target this form of the accelerate discovery and drug development efforts. Targets receptor. The combination of a well designed active 4:25 Refreshment Break in the Exhibit Hall with »» GPCR-Based Drug Discovery • September 26-27 Conference: Targeting the Ubiquitin-Proteasome System drug and a clear patient selection strategy led to one Poster Viewing »» Constrained Peptides and of the fastest approvals of an Oncology drug. Macrocyclics • September 27-28 Conference: Kinase CLINICAL AND ADVANCED »» Lead Generation Strategies Inhibitor Discovery 3:25 Illuminating the Darkness…PKC Inhibitors for »» Target Identification and Metastatic Uveal Melanoma INHIBITORS (CONT.) • September 27 Short Course 15: Introduction to Michael Visser, PhD, Group Leader, Senior Investigator, Validation - Part 1 & Part 2 5:00 ARQ 531, a Reversible BTK Inhibitor Exhibits Targeted Covalent Inhibitors Novartis Institutes for BioMedical Research, Inc. »» Antibacterial Discovery and Distinct Kinase Selectivity and Demonstrates Uveal Melanoma (UM) is the most common primary Development Potent Anti-Tumor Activity in Ibrutinib intraocular malignancy of the adult eye, with an »» Targeting Gram-Negative Thursday, September 27 Resistant Tumor Models incidence of five to six cases per million. Despite Sudharshan Eathiraj, PhD, Senior Lead Investigator, Pathogens aggressive local management of primary UM, the »» NASH and Fibrosis 11:50 am Conference Registration Open Translational Medicine, ArQule, Inc. development of metastases is common and occurs ARQ 531 is an ATP competitive reversible inhibitor of »» Targeting the Microbiome in ~50% of patients. There are currently no effective »» Antibody Discovery Forum - 12:20 pm Plenary Keynote Program BTK. Kinase selectivity profile combined with pathway treatment options for metastatic disease and median analysis data suggests that ARQ 531 targets multiple Part 1 & Part 2 Click here for details. survival is around nine months. Genetic analysis oncogenic signaling pathways and potently inhibits »» Antibodies Against Membrane of UM samples reveals the presence of activating tumor growth in the mouse xenografts of cell lines Protein Targets - Part 1 & Part 2 2:00 Refreshment Break in the Exhibit Hall with mutations in the Gq alpha subunits, GNAQ and primarily resistant to previously approved BTK inhibitor, GNA11. One of the key downstream targets of the Hotel & Travel Poster Viewing ibrutinib. ARQ 531 monotherapy is currently being constitutively active Gq alpha subunits is the protein investigated in a Phase 1 dose-escalation study in kinase C (PKC) signaling pathway. We describe the Registration Information CLINICAL AND ADVANCED B-cell hematologic malignancies. discovery of NVP-LXS196, a potent, selective PKC INHIBITORS inhibitor. The lead series was optimized for kinase 5:30 Full Kinome and Cancer Cell Panel Profiling of Click Here to Register 2:45 Welcome Remarks and off target selectivity to afford a compound All Kinase Inhibitor Drugs Approved for Clinical Use DiscoveryOnTarget.com Victoria Mosolgo, Conference Producer, Cambridge that is rapidly absorbed and well tolerated in pre- Guido Zaman, PhD, Managing Director & Head of Healthtech Institute clinical species. NVP-LXS196 is currently in Phase Biology, Netherlands Translational Research Center B.V. I clinical trials to assess the safety, tolerability and All small molecule kinase inhibitors approved pharmacokinetic profile in metastatic uveal melanoma for clinical use were profiled on a panel of 275 biochemical kinase assays and 102 cancer cell line

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Cover proliferation assays (Oncolines). Novel genomic Tumor Efficacy in Monotherapy and Combination in PHOSPHATASES biomarkers predictive of drug response in human Preclinical Tumor Models Conference tumor cells were discovered. Comparative analyses Ulrich Luecking, PhD, Principal Scientist, Medicinal 10:45 A Genomic Perspective on Protein and At-A-Glance of biochemical and cellular profiling data yielded Chemistry, Bayer Lipid Phosphatases Gerard Manning, PhD, Director, Bioinformatics and Sponsorship & Exhibit new insight into the mechanism of action of different The identification of ATR inhibitor BAY 1895344 is kinase inhibitor drugs acting via the same primary reported. In vitro, BAY 1895344 was shown to be a Computational Biology Genentech Short Courses target or signaling pathway. very potent and highly selective ATR inhibitor, which Kinases and phosphatases jointly control most biological pathways. Many phosphatases are Symposia potently inhibits proliferation of a broad spectrum COVALENT INHIBITORS of human tumor cell lines. BAY 1895344 revealed altered in disease but have been challenging to Training Seminar good bioavailability across species. Moreover, BAY target. We have cataloged all human protein and 6:00 The Meisenheimer Complex as a Novel Paradigm lipid phosphatases (the phosphatome) to serve as a Plenary Keynotes in Drug Discovery: Targeting PLK1 through a Novel 1895344 demonstrated potent anti-tumor efficacy in monotherapy in DNA damage response deficient global resource for understanding all phosphorylation Agenda Covalent Mechanism tumor models as well as in combination treatment events, and to derive new targets and biomarkers. »» Small Molecules for Cancer Campbell McInnes, PhD, Professor, Drug Discovery and I will review our findings and potential for new Biomedical Sciences, University of South Carolina with DNA damage-inducing and DNA repair- Immunotherapy therapeutic development.. This talk will describe novel inhibitors of PLK1 kinase compromising therapies. »» Autoimmune and Inflammation activity that inhibit through the unique covalent 9:05 Discovery of Novel, Soft JAK Kinase Inhibitors 11:15 Novel Inhibitor Design Concepts for Protein Drug Targets strategy that reversibly inhibits kinase activity by for Topical Treatment of Psoriasis Kinases and Phosphatases »» NK Cell-Based Cancer formation of a Meisenheimer Complex. The discovery Daniel R. Greve, PhD, Senior Manager, Head of Medicinal Gerhard Mueller, PhD, CSO, Gotham Therapeutics Immunotherapy and optimization of these inhibitors is described in Chemistry, LEO Pharma A/S The last 20 years of research on small molecule »» Targeting Tumor Myeloid Cells addition to confirmation of their on-target anti-tumor The presentation covers our efforts in a recent protein kinase inhibitors resulted in approximately 40 »» Targeting the Ubiquitin- mode of action through selective PLK1 inhibition. research project aiming for novel, selective pan- small molecule kinase inhibitors that received market Proteasome System approval. Apart from the traditional design paradigm, 6:30 Dinner Short Course Registration JAK inhibitors to treat psoriasis topically. The small »» Kinase Inhibitor Discovery i.e. optimizing compounds to competitively bind into Click here for details on short courses offered. molecule inhibitors have a pharmacokinetic profile »» CNS and Neurodegenerative that allows for high local exposure combined with the ATP site, a number of allosteric inhibitor binding Targets 9:30 Close of Day low systemic exposure, by optimizing human hepatic modalities have been discovered that allow to engineer »» GPCR-Based Drug Discovery clearance. The best compounds are efficacious in molecular properties such as target residence time. In »» Constrained Peptides and Friday, September 28 our mouse xenograft model of plaque psoriasis, while contrast to the kinase field, the target family of protein Macrocyclics being rapidly cleared from systemic circulation. phosphatases is and remains an underexplored area 7:00 am Registration Open even though individual members are well-validated »» Lead Generation Strategies 9:35 Discovery of AS-871, a Selective and Non- »» Target Identification and drug targets for therapeutic intervention into a 7:30 Interactive Breakfast Breakout Covalent BTK Inhibitor for the Treatment of number of disease states. The medicinal chemistry Validation - Part 1 & Part 2 Discussion Groups Rheumatoid Arthritis approaches that have been chosen to inhibit protein »» Antibacterial Discovery and Grab a cup of coffee and join a breakout discussion Masaaki Sawa, PhD, CSO, Carna Biosciences, Inc. phosphatases will be highlighted, again emphasizing Development group. These are informal, moderated discussions We have developed a novel non-covalent inhibitor of the relevance of allosteric binding mechanisms over »» Targeting Gram-Negative with brainstorming and interactive problem solving, BTK through the optimization of a lead compound traditional active site-directed design approaches. Pathogens allowing participants from diverse backgrounds which was derived from our SYK/BTK dual inhibitor »» NASH and Fibrosis program. During the lead optimization, we employed a 11:45 Exploring Kinase Inhibitor Sponsored by to exchange ideas and experiences and develop Selectivity and Affinity in Live Cells »» Targeting the Microbiome future collaborations around a focused topic. Details dual screening approach using two conformationally »» Antibody Discovery Forum - different BTK proteins, an activated form of BTK and Using NanoBRET on the topics and moderators are available on the Matthew Robers, Senior Research Part 1 & Part 2 an unactivated form of BTK to enhance the selectivity. conference website. Scientist, Group Leader, Biology, Promega »» Antibodies Against Membrane AS-871 displayed potent inhibitory activities in cellular Corporation Protein Targets - Part 1 & Part 2 assays and demonstrated significant efficacies in Yuren Wang, Director, Pharmacology and QC, Cell-Based SELECTIVE INHIBITORS & several in vivo models. Hotel & Travel Assay Group, Reaction Biology Corp. PROMISING CANDIDATES 10:05 Coffee Break in the Exhibit Hall with Poster We will describe the application of an energy Viewing and Poster Competition Winner Announced Registration Information 8:30 Chairperson’s Remarks transfer technique (NanoBRET) that enables the first Istvan Enyedy, PhD, Computational Chemistry, Biogen quantitative approach to broadly profile fractional occupancy and compound affinity for kinases in live Click Here to Register 8:35 Discovery of ATR Inhibitor BAY 1895344 cells. Through a collaboration with Reaction Biology DiscoveryOnTarget.com with Favorable PK Properties and Promising Anti- Corp (RBC), the NanoBRET technology has been scaled into a high-throughput cell-based profiling format. The validated Promega’s NanoBRET cell-based assay technology platform is compatible with RBC’s

A Division of Cambridge Innovation Institute Kinase Inhibitor Discovery DiscoveryOnTarget.com • 29 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover broad spectrum in vitro biochemical radioactive kinase 2:30 Conformational Adaption May Explain the Slow To identify novel, potent and selective kinase inhibitors assay platform. Dissociation Kinetics of Roniciclib (BAY 1000394), for the treatment of oncological and immunological Conference 12:15 pm Session Break a Type I CDK Inhibitor with Kinetic Selectivity disorders, we established a Kinase Platform Project At-A-Glance for CDK2 and CDK9 team to leverage kinase-target profiling,de novo 12:25 Luncheon Presentation (Sponsorship Sponsorship & Exhibit Christian Stegmann, PhD, Management Support, design, fragment screening and covalent approaches Opportunity Available) or Enjoy Lunch on Your Own Research & Development, Pharmaceuticals, Bayer AG targeted to individual kinases and kinase mini-panels. Short Courses 1:15 Refreshment Break in the Exhibit Hall with Roniciclib (BAY 1000394) is a type I pan-CDK (cyclin- In this presentation, we highlight our implementation Symposia Poster Viewing dependent kinase) inhibitor which has revealed of drug discovery technologies that led to the potent efficacy in xenograft cancer models. We could identification and development of two clinical Training Seminar BINDING KINETICS AND PROFILING show that roniciclib displays prolonged residence candidates, evobrutinib and M2698. Plenary Keynotes 1:55 Chairperson’s Remarks times on CDK2 and CDK9, whereas residence times 3:30 Strategies for Designing Selective on other CDKs are transient, thus giving rise to a Agenda Guido Zaman, PhD, Managing Director & Head of Kinase Inhibitors kinetic selectivity of roniciclib. In tumor cells, the »» Small Molecules for Cancer Biology, Netherlands Translational Research Center B.V. Istvan Enyedy, PhD, Computational Chemistry, Biogen prolonged residence times of roniciclib on CDK2 and Designing selective kinase inhibitors has been Immunotherapy 2:00 Kinetic Selectivity and Target Vulnerability in CDK9 are reflected in a sustained inhibitory effect on challenging. The desired selectivity of a kinase »» Autoimmune and Inflammation Drug Discovery retinoblastoma protein (RB) phosphorylation, indicating inhibitor depends on the therapeutic area. Drug Targets Peter Tonge, PhD, Professor, Chemistry, Stony Brook that the target residence time on CDK2 may contribute Polypharmacology is often desired in oncology, »» NK Cell-Based Cancer University to sustained target engagement and antitumor efficacy. Since a drug can bind to two targets with the same while highly selective inhibitors are usually needed Immunotherapy 3:00 A Kinase Platform for the Discovery of for other therapeutic areas. Strategies for designing »» Targeting Tumor Myeloid Cells affinity but different on and off rates, drug selectivity has both a thermodynamic and a kinetic component. Reversible and Covalent Kinase Inhibitors selective inhibitors vary from targeting residues that »» Targeting the Ubiquitin- Igor Mochalkin, PhD, Associate Director, EMD Serono are less conserved to exploiting differences in the Proteasome System Using systems such as Bruton’s tyrosine kinase as an example, we discuss the utility of kinetic selectivity, and Protein kinases play an important role in signaling flexibility of the kinase domain when selectivity among »» Kinase Inhibitor Discovery the role of target turnover and target vulnerability in the pathways that control cell growth, metabolism, isoforms is desired. »» CNS and Neurodegenerative translation of kinetic selectivity to in vivo drug activity. proliferation and apoptosis, and the dysregulation of 4:00 Close of Conference Targets kinase functions can fuel cancers and other diseases. »» GPCR-Based Drug Discovery »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Kinase Inhibitor Discovery DiscoveryOnTarget.com • 30 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register 2nd Annual | September 26-27 CNS and Neurodegenerative Targets Cover Targets and Tools for Developing CNS Therapies Conference At-A-Glance Sponsorship & Exhibit Short Courses The identification of therapeutic targets based on novel mechanistic approaches is urgently needed for MACHINE LEARNING, AI AND Symposia CNS and neurodegenerative diseases, particularly for conditions such as Alzheimer’s and Parkinson’s which represent extensive unmet medical need and blockbuster potential for the right therapy. Driven by an improving SCREENING TO IMPROVE CNS DRUG Training Seminar understanding of CNS disease biology and the emergence of new mechanisms and targets, Cambridge DISCOVERY Plenary Keynotes Healthtech Institute’s CNS and Neurodegenerative Targets conference profiles the latest tools, targets and 9:10 Machine Learning Models in CNS Drug Discovery platforms driving today’s CNS drug discovery strategies, with critical updates and findings in key areas such as Agenda Istvan Enyedy, PhD, Principal Scientist, Biogen new targets for misfolded proteins, tau, GCPRs, gene therapy, and neuroinflammation. »» Small Molecules for Cancer For CNS targets, the design of modulators that permeate the blood-brain barrier is challenging. The Immunotherapy 8:10 KEYNOTE PRESENTATION: promiscuity of efflux transporters is the main reason »» Autoimmune and Inflammation RECOMMENDED ALL ACCESS Progress in Deciphering Alzheimer’s for stopping the blood-brain barrier penetration of Drug Targets PACKAGE: Choose 2 Short Courses and Parkinson’s Diseases Predicts a large variety of compounds. Machine learning »» NK Cell-Based Cancer or 1 Symposium and 2 Conferences/ New Therapeutic Approaches methods have been used for building models for Immunotherapy Training Seminars Dennis J. Selkoe, MD, The Vincent and predicting substrates of efflux transporters. The »» Targeting Tumor Myeloid Cells Stella Coates Professor of Neurologic Diseases, performance of several models will be presented. »» Targeting the Ubiquitin- • September 25 Symposium: Harvard Medical School; Co-Director, Center for Proteasome System Regenerative Medicine 9:40 Grand Opening Coffee Break in the Exhibit Hall Neurologic Diseases, Department of Neurology, with Poster Viewing »» Kinase Inhibitor Discovery • September 25 Short Course 9: CNS Brigham and Women’s Hospital »» CNS and Neurodegenerative Translational Strategies There are specific reasons for the failure of 10:25 Phenotypic Screening for Novel Inhibitors of Targets Tau Aggregation in Human iPSC-Derived Neurons • September 26-27 Conference: CNS and certain clinical trials in AD, and the underlying »» GPCR-Based Drug Discovery Bhavya Voleti, PhD, Associate Principal Scientist, Neurodegenerative Targets biological understanding of the disease is »» Constrained Peptides and sound and steadily improving. Here, we will Neurodegenerative Diseases Discovery WP, Merck Macrocyclics • September 27-28 Conference: Lead review the basic science of AD pathogenesis. Research Laboratories »» Lead Generation Strategies Generation Strategies We will also discuss a new hypothesis for the Tauopathies are neurodegenerative diseases »» Target Identification and • September 27 Short Course 16: initiation of dopaminergic neurodegeneration in characterized by the presence of aggregates of abnormally hyperphosphorylated tau. Due to the Validation - Part 1 & Part 2 Immunology Basics Parkinson’s disease. intrinsic differences in clearance mechanisms »» Antibacterial Discovery and between neuronal and non-neuronal cells, human iPSC- Development Wednesday, September 26 8:40 Translating Targets into Therapeutic Candidates derived neurons were used to develop a biologically »» Targeting Gram-Negative for Alzheimer’s Disease relevant tau model. The goal of this work is to uncover Pathogens 7:00 am Registration Open and Morning Coffee Stephen Wood, PhD, Director, Neuroscience Discovery key targets/MOAs of interest involved in the clearance »» NASH and Fibrosis Research, Amgen, Inc. of tau aggregates that could become potential »» Targeting the Microbiome LATEST BIOLOGY, PATHWAYS Information coming from human genetic studies has strategies to cure neurodegenerative disorders »» Antibody Discovery Forum - AND CHALLENGES FOR CNS implicated several key pathways in the pathogenesis associated with tau. Part 1 & Part 2 of Alzheimer’s disease (AD). These include processing 10:55 Evolving the Concept of Phenotypic Screening »» Antibodies Against Membrane THERAPEUTICS of the Amyloid Precursor Protein and activation of the to a New Level of Data-Driven, Systems Oriented Protein Targets - Part 1 & Part 2 8:00 Welcome Remarks innate immune response. Here we describe efforts Drug Discovery Daniel Barry, Senior Conference Director, Cambridge to understand the biology of targets in each of these Hotel & Travel Healthtech Institute Peder Svensson, PhD, Director, Comp Chem & Biol, CIO, pathways in order to help translate that into potential, Integrative Research Laboratories 8:05 Chairperson’s Opening Remarks disease-modifying therapeutics for the treatment of AD. Registration Information ISP represents a systems-oriented approach to CNS Dario Doller, PhD, Senior Director, Exploratory Science, drug discovery, with the potential to significantly improve SAGE Therapeutics the discovery process, reducing resource needs, and Click Here to Register development risks. The technology emanates from an DiscoveryOnTarget.com integrative view on disease states and drug-induced states. Hence, pharmacological evaluation is focused on comprehensive, phenotypic characterization. We discuss theoretical considerations, as well as practical

A Division of Cambridge Innovation Institute CNS and Neurodegenerative Targets DiscoveryOnTarget.com • 31 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover applications of ISP, illustrating with compounds 1:55 ANAVEX 2-73, a Sigma-1 Receptor Agonist, in 4:35 Oligomerix - Targeting Tau in Alzheimer’s discovered and characterized by the principles outlined. Phase IIb/III for the Treatment of Alzheimer’s Disease Disease and Related Dementias Conference Daniel Klamer, PhD, MBA, Vice President, Business James Moe, PhD, MBA, President and CEO, At-A-Glance 11:25 Mechanistic Insights into the Use of Mevalonate Pathway Modulators as Development & Scientific Strategy, Anavex Life Oligomerix, Inc. Sponsorship & Exhibit Cognitive Enhancers Sciences Corp. Oligomerix is discovering and developing small Anavex Life Sciences Corp.’s lead drug candidate, molecule disease modifying drugs for Alzheimer’s Short Courses Angela Mabb, PhD, Assistant Professor, Georgia State University, Neuroscience Institute ANAVEX 2-73, recently completed a successful disease that target the initial step in tau aggregation Symposia To identify specific targets in the mevalonate pathway Phase IIa clinical trial for Alzheimer’s disease. leading to the formation of tau oligomers, the ANAVEX 2-73 is an orally available drug candidate toxic tau aggregates responsible for neuronal loss, Training Seminar that promote AMPAR abundance, we established a high-content surface AMPAR assay in mouse primary that restores cellular homeostasis by activating the impairment of memory formation and transmission Plenary Keynotes hippocampal neurons. Using this assay, we found that sigma-1 receptor. Full genomic analysis of the study of tau pathology during disease progression. The lead participants resulted in the identification of genetic compound from our program inhibited tau aggregation Agenda tocotrienols increased surface AMPAR expression. mutations linked to treatment response. Clinical in transgenic mice expressing human tau, best »» Small Molecules for Cancer Tocotrienol-mediated upregulation of surface AM- PARs was also associated with reduced expression of studies in several indications are planned or underway representing tau aggregation in AD. Immunotherapy Arc protein, suggesting a mechanistic link of tocotri- utilizing a precision medicine approach. »» Autoimmune and Inflammation enol action on AMPAR abundance. 2:25 M3 Biotechnology: Neuro-Regenerative Disease- 5:05 Interactive Breakout Discussion Groups Drug Targets Sponsored by Modifying Therapies Join a breakout discussion group. These are informal, »» NK Cell-Based Cancer 11:55 Applications of AI in Drug Target Discovery Leen Kawas, PhD, CEO, M3 Biotechnology moderated discussions with brainstorming and Immunotherapy A clinical-stage biotechnology company with a interactive problem solving, allowing participants »» Targeting Tumor Myeloid Cells Jane Yu, Technical Pre-Sales, IBM Watson for Drug Discovery, IBM Watson Health platform of novel small molecule therapeutics for from diverse backgrounds to exchange ideas and »» Targeting the Ubiquitin- neurodegeneration with a focus on Alzheimer’s experiences and develop future collaborations around Proteasome System With millions of scientific research articles published each year, innovation in the life sciences suffers from disease. M3’s lead therapeutic is a modulator a focused topic. Details on the topics and moderators »» Kinase Inhibitor Discovery knowledge waste and lack of knowledge integration. of a novel neurotrophic growth factor shown to are available on the conference website. »» CNS and Neurodegenerative IBM Watson for Drug Discovery addresses this issue slow disease progression, exhibit neuroprotective Targets by extensively mining literature and data to help and regenerative properties and restore cognitive 6:05 Welcome Reception in the Exhibit Sponsored by »» GPCR-Based Drug Discovery scientists accelerate biomedical research. Using function in preclinical studies of AD. Currently Hall with Poster Viewing »» Constrained Peptides and in human clinical trials, the lead is assessed for advanced analytics and machine learning, the platform 7:10 Close of Day Macrocyclics can also predict novel relationships, as demonstrated safety, tolerability, pharmacokinetics and EEG as a » pharmacodynamic biomarker. » Lead Generation Strategies through our recent work with Barrow Neurological in Thursday, September 27 »» Target Identification and ALS disease, and Pfizer in immuno-oncology, among 2:55 Sponsored Presentation (Opportunity Available) Validation - Part 1 & Part 2 many projects. 3:25 Refreshment Break in the Exhibit Hall with Poster 7:30 am Registration Open and Morning Coffee »» Antibacterial Discovery and 12:25 pm Session Break Viewing and Poster Competition Winner Announced 8:00 Chairperson’s Remarks Development Stephan Schann, Head of Research & Development, »» Targeting Gram-Negative 12:35 Luncheon Presentation (Sponsorship 4:05 Non-Fibrillar Amyloid-Beta Oligomers – It’s Time Domain Therapeutics Pathogens Opportunity Available) or Enjoy Lunch on Your Own to Intercept the Most Relevant AD Target »» NASH and Fibrosis 1:15 Refreshment Break in the Exhibit Hall with Grant A. Krafft, PhD, Chairman and Chief Scientist, 8:05 Targeting Protein Degradation Pathways in »» Targeting the Microbiome Poster Viewing Acumen Pharmaceuticals, Inc. Neurodegenerative Disease »» Antibody Discovery Forum - Alzheimer’s disease (AD) affects more than 45M Michael K. Ahlijanian, PhD, Head, Neuroscience, FORMA people worldwide, yet no treatment affords meaningful Therapeutics Part 1 & Part 2 TARGETING AND DEVELOPING symptomatic or disease modifying benefits. Recent Over the past several years, mutations in genes »» Antibodies Against Membrane NOVEL CNS TARGETS failures of amyloid-directed therapeutics have cast associated with genetic or familial forms of these Protein Targets - Part 1 & Part 2 1:50 Chairperson’s Remarks doubt on the amyloid hypothesis; however, none of the diseases have been identified. Several of these genes Hotel & Travel Daniel Klamer, PhD, MBA, Vice President, Business failed drugs directly targeted non-fibrillar amyloid β are components of cellular protein degradation Development & Scientific Strategy, Anavex Life oligomers (AbOs), now widely recognized as the AD- networks including autophagy and the unfolded Registration Information Sciences Corp. relevant Aβ structures. This presentation will highlight protein response (UPR). This talk will describe the the AbO-AD linkage and profile ACU193, the first AbO- links between genes associated with genetic forms selective AD immunotherapeutic. of neurodegenerative diseases, including Parkinson’s Click Here to Register disease and Amylotrophic Lateral Sclerosis, protein DiscoveryOnTarget.com degradation networks and the potential for developing novel therapeutics that target discrete components of protein degradation in neurons.

A Division of Cambridge Innovation Institute CNS and Neurodegenerative Targets DiscoveryOnTarget.com • 32 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover 8:35 FEATURED PRESENTATION: Effects of 9:05 Sponsored Presentation (Opportunity Available) a novel series of potent mGluR4 PAMs and to the USP14 Inhibition on Proteasomal Degradation in nomination of Foliglurax, the first mGluR4 PAM clinical Conference 9:35 Coffee Break in the Exhibit Hall with Mammalian Cells Poster Viewing candidate currently evaluated in a Phase II study for At-A-Glance Qi Wang, PhD, Director, Discovery Biology Neuroscience the treatment of PD. 10:20 Update on Merck’s LRRK2 Parkinson’s Sponsorship & Exhibit IMED Biotech Unit, AstraZeneca Disease Program 11:20 Luncheon Presentation (Sponsorship Inhibition of the proteasome-associated Opportunity Available) or Enjoy Lunch on Your Own Short Courses deubiquitinase (DUB) USP14 has been considered Matt Fell, PhD, Principal Scientist, Neuroscience, Merck 11:50 Conference Registration Open Symposia a therapeutic strategy for accelerating degradation 10:50 Discovery of Foliglurax, an mGluR4 PAM for the of aggregation-prone proteins involved in Treatment of Parkinson’s Disease Training Seminar neurodegenerative diseases. In the attempt to Stephan Schann, Head of Research & Development, 12:20 pm Plenary Keynote Program Plenary Keynotes validate this target, we studied the effects of Domain Therapeutics Click here for details. inhibiting proteasomal DUBs on protein degradation mGluR4 is an emerging target for the treatment of Agenda in mammalian cells. I will present these data and Parkinson’s disease (PD). However, since the discovery »» Small Molecules for Cancer discuss the limitation of USP14 as a target to of its therapeutic potential, no ligand has been 2:00 Refreshment Break in the Exhibit Hall with Immunotherapy accelerate proteasomal degradation. successfully developed. Starting from the (-) PHCCC, Poster Viewing »» Autoimmune and Inflammation medicinal chemistry efforts lead to the discovery of 2:45 Close of Conference Drug Targets »» NK Cell-Based Cancer Immunotherapy »» Targeting Tumor Myeloid Cells »» Targeting the Ubiquitin- Proteasome System »» Kinase Inhibitor Discovery »» CNS and Neurodegenerative Targets »» GPCR-Based Drug Discovery »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute CNS and Neurodegenerative Targets DiscoveryOnTarget.com • 33 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register 13th Annual | September 27-28 GPCR-Based Drug Discovery Cover Exploiting Signaling Complexities for Better Therapeutics Conference At-A-Glance Sponsorship & Exhibit

Short Courses G protein-coupled receptors (GPCRs), which relay chemical signals such as hormones from outside to the inside mechanism using molecular dynamics simulation. Symposia of cells, are the targets of approximately a third of the medicines on the market today. The receptors’ signaling These results shed light on the general mechanism of complexities due to their ability to couple to a variety of G proteins (biased signaling) are now more understood class A receptor activation and functional selectivity. Training Seminar and capitalized upon to design more selective drugs. CHI’s well-established GPCR-Based Drug Discovery 3:55 Biophysical Methods in Drug Sponsored by Plenary Keynotes conference will continue to convene prominent scientists in both academia and industry to share and discuss the Discovery Dedicated to Membrane latest advances in applied GPCR research. Presentations will touch on a range of topics, such as new screening Agenda Protein Targets assays, biophysical techniques, structure-based drug development, medicinal chemistry optimization case »» Small Molecules for Cancer Michael Hennig, PhD, CEO, leadXpro AG studies and examples of GPCR-targeted compounds in development. leadXpro combines high-quality transmembrane Immunotherapy protein generation with structure determination »» Autoimmune and Inflammation 2:55 Structural Pharmacology of GPCRs in Asthma methods like X-ray (SwissFEL/SLS) and cryo-EM as Drug Targets RECOMMENDED ALL ACCESS and Structure-Based Drug Development well as wave-guided interferometry to characterize »» NK Cell-Based Cancer PACKAGE: Choose 2 Short Courses Cheng Zhang, PhD, Assistant Professor, Pharmacology molecular interactions with drug targets. Examples will Immunotherapy or 1 Symposium and 2 Conferences/ and Chemical Biology, University of Pittsburgh School illustrate the high sensitivity of Creoptix’ instruments »» Targeting Tumor Myeloid Cells Training Seminars of Medicine and the accurate measurement of ligand binding and »» Targeting the Ubiquitin- The commonly used medication for controlling asthma kinetics to support drug design. Proteasome System • September 25 Short Course 1: Introduction to includes bronchodilators and anti-inflammation drugs. 4:10 Complexity Simplified: Using Sponsored by »» Kinase Inhibitor Discovery GPCR-Based Drug Discovery Almost all bronchodilators are the agonists of beta2 Smart Drug Discovery Software to »» CNS and Neurodegenerative • September 26-27 Conference: Antibodies adrenergic receptor (beta2AR). We report a crystal Manage Disperse Assay Data Targets Against Membrane Protein Targets - Part 1 structure of human beta2AR bound to the most »» GPCR-Based Drug Discovery widely used asthma drug salmeterol, which reveals Dan Robinhold, Research Informatics, • September 27-28 Conference: GPCR-Based Collaborative Drug Discovery, Inc. »» Constrained Peptides and Drug Discovery the bitopic nature of salmeterol and an additional Macrocyclics ligand binding site in the receptor. The results Research of tomorrow is moving quickly toward »» Lead Generation Strategies • September 27 Short Course 13: GPCR provide a structural explanation for the prominent a more collaborative, open source and platform- »» Target Identification and Structured-Based Drug Discovery pharmacological characteristics of salmeterol independent environment. CDD Vault (Assay Reg/ ELN/Viz) now incorporates “BioAssay Express” that Validation - Part 1 & Part 2 including high receptor-subtype selectivity and utilizes machine learning to scan and catalog libraries »» Antibacterial Discovery and long-lasting action. We also present the first crystal Thursday, September 27 of human-readable assay text into computer-readable Development structures of a lipid GPCR, the CRTH2, as a new target format to better access private, collaborative and »» Targeting Gram-Negative for developing small molecule anti-inflammation drugs 11:50 am Conference Registration Open public assay data. Pathogens for asthma. The structures reveal critical features for »» NASH and Fibrosis the binding of CRTH2 antagonists including a Phase III 4:25 Refreshment Break in the Exhibit Hall with 12:20 pm Plenary Keynote Program drug candidate, fevipiprant. They also suggest a novel Poster Viewing »» Targeting the Microbiome Click here for details. »» Antibody Discovery Forum - mechanism for the recognition of endogenous lipid mediators by GPCRs. Based on the structures, we have Part 1 & Part 2 NEW GPCR-TARGETED ASSAYS AND identified compounds with novel structural scaffolds »» Antibodies Against Membrane 2:00 Refreshment Break in the Exhibit Hall with COMPOUNDS as potential antagonists of CRTH2, and propose new Protein Targets - Part 1 & Part 2 Poster Viewing strategies for further drug development. 5:00 Identification and Optimization of a CGRP Receptor Antagonist of Novel Chemotype Hotel & Travel GPCR STRUCTURES AND TARGETED 3:25 Apelin Receptor Structure and Signaling Brendan Crowley, PhD, Associate Principal Scientist, DRUG DESIGN IMPLICATIONS Liaoyuan Hu, PhD, Scientific Director, Discovery Neuroscience, Merck Research Labs Registration Information Pharmacology, Amgen Asia R&D Center 2:45 Welcome Remarks I describe our strategy to rapidly evolve a series of The apelin receptor (APJ) is a potential target for CGRP receptor antagonists utilizing physical property, Anjani Shah, PhD, Conference Director, Cambridge the treatment of a variety of diseases. We will report Click Here to Register Healthtech Institute ligand efficiency, and diversity-guided iterative library DiscoveryOnTarget.com the high-resolution structure of APJ, especially in design as well as evidence that these molecules make 2:50 Chairperson’s Opening Remarks ligand binding pocket, and the molecular mechanism novel interactions in the binding site (from receptor Dean G. Brown, PhD, Director of External Chemistry, on receptor activation and signaling pathways. We mutagenesis, X-ray crystallography, and NMR data). Hit Discovery, Discovery Sciences, IMED Biotech Unit, identified a critical residue for signaling selectivity I also discuss lead optimization efforts that led to an AstraZeneca (biased receptor) and rationalized the structure advanced candidate with high affinity for the receptor,

A Division of Cambridge Innovation Institute GPCR-Based Drug Discovery DiscoveryOnTarget.com • 34 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover potent in vivo activity, good off-target selectivity, and a 7:30 Interactive Breakfast Breakout will focus on different approaches used in novel ligand low potential human dose. Discussion Groups identification for the treatment of pain and addiction. Conference Grab a cup of coffee and join a breakout discussion At-A-Glance 5:30 TruPath: An Open-Source Platform for 9:35 Angiotensin Receptor Structure and Implications Comprehensive Screening of GPCR Signal group. These are informal, moderated discussions for Biased Signaling Sponsorship & Exhibit Transduction Pathways with brainstorming and interactive problem solving, Laura M. Wingler, PhD, Postdoctoral Researcher, Howard allowing participants from diverse backgrounds Short Courses Ryan T. Strachan, PhD, Research Assistant Professor, Hughes Medical Institute, Lefkowitz Lab, Department of Pharmacology, University of North Carolina – Chapel Hill to exchange ideas and experiences and develop Medicine, Duke University Medical Center Symposia Our understanding of G Protein-Coupled Receptor future collaborations around a focused topic. Details The angiotensin II type 1 receptor is a premier model on the topics and moderators are available on the Training Seminar (GPCR) signaling remains incomplete and likely system for studies of biased agonism in GPCRs, as conceals therapeutically useful bias. Here we present conference website. it has both Gq-biased and β-arrestin-biased agonists Plenary Keynotes an open source, optimized BRET-based Transducer that have been exceptionally well characterized. Here Pathway screening platform (dubbed ‘TruPath’) that we use multiple structural techniques to elucidate the Agenda RECEPTOR PHARMACOLOGY, »» Small Molecules for Cancer measures activation of 18 different G-protein signaling distinct angiotensin receptor conformations stabilized pathways. When combined with our GPCRome library, by functionally diverse ligands. Our findings suggest Immunotherapy BIASED SIGNALING AND TruPath enables potency and efficacy profiling for mechanisms by which biased agonists induce the »» Autoimmune and Inflammation STRUCTURAL INSIGHTS both established (e.g., opioid) and understudied receptor to couple selectively to particular transducers Drug Targets (e.g., MRGPRX2) receptors and their ligands, thereby 8:30 Chairperson’s Remarks and achieve their different biological profiles. »» NK Cell-Based Cancer revealing the full extent of transducer promiscuity and Lakshmi Devi, PhD, Professor, Department of Immunotherapy Pharmacology, Mount Sinai School of Medicine 10:05 Coffee Break in the Exhibit Hall with Poster bias. We hope that such a panoramic understanding Viewing and Poster Competition Winner Announced »» Targeting Tumor Myeloid Cells of GPCR signaling reveals new biology and »» Targeting the Ubiquitin- therapeutic strategies. 8:35 FEATURED PRESENTATION: Mu Opioid Proteasome System RECEPTOR KINETICS AND 6:00 Exploration of Endosomal GPCR Signaling Using Receptor Pharmacology: A Window into Another »» Kinase Inhibitor Discovery ALLOSTERIC MODULATION Electron Microscopy Dimension of GPCR Function »» CNS and Neurodegenerative Alex Thomsen, PhD, Assistant Professor, Department of Gavril Pasternak, MD, PhD, Chair and Professor Targets Surgery, Columbia University of Neurology, Neuroscience, Pharmacology and 10:45 FEATURED PRESENTATION: Receptor »» GPCR-Based Drug Discovery We recently demonstrated that a class of GPCRs Psychiatry, Weill Cornell Medical College; Laboratory Kinetics for Probing Allosteric Modulation and »» Constrained Peptides and promotes endosomal signaling by forming Head, Molecular Pharmacology Program, Memorial Biased Signaling Macrocyclics “megaplexes” composed of a single GPCR that Sloan Kettering Cancer Center Terry Kenakin, PhD, Professor, Department of »» Lead Generation Strategies interacts simultaneously with β-arrestin, which drives The mu opioid receptor Oprm1 is a member of the Pharmacology, University of North Carolina School »» Target Identification and the receptor internalization, and G protein, which G-protein coupled receptor family. First demonstrated of Medicine Validation - Part 1 & Part 2 initiates signaling from internalized compartments. in 1973, it led to the discovery of the endogenous I will compare the muscarinic receptor Gq protein »» Antibacterial Discovery and Now we are applying a variety of electron microscopy opioids and the ‘sodium effect’ in which sodium ions activation profiles of five exemplar molecules (slow Development (EM) and computational methods to obtain high- allosterically transition receptors between agonist binding agonists, partial agonists, inverse agonists, »» Targeting Gram-Negative resolution structural information about the megaplex and antagonist conformations – now established PAM-Agonists and Beta-PAMs) in calcium and IP1 Pathogens (cryo-EM), and to visualize GPCR signaling on the with most GPCRs. Cloning the receptor uncovered assays to illustrate how quantitative comparisons »» NASH and Fibrosis endosomal surface within living cells. a vast array of Oprm1 splice variants, including an to pharmacological models can both identify atypical target capable of eliciting analgesia without mechanisms of action and also convert descriptive »» Targeting the Microbiome 6:30 Dinner Short Course Registration »» Antibody Discovery Forum - the side effects associated with classical opioids. findings to predict data for therapeutic systems. Click here for details on short courses offered. Using these models optimally allows the identification Part 1 & Part 2 9:30 Close of Day of consistent and simple scales of activity that can »» Antibodies Against Membrane 9:05 GPCR Dimerization and Deorphanization: Impact guide medicinal chemistry. Protein Targets - Part 1 & Part 2 on Drug Discovery Friday, September 28 Lakshmi Devi, PhD, Professor, Department of Hotel & Travel 7:00 am Registration Open Pharmacology, Mount Sinai School of Medicine 11:15 Drug-Target Binding Kinetics - A Studies in Dr. Lakshmi Devi’s laboratory aim at Case for GPCRs Registration Information unraveling the molecular mechanisms of signal Dong Guo, PhD, Jiangsu Key Laboratory of New Drug transduction mediated by G-protein coupled receptors Research and Clinical Pharmacy, Xuzhou Medical Click Here to Register (GPCRs) and their regulation in health and disease. University, China DiscoveryOnTarget.com Recent studies have focused on the identification of The success rate of a candidate drug moving through compounds targeting opioid receptor heteromers the clinical development phase is disappointingly low as well as ligands targeting recently deorphanized despite the fact that properties of drug candidates for hypothalamic neuropeptide GPCRs. This presentation a given therapeutic target are mostly optimized with respect to standard pharmacological parameters of

A Division of Cambridge Innovation Institute GPCR-Based Drug Discovery DiscoveryOnTarget.com • 35 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover affinity, potency and intrinsic activity. Determining drawback of other existing technologies, enabling These results illustrate the power of integrating drug target binding kinetics, next to traditional potency high-throughput detection of β-arrestin translocation stabilized GPCR technologies into established Conference measures, may increase the rate of success. Our work induced by native GPCRs in vitro and in vivo for the screening paradigms. At-A-Glance provides new insights in ligand-GPCR interactions first time. This presentation will highlight these novel 2:30 Integrating Biophysical and Structural Data Sponsorship & Exhibit and underlines the importance of measuring binding features and the robustness of this assay among other Provides Comprehensive View of GPCR Function kinetics of both drug candidates and competing updates of our portfolio. Short Courses Matthew Eddy, PhD, Assistant Professor, Department of endogenous ligands. 1:15 Refreshment Break in the Exhibit Hall with Chemistry, University of Florida and Affiliated Faculty, Symposia 11:45 Biortus Delivers Cryo-EM Service Sponsored by Poster Viewing National High Magnetic Field Laboratory Training Seminar to Drug Discovery 3:00 Characterization of Wild Type GPCRs Using Xiaodong Yan, Executive Director, BIOPHYSICAL APPROACHES Plenary Keynotes Surface Plasmon Resonance Biology, Biortus 1:55 Chairperson’s Remarks Iva Navratilova, PhD, Staff Scientist, Department of Agenda Wuxi Biortus Biosciences Co. Ltd Brian J. Murphy, PhD, Senior Principal Scientist, Molecular Biology, University of Dundee »» Small Molecules for Cancer (founded in 2009) is located in Wuxi within the greater Metabolic Disease Biology, Bristol-Myers Squibb Co. Expressing, purifying and analysing membrane Shanghai area of China. As an innovation-driven CRO, Immunotherapy proteins using SPR is routinely challenging. In this Biortus is the first and the only company available in »» Autoimmune and Inflammation presentation, we will present our latest results China who delivers the cutting-edge cryo-EM service to 2:00 Discovery of Small Molecule Protease-Activated Drug Targets demonstrating a scalable method for the successful drug discovery industry. Receptor 2 (PAR2) Antagonists Using a Stabilized »» NK Cell-Based Cancer GPCR, Fragment-Based Lead Generation and DNA- development of SPR assays for a wide range of wild- Immunotherapy 12:15 pm Session Break Encoded Library Screening type GPCRs. The SPR assays can be exploited for »» Targeting Tumor Myeloid Cells 12:25 Luncheon Presentation: Sponsored by Dean G. Brown, PhD, Director of External Chemistry, fragment screening and kinetic characterization to »» Targeting the Ubiquitin- Measure β-Arrestin Signaling Through Hit Discovery, Discovery Sciences, IMED Biotech Unit, discover novel ligands. Proteasome System Native GPCRs In High Throughput AstraZeneca 3:30 Nanodiscs for Membrane Protein Drug »» Kinase Inhibitor Discovery Lisa Minor, Scientific Consultant, Business We employed two screening strategies to identify Discovery Applications »» CNS and Neurodegenerative Development, Multispan, Inc. antagonists at protease activated receptor (PAR2), Nasr Mahmoud, PhD, Postdoctoral Fellow, Laboratory Targets Screening compounds for biased signaling using one being a DNA-encoded library screen on PAR2 of Gerhard Wagner, Department of Biological Chemistry »» GPCR-Based Drug Discovery native GPCR in one cellular environment may lead to and the second a fragment screen using a stabilized and Molecular Pharmacology, Harvard Medical School »» Constrained Peptides and selective perturbation of disease-specific pathways. PAR2 GPCR receptor. From these efforts, we identified 4:00 Close of Conference Macrocyclics Our newly developed proprietary MultiScreenTM two lead series of compounds, each of which bind »» Lead Generation Strategies β-arrestin technology overcomes the receptor-tagging to distinct and previously unknown allosteric sites. »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome INTERACTIVE BREAKOUT DISCUSSION GROUPS » » Antibody Discovery Forum - Join a breakout discussion group. These are informal, moderated discussions with brainstorming Part 1 & Part 2 and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas »» Antibodies Against Membrane and experiences and develop future collaborations around a focused topic. Details on the topics and Protein Targets - Part 1 & Part 2 moderators are available on the conference website. Hotel & Travel

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A Division of Cambridge Innovation Institute GPCR-Based Drug Discovery DiscoveryOnTarget.com • 36 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register 2nd Annual | September 26-27 Constrained Peptides and Macrocyclics Cover Cell-Penetrating Middle-Sized Molecules for Better Therapeutics Conference At-A-Glance Sponsorship & Exhibit

Short Courses This meeting covers the progress and challenges of accessing new chemical space – the middle space – to 9:10 Targeting a Metabolic Vulnerability in Symposia find molecules with drug potential that are bigger than small molecules but smaller than biologics.The hope is Parasitic Nematodes with Nucleic Acid-Encoded that these middle-sized molecules are big enough for more specific interactions with protein-protein interaction Peptide Libraries Training Seminar surfaces but small enough to penetrate the cell, reach intracellular drug targets and be orally bioavailable. James Inglese, PhD, Director, Assay Development and Plenary Keynotes However, theory is still meeting practice. Researchers continue to refine the ‘rules’ and properties for the best Screening Technologies, National Center for Advancing design of this class of molecules which mainly consist of constrained peptides and synthetic macrocyclics. Translational Sciences (NCATS), NIH Agenda iPGM is the nematode isozyme of the human glycolytic »» Small Molecules for Cancer 8:10 KEYNOTE PRESENTATION: enzyme, phosphoglycerate mutase, and represents Immunotherapy RECOMMENDED ALL ACCESS Peptide Drug Hunter: An a potential drug target for tropical diseases. Small »» Autoimmune and Inflammation PACKAGE: Choose 2 Short Courses Extraordinary Trek into Intracellular molecule high throughput screening efforts by Drug Targets or 1 Symposium and 2 Conferences/ Target Space others have failed to identify inhibitors. We used »» NK Cell-Based Cancer mRNA-display affinity selection to identify isozyme- Training Seminars Tomi K. Sawyer, PhD, Distinguished Immunotherapy Scientist, Peptide Drug Discovery & Innovative selective phosphoglycerate mutase ligands, termed »» Targeting Tumor Myeloid Cells • September 25 Symposium: Antivirals: Technologies, Merck & Co., Inc. Ipglycermides that potently inhibit the catalytic »» Targeting the Ubiquitin- Targeting HBV and Beyond Macrocyclic peptides can modulate intracellular activity of all nematode iPGM orthologs tested to Proteasome System • September 25 Short Course 11: Mechanistic protein-protein interaction target space; however, date. Progress in the pharmacological evaluation »» Kinase Inhibitor Discovery Understanding of Pharmacological Probes for achieving cell permeability is challenging of ipglycermide analogs aimed at developing a »» CNS and Neurodegenerative the Ubiquitin-Proteasome System and is hindering their therapeutic potential. therapeutics agent will be discussed. Targets • September 26-27 Conference: Constrained Accordingly, we have focused a multidisciplinary 9:40 Grand Opening Coffee Break in the Exhibit Hall »» GPCR-Based Drug Discovery Peptides and Macrocyclics effort on macrocyclic peptides to understand with Poster Viewing »» Constrained Peptides and their structure-cell permeability relationships. • September 27 Short Course 14: 10:25 Stapled Peptides Targeting MCL-1 and BFL-1 to Macrocyclics As a benchmark and model system, we have Reactivate Apoptosis in Cancer »» Lead Generation Strategies Advancing Tools and Technologies for studied a series of analogs of ATSP-7041, a Fragment-Based Design Loren D. Walensky, MD, PhD, Professor, Department of »» Target Identification and stapled peptide dual antagonist of MDM2 and Pediatric Oncology, Dana-Farber Cancer Institute, Boston Validation - Part 1 & Part 2 • September 27-28 Conference: Lead MDMX, to evaluate and correlate their biological, Children’s Hospital, Harvard Medical School »» Antibacterial Discovery and Generation Strategies biophysical, permeability and metabolic The “helix-in-groove” mode of protein-protein Development stability properties. interaction underlies a series of oncogenic signaling »» Targeting Gram-Negative Wednesday, September 26 events that drive human cancer. Indeed, a nearly Pathogens 8:40 Modulation of Intracellular Protein-Protein universal mechanism of apoptotic suppression in »» NASH and Fibrosis 7:00 am Registration Open and Morning Coffee Interactions with Bicyclic Peptides cancer is governed by the entrapment of pro-death »» Targeting the Microbiome Dehua Pei, PhD, Professor of Chemistry and helices by the surface grooves of anti-apoptotic BCL-2 »» Antibody Discovery Forum - INHIBITING INTRACELLULAR Biochemistry, The Ohio State University family proteins. Here, we developed both non-covalent Part 1 & Part 2 PROTEIN-PROTEIN INTERACTIONS We are developing bicyclic peptides as a novel class and covalent stapled peptide inhibitors to dissect and »» Antibodies Against Membrane target the apoptotic blockades imposed by MCL-1 and 8:00 Welcome Remarks of inhibitors against intracellular protein-protein Protein Targets - Part 1 & Part 2 BFL-1, yielding new drug prototypes for cancer therapy. Anjani Shah, PhD, Conference Director, Cambridge interactions (PPIs), which are challenging targets for Healthtech Institute conventional drug modalities. These bicycles feature 10:55 Discovery of ALRN-6924, a first-in-class Hotel & Travel highly active cell-penetrating peptides (CPPs) in one MDMX and MDM2 Dual Inhibitor Stapled Peptide in 8:05 Chairperson’s Opening Remarks ring for cellular entry and specific target-binding Clinical Trials Registration Information Scott Lokey, PhD, Professor, Chemistry and sequences in the second ring. Potent, selective, Vincent Guerlavais, PhD, Director, Medicinal Chemistry, Biochemistry, University of California, Santa Cruz proteolytically stable, and cell-permeable bicyclic Aileron Therapeutics Click Here to Register peptidyl inhibitors have been generated against a 11:25 Late Breaking Presentation DiscoveryOnTarget.com variety of intracellular proteins including protein tyrosine phosphatases, peptidyl-prolyl isomerase, 11:55 Sponsored Presentation (Opportunity Available) K-Ras, and NFkB essential modulator. 12:25 pm Session Break

A Division of Cambridge Innovation Institute Constrained Peptides and Macrocyclics DiscoveryOnTarget.com • 37 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover 12:35 Luncheon Presentation (Sponsorship target for a variety of disease indications, peptidic 8:05 The Permeability Landscape around Lariat Opportunity Available) or Enjoy Lunch on Your Own macrocycles may provide additional advantages in Cyclic Peptides Conference terms of potency, selectivity, and reduced off-target Scott Lokey, PhD, Professor, Chemistry and At-A-Glance 1:15 Refreshment Break in the Exhibit Hall with Poster Viewing activity. We report on a series of peptidic macrocycles Biochemistry, University of California, Santa Cruz Sponsorship & Exhibit that bind to CXCR7 and also incorporate an N-linked Heterodetic cyclic peptides (lariat peptides) differ from NON-PEPTIDIC SYNTHETIC peptoid functionality in order to overcome the poor simple homodetic cyclic peptides by the addition of a Short Courses permeability associated with peptides. The peptoid tail extending from the cyclic portion. Although lariat Symposia MACROCYCLICS group also enabled us to explore side chain diversity peptides comprise a large portion of bioactive cyclic 1:50 Chairperson’s Remarks well beyond that of natural amino acids. peptide natural products, exploration of permeability Training Seminar Alec Flyer, PhD, Senior Scientist, Global Discovery 4:35 Lessons for the Design of Synthetic Macrocycles in this space has been limited. We recently discovered Plenary Keynotes Chemistry, Novartis Institutes Biomedical Research from Machine Learning a simple lariat scaffold based on a natural product, Xentrivalpeptide A, composed entirely of non-N- Agenda 1:55 Advances in the Synthesis and Applications Adrian Whitty, PhD, Professor, Biochemistry, Boston methylated alpha amino acids. I describe the synthesis »» Small Molecules for Cancer of Macrocycles University Andrei K. Yudin, PhD, Professor, Department of We identified several novel macrocycle-specific and properties of several passively permeable lariat Immunotherapy Chemistry, University of Toronto molecular descriptors based on structural or peptides with six H-bond donors and molecular »» Autoimmune and Inflammation Synthetic tools that allow one not only to cyclize physicochemical features, for assessing macrocyclic weights greater than 800. Drug Targets linear precursors but also to exercise control over chemotype diversity and predicting the key ADME 8:35 Measuring Cytosolic Penetration Using the »» NK Cell-Based Cancer conformation-driven cellular permeability are in high property of membrane permeability. These descriptors Chloroalkane Penetration Assay Immunotherapy demand. This lecture will summarize our ongoing should help inform the design of pharmaceutically Joshua A. Kritzer, PhD, Associate Professor, Department »» Targeting Tumor Myeloid Cells efforts in this area and will highlight key experimental useful macrocycles or macrocycle libraries, which of Chemistry, Tufts University »» Targeting the Ubiquitin- findings obtained in the past few months. because they contain non-traditional drug chemotypes, Cell penetration is a major obstacle for developing Proteasome System 2:25 Structure-Based Design of Small- need rules beyond those considered in traditional peptide, protein and nucleic acid therapeutics. »» Kinase Inhibitor Discovery Molecule Macrocycles assessments of drug likeness. I also describe various Most commonly used techniques for measuring »» CNS and Neurodegenerative Maxwell D. Cummings, PhD, Senior Principal Scientist, machine learning techniques we used for evaluating cell penetration are qualitative, and most cannot Targets Computational Chemistry, Discovery Sciences, the utility of the descriptors we identified. distinguish cytosolic material from material trapped »» GPCR-Based Drug Discovery Janssen R&D at the cell surface or in endosomes. We have devised »» Constrained Peptides and Despite having diverse chemical structures, 5:05 Interactive Breakout Discussion Groups a new technique, the chloroalkane penetration assay Macrocyclics macrocycles are often considered as a single Join a breakout discussion group. These are informal, (CAPA), that measures penetration to the cytosol »» Lead Generation Strategies chemotype. A recent survey covering macrocyclic moderated discussions with brainstorming and in a high-throughput, quantitative manner. Here, we »» Target Identification and drugs and clinical candidates captures their diversity in interactive problem solving, allowing participants describe the advantages and disadvantages of CAPA Validation - Part 1 & Part 2 both chemical structure and discovery provenance. We from diverse backgrounds to exchange ideas and and demonstrate some of its applications. »» Antibacterial Discovery and are interested in the structure-based design of purely experiences and develop future collaborations around 9:05 Sponsored Presentation (Opportunity Available) Development synthetic small-molecule macrocycles, an area of a focused topic. Details on the topics and moderators 9:35 Coffee Break in the Exhibit Hall with »» Targeting Gram-Negative drug discovery that has not been heavily explored. We are available on the conference website. Poster Viewing Pathogens present simple metrics that facilitate the detection and »» NASH and Fibrosis prioritization of bound ligands that may be particularly 10:20 Identification of Novel Constrained Peptides 6:05 Welcome Reception in the Exhibit Sponsored by and Scaffolds against Cap-Dependent Translation »» Targeting the Microbiome suited to macrocyclization. Representative examples Hall with Poster Viewing »» Antibody Discovery Forum - of such macrocyclic-like compounds will be presented Christopher J. Brown, PhD, Research Scientist, 7:10 Close of Day p53lab, A*STAR Part 1 & Part 2 for discussion. The eIF4F complex is frequently dysregulated »» Antibodies Against Membrane 2:55 Sponsored Presentation (Opportunity Available) Thursday, September 27 in human cancers leading to an increase in cap- Protein Targets - Part 1 & Part 2 3:25 Refreshment Break in the Exhibit Hall with Poster dependent translation, which causes the upregulation 7:30 am Registration Open and Morning Coffee Hotel & Travel Viewing and Poster Competition Winner Announced of key oncogenic related proteins. Rational stapled peptide design and constrained peptide phage display 4:05 Discovery of Potent and Orally Bioavailable CYCLIC PEPTIDE DESIGN Registration Information Macrocyclic Peptide-Peptoid Hybrid have identified new modalities that inhibit eIF4F CXCR7 Modulators CHALLENGES activity. These activi-ties have enabled an alternative Markus Boehm, PhD, Associate Research Fellow, 8:00 Chairperson’s Remarks interaction motif against the eIF4E:4G interface critical Click Here to Register for eIF4F assembly to be discovered, enabling the DiscoveryOnTarget.com Medicinal Chemistry, Pfizer Susanne Saalau, PhD, Senior Director, Chemistry, While several small molecules have been identified FOG Pharma exploration of new chemical space. that modulate the activity of CXCR7, an attractive drug

A Division of Cambridge Innovation Institute Constrained Peptides and Macrocyclics DiscoveryOnTarget.com • 38 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover 10:50 Artificial Intelligence Designed TLR4 Peptide Activators Conference Immanuel Lerner, PhD, CEO, Pepticom At-A-Glance The use of artificial intelligence (AI) for the target Sponsorship & Exhibit based discovery of novel peptides. Relevant results and background regarding discovery projects will Short Courses be presented with emphasis on the discovery and Symposia validation of TLR4 agonist cyclic peptides (composed of D,L and non natural amino acids). Training Seminar 11:20 Luncheon Presentation (Sponsorship Plenary Keynotes Opportunity Available) or Enjoy Lunch on Your Own Agenda 11:50 Conference Registration Open »» Small Molecules for Cancer Immunotherapy 12:20 pm Plenary Keynote Program »» Autoimmune and Inflammation Click here for details. Drug Targets »» NK Cell-Based Cancer Immunotherapy 2:00 Refreshment Break in the Exhibit Hall with »» Targeting Tumor Myeloid Cells Poster Viewing »» Targeting the Ubiquitin- 2:45 Close of Conference Proteasome System »» Kinase Inhibitor Discovery »» CNS and Neurodegenerative Targets »» GPCR-Based Drug Discovery »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Constrained Peptides and Macrocyclics DiscoveryOnTarget.com • 39 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register 2nd Annual | September 27-28 Lead Generation Strategies Cover Biophysical Techniques and New Methods for Drug Discovery Conference At-A-Glance Sponsorship & Exhibit

Short Courses Finding new drug leads as fast as possible, but also as accurately as possible, in other words compounds with 3:55 Integrated Drug Discovery Engine Sponsored by Symposia high drug potential, has always been the goal in early drug discovery. Often the process is separated into two for the Development of the Next- steps: ‘hit’ generation which focuses on quickly finding large numbers of compounds with questionable drug Generation Kinase Inhibitors Training Seminar potential followed by ‘lead’ optimization to whittle down the number of hits into promising, high-drug potential Alexis Denis, Head, Discovery Division, Plenary Keynotes leads. However, automation and other advances in biophysical approaches have married the two processes to Oncodesign enable smaller numbers but higher quality drug leads to be found from the start. After the successful launch of Nanocyclix is a medicinal chemistry technology Agenda CHI’s Lead Generation Strategies conference last year, we return to convene discovery biologists and chemists based on the macrocyclization of small Lead-like »» Small Molecules for Cancer to share best practices and discuss how to implement new approaches towards faster and higher quality lead molecules. It is a kinase-focused library designed Immunotherapy generation for drug discovery. in a chemocentric approach to identify drug- »» Autoimmune and Inflammation like and selective inhibitors across the kinome. Drug Targets NEW APPROACHES FOR BETTER HIT Nanocyclix leads have potential application in several »» NK Cell-Based Cancer RECOMMENDED ALL ACCESS indications: Oncology, Immuno-inflammation and Immunotherapy PACKAGE: Choose 2 Short Courses ASSESSMENT Parkinson disease. »» Targeting Tumor Myeloid Cells or 1 Symposium and 2 Conferences/ 2:45 Welcome Remarks 4:10 Sponsored Presentation (Opportunity Available) »» Targeting the Ubiquitin- Anjani Shah, PhD, Conference Director, Cambridge Proteasome System Training Seminars Healthtech Institute 4:25 Refreshment Break in the Exhibit Hall with Poster Viewing »» Kinase Inhibitor Discovery • September 25 Symposium: Antivirals: 2:50 Chairperson’s Opening Remarks »» CNS and Neurodegenerative Targeting HBV and Beyond Joe Patel, PhD, Director, Structural Biology, C4 5:00 Targeted Degradation Strategies for Targets • September 25 Short Course 11: Mechanistic Therapeutics New Drug Leads »» GPCR-Based Drug Discovery Understanding of Pharmacological Probes for Joe Patel, PhD, Director, Structural Biology, C4 Therapeutics »» Constrained Peptides and the Ubiquitin-Proteasome System 2:55 KEYNOTE PRESENTATION: Macrocyclics Targeted protein degradation has emerged as an • September 26-27 Conference: Constrained Mechanistic Pharmacology-Driven exciting new approach for drug discovery. This talk will »» Lead Generation Strategies Peptides and Macrocyclics Lead Discovery »» Target Identification and provide a brief overview of the technology and how • September 27-28 Conference: Lead Peter Tummino, PhD, Vice President, degraders exploit the ubiquitin-proteasome system Validation - Part 1 & Part 2 Generation Strategies Global Head, Lead Discovery, Janssen before describing therapeutic applications of targeted »» Antibacterial Discovery and Research and Development protein degradation to BET bromodomain proteins and Development • September 27 Short Course 14: Decades of effort in small molecule screening to the control of tumor cell-killing by CAR T-cells. »» Targeting Gram-Negative Advancing Tools and Technologies for has focused on increasing throughput and Pathogens Fragment-Based Design com-pound library size. Generally, these large 5:30 Encoded Library Technology (ELT): A Platform »» NASH and Fibrosis efforts have not yielded major advancements in for Lead Discovery at GSK »» Targeting the Microbiome providing quality lead molecules. An alternative Svetlana Belyanskaya, PhD, Scientific Leader, Encoded »» Antibody Discovery Forum - Thursday, September 27 approach is to design screening assays Library Technologies, R&D Platform Technology & Science, GSK Boston Part 1 & Part 2 that are more disease-relevant, incorporate 11:50 am Conference Registration Open DNA Encoded Library Technology is an affinity-based »» Antibodies Against Membrane knowledge from detailed mechanistic studies, screening platform that is routinely used for lead Protein Targets - Part 1 & Part 2 and possess multiparametric readouts. This 12:20 pm Plenary Keynote Program approach, combined application of machine discovery at GSK. It was successfully applied for Hotel & Travel Click here for details. learning to data analysis, may provide a stronger discovery of potent and selective inhibitors to multiple engine for lead ID. challenging targets. The platform has evolved and Registration Information a quantitative on-DNA binding assay has recently 2:00 Refreshment Break in the Exhibit Hall with been developed for simultaneous characterization of Poster Viewing 3:25 Do We Need to Change the Definition of Drug- billions of compounds in the selection. A case study Click Here to Register Like Properties? will be presented to illustrate its application for a hit DiscoveryOnTarget.com Michael Shultz, PhD, Associate Director and Group identification program. Leader, Cardiovascular and Metabolism, Medicinal Chemistry, Novartis Institutes for Biomedical Research

A Division of Cambridge Innovation Institute Lead Generation Strategies DiscoveryOnTarget.com • 40 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover 6:00 CETSA (Cellular Thermal Shift Assay) HT to 9:05 AbbVie’s Fragment-Based Drug Design Platform and stabilities of large, complex macromolecular Measure Intracellular Target Engagement with the for Tool and Lead Generation machines, as well as the influence of large libraries Conference Androgen Receptor Ashley Adams, Ph.D., Senior Scientist, Discovery of conformationally-selective small molecule At-A-Glance Joseph Shaw, PhD, Senior Scientist, Lead Generation, Chemistry and Technology, AbbVie, Inc. binders and protein-based biotherapeutics. Such Sponsorship & Exhibit AstraZeneca This presentation will cover a recent application of endeavours are nearly insurmountable with current CETSA (Cellular Thermal Shift Assay) is an exciting AbbVie’s revamped fragment library featuring an tools. In this presentation, I will discuss recent Short Courses technology increasingly being used to determine in-cell example where a fragment with high fsp3 character developments surrounding the activation of gas-phase Symposia target engagement in early drug discovery campaigns was quickly advanced to lead with high BEI, LE, and protein complex ions aimed at bridging this gap in in a label-free and disease relevant manner. We report LipE as well as good oral bioavailability. The unique basic technology. Training Seminar a new high-throughput CETSA assay for the high value properties associated with fragments with high 11:45 Every Compound Counts – Plenary Keynotes oncology target Androgen Receptor, and demonstrate sp3 character and some lessons learned on the Virtual Screening and Computer-Aided Drug Design a novel application of CETSA enabling determination efficiency of chemistry to iterate 3D fragment hits will Agenda for a More Efficient Route to Drug Discovery of intracellular binding affinities. Application of also be discussed. »» Small Molecules for Cancer Trevor Perrior, CSO, Domainex high-throughout CETSA technology can guide lead 9:35 Solid-State NMR for Peptide Drug Optimization Domainex clients have seen the benefit of its efficient Immunotherapy generation campaigns using direct measures of Yongchao Su, PhD, Associate Principal Scientist and approach, which significantly increases the speed »» Autoimmune and Inflammation binding to the desired target in cells. Head of the Pharmaceutical NMR Lab in Preclinical from drug target to candidate molecule. An important Drug Targets 6:30 Dinner Short Course Registration Sciences, Merck & Co., Inc. part of this philosophy is the use of computational »» NK Cell-Based Cancer Click here for details on short courses offered. We used solid state (ss) NMR to determine the high- techniques for the selection of screening libraries, and Immunotherapy 9:30 Close of Day resolution structure of fibrils from a pharmaceutical for the design of compounds during lead optimisation. »» Targeting Tumor Myeloid Cells peptide. This is the first time in pharmaceutical » 12:15 pm Session Break » Targeting the Ubiquitin- Friday, September 28 sciences that a high resolution molecular structure Proteasome System of insoluble aggregate of a peptide drug has been 12:25 Luncheon Presentation: Sponsored by »» Kinase Inhibitor Discovery 7:00 am Registration Open determined. The structure enabled us to identify and Protein Domain Trapping - Large Scale »» CNS and Neurodegenerative test residues in the fibril core that lead to backbone Protein Engineering Enables Biophysics Targets and Structural Biology in Drug Discovery 7:30 Interactive Breakfast Breakout rearrangement, which should facilitate optimization of »» GPCR-Based Drug Discovery peptide drugs with lower risks of aggregation. Jan Schultz, Director, Business Discussion Groups Development, ZoBio »» Constrained Peptides and Grab a cup of coffee and join a breakout discussion 10:05 Coffee Break in the Exhibit Hall with Poster Macrocyclics With novel targets the rate limiting step in small group. These are informal, moderated discussions Viewing and Poster Competition Winner Announced molecule drug discovery often becomes the availability »» Lead Generation Strategies with brainstorming and interactive problem solving, »» Target Identification and 10:45 Using Stable Isotope Tracers to Interrogate of protein in an appropriate, well-behaved form. allowing participants from diverse backgrounds Pathway Biology and Differentiate Potential Hits Standard methods for generating constructs are Validation - Part 1 & Part 2 to exchange ideas and experiences and develop Nathan Hatcher, PhD, Principal Scientist, Department of far too slow and sample only a fraction of the great »» Antibacterial Discovery and future collaborations around a focused topic. Details Neuroscience, Movement Disorders and Translational number of possibilities. ZoBio has developed PDT to Development on the topics and moderators are available on the Capabilities, Merck & Co., Inc. screen millions of protein variations for those that »» Targeting Gram-Negative conference website. This presentation will consider how to probe express high levels of soluble, well-behaved protein Pathogens biochemical flux via stable isotope tracer methods. with the desired biological activity. Initial feasibility »» NASH and Fibrosis Focus will be placed on differentiation of possible lead studies require only 4-6 weeks. »» Targeting the Microbiome BIOPHYSICAL METHODS FOR MORE candidates. Attention will be directed towards cell- »» Antibody Discovery Forum - 1:15 Refreshment Break in the Exhibit Hall with EFFICIENT LEAD GENERATION based screening efforts; however, we will discuss the Poster Viewing Part 1 & Part 2 8:30 Chairperson’s Remarks potential for translational opportunities using in vivo »» Antibodies Against Membrane Daniel A. Erlanson, PhD, Co-Founder, Carmot models. Example problems will be described which BIOPHYSICAL APPROACHES FOR Protein Targets - Part 1 & Part 2 Therapeutics, Inc. consider “classical” metabolic pathways, e.g., glucose flux, as well. We will consider problems regarding MEMBRANE PROTEINS Hotel & Travel 8:35 Novel Approaches in Using NMR and SPR for protein kinetics. 1:55 Chairperson’s Remarks Fragment Hit Identification and Validation Brian J. Murphy, PhD, Senior Principal Scientist, Registration Information 11:15 New Gas-Phase Tools for the Simultaneous Anil Padyana, PhD, Associate Director, Structural Biology Metabolic Disease Biology, Bristol-Myers Squibb Co. and Biophysics, Department of Biochemistry, Agios Determination of Protein Complex Structure, Pharmaceuticals Stability and Sequence Click Here to Register Brandon Ruotolo, PhD, Associate Professor, Department DiscoveryOnTarget.com of Chemistry, University of Michigan The next generation of medicines will rely heavily upon our ability to quickly assess the structures

A Division of Cambridge Innovation Institute Lead Generation Strategies DiscoveryOnTarget.com • 41 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover 2:00 Discovery of Small Molecule Protease-Activated These results illustrate the power of integrating presentation, we will present our latest results Receptor 2 (PAR2) Antagonists Using a Stabilized stabilized GPCR technologies into established demonstrating a scalable method for the successful Conference GPCR, Fragment-Based Lead Generation and DNA- screening paradigms. development of SPR assays for a wide range of wild- At-A-Glance Encoded Library Screening 2:30 Integrating Biophysical and Structural Data type GPCRs. The SPR assays can be exploited for Sponsorship & Exhibit Dean G. Brown, PhD, Director of External Chemistry, Provides Comprehensive View of GPCR Function fragment screening and kinetic characterization to Hit Discovery, Discovery Sciences, IMED Biotech Unit, discover novel ligands. Short Courses Matthew Eddy, PhD, Assistant Professor, Department of AstraZeneca Chemistry, University of Florida and Affiliated Faculty, 3:30 Nanodiscs for Membrane Protein Drug Symposia We employed two screening strategies to identify National High Magnetic Field Laboratory Discovery Applications antagonists at protease activated receptor (PAR2), Training Seminar Nasr Mahmoud, PhD, Postdoctoral Fellow, Laboratory one being a DNA-encoded library screen on PAR2 3:00 Characterization of Wild Type GPCRs Using Surface Plasmon Resonance of Gerhard Wagner, Department of Biological Chemistry Plenary Keynotes and the second a fragment screen using a stabilized and Molecular Pharmacology, Harvard Medical School PAR2 GPCR receptor. From these efforts, we identified Iva Navratilova, PhD, Staff Scientist, Department of Agenda two lead series of compounds, each of which bind Molecular Biology, University of Dundee 4:00 Close of Conference »» Small Molecules for Cancer to distinct and previously unknown allosteric sites. Expressing, purifying and analysing membrane Immunotherapy proteins using SPR is routinely challenging. In this »» Autoimmune and Inflammation Drug Targets »» NK Cell-Based Cancer Immunotherapy »» Targeting Tumor Myeloid Cells »» Targeting the Ubiquitin- Proteasome System »» Kinase Inhibitor Discovery »» CNS and Neurodegenerative Targets »» GPCR-Based Drug Discovery »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Lead Generation Strategies DiscoveryOnTarget.com • 42 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register 15th Annual | September 26-27 Target Identification and Validation Part 1 Cover Focus on Functional Genomics and Computational Screening Conference At-A-Glance Sponsorship & Exhibit

Short Courses Finding novel, druggable targets for therapeutic intervention remains a top priority for the pharma/biotech 9:10 Building CRISPR/Cas9-Based Platforms for Symposia industry, especially when it comes to building a robust drug discovery pipeline. It also remains a formidable Therapeutic Target Identification and Validation challenge and companies continue to invest a lot of time and resources in identifying and validating good drug Rui Wang, PhD, Senior Scientist, Department of Training Seminar targets to pursue. What are the challenges in target discovery? What tools and strategies are being used and Immunology, AbbVie Bioresearch Center Plenary Keynotes how well are they working? What’s being done to ensure that validated targets lead to better and safer therapies? To better understand the immune system and discover Cambridge Healthtech Institute’s conference on Target Identification and Validation will bring together leading novel therapeutics for autoimmune diseases, we have Agenda experts to discuss some of these critical questions. built CRISPR/Cas9-based platforms for new target »» Small Molecules for Cancer identification, target exploration and validation, and Immunotherapy Part 1: Focus on Functional Genomics and Computational Screening evaluation of the efficacy and toxicity for early targets. »» Autoimmune and Inflammation This part of the Target Identification and Validation conference will highlight some of the existing and emerging With those platforms, we aim to build a mechanism Drug Targets functional genomics, artificial intelligence and machine learning tools that are being used for generating novel to continuously screen new targets from various data »» NK Cell-Based Cancer drug targets. The use of such tools and screens for validating existing targets or associating them with new sources and to explore novel biology involved in the Immunotherapy disease indications will also be discussed. immunological diseases. »» Targeting Tumor Myeloid Cells 9:40 Grand Opening Coffee Break in the Exhibit Hall »» Targeting the Ubiquitin- 8:05 Chairperson’s Opening Remarks with Poster Viewing Proteasome System RECOMMENDED ALL ACCESS Roderick Beijersbergen, PhD, Group Leader, Division 10:25 Target Deconvolution Using CRISPR »» Kinase Inhibitor Discovery PACKAGE: Choose 2 Short Courses of Molecular Carcinogenesis and NKI Robotics and Mutagenesis Scanning »» CNS and Neurodegenerative or 1 Symposium and 2 Conferences/ Screening Center, The Netherlands Cancer Institute Dirk Daelemans, PhD, Associate Professor, Rega Institute Targets Training Seminars 8:10 Exploring New Biology and Targets Identified - Laboratory of Virology and Chemotherapy, KU Leuven »» GPCR-Based Drug Discovery through Big CRISPR Data Deconvoluting and validating the molecular target »» Constrained Peptides and • September 25 Symposium: Targeting Autophagy Scott Martin, PhD, Group Lead, Functional Genomics, of small-molecule hits from a screen is still a major Macrocyclics Genentech challenge but is a must for further drug development. »» Lead Generation Strategies • September 25 Short Course 10: Applications of CRISPR screening has rapidly transformed our The discovery of mutations that confer resistance is »» Target Identification and Artificial Intelligence and Machine Learning in approaches towards new target discovery. A major recognized as the gold standard proof for a drug’s Validation - Part 1 & Part 2 Drug Discovery and Development hope for these efforts is to identify new dependencies target. We will present a high-density tiling CRISPR »» Antibacterial Discovery and • September 26-27 Conference: Target in cancer that remain undiscovered by analogous genetic screening approach to rapidly deconvolute Development Identification and Validation - Part 1 RNAi-based screens. I will discuss efforts to the target protein and binding site of small-molecule »» Targeting Gram-Negative • September 27-28 Conference: Target leverage large-scale CRISPR screening data for this inhibitors based on drug resistance mutations. Pathogens Identification and Validation - Part 2 purpose, including both computational and bench- 10:55 Investigating Cancer Drug Specificity with »» NASH and Fibrosis level approaches. CRISPR/Cas9 Mutagenesis »» Targeting the Microbiome • September 27 Short Course 18: Practical Phenotypic Screening 8:40 Leveraging Functional Genomics to Identify and Jason Sheltzer, PhD, Principal Investigator, Cold Spring »» Antibody Discovery Forum - Characterize Novel Targets Harbor Laboratory Part 1 & Part 2 Lauren Drowley, PhD, Functional Genomics Lead, CRISPR/Cas9 gene editing can be applied to »» Antibodies Against Membrane Wednesday, September 26 Translational Medicine, UCB Pharma characterize potential genetic dependencies in cancer. Protein Targets - Part 1 & Part 2 Functional genomics provides tools that enable We show that cancer cells can tolerate CRISPR/Cas9 7:00 am Registration Open and Morning Coffee identification and interrogation of complex disease mutagenesis of many reported cancer drug targets Hotel & Travel mechanisms in patient samples and relevant cellular with no loss in cell fitness. In contrast, RNAi hairpins USE OF CRISPR, RNAi AND OTHER models, improving disease understanding. Using a and small-molecules designed against those targets Registration Information GENOMIC SCREENS FOR FINDING suite of functional genomic capabilities including continue to kill cancer cells, even when their putative NOVEL TARGETS CRISPR, investigation/modulation of regulatory target is knocked out using CRISPR. We suggest Click Here to Register elements and examining chromatin structure, UCB that many RNAi constructs and clinical compounds DiscoveryOnTarget.com 8:00 Welcome Remarks is improving understanding of the role of genome exhibit greater target-independent killing than Tanuja Koppal, PhD, Conference Director, Cambridge structure and function in health and disease allowing previously realized. Healthtech Institute for more directed and improved therapies in the future.

A Division of Cambridge Innovation Institute Target Identification and Validation - Part 1 DiscoveryOnTarget.com • 43 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover 11:25 TECHNOLOGY PANEL DISCUSSION: Do We 12:10 pm Development of High- Sponsored by lines. Although valuable, these limit the type of assay, Have the Right Tools to Find Drug Targets That Are Throughput Cellular Thermal Shift model system or phenotype that one can screen. Conference Difficult to Identify and Validate? Assays: Cellular Mechanistic Assays We have developed ready-to-transfect chemically At-A-Glance This panel will bring together speakers and 3-5 in Early Drug Discovery modified single guide CRISPR libraries, that simplify Sponsorship & Exhibit technical experts from leading technology and Marc Holbert, PhD, Scientific Leader Protein, Cellular and high-fidelity arrayed screening in a wide variety of cell service companies to discuss improvements and Structural Sciences, GSK types, including Primary T cells & induced Pluripotent Short Courses limitations in assays, platforms, and data analysis A problem in early drug discovery is lack of rank-order Stem Cells (iPSCs). Here, we discuss various screens Symposia tools available for target discovery and validation. correlation between biochemical potencies from in T cells, iPSCs & immortalized cell lines where we initial screens and diminished potency and efficacy monitor a variety of assays. High efficiency protein Training Seminar Roderick Beijersbergen, PhD, Group Leader, Division of Molecular Carcinogenesis and NKI Robotics in cellular phenotypic assays. Cellular thermal shift knockouts were confirmed by genotypic, protein and Plenary Keynotes and Screening Center, The Netherlands Cancer assays bridge this gap, enabling assessment of drug functional analyses, indicating that these screens are target engagement in live cells based on ligand- capable of producing high confidence hits with low Agenda Institute (Moderator) induced changes in protein thermal stability. false negatives. These results highlight the ease & »» Small Molecules for Cancer Sponsored by 12:25 Session Break power of arrayed screening in immortalized cell lines, Immunotherapy 11:55 Efficient Tools to Enable Drug Sponsored by or biologically relevant primary & stem cells using »» Autoimmune and Inflammation Target and Biomarker Discovery 12:35 Luncheon Presentation: chemically modified single guide RNAs. Drug Targets Paul Diehl, PhD, COO, Cellecta, Inc. Enabling Arrayed CRISPR Screens in 1:15 Refreshment Break in the Exhibit Hall with »» NK Cell-Based Cancer Cellecta’s technologies allow for Primary T Cells, iPSCs & Poster Viewing Immunotherapy precise and convenient analysis of the Immortalized Cell Lines genes responsible for driving biological responses. Abhi Saharia, PhD, Director, Product »» Targeting Tumor Myeloid Cells NEW FUNCTIONAL GENOMICS »» Targeting the Ubiquitin- Using NGS with multiplex RT-PCR in our DriverMap Management, Synthego Proteasome System Genome-wide Expression Profiling Assay enables Loss-of-function screens in primary & stem cells ASSAYS, LIBRARIES & PLATFORMS rapid association of gene expression changes in large can be incredibly valuable in identifying novel drug »» Kinase Inhibitor Discovery FOR TARGET IDENTIFICATION numbers of cell, tissue, and blood samples. Examples targets or uncovering functional complexity within the »» CNS and Neurodegenerative of this approach will be discussed. human genome. To date, loss-of-function CRISPR- 1:50 Chairperson’s Remarks Targets Cas9 screens have largely been conducted using Scott Martin, PhD, Group Lead, Functional Genomics, »» GPCR-Based Drug Discovery pooled lentiviral libraries and/or in immortalized cell Genentech »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis Dedicated Poster Sessions for Symposia and Conference Tracks »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their Protein Targets - Part 1 & Part 2 work in the poster sessions. To secure a poster board and inclusion in the conference materials, your abstract must be submitted, approved and your registration paid in full by August 10, 2018. Hotel & Travel

Registration Information Reasons you should present your research poster at this conference: • Your poster will be available American Express Gift Certificate More information available Click Here to Register to 1,300+ delegates • $50 off your registration fee at DiscoveryOnTarget.com DiscoveryOnTarget.com • You’ll automatically be entered • Your research will be seen by leaders into our poster competition where from pharmaceutical, biotech, two winners each will receive an academic and government institutes

A Division of Cambridge Innovation Institute Target Identification and Validation - Part 1 DiscoveryOnTarget.com • 44 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover 1:55 FEATURED PRESENTATION: Dissecting resistance mechanisms and novel combinations. The validation approach for generating further evidence Functional Genomics development and implementation of such models will on targets. We conclude by sharing a conceptual Conference Michael T. McManus, PhD, Professor, University of be presented and discussed. approach that may be broadly applied for target At-A-Glance California, San Francisco 4:35 3’-Digital Gene Expression Transcriptional Screening identification and validation. Sponsorship & Exhibit The field of human genetics and epigenetics has Sarah Boswell, PhD, Director of Sequencing 8:35 A High-Throughput Imaging-Genetic Screen been rife with scientific debate as scientists struggle Short Courses Technologies, Laboratory of Systems Pharmacology Identifies MEK-PI3K Modulation for TNBC to understand the complex nature of population and and Director, Single-Cell Sequencing Core, Harvard Arvind Rao, PhD, Associate Professor, Department Symposia familial incidence patterns and their relationships Medical School of Computational Medicine and Bioinformatics, The to molecular mechanism of gene expression. A Training Seminar 3’ Digital Gene Expression (3’-DGE) was developed University of Michigan, Ann Arbor cornerstone in the debate is the unresolved genetic by the Broad Institute as a single-cell sequencing As combination therapies enter mainstream clinical Plenary Keynotes architecture of complex disease and the functional method. Here, we implement 3’-DGE as a low-read oncology, there is now a need for infrastructure to relationship between genes. We have developed Agenda density transcriptome (mRNA) profiling method. A integrate multiple modalities of data to prioritize drug powerful tools and methodologies to dissect »» Small Molecules for Cancer few thousand cells are plated and treated in 384-well combinations rationally. In this vein, we examine a polygenic architecture and dissect functional format. 3’-DGE libraries sequenced at 1-2 million scenario using machine learning methods to prioritize Immunotherapy genomics as related to genetic epistasis, in both cells reads per sample yield 4,000-6,000 transcripts per drug combinations selected based on phenotypic »» Autoimmune and Inflammation and in vivo models. well all for roughly $4000. Using 3’-DGE we obtain screening via RNAi, coupled with known genetic Drug Targets information about drug targets, polypharmacology, vulnerabilities in Triple Negative Breast Cancer cells. »» NK Cell-Based Cancer 2:25 Up, Down, and Out: Complementary CRISPR and toxicity in one assay. Such a strategy leverages imaging and genetic Immunotherapy Technologies for Genetic Screens information to prioritize the MEKi+PI3Ki combination »» Targeting Tumor Myeloid Cells John Doench, PhD, Associate Director, Genetic 5:05 Interactive Breakout Discussion Groups as a possible regimen. »» Targeting the Ubiquitin- Perturbation Platform, Broad Institute of Proteasome System Join a breakout discussion group. These are informal, 9:05 Applications of AI in Drug Sponsored by Harvard and MIT moderated discussions with brainstorming and Target Discovery »» Kinase Inhibitor Discovery The ease of programming Cas9 with an sgRNA interactive problem solving, allowing participants Eric Baldwin, Solutions Executive, »» CNS and Neurodegenerative presents an abundance of potential target sites, from diverse backgrounds to exchange ideas and IBM Watson for Drug Discovery, Targets but the on-target activity and off-target effects of experiences and develop future collaborations around IBM Watson Health »» GPCR-Based Drug Discovery individual sgRNAs can vary. We will discuss the design a focused topic. Details on the topics and moderators With millions of scientific research articles published »» Constrained Peptides and and use of libraries for conventional CRISPR-based are available on the conference website. each year, innovation in the life sciences suffers from Macrocyclics knockout screens, as well as activation (CRISPRa) and knowledge waste and lack of knowledge integration. »» Lead Generation Strategies interference (CRISPRi) approaches. 6:05 Welcome Reception in the Exhibit Sponsored by IBM Watson for Drug Discovery addresses this issue »» Target Identification and Sponsored by 2:55 CRISPR Technology Mimicking the Hall with Poster Viewing by extensively mining literature and data to help Validation - Part 1 & Part 2 Fibrosis Process scientists accelerate biomedical research. Using »» Antibacterial Discovery and Lieke Geerts, PhD, Senior Scientist, Biology, Charles River 7:10 Close of Day advanced analytics and machine learning, the platform Development CRISPR technology is an asset for target validation in can also predict novel relationships, as demonstrated »» Targeting Gram-Negative the drug discovery process with its ability to generate Thursday, September 27 through our recent work with Barrow Neurological in Pathogens full gene knockouts. Using an adenovirus delivery 7:30 am Registration Open and Morning Coffee ALS disease, and Pfizer in immuno-oncology, among »» NASH and Fibrosis system, efficient CRISPR-mediated gene knockout was many projects. »» Targeting the Microbiome obtained in a complex cellular assay mimicking the NEW SCREENING PLATFORMS 9:35 Coffee Break in the Exhibit Hall with »» Antibody Discovery Forum - fibrosis process. Poster Viewing Part 1 & Part 2 AND COMPUTATIONAL TOOLS FOR 3:25 Refreshment Break in the Exhibit Hall with Poster 10:20 Development of a Biologically Intelligent High- »» Antibodies Against Membrane FINDING NOVEL TARGETS Viewing and Poster Competition Winner Announced Throughput Assay Platform for Phenotypic Screening Protein Targets - Part 1 & Part 2 4:05 The Screen Drives the Targets: Development of 8:00 Chairperson’s Remarks - Redefining the Screening Toolbox Deepak K. Rajpal, PhD, Senior Scientific Director, Hotel & Travel Clinically Relevant Screening Models Madhu Lal-Nag, PhD, Team Leader, RNAi Screening, Roderick Beijersbergen, PhD, Group Leader, Division Computational Biology, GlaxoSmithKline R&D National Center for Advancing Translational Sciences, Registration Information of Molecular Carcinogenesis and NKI Robotics and 8:05 Target Identification & Validation for Immune- National Institutes of Health Screening Center, The Netherlands Cancer Institute Mediated Indications Developing physiologically relevant assays with A major challenge is the large genomic and Deepak K. Rajpal, PhD, Senior Scientific Director, predictive, measurable phenotypic end points has Click Here to Register epigenomic diversity of human cancers. The Computational Biology, GlaxoSmithKline R&D been the pain point for high-throughput screening in DiscoveryOnTarget.com development of appropriate cell line models for large We share an overview of our computational drug discovery. Here we describe the development scale in vitro screens with strong predictive powers to approaches to identify targets. Additionally, we share of a platform of physiologically relevant screenable clinical utility remains crucial. This will be crucial for application of disease signatures in our drug discovery phenotypes and biologically intuitive analysis the discovery of novel targets, elucidation of potential approaches, along with some thoughts on creating a algorithms that capture and define these phenotypes

A Division of Cambridge Innovation Institute Target Identification and Validation - Part 1 DiscoveryOnTarget.com • 45 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover in a physiologically relevant context. This also Cancer Medicine, The University of Texas MD Anderson 11:20 Luncheon Presentation (Sponsorship encompasses the development of a biologist’s Cancer Center Opportunity Available) or Enjoy Lunch on Your Own Conference toolbox designed to target a majority of diverse We have developed a PDXEx model that closely 11:50 Conference Registration Open At-A-Glance biological phenotypes. replicates the tissue architecture of the original tumor Sponsorship & Exhibit 10:50 Patient-Derived Xenograft-Derived ex and has a gene expression profile showing a high degree of correlation to that of the original tumor. Our 12:20 pm Plenary Keynote Program Short Courses vivo (PDXEx) Model for Evaluation of Tumor- Click here for details. Specific Therapies model has great application as a screening platform Symposia Geoffrey Bartholomeusz, PhD, Associate Professor and exhibiting a high predictive value in identifying effective tumor-specific therapies in a resource-, time-, Training Seminar Director, Target Identification and Validation Program, 2:00 Refreshment Break in the Exhibit Hall with Department of Experimental Therapeutics, Division of and cost-efficient manner. Poster Viewing Plenary Keynotes 2:45 Close of Conference Agenda »» Small Molecules for Cancer Immunotherapy »» Autoimmune and Inflammation Drug Targets »» NK Cell-Based Cancer Immunotherapy »» Targeting Tumor Myeloid Cells »» Targeting the Ubiquitin- Proteasome System »» Kinase Inhibitor Discovery »» CNS and Neurodegenerative Targets »» GPCR-Based Drug Discovery »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Target Identification and Validation - Part 1 DiscoveryOnTarget.com • 46 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register 15th Annual | September 27-28 Target Identification and Validation Part 2 Cover Focus on Chemical Biology and Phenotypic Screening Conference At-A-Glance Sponsorship & Exhibit

Short Courses Finding novel, druggable targets for therapeutic intervention remains a top priority for the pharma/biotech 3:25 Comprehensive Proteomics Characterization of Symposia industry, especially when it comes to building a robust drug discovery pipeline. It also remains a formidable a Selective Cyclin-Dependent Kinase Inhibitor challenge and companies continue to invest a lot of time and resources in identifying and validating good drug J. Adam Hendricks, PhD, Associate Principal Scientist, Training Seminar targets to pursue. What are the challenges in target discovery? What tools and strategies are being used and Discovery Biology, Discovery Sciences, IMED Biotech Plenary Keynotes how well are they working? What’s being done to ensure that validated targets lead to better and safer therapies? Unit, AstraZeneca Cambridge Healthtech Institute’s conference on Target Identification and Validation will bring together leading We describe a comprehensive characterization of a Agenda experts to discuss some of these critical questions. The conference will help attendees meet and interact with cyclin-dependent kinase inhibitor using a combination »» Small Molecules for Cancer experts and peers from around the world to share ideas and hear about new strategies and technologies helping of affinity enrichment-based chemoproteomics and Immunotherapy target discovery. thermal proteome profiling strategies. Application »» Autoimmune and Inflammation of these orthogonal approaches enabled “static Drug Targets Part 2: Focus on Chemical Biology and Phenotypic Screening and dynamic” proteome characterization of a »» NK Cell-Based Cancer This part of the Target Identification and Validation conference will describe how phenotypic screening and CDK9 inhibitor. This case study highlights the Immunotherapy chemical biology can be used to find new drug targets, validate existing targets for new indications, and better advantages and limitations of different proteomics »» Targeting Tumor Myeloid Cells understand how inhibiting or activating these targets could impact other cellular pathways. readouts and their applications in drug discovery »» Targeting the Ubiquitin- toward understanding the mechanism of action of Proteasome System clinical candidates. RECOMMENDED ALL ACCESS EXPLORING VARIOUS ASSAYS »» Kinase Inhibitor Discovery & PLATFORMS FOR HIGH- 3:55 Preclinical Strategies for Sponsored by »» CNS and Neurodegenerative PACKAGE: Choose 2 Short Courses Evaluating Treatment Efficacy to Targets or 1 Symposium and 2 Conferences/ THROUGHPUT SCREENING Prevent or Cure Auditory Disorders »» GPCR-Based Drug Discovery Training Seminars 2:45 Welcome Remarks Sylvie Cosnier-Pucheu, CSO, CILcare »» Constrained Peptides and Tanuja Koppal, PhD, Conference Director, Cambridge No effective treatment exists to cure Macrocyclics • September 25 Symposium: Healthtech Institute hearing loss (affecting 360 million persons worldwide) Targeting Autophagy »» Lead Generation Strategies 2:50 Chairperson’s Opening Remarks and tinnitus (which affects around 10–15% of the »» Target Identification and • September 25 Short Course 10: Applications of James Inglese, PhD, Head, Assay Development & general population). This presentation provides Validation - Part 1 & Part 2 Artificial Intelligence and Machine Learning in Screening Technologies, National Center for Advancing an overview of current animal models of hearing »» Antibacterial Discovery and Drug Discovery and Development Translational Sciences, NIH disorders and potential targets for new therapies. Development • September 26-27 Conference: Target 2:55 Strategies for the Development of Quantitative 4:10 ZeCardio: A Zebrafish-Based Sponsored by »» Targeting Gram-Negative Identification and Validation - Part 1 HTS Assays Targeting Rare Diseases Screening Platform for Genetic Pathogens • September 27-28 Conference: Target James Inglese, PhD, Head, Assay Development & Association Studies in »» NASH and Fibrosis Identification and Validation - Part 2 Screening Technologies, National Center for Advancing Cardiovascular Disease »» Targeting the Microbiome Translational Sciences, NIH Vincenzo Di Donato, PhD, Project Manager, Genome »» Antibody Discovery Forum - • September 27 Short Course 18: Practical Editing Platform, ZeClinics Phenotypic Screening Phenotypic assays enabled by genome editing in Part 1 & Part 2 combination with novel reporter gene and high The advent of CRISPR/Cas9 methodologies has »» Antibodies Against Membrane content imaging technology were integrated to create greatly expanded the possibilities of in vivo target identification and validation. However, the generation Protein Targets - Part 1 & Part 2 Thursday, September 27 quantitative HTS assays. The assays were designed to target pathophysiology arising from gene duplication, of knockout animal models is a low-throughput and Hotel & Travel 11:50 am Conference Registration Open haploinsufficiency, defective organelle biogenesis or time-consuming process. Here, we will present a genes with implied protective properties, associated zebrafish-based mutagenesis platform allowing high- Registration Information with CMT, Dravet syndrome, Parkinson’s and more. throughput phenotypical validation of candidate genes 12:20 pm Plenary Keynote Program readily in the F0 generation. Click here for details. Our goal was to identify transcriptional and post- Click Here to Register translationally active pharmacological agents acting 4:25 Refreshment Break in the Exhibit Hall with DiscoveryOnTarget.com by a variety of mechanisms, including chromatin co- Poster Viewing 2:00 Refreshment Break in the Exhibit Hall with regulators accessible by our assay. Poster Viewing

A Division of Cambridge Innovation Institute Target Identification and Validation - Part 2 DiscoveryOnTarget.com • 47 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover 5:00 A Membranome cDNA Library for Biologics Friday, September 28 9:35 Chemo-Genomic Screening in AML: A New Discovery and Phenotypic Screening Approach to Identify Therapeutic Strategies Conference Xi Ai, PhD, Associate Principal Scientist, Screening & 7:00 am Registration Open Anne Marinier, PhD, Principal Investigator and Director At-A-Glance Compound Profiling, Merck Research Laboratories of Medicinal Chemistry, IRIC and Associate Professor, Sponsorship & Exhibit About 20-30% of all proteins are membrane proteins, 7:30 Interactive Breakfast Breakout Department of Chemistry, Université de Montréal which accounts for over 50% of marketed drug Capitalizing on new leukemia stem cell culture Short Courses Discussion Groups targets. We have established a human membranome Grab a cup of coffee and join a breakout discussion conditions, we developed a chemo-genomic screening Symposia cDNA library consisting of 2900 membrane group. These are informal, moderated discussions approach using genetically and clinically characterized protein genes and developed a live-cell assay for acute myeloid leukemia (AML) specimens and a Training Seminar with brainstorming and interactive problem solving, screening. The library will enable us to study novel allowing participants from diverse backgrounds structurally diverse compound collection. Clustering Plenary Keynotes cell surface receptor/ligand interaction for early to exchange ideas and experiences and develop of hits demonstrating similar specimen inhibition target identification and cell surface receptor de- patterns generated CCCs (Compound Correlation Agenda future collaborations around a focused topic. Details orphanization, as well as antibody specificity profiling. Clusters) which reveal sensitized target pathways »» Small Molecules for Cancer on the topics and moderators are available on the 5:30 Novel Targets and Compounds for Lung Fibrosis: conference website. essential to tumor survival. The CCCs’ therapeutic Immunotherapy Screening for Genes and Compounds that Control relevance will be exemplified by the identification of a »» Autoimmune and Inflammation Fibroblast YAP/TAZ Activation novel target for poor prognosis AML. Drug Targets Daniela M. Santos, PhD, Postdoctoral Fellow, Division PHENOTYPIC SCREENING 10:05 Coffee Break in the Exhibit Hall with Poster »» NK Cell-Based Cancer of Pulmonary and Critical Care Medicine, The Andrew FOR TARGET DISCOVERY AND Viewing and Poster Competition Winner Announced Immunotherapy M. Tager Fibrosis Research Center and Center for »» Targeting Tumor Myeloid Cells MECHANISM-OF-ACTION STUDIES 10:45 Phenotypic High-Content Approach to Identify Immunology and Inflammatory Diseases, Department of Novel Targets of Autophagy »» Targeting the Ubiquitin- Medicine, Massachusetts General Hospital and Harvard 8:30 Chairperson’s Remarks Proteasome System Stephen Walker, PhD, Senior Research Scientist III, High Medical School Fabien Vincent, PhD, Associate Research Fellow, Hit Throughput Screening, AbbVie »» Kinase Inhibitor Discovery Idiopathic Pulmonary Fibrosis is a lethal disease Discovery and Lead Profiling Group, Pfizer We have established various phenotypic screening »» CNS and Neurodegenerative driven by pathological fibroblast accumulation 8:35 Hit Triage and Validation for Phenotypic approaches and conducted small molecule screens Targets and differentiation. Recent evidence indicates that Screening: Considerations and Strategies for diverse indications using physiologically relevant »» GPCR-Based Drug Discovery transcription co-activators YAP and TAZ integrate Fabien Vincent, PhD, Associate Research Fellow, Hit disease models. This presentation will highlight »» Constrained Peptides and the chemical and mechanical signals that activate Discovery and Lead Profiling Group, Pfizer the workflow performed for a screen combining Macrocyclics fibroblasts. We designed a small molecule and siRNA Phenotypic screening is a validated approach to autophagy specific cellular models with high content »» Lead Generation Strategies screen to identify YAP inhibitors and new pathways identify novel therapeutic targets. However, significant multi-parametric analysis to identify autophagic »» Target Identification and controlling YAP activation in human fibroblasts. The differences exist between target-based and phenotypic regulators for clearance of accumulated proteins. Hits Validation - Part 1 & Part 2 resulting hits may lead to the development of novel screening, prompting a need to re-assess our from a screen utilizing a focused library of annotated »» Antibacterial Discovery and anti-fibrotic therapies. strategies and processes to most effectively prosecute compounds are being further characterized in disease- Development 6:00 Building Precision in vivo Models Using phenotypic projects. The hit triage and validation specific models and prioritized for target identification. »» Targeting Gram-Negative CRISPR-Based Editing process was critically re-evaluated in light of the 11:15 Identification of Essential Genes for Pathogens Maria Paz Zafra Martin, PhD, Postdoctoral Fellow, unique characteristics of phenotypic screening. Key Cancer Immunotherapy Using High-Throughput »» NASH and Fibrosis Department of Medicine, Hematology and Medical considerations and specific strategies will be shared Genome Engineering »» Targeting the Microbiome Oncology, Sandra and Edward Meyer Cancer Center, and illustrated by in house and literature examples. Neville Sanjana, PhD, Assistant Professor, Departments »» Antibody Discovery Forum - Weill Cornell Medicine 9:05 Understanding the Mechanism of of Biology, Neuroscience and Physiology, New Part 1 & Part 2 The development of animal models that precise Kinase Inhibitors York University; Core Faculty Member, New York »» Antibodies Against Membrane reflect the genetic changes that occur in human Lyn Jones, PhD, Vice President, Chemistry and Chemical Genome Center Protein Targets - Part 1 & Part 2 tumors is a key step in developing immunocompetent Biology, Jnana Therapeutics We have developed two-cell type whole-genome pre-clinical models. I will discuss our efforts using Advances in the development of chemoproteomic CRISPR screens to dissect the complex interactions Hotel & Travel CRISPR to engineer single nucleotide variants (SNVs) profiling technologies are enabling a deeper between tumor cells and primary immune cells in animal models, to understand the impact of defined understanding of the selectivity and hence mechanism in cancer immunotherapy. Using primary human Registration Information genetic changes on tumor initiation, progression and of action of small molecule kinase inhibitors. cytotoxic T cells, we identify loss-of-function therapy response. Additionally, many ATP-site binders have been found mutations genome-wide that drive resistance to Click Here to Register 6:30 Dinner Short Course Registration to degrade their cognate target kinases. The drug immunotherapy with transgenic TCR T cells and DiscoveryOnTarget.com Click here for details on short courses offered. discovery impact of kinase profiling and MoA studies validate several novel immunotherapy resistance 9:30 Close of Day will be presented. mechanisms across different melanomas, cancers, and antigens (in collaboration with N. Restifo’s, National Cancer Institute).

A Division of Cambridge Innovation Institute Target Identification and Validation - Part 2 DiscoveryOnTarget.com • 48 TARGET-BASED DISCOVERY & VALIDATION Final Weeks to Register

Cover 11:45 Computational Methods to Help Find Chemical 2:00 Chemical Probes in Target Discovery 3:00 Small Molecule Modulators of Conformationally Matter to Uncover Novel Biology Paul Brennan, PhD, Associate Professor, Medicinal Dynamic Protein Targets Conference Yuan Wang, PhD, Investigator III, Data Science, Chemistry, University of Oxford; Principal Investigator, Evripidis (Evris) Gavathiotis, PhD, Associate Professor, At-A-Glance Chemical Biology & Therapeutics, Novartis Institutes for Target Discovery Institute, Structural Genomics Consortium Department of Biochemistry and Medicine, Albert Sponsorship & Exhibit BioMedical Research Chemical probes are selective small molecule Einstein College of Medicine To explore new targets and biology, phenotypic inhibitors that can be used in cellular assays to My presentation will discuss approaches for targeting Short Courses screens are increasingly utilized in drug discovery. induce a phenotype and link it to a small set of protein two conformationally dynamic protein targets that Symposia Potent and selective chemical tool compounds against targets. Chemical probes have been developed critically control cell death and cell survival pathways well-defined targets can be used as probes in disease- for many bromodomains, the principal epigenetic converging at the mitochondria. Validation of novel Training Seminar relevant phenotypes. In Novartis we have designed readers of histone lysine acetylation, and been used targets and mechanisms go hand-in-hand with the Plenary Keynotes an evidence-based metric to systematically rank tool to decipher the biology of bromodomains in cancer discovery of small molecules. Structure-based drug compounds and collected over 4000 compounds and inflammation. We are current developing chemical design, biochemical, cell-based and in vivo proof- Agenda (“MOAbox”) to connect targets with novel biology. probes for new protein families. of-concept studies provided lead compounds and »» Small Molecules for Cancer We are also exploring algorithms that can connect 2:30 Target Validation in the IL17 Signaling Pathway: insights on modulating dynamic protein targets. Immunotherapy previously un-drugged targets to known ones. Challenges and Opportunities 3:30 Small Molecule Modulators of Inflammation »» Autoimmune and Inflammation 12:15 pm Session Break Alex Lipovsky, PhD, Senior Scientist, Foundational Sinu John, PhD, Staff Scientist, Signaling Systems Drug Targets Immunology, AbbVie Section, Laboratory of Immune System Biology, National »» NK Cell-Based Cancer 12:25 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own The IL23/IL17 signaling axis plays a key role in the Institute of Allergy and Infectious Diseases, National Immunotherapy pathophysiology of psoriasis. We conducted a small Institutes of Health »» Targeting Tumor Myeloid Cells 1:15 Refreshment Break in the Exhibit Hall with molecule and a CRISPR screen in primary human Recent studies have shown that a macrophage-driven »» Targeting the Ubiquitin- Poster Viewing keratinocytes to identify druggable targets in the inflammatory signature is common to a large majority Proteasome System IL17 signaling pathway. I will discuss functional of the diseases. We have developed a TNF reporter »» Kinase Inhibitor Discovery CASE STUDIES ON HOW TO genomics approaches, technology platforms, and assay that can be used to identify small molecule »» CNS and Neurodegenerative DECONVOLUTE EXISTING TARGETS target validation strategies to confirm and prioritize modulators of the human macrophage inflammatory Targets & TACKLE CHALLENGING ONES screen hits. Examples of successful gene perturbation response. We have conducted a screen of biologically »» GPCR-Based Drug Discovery in primary cells with CRISPR RNPs and RNAi will active small molecules and identified several »» Constrained Peptides and 1:55 Chairperson’s Remarks be highlighted. compounds that have substantial modulatory effects Macrocyclics Paul Brennan, PhD, Associate Professor, Medicinal on the TNF response. In validation studies, we find »» Lead Generation Strategies Chemistry, University of Oxford; Principal Investigator, that these molecules can be grouped into classes with »» Target Identification and Target Discovery Institute, Structural Genomics Consortium both negative and positive effects on the inflammatory Validation - Part 1 & Part 2 response, with therapeutic potential. »» Antibacterial Discovery and 4:00 Close of Conference Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Target Identification and Validation - Part 2 DiscoveryOnTarget.com • 49 HOT & EMERGING Final Weeks to Register 5th Annual | September 26-27 Antibacterial Discovery and Development Cover Helping Antibacterial Development to Move Forward Conference At-A-Glance Sponsorship & Exhibit

Short Courses New discovery platforms, novel screens and approaches are vital for the discovery of new antibacterials and killing persister cells (ADEP, lassomycin). ADC56 is a Symposia for ceasing the dangerous trend of multidrug microbial resistance. Cambridge Healthtech Institute’s 5th Annual novel antimicrobial with coverage of Gram negative Antibacterial Discovery and Development track will focus on the general, strategic issues and solutions that ESKAPE pathogens. Lyme disease is caused by B. Training Seminar would allow new antibacterial development to move forward. The conference will be held as part of the 5th burgdorferi, and we identified compounds acting Plenary Keynotes Annual Re-Entering Antibacterial Discovery and Development Summit, and it will be followed by Targeting Gram- selectively against this pathogen. Selectively killing Negative Pathogens. pathobionts of the human microbiome is a new Agenda area for antimicrobial drug discovery, and we will »» Small Molecules for Cancer Advisors: Lynn Silver, LL Silver Consulting; Ruben Tommasi, Entasis Therapeutics; Joyce Sutcliffe, Formerly discuss it as well. Immunotherapy Tetraphase; Todd Black, Merck 9:40 Grand Opening Coffee Break in the Exhibit Hall »» Autoimmune and Inflammation with Poster Viewing Drug Targets 8:10 KEYNOTE PRESENTATION: »» NK Cell-Based Cancer RECOMMENDED ALL ACCESS Culture Independent Discovery of DISCOVERY PLATFORMS (CONT.) Immunotherapy PACKAGE: Choose 2 Short Courses New Antibiotics »» Targeting Tumor Myeloid Cells 10:25 Mining the Actinomycete Armamentarium for or 1 Symposium and 2 Conferences/ Sean Brady, PhD, Associate Professor, Novel Antibiotics »» Targeting the Ubiquitin- The Laboratory of Genetically Proteasome System Training Seminars Laurence E. Reid, PhD, CEO, Warp Drive Bio Encoded Small Molecules, Rockefeller University Warp Drive Bio is deploying state-of-the-art, genome »» Kinase Inhibitor Discovery • September 25 Short Course 10: Applications of ­ Uncultivated microorganisms are an attractive mining technologies to access natural molecules that »» CNS and Neurodegenerative Artificial Intelligence and Machine Learning in source of potentially new antibiotics. have been historically “hidden” within microbes. We have Targets Drug Discovery and Development Although there is no easy way to culture most built databases of genomic sequence from over 135,000 »» GPCR-Based Drug Discovery • September 26-27 Conference: Antibacterial environmental bacteria, it is possible to clone strains, encoding more than four million biosynthetic »» Constrained Peptides and Discovery and Development microbial DNA directly from environmental gene clusters. We are exploiting this database to isolate Macrocyclics • September 27-28 Conference: Targeting Gram- samples and study this DNA in the lab. We clusters that synthesize natural products that have »» Lead Generation Strategies Negative Pathogens are using both functional and sequence- not been previously studied and which have predicted »» Target Identification and based metagenome screening strategies to • September 27 Short Course 17: Technologies antimicrobial activity. We will review our results to date Validation - Part 1 & Part 2 identify antibiotics encoded by environmental to Assess Permeability and Efflux in Gram- regarding discovery of novel antimicrobials. »» Antibacterial Discovery and bacteria. Antibiotics isolated in these studies Negative Bacterial Pathogens 10:55 Near Future Prospects from Natural Products Development will be discussed. Jose Ruben Tormo, PhD, Associate Area Head & »» Targeting Gram-Negative Collection Manager, Chemistry, Fundacion MEDINA Pathogens Wednesday, September 26 8:40 Forging Novel Classes of Antibiotics Microbial natural products (NPs) are one of the most »» NASH and Fibrosis Zachary Zimmerman, PhD, CEO, Co-Founder, Forge prolific sources of new leads for the discovery of novel »» Targeting the Microbiome 7:00 am Registration Open and Morning Coffee Therapeutics, Inc. antibiotics with a large number of molecules and »» Antibody Discovery Forum - Forge Therapeutics is focused on developing small analogs still today in the clinic. NPs present a unique Part 1 & Part 2 DISCOVERY PLATFORMS: NATURAL molecule, direct-acting, novel antibiotics that inhibit chemical space with potency and selectivity being »» Antibodies Against Membrane PRODUCTS AND GENOME MINING select metalloenzymes to treat infections caused the result of an extended evolutionary selection. New Protein Targets - Part 1 & Part 2 8:00 Welcome Remarks from high priority drug-resistant bacteria. We are integrated NPs discovery approaches are playing a currently in late lead optimization for the first-ever key role in the identification of new molecules to be Hotel & Travel Mana Chandhok, Associate Conference Producer, Cambridge Healthtech Institute non-hydroxamate inhibitor of LpxC, a bacterial Zn2+ developed to fill the antibiotic pipeline. hydrolase, for IV/oral treatment of urinary tract Registration Information 11:25 Progress toward Selective Bacterial Protein 8:05 Chairperson’s Opening Remarks infection (‘FG-LpxC-UTI’). Zachary Zimmerman, PhD, CEO, Co-Founder, Forge Synthesis Antibacterials Therapeutics, Inc. 9:10 Antimicrobials for Unmet Medical Needs Chad Testa, PhD, Vice President, Cūrza Global, LLC Click Here to Register Kim Lewis, PhD, University Distinguished Professor, Inspired by a natural product, Cūrza is developing DiscoveryOnTarget.com Biology; Director of Antimicrobial Discovery Center, antibiotics that selectively inhibit bacterial protein Biology, Northeastern University synthesis by acting on a clinically undrugged binding We identified compounds with no detectable site on the ribosome. CZ-02s have excellent drug-like resistance (Teixobactin, Novo29), and capable of properties, do not show cross-resistance to other

A Division of Cambridge Innovation Institute Antibacterial Discovery and Development DiscoveryOnTarget.com • 50 HOT & EMERGING Final Weeks to Register

Cover protein synthesis inhibitors (e.g., aminoglycosides, once-weekly or bi-weekly dosing, making them well contain the infection. Improved understanding of tetracyclines), are efficacious in murineE. coli infection suited as immunotherapeutic agents to prevent cause-effect relationships between the microbiome Conference models, have potent selective inhibition of bacterial and treat life-threatening multidrug-resistant Gram- and immunity will lead to new treatment modalities At-A-Glance protein synthesis and are not cytotoxic. negative infections. that complement conventional antibiotics. Sponsorship & Exhibit 11:55 Fixing the Broken Antibiotics Business Model 2:35 Anti-Persister Strategy for the Treatment of 4:35 Mining the Human Microbiome for Novel Gram- Short Courses through Molecular Diagnostics Chronic, Recurrent Infections Negative Antibiotics Andreas E. Posch, PhD, Founder & Managing Director, Diane Joseph-McCarthy, PhD, Vice President, Jessica Ferreyra, PhD, Scientist, Biology, NGM Symposia Ares Genetics GmbH Translational Science, EnBiotix Biopharmaceuticals Training Seminar Ares Genetics’ vision is to revolutionize infectious Bacteria can enter into a persister state in response to We have identified human microbiota-derived peptides disease diagnostics and therapeutics by translating various stresses including antibiotic treatment. In this that exhibit antimicrobial activity against human Plenary Keynotes success stories from treatment response prediction metabolically dormant state, bacteria become tolerant pathogens. Using two bioinformatics discovery pipelines, Agenda in cancer to microbial infections. To achieve or “transiently resistant” to antibiotics, which can lead we identified 1,204 candidate antimicrobial products »» Small Molecules for Cancer this, Ares Genetics makes use of high-resolution to chronic, recurrent infections including persistent from 2,161 microbial genomes of bacteria associated Next Generation Sequencing (NGS) technology in lung infections. Combinations of aminoglycosides with human gut, mouth, skin and urogenital sites. Immunotherapy combination with a proprietary pathogen and drug with bacterial metabolites as proton-motive force »» Autoimmune and Inflammation resistance biomarker database, ARESdb, for result enhancing potentiators were investigated. Pairwise Drug Targets 5:05 Interactive Breakout Discussion Groups interpretation. In this talk, we will present how combinations were screened using the time-kill »» NK Cell-Based Cancer Join a breakout discussion group. These are informal, ARESdb can be used for (a) diagnosing microbial method as well as biofilm assays. Eliminating bacterial moderated discussions with brainstorming and Immunotherapy infections and drug response prediction, as well persisters early may be a key to limiting further »» Targeting Tumor Myeloid Cells interactive problem solving, allowing participants as, (b) accelerating and informing antibiotic drug resistance and prolonging the lifetime of clinically from diverse backgrounds to exchange ideas and »» Targeting the Ubiquitin- development across the product life cycle. important anti-infective agents. Proteasome System experiences and develop future collaborations around 12:25 pm Session Break 2:55 Predicting Antibiotic Resistance with Bacterial a focused topic. Details on the topics and moderators »» Kinase Inhibitor Discovery Synthetic Biology are available on the conference website. »» CNS and Neurodegenerative 12:35 Luncheon Presentation (Sponsorship Ákos Nyerges, Project leader, Csaba Pál Lab, Synthetic Targets Opportunity Available) or Enjoy Lunch on Your Own and Systems Biology Unit, Hungarian Academy »» GPCR-Based Drug Discovery 1:15 Refreshment Break in the Exhibit Hall with 6:05 Welcome Reception in the Exhibit Sponsored by of Sciences Hall with Poster Viewing »» Constrained Peptides and Poster Viewing Forecasting resistance evolution at an early stage Macrocyclics of drug development would be useful to identify 7:10 Close of Day »» Lead Generation Strategies ALTERNATIVE THERAPIES less resistance-prone antimicrobials. To this aim, »» Target Identification and 1:50 Chairperson’s Remarks by building on synthetic biology, we developed a Thursday, September 27 Validation - Part 1 & Part 2 Neeraj (Neil) Surana, MD, PhD, Instructor, Infectious method (DIvERGE) that enables precise mutagenesis 7:30 am Registration Open and Morning Coffee »» Antibacterial Discovery and Diseases, Boston Children’s Hospital of drug targets, directly in pathogenic bacteria. This Development 1:55 The Efficacy, Safety, and Tolerability of method allowed us to predict resistance evolution to FUNDERS AND ACCELERATORS »» Targeting Gram-Negative Gepotidacin (GSK2140944) antibiotics in a high-throughput manner. With DIvERGE, Pathogens we also predicted probable resistance processes for 8:00 Chairperson’s Remarks David Gardiner, Medicine Development Leader, Vikas Goyal, Associate, SR One »» NASH and Fibrosis Gepotidacin, GSK antibiotics that are in clinical trials »» Targeting the Microbiome Gepotidacin is a novel, first-in-class, 3:25 Refreshment Break in the Exhibit Hall with Poster 8:05 Replenishing and Enabling the Pipeline for Anti- »» Antibody Discovery Forum - triazaacenaphthylene antibacterial agent which has Viewing and Poster Competition Winner Announced Infective Resistance (REPAIR) Part 1 & Part 2 in vitro activity against causative pathogens of acute Aleks Engel, PhD, Partner, Novo Seeds, Nova Holdings »» Antibodies Against Membrane bacterial skin and skin structure infections (ABSSSIs). UTILIZING THE MICROBIOME The REPAIR Impact Fund will invest $165m over 3-5 Protein Targets - Part 1 & Part 2 years in novel anti-infective therapies between lead 2:15 Cloudbreak Antibody-Drug Conjugates for 4:05 Exploiting Host–Microbiome Interactions to optimization and end of Phase I. Hotel & Travel Treatment of MDR Gram Negative Bacterial Infections Treat Infectious Diseases James Levin, PhD, Director of Preclinical Development, Neeraj (Neil) Surana, MD, PhD, Assistant Professor of 8:25 Funding Opportunities with CARB-X Kevin Outterson, Professor of Law, N. Neal Pike Scholar Registration Information Cidara Therapeutics Pediatrics, Molecular Genetics and Microbiology, Duke Cloudbreak ADCs physically link the pathogen and University in Health and Disability Law, Boston University; Executive the immune component to eradicate pathogens via Although investigators are working on developing new Director, CARB-X Click Here to Register dual killing mechanisms. The engagement of specific antibiotics, the history of the past ~75 years suggests CARB-X is a $455M public-private partnership funded DiscoveryOnTarget.com innate immune system components confers potential that success will be short-lived before confronting by BARDA, the Wellcome Trust, and NIAID. We to largely limit resistance development in target resistance. An alternative to drugs that directly provide non-dilutive awards to companies to support pathogens. Furthermore, by linking to an antibody target the pathogen is to augment the host immune innovative preclinical and Phase I development Fc, ADCs possess extended half-lives to support response—in a pathogen agnostic manner—to better focused on priority bacterial pathogens.

A Division of Cambridge Innovation Institute Antibacterial Discovery and Development DiscoveryOnTarget.com • 51 HOT & EMERGING Final Weeks to Register

Cover 8:45 How BARDA Is Addressing the Global Threat – addresses global public health needs by developing 10:20 PANEL DISCUSSION: Filling in of Antimicrobial Resistance by Stimulating the affordable new or improved antibiotic treatments. the Funding Gaps Conference End-to-End Research and Development of Novel Initiated by the World Health Organization (WHO) and Vikas Goyal, Associate, SR One (Moderator) At-A-Glance Antibacterial Products the Drugs for Neglected Disease initiative (DNDi) in Mark Albrecht, Acting Branch Chief, Antibacterials Sponsorship & Exhibit Mark Albrecht, Acting Branch Chief, Antibacterials 2016, GARDP is an important element of WHO’s Global Program, Biomedical Advanced Research and Program, Biomedical Advanced Research and Action Plan on antimicrobial resistance that calls for Development Authority Short Courses Development Authority new public-private partnerships to encourage research Kevin Outterson, Professor of Law, N. Neal Pike Symposia Since 2010, the Biomedical Advanced Research and and development (R&D) of new antimicrobial agents Scholar in Health and Disability Law, Boston University; Development Authority (BARDA) has addressed the rising and diagnostics. GARDP capitalizes on DNDi’s track Executive Director, CARB-X Training Seminar threat of antimicrobial resistance by providing direct record of developing, delivering, and implementing Aleks Engel, PhD, Partner, Novo Seeds, Nova Holdings Plenary Keynotes funding, access to core development and manufacturing seven new treatments since 2003 for neglected François Franceschi, PhD, Project Leader ¦ Antimicrobial services, and technical and business support to small diseases, and a pipeline of new chemical entities, as Memory Recovery and Exploratory Programme Agenda biotechs and large, global pharmaceutical companies well as from WHO’s technical expertise and leadership. (AMREP), Global Antibiotic R&D Partnership (GARDP) »» Small Molecules for Cancer supporting the clinical development of new antibiotics. GARDP prioritizes its R&D strategies based on global With the past years filled with energetic activism Immunotherapy In 2016, BARDA, along with the Wellcome Trust and the health priorities, clear target product profiles and from the antibacterial community, the world is joining »» Autoimmune and Inflammation National Institutes of Health, established the Combatting R&D roadmaps. This approach creates a favourable together to fight antibacterial drug resistance. This Drug Targets Antibiotic Resistant Bacteria Accelerator, or CARB-X, a environment for equitable access by developing a panel will discuss current funding opportunities, »» NK Cell-Based Cancer public-private partnership managed by Boston University sustainable and fair pricing system. Partnerships are challenges to overcome and hope for the future. Immunotherapy accelerating the preclinical research and development key to GARDP programmes and include contractual »» Targeting Tumor Myeloid Cells innovative products addressing the AMR threat. Together, arrangements with pharmaceutical companies, 11:20 Luncheon Presentation (Sponsorship »» Targeting the Ubiquitin- BARDA is providing end-to-end support to developers research institutions, and academic partners. Current Opportunity Available) or Enjoy Lunch on Your Own Proteasome System of novel diagnostics, preventatives and treatments to programmes comprise neonatal sepsis, sexually- 11:50 Conference Registration Open »» Kinase Inhibitor Discovery beat back the growing global threat of antibacterial transmitted infections, paediatric antibiotics and »» CNS and Neurodegenerative resistant bacteria. the antimicrobial memory recovery and exploratory Targets 9:05 Global Antibiotic Research and Development programme, which includes REVIVE – an online 12:20 pm Plenary Keynote Program »» GPCR-Based Drug Discovery Partnership (GARDP) resource connecting and supporting the antimicrobial Click here for details. »» Constrained Peptides and François Franceschi, PhD, Project Leader, Antimicrobial R&D community. A key component of GARDP’s model Macrocyclics Memory Recovery and Exploratory Programme (AMREP), is a tailored approach to ensuring sustainable access – embedding stewardship and conservation within an 2:00 Refreshment Break in the Exhibit Hall with »» Lead Generation Strategies Global Antibiotic R&D Partnership (GARDP) Poster Viewing »» Target Identification and The Global Antibiotic Research and Development access approach. 2:45 Close of Conference Validation - Part 1 & Part 2 Partnership (GARDP) – a not-for-profit drug developer 9:35 Coffee Break in the Exhibit Hall with Poster Viewing »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Antibacterial Discovery and Development DiscoveryOnTarget.com • 52 HOT & EMERGING Final Weeks to Register 2nd Annual | September 27-28 Targeting Gram-Negative Pathogens Cover Small Molecules, Biologics and More Conference At-A-Glance Sponsorship & Exhibit

Short Courses Multidrug-resistant Gram-negative bacteria are one of the main challenges for the healthcare system and public 4:25 Refreshment Break in the Exhibit Hall with Symposia health in general. Gram-negative bacteria have specific scientific problems, such as low permeability of the outer Poster Viewing membrane that must be overcome, complicated and multiple resistance mechanisms, etc. Cambridge Healthtech Training Seminar 5:00 In vitro Activity of Imipenem-Relebactam against Institute’s 2nd Annual Targeting Gram-Negative Pathogens conference will be taking place as a part of the 5th Gram-Negative ESKAPE Pathogens Plenary Keynotes Annual Re-Entering Antibacterial Discovery and Development Summit. It will be preceded by the more general Katherine Young, MS, Senior Principal Scientist, Antibacterial Discovery and Development. Agenda Richard T. Clark Fellow for Global Health, Infectious »» Small Molecules for Cancer Diseases, Merck Advisors: Lynn Silver, LL Silver Consulting; Ruben Tommasi, Entasis Therapeutics; Joyce Sutcliffe, Formerly Relebactam (formerly MK-7655) is an inhibitor of Immunotherapy Tetraphase; Todd Black, Merck class A and C β-lactamases, including Klebsiella »» Autoimmune and Inflammation pneumoniaecarbapenemase (KPC), and is currently Drug Targets 2:50 Chairperson’s Opening Remarks in clinical development in combination with »» NK Cell-Based Cancer RECOMMENDED ALL ACCESS Todd A. Black, PhD, Executive Director, Infectious imipenem-cilastatin. Using Clinical and Laboratory Immunotherapy PACKAGE: Choose 2 Short Courses Diseases, Basic Research, Merck Research Laboratories Standards Institute (CLSI)-defined broth microdilution »» Targeting Tumor Myeloid Cells or 1 Symposium and 2 Conferences/ methodology, we evaluated the in vitro activities of »» Targeting the Ubiquitin- imipenem-relebactam, imipenem, and seven routinely Proteasome System Training Seminars 2:55 KEYNOTE PRESENTATION: Staphylococcus aureus mAbs in tested parenteral antimicrobial agents against Gram- »» Kinase Inhibitor Discovery • September 25 Short Course 10: Applications of Development negative ESKAPE pathogens. »» CNS and Neurodegenerative Artificial Intelligence and Machine Learning in Steven Projan, PhD, Former Senior 5:30 Innovation and Challenges in the Development of Targets Drug Discovery and Development Vice President, MedImmune; Beat Beta-Lactamase Inhibitor Combinations »» GPCR-Based Drug Discovery • September 26-27 Conference: Antibacterial the Reaper, LLC Michael N. Dudley, PharmD, FIDSA, Senior Vice »» Constrained Peptides and Discovery and Development There has been an increasing focus on the President, CSO, Head of Infectious Disease Global Macrocyclics • September 27-28 Conference: Targeting Gram- potential use of immunotherapies for bacterial Innovation, The Medicines Company »» Lead Generation Strategies Negative Pathogens infections (in what can best be called a back to Development of new antibiotics for resistant gram- »» Target Identification and • September 27 Short Course 17: Technologies the future approach as immune anti sera were negative infections has been most successful by Validation - Part 1 & Part 2 to Assess Permeability and Efflux in Gram- raised in large animals in the latter part of the restoring the activity of proven β-lactam antibiotics »» Antibacterial Discovery and Negative Bacterial Pathogens nineteenth century with Emil von Behring winning through use of novel β-lactamase inhibitors. However, Development first Nobel Prize for Physiology or Medicine). combination therapy presents challenges in getting the »» Targeting Gram-Negative Now in the 21st century the use of (fully human) right partner agent as well as getting the PK-PD right. Pathogens Thursday, September 27 monoclonal antibodies are being aggressively Examples of successes and failures will be discussed. »» NASH and Fibrosis investigated in human clinical studies with 6:00 Restoring β-Lactam Efficacy against Methicillin- »» Targeting the Microbiome 11:50 am Conference Registration Open Staphylococcus aureus being the prime pathogen Resistant Staphylococci »» Antibody Discovery Forum - being target. Can the neutralization of one Holly Sutterlin, PhD, Director of Biology, Prokaryotics Part 1 & Part 2 12:20 pm Plenary Keynote Program or a handful of the 300 plus virulence factors β-lactam antibiotics have served as the most impactful »» Antibodies Against Membrane Click here for details. that Staph produces have a therapeutic or class of antibiotics but their efficacy has been Protein Targets - Part 1 & Part 2 prophylactic effect? The role of many of these eroded by the emergence of MRSA/E. To re-establish virulence factors is evading the host response to β-lactams as a standard of care therapy for MRSA/E Hotel & Travel 2:00 Refreshment Break in the Exhibit Hall with infection but does the bacterium have an achilles infections, we are developing inhibitors of wall teichoic Poster Viewing heal? Preclinical data suggest this is the case acid biosynthesis that exhibit bactericidal synergy in Registration Information with alpha toxin being one of the prime targets. combination with broad-spectrum β-lactam antibiotics BREAKING OPEN BARRIERS against diverse MRSA/E clinical isolates and show Click Here to Register 2:45 Welcome Remarks robust efficacy in a murine MRSA infection model. DiscoveryOnTarget.com Mana Chandhok, Associate Conference Producer, EXTENDED-SPECTRUM BETA- 6:30 Dinner Short Course Registration Cambridge Healthtech Institute LACTAMASE INHIBITORS: UPDATES Click here for details on short courses offered. 3:55 Sponsored Presentation (Opportunity Available) 9:30 Close of Day

A Division of Cambridge Innovation Institute Targeting Gram-Negative Pathogens DiscoveryOnTarget.com • 53 HOT & EMERGING Final Weeks to Register

Cover Friday, September 28 9:35 Next-Generation Approaches to Antibody resistance to current therapies, consistent with novel Discovery for Treatment and Prevention of Infections chemistry and mechanism, including ESBLs, KPCs, Conference 7:00 am Registration Open Caused by Gram-Negative MDR Pathogens NDMs, mcr-1 and high-efflux-expressing P. aeruginosa. At-A-Glance Dante Ricci, PhD, Scientist, Early Research, Achaogen The structure-based design process has allowed us to Sponsorship & Exhibit 7:30 Interactive Breakfast Breakout Cases of neonatal infection are increasingly attributed problem-solve in the areas of in vitro activity, animal to Gram-negative pathogens, with multi-drug-resistant efficacy and preclinical safety. Herein, we present the Short Courses Discussion Groups Grab a cup of coffee and join a breakout discussion Acinetobacter baumannii emerging as a major dossiers of several pyrrolocytosine leads in preclinical Symposia group. These are informal, moderated discussions underlying cause of neonatal sepsis and consequent development with credentials for addressing drug- mortality. I will discuss the advantages of antibody- resistant Neisseria gonorrhoeae, carbapenem- Training Seminar with brainstorming and interactive problem solving, allowing participants from diverse backgrounds based approaches to prevention and treatment of resistant Enterobacteriaceae and infections caused by Plenary Keynotes to exchange ideas and experiences and develop Gram-negative infections, and describe a platform for pathogens across the full ESKAPE spectrum. the efficient identification of broadly cross-reactive Agenda future collaborations around a focused topic. Details 11:45 Sponsored Presentation (Opportunity Available) anti-Acinetobacter mAbs that bind live bacteria and »» Small Molecules for Cancer on the topics and moderators are available on the 12:15 pm Session Break conference website. forestall infection. Immunotherapy 10:05 Coffee Break in the Exhibit Hall with Poster 12:25 Luncheon Presentation (Sponsorship »» Autoimmune and Inflammation Viewing and Poster Competition Winner Announced Opportunity Available) or Enjoy Lunch on Your Own Drug Targets GRAM-NEGATIVE BIOLOGICS 1:15 Refreshment Break in the Exhibit Hall with »» NK Cell-Based Cancer ANTI-GRAM NEGATIVE SMALL Poster Viewing Immunotherapy 8:30 Chairperson’s Remarks Antonio DiGiandomenico, PhD, Principal Scientist, MOLECULES: DISCOVERY AND »» Targeting Tumor Myeloid Cells CASE STUDIES AND »» Targeting the Ubiquitin- Microbial Sciences, MedImmune DEVELOPMENT COMPUTATIONAL APPROACHES Proteasome System 8:35 Immunotherapeutics Targeting Antibiotic- 10:45 Phenotypic Screening Strategies and Outcomes »» Kinase Inhibitor Discovery Resistant Pseudomonas aeruginosa Directed towards Novel Gram-Negative Targets 1:55 Chairperson’s Remarks »» CNS and Neurodegenerative Antonio DiGiandomenico, PhD, Principal Scientist, Carl Balibar, PhD, Principal Scientist, Infectious Sharookh Bomi Kapadia, Senior Scientist, Infectious Targets MedImmune Diseases, Merck Diseases, Genentech »» GPCR-Based Drug Discovery P. aeruginosa is a major challenge for new The emergence of multi-drug resistant bacteria is 2:00 Bacterial Chemical Genomics: A Path of »» Constrained Peptides and antimicrobial drug discovery efforts because of its eroding the efficacy of existing antibiotics. Although Ceased Resistance Macrocyclics versatile lifestyle and ability to develop antibiotic genomics has greatly contributed to the identification Eric Brown, PhD, Professor, Biochemistry and Biomedical »» Lead Generation Strategies resistance. This rise in resistance coupled with the of novel antibacterial targets, it has failed to exploit Sciences, McMaster University »» Target Identification and dearth in discovery of new antibiotic classes requires such targets to impact antibiotic discovery. Phenotypic Antibiotic drug resistance has reached crisis development of alternative antimicrobials, such as Validation - Part 1 & Part 2 screening remains the primary source for new proportions, owing to a dearth of new antibiotics. In pathogen-specific monoclonal antibodies (mAbs). »» Antibacterial Discovery and antibacterial compounds; however, it is imperative the Brown lab, we are developing chemical-genomic In this presentation, I will introduce novel anti- Development to design screens with intent, target bias, and hit- approaches with utility in exploring complex biology Pseudomonal mAbs and discuss their mechanisms of »» Targeting Gram-Negative prioritization strategies if high potential inhibitors and and enigmatic processes that are essential for action in multiple infection models. Pathogens targets are to be discovered. bacterial survival. Efforts to date have resulted in »» NASH and Fibrosis 9:05 Monoclonal Antibody Targeting the β-barrel 11:15 On the Design and Optimization of the new understanding, platforms, chemical probes »» Targeting the Microbiome Assembly Machine of Escherichia coli Is Bactericidal Pyrrolocytosines and lead compounds for antibacterial research. The »» Antibody Discovery Forum - Steven Rutherford, PhD, Scientist, Genentech Erin M. Duffy, PhD, CSO, Melinta Therapeutics, Inc. ultimate goal is to contribute fresh directions for new Folding β-barrel proteins into the outer membrane is antibacterial therapies. Part 1 & Part 2 Our approach to the design of new antibiotics is essential in Gram-negative bacteria. We discovered »» Antibodies Against Membrane unique, proprietary, and powerful, combining X-ray 2:30 The Grim Reaper Is Lurking, What Matters More an antibody, MAB1, that inhibits BamA, an outer Protein Targets - Part 1 & Part 2 crystallography of the bacterial ribosome with a Death, Efficacy, or Safety? membrane protein required for β-barrel assembly in structure-based design process that we have refined Gary Eldridge, President & CEO, Sequoia Sciences, Inc. Hotel & Travel Escherichia coli. MAB1 is bactericidal when the LPS over many antibiotic programs and that allows us to Sepsis from UTI leads to more deaths annually than is truncated and it inhibits β-barrel folding, induces exploit existing as well as novel binding sites. The breast cancer. Sequoia Sciences is developing a Registration Information periplasmic stress, and disrupts outer membrane pyrrolocytosines represent completely novel small- vaccine to reduce the recurrences of UTI. Sequoia integrity. MAB1 highlights the potential for new molecule ribosome inhibitors from a de novo design has evaluated its vaccine in women with and without mechanisms of antibiotics to inhibit bacterial growth effort targeting a validated but unexploited binding a history of recurrent UTI. The vaccine has been Click Here to Register by targeting extracellular epitopes. DiscoveryOnTarget.com site, rationally designed to enhance bacterial influx well-tolerated and highly immunogenic, and elicited and minimize bacterial efflux. The net result is robust functional antibody responses. The results of these coverage of ESKAPE pathogens as well as other human studies, including preliminary clinical evidence urgent and serious threats on the CDC and WHO of efficacy, and the design of future clinical studies priority lists. Lead compounds are unaffected by will be presented.

A Division of Cambridge Innovation Institute Targeting Gram-Negative Pathogens DiscoveryOnTarget.com • 54 HOT & EMERGING Final Weeks to Register

Cover 3:00 Gram-Negative Lipoprotein Biosynthesis and Transport Conference Sharookh Bomi Kapadia, Senior Scientist, Infectious At-A-Glance Diseases, Genentech Sponsorship & Exhibit Antibiotic discovery for Gram-negative bacteria pose further challenges due to the impermeability of the Short Courses asymmetric LPS-containing outer membrane. Here, Symposia we will discuss our efforts to better understand the bacterial lipoprotein synthesis and transport pathways Training Seminar and highlight the success and challenges associated Plenary Keynotes with targeting them. Agenda 3:30 Bacterial Outer Membranes and Interactions with »» Small Molecules for Cancer Membrane Proteins Wonpil Im, PhD, Presidential Endowed Chair in Health, Immunotherapy Science and Engineering, Professor of Biological »» Autoimmune and Inflammation Sciences and Bioengineering, Lehigh University Drug Targets The outer membrane of Gram-negative bacteria is a »» NK Cell-Based Cancer unique asymmetric membrane bilayer: phospholipids Immunotherapy in the inner leaflet and lipopolysaccharides in the outer »» Targeting Tumor Myeloid Cells leaflet. Its function as a selective barrier is crucial for »» Targeting the Ubiquitin- the survival of bacteria, and it also renders gram- Proteasome System negative bacteria resistant to antibiotics. I will present »» Kinase Inhibitor Discovery our ongoing molecular modeling and simulation »» CNS and Neurodegenerative studies on various bacterial outer membranes and Targets their interactions with outer membrane proteins. »» GPCR-Based Drug Discovery 4:00 Close of Conference »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Targeting Gram-Negative Pathogens DiscoveryOnTarget.com • 55 HOT & EMERGING Final Weeks to Register 2nd Annual | September 26-27 NASH and Fibrosis Cover Drug Development for the Fatty Liver Conference At-A-Glance Sponsorship & Exhibit

Short Courses Non-alcoholic Steatohepatitis (NASH) is a disease of the liver that starts with an accumulation of fat and Phase II for NASH. We demonstrate that DNL inhibition Symposia proceeds to inflammation and scarring of the liver. The scarring begins as fibrosis, but can worsen to cirrhosis suppresses the activation of hepatic stellate cells and eventual liver failure. The global incidence of NASH is rapidly rising and no medical treatments exist. (HSCs) in vitro and reduces liver fibrosis in two rodent Training Seminar Advances in the scientific understanding of the fibrotic disease process in other organs are also rapidly models. These data demonstrate that, in addition to Plenary Keynotes occurring. This conference convenes discovery scientists in academics, biotech and pharma who work in the decreasing lipotoxicity in hepatocytes, ACC inhibition area of fibrosis, inflammation or liver disease to share insights, tools and stay abreast of this emerging and directly inhibits HSC activation. Agenda rapidly progressing field. »» Small Molecules for Cancer 11:25 LXR Inverse Agonists for the Treatment of NASH Immunotherapy Professor of Internal Medicine, Saint Louis Claus Kremoser, PhD, CEO, Phenex »» Autoimmune and Inflammation RECOMMENDED ALL ACCESS University School of Medicine Nuclear Receptor targeted drugs such as FXR, Drug Targets PACKAGE: Choose 2 Short Courses NASH is histologic phenotype that represents TRbeta or PPAR agonists have emerged as effective »» NK Cell-Based Cancer or 1 Symposium and 2 Conferences/ the consequences of stress on multiple approaches to combat NASH but they all come Immunotherapy Training Seminars metabolic, inflammatory and fibrogenic with limitations. LXR is known as a functional »» Targeting Tumor Myeloid Cells pathways. It can thus be expected that counterplayer of FXR and as such, inhibiting LXR »» Targeting the Ubiquitin- • September 25 Symposium: Antivirals: patients develop NASH due to environmental, function by inverse agonist ligands should yield Proteasome System Targeting HBV and Beyond metabolic, genetic and epigenetic reasons that similar effects than activating FXR. Animal data show »» Kinase Inhibitor Discovery • September 25 Short Course 2: Drug vary among individuals. This talk will provide that beyond strong anti-steatotic properties, LXR »» CNS and Neurodegenerative Metabolism and Its Role in Discovery and a high-level overview of the pathways thought inverse agonists demonstrate novel, unprecendeted Targets Drug Development to be mechanistically important in both the antidiabetic effects. »» GPCR-Based Drug Discovery • September 26-27 Conference: pathogenesis of NASH and the resulting fibrosis 11:55 How HepQuant Tests May Aid Sponsored by »» Constrained Peptides and NASH and Fibrosis and how these pathways might be targeted with Drug Development Macrocyclics pharmacotherapy. • September 27-28 Conference: Autoimmune Steve Helmke, CSO, HepQuant, LLC »» Lead Generation Strategies Hepquant tests are minimally invasive, blood-based »» Target Identification and and Inflammation Drug Targets 9:10 Thyroid Hormone Receptor Agonists and use cholates as probes to measure the effects Validation - Part 1 & Part 2 • September 27 Short Course 16: for Treating NASH of disease on liver function and physiology. The main »» Antibacterial Discovery and Immunology Basics Rebecca Taub, MD, CMO & Executive Vice President, output, Disease Severity Index (DSI), is a liver score from Development Research & Development, Madrigal Pharmaceuticals 0 to 50 that is reproducible and can quantify disease »» Targeting Gram-Negative severity and track changes over time. Pathogens Wednesday, September 26 9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing 12:25 pm Session Break »» NASH and Fibrosis 7:00 am Registration Open and Morning Coffee »» Targeting the Microbiome 12:35 Luncheon Presentation (Sponsorship NASH DRUG CANDIDATES Opportunity Available) or Enjoy Lunch on Your Own »» Antibody Discovery Forum - NASH DRUG CANDIDATES Part 1 & Part 2 AND TARGETS 1:15 Refreshment Break in the Exhibit Hall with 8:00 Welcome Remarks »» Antibodies Against Membrane Poster Viewing Anjani Shah, PhD, Conference Director, Cambridge 10:25 Therapeutic Approaches to Cirrhotic versus Protein Targets - Part 1 & Part 2 Healthtech Institute Pre-cirrhotic NASH Peter Traber, MD, Partner, Alacrita Consulting; Adjunct EMERGING TARGETS FOR Hotel & Travel 8:05 Chairperson’s Opening Remarks Professor of Medicine, University of Pennsylvania School LIVER FIBROSIS Bryan C. Fuchs, PhD, Assistant Professor of Surgery, of Medicine Registration Information Harvard Medical School 1:50 Chairperson’s Remarks 10:55 ACC Inhibitor for NASH H. James Harwood Jr., PhD, Founder and CEO, Delphi Jamie Bates, PhD, Senior Research Scientist, I BioMedical Consultants, LLC Click Here to Register 8:10 KEYNOTE PRESENTATION: Fibrosis, Gilead DiscoveryOnTarget.com NASH Basic Science Overview and 1:55 Is Combination Therapy the Future of ACC1 and 2 catalyze the rate-limiting step of de novo NASH Treatment? Medical Landscape lipogenesis (DNL) and inhibit mitochondrial fatty Brent Tetri, MD, Director, Division of Star Seyedkazemi, PharmD, Associate Vice President, acid oxidation, respectively. GS-0976, a liver-directed Clinical Development, Liver Therapeutic Area, Allergan Gastroenterology and Hepatology; acetyl-CoA carboxylase (ACC) inhibitor is currently in

A Division of Cambridge Innovation Institute NASH and Fibrosis DiscoveryOnTarget.com • 56 HOT & EMERGING Final Weeks to Register

Cover 2:25 A Bispecific Antibody Mimetic of FGF21 for 5:05 Interactive Breakout Discussion Groups invasive, variable and a non-representative technique. Metabolic Diseases and NASH Join a breakout discussion group. These are informal, We will summarize soluble biomarkers which have Conference James A. Ernst, PhD, Senior Scientist, Department of moderated discussions with brainstorming and shown most promising results in terms of fibrosis and At-A-Glance Protein Science, Genentech, Inc. interactive problem solving, allowing participants NASH staging, and measuring the anti-fibrotic activity Sponsorship & Exhibit Activation of the FGF21 pathway has been shown from diverse backgrounds to exchange ideas and in clinical trials. to improve several features of metabolic disease in experiences and develop future collaborations around 9:05 Sponsored Presentation (Opportunity Available) Short Courses animals. Here we describe a novel bispecific antibody a focused topic. Details on the topics and moderators 9:35 Coffee Break in the Exhibit Hall with Symposia that mimics the function and metabolic effects are available on the conference website. of FGF21. Treatment with this antibody improves Poster Viewing Training Seminar glycemic and lipid profiles in mouse disease models 6:05 Welcome Reception in the Exhibit Sponsored by 10:20 Targeting Integrins for the Plenary Keynotes and reduces body weight in mice and non-human Hall with Poster Viewing Treatment of Fibrosis primates. These effects mimic the activity of FGF21 on Scott M. Turner, PhD, Vice President, Translational Agenda both mice and non-human primates, suggesting that 7:10 Close of Day Sciences, PLIANT Therapeutics »» Small Molecules for Cancer antibody-mediated activation of FGF21 pathway would Integrin receptors regulate multiple processes involved Immunotherapy Thursday, September 27 be an effective treatment for type 2 diabetes. in inflammation, cell adhesion and fibrosis.v α integrins »» Autoimmune and Inflammation 2:55 Sponsored Presentation (Opportunity Available) 7:30 am Registration Open and Morning Coffee are of interest as antifibrotic targets due to their role Drug Targets in cell-specific TGFβ activation and promotion of 3:25 Refreshment Break in the Exhibit Hall with Poster »» NK Cell-Based Cancer TOOLS AND TARGETS FOR FIBROSIS fibrosis. Selective targeting of specific integrins with Immunotherapy Viewing and Poster Competition Winner Announced small molecule inhibitors can interrupt the pro-fibrotic »» Targeting Tumor Myeloid Cells 4:05 Targeting Liver Fibrosis through Modulating 8:00 Chairperson’s Remarks TGFβ pathway, without the risks associated with »» Targeting the Ubiquitin- the Wnt Pathway Rebecca Taub, MD, CMO & Executive Vice President, systemic TGFβ inhibition. We have developed oral Proteasome System Weilin Xie, PhD, Senior Principal Scientist, Research & Development, Madrigal Pharmaceuticals small molecule integrin inhibitors with demonstrated »» Kinase Inhibitor Discovery Biotherapeutics, Celgene antifibrotic activity in primary human tissue slices and »» CNS and Neurodegenerative 4:35 CSTI-100, a Melanin-Concentrating 8:05 FEATURED PRESENTATION: Animal preclinical models of fibrosis. Targets Hormone Receptor 1 (MCHR1) Antagonist, for the Models for NASH »» GPCR-Based Drug Discovery Treatment of NASH Bryan C. Fuchs, PhD, Assistant Professor of Surgery, 10:50 FEATURED PRESENTATION: Development of a »» Constrained Peptides and Pete Guzzo, PhD, Founder and CEO, ConSynance Harvard Medical School Novel Targeted HSP47 siRNA Lipid Nanoparticle for Macrocyclics Therapeutics, Inc. Generating robust fibrosis in the setting of a the Treatment of Hepatic Fibrosis »» Lead Generation Strategies MCHR1 antagonism is a new target approach for the metabolic syndrome that resembles human clinical Edgar D. Charles, MD, Clinical Development Lead, Liver »» Target Identification and treatment of NASH and CSTI-100 appears to be the NASH remains a challenge for preclinical animal Fibrosis, Bristol-Myers Squibb models. Despite these limitations, a plethora of Validation - Part 1 & Part 2 furthest advanced compound in the industry. Emerging animal models have been utilized in the NASH drug »» Antibacterial Discovery and evidence from studies with CSTI-100 and the literature development landscape. Here, we will summarize 11:20 Luncheon Presentation (Sponsorship Development suggest this approach may have advantages over the most commonly used models and discuss Opportunity Available) or Enjoy Lunch on Your Own »» Targeting Gram-Negative current clinical approaches. In addition, Jim Harwood their relevance to the human disease and how they Pathogens has been a consultant to this program for about 10 11:50 Conference Registration Open years, and he recommended we apply to present at might be better utilized to enhance translation »» NASH and Fibrosis into the clinic. »» Targeting the Microbiome this prestigious forum. 12:20 pm Plenary Keynote Program »» Antibody Discovery Forum - Click here for details. 8:35 NASH and Fibrosis Serum Biomakers Part 1 & Part 2 Saurabh Gupta, PhD, Director, Translational Medicine and »» Antibodies Against Membrane Early Clinical, Takeda Pharmaceuticals Interational Co. 2:00 Refreshment Break in the Exhibit Hall with Protein Targets - Part 1 & Part 2 Clinical Diagnosis of NASH and evaluation of anti- Poster Viewing Hotel & Travel fibrotic activity in clinical trials heavily relies on the 2:45 Close of Conference histological readouts based on liver biopsy, a highly Registration Information

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A Division of Cambridge Innovation Institute NASH and Fibrosis DiscoveryOnTarget.com • 57 HOT & EMERGING Final Weeks to Register 4th Annual | September 27-28 Targeting the Microbiome Cover Microbiota-Targeted Therapies to Treat and Prevent Disease Conference At-A-Glance Sponsorship & Exhibit

Short Courses Basic and applied biomedical research from the Human Microbiome Project and other independent studies 3:55 Small Molecules at the Sponsored by Symposia prove that a disruption of a stable microbiome ecosystem results in dysbiosis. This imbalance leads to chronic Intersection of Health and Microbiota disease and health conditions. There is great promise in correlating the microbiome compositions with these Karen DeBalsi, PhD, Senior Study, Director, Training Seminar diseases and using the microbiome as a tool for therapeutic development. Cambridge Healthtech Institute’s Metabolon Plenary Keynotes 4th Annual Targeting the Microbiome tracks both the scientific and clinical progress being made to discover Metabolites serve as a language that mediates and develop microbiome-derived biomarkers, drug targets, and bioactive molecules as potential treatments for cross-species relationships and Metabolon’s unbiased Agenda chronic disease and health conditions. Through interactive sessions and panel discussions, leading researchers global metabolomics approach provides a great tool »» Small Molecules for Cancer and thought leaders will explore how the microbiome can become a potential point of intervention to impact to decipher the complex biological story. This talk Immunotherapy progression to disease. will cover how one can best leverage this technology »» Autoimmune and Inflammation to address their microbiome research questions as Drug Targets 2:50 Chairperson’s Opening Remarks supported by case studies. »» NK Cell-Based Cancer RECOMMENDED ALL ACCESS 2:55 Targeting the Human Host-Microbiome Interface 4:25 Refreshment Break in the Exhibit Hall with Immunotherapy PACKAGE: Choose 2 Short Courses Poster Viewing »» Targeting Tumor Myeloid Cells in Metabolic Disease or 1 Symposium and 2 Conferences/ James R. Brown, MSc, PhD, GSK Senior Fellow and »» Targeting the Ubiquitin- TARGETING THE MICROBIOME IN Proteasome System Training Seminars Director in Computational Biology for Infectious Disease and Oncology, GlaxoSmithKline, Collegeville PA »» Kinase Inhibitor Discovery • September 25 Symposium: ORAL HEALTH & NUTRITION Recent studies have highlighted the role of »» CNS and Neurodegenerative Targeting Autophagy 5:00 The Oral Microbiome as a Gateway to gastrointestinal tract microbial communities in Targets Systemic Health • September 25 Short Course 9: CNS metabolic health and disease. The microbiome, »» GPCR-Based Drug Discovery Translational Strategies Bonnie Feldman, DDS, MBA, Digital Health Analyst and the collective genomic and metabolic potential of Chief Growth Officer, DrBonnie360 »» Constrained Peptides and • September 26-27 Conference: CNS and the gut microbiota, has a key role in many chronic Macrocyclics The oral cavity is home to an immensely diverse Neurodegenerative Targets diseases through its mitigation of host immune- microbiome: an estimated 20 billion microbes (more »» Lead Generation Strategies inflammatory responses. In this presentation, we »» Target Identification and • September 27-28 Conference: Targeting than 700 species) live in our mouths, with distinct the Microbiome provide a pharmaceutical industry perspective on populations predominating in different oral habitats. Validation - Part 1 & Part 2 the importance of the gut microbiome in metabolic The status of our oral microbiome and health may »» Antibacterial Discovery and • September 27 Short Course 16: and inflammatory diseases, its impact on drug provide an early indicator of systemic diseases such Development Immunology Basics pharmacology and the promise and challenges as diabetes, heart disease, stroke, rheumatoid arthritis »» Targeting Gram-Negative of exploiting human host-microbiome cross-talk and other autoimmune diseases. As advances in Pathogens pathways and networks for novel therapeutic targets. Thursday, September 27 big data analytics, next-generation sequencing, and »» NASH and Fibrosis 3:25 Gut Microbiome Mediates Sex Differences in the systems immunology advance our knowledge about »» Targeting the Microbiome 11:50 am Conference Registration Open Obesity and Metabolic Syndrome in Mice the human microbiome, our understanding of and »» Antibody Discovery Forum - Kanakaraju “Raj” Kaliannan, MD, Instructor, Medicine, approach toward oral health, systemic immunity, Part 1 & Part 2 12:20 pm Plenary Keynote Program Harvard Medical School; Senior Research Fellow, and systemic health will also evolve. Learn about »» Antibodies Against Membrane Click here for details. Laboratory for Lipid Medicine and Technology (LLMT), the latest research connecting the oral microbiome Protein Targets - Part 1 & Part 2 Massachusetts General Hospital and gut with chronic and autoimmune diseases and Gut microbiome mediates sex differences in systemic health. Hotel & Travel 2:00 Refreshment Break in the Exhibit Hall with the obesity and metabolic syndrome. Estrogen 5:30 Nutrition and the Gut Microbiome: Where Are We Poster Viewing or estrogen-like compounds-induced elevated Registration Information Now? Where Are We Going? intestinal alkaline phosphatase levels and Leigh A. Frame, PhD, MHS, Program Director, Integrative TARGETING THE MICROBIOME subsequent gut microbiome changes lower bacterial Medicine, The George Washington University School of Click Here to Register IN OBESITY AND METABOLIC lipopolysaccharide production and gut permeability, Medicine and Health Sciences DiscoveryOnTarget.com resulting in reduced metabolic endotoxemia and DISORDERS When the gut microbiome (gBiome) is in an unhealthy systemic low-grade chronic inflammation with state, an individual is in dysbiosis, which may be 2:45 Welcome Remarks subsequent reduction in the susceptibility to develop related to their diet and its nutritional value. The role Cindy Crowninshield, RDN, LDN, HHC, Senior Conference western-diet-induced metabolic syndrome in estrogen of nutrition and the gBiome in health and disease has Director, Cambridge Healthtech Institute treated males and post-menopausal women.

A Division of Cambridge Innovation Institute Targeting the Microbiome DiscoveryOnTarget.com • 58 HOT & EMERGING Final Weeks to Register

Cover rapidly grown with the understanding of each, their 8:35 KEYNOTE PRESENTATION: Bacterial COMMERCIALIZING interactions, and the links to gastrointestinal disease, Transformations in Autoimmune Drug Conference obesity, and chronic disease. In the last decade, the Metabolism TRANSLATIONAL APPLICATIONS & At-A-Glance availability of affordable next-generation sequencing Jason Michael Crawford, PhD, Maxine F. Singer MICROBIOME PRODUCTS Sponsorship & Exhibit and gnotobiotics (germ-free animal models) has ’57 Ph.D. Associate Professor of Chemistry and 10:45 Standards for Microbiome and Metagenomics: facilitated a major advancement in our understanding Associate Professor of Microbial Pathogenesis, Short Courses Supporting the Commercial Translation of of the gBiome and the interaction with nutrition. Yale University Microbiome Science Symposia 6:00 Oral Blis - Streptococcus salivarius Probiotics to Photorhabdus asymbiotica is a Scott A. Jackson, PhD, Leader, Complex Microbial gammaproteobacterial pathogen that causes Training Seminar Promote a Healthy Oral Microbiome Systems Group, Biosystems and Biomaterials Division, John Hale, PhD, Chief Technology Officer, Blis systemic and severe soft tissue infections in National Institute of Standards and Technology Plenary Keynotes Technologies Ltd humans. During infection, it produces tapinarof, At NIST, we are improving microbiome science and an immunomodulatory drug developed to treat Agenda Streptococcus salivarius is a commonly-occurring supporting the National Microbiome Initiative by psoriasis and atopic dermatitis. We show that »» Small Molecules for Cancer commensal bacterium found both exclusively in developing standards for microbiome measurements humans. S. salivarius strains K12 and M18 have bacteria transform tapinarof into other novel that will enable federal, academic, and industry Immunotherapy been characterized and developed as probiotics metabolites that regulate arylhydrocarbon labs to reliably reproduce and advance each »» Autoimmune and Inflammation providing many benefits to consumers by promoting receptor and Nrf2 antioxidant signaling, other’s results. Microbiome standards will support Drug Targets microbial equilibrium. This talk will present examples phenotypes responsible for tapinarof’s clinical research investigations and commercial translation »» NK Cell-Based Cancer of how application of these probiotics has led to efficacy. We also show that closely related of microbiome science by providing measurement Immunotherapy the promotion of improved health. Future studies dietary metabolites associated with “alternative” assurance tools: standardized protocols, reference »» Targeting Tumor Myeloid Cells embracing microbiome technology will further IBD treatments undergo similar novel materials, validated measurements and critically »» Targeting the Ubiquitin- validate the specific roles probiotics have in transformations. evaluated reference data. Proteasome System improving oral health. 11:15 Considerations in Developing a »» Kinase Inhibitor Discovery 6:30 Dinner Short Course Registration 9:05 Reverse Translation for Therapeutic Microbiome Therapeutic »» CNS and Neurodegenerative Click here for details on short courses offered. Development in the Human Microbiome Jeannie Rojas, PhD, MBA, Portfolio Leader, Research and Targets Ulrich Thienel, MD, PhD, CMO, Finch Therapeutics, Inc. Development, Janssen R&D »» GPCR-Based Drug Discovery 9:30 Close of Day A major challenge in microbiome research is When developing a commercial microbiome product, »» Constrained Peptides and Friday, September 28 interpreting correlations observed in human cohort the development pathway and regulatory submission Macrocyclics studies or murine models. However, with the strategy will be different depending on whether »» Lead Generation Strategies 7:00 am Registration Open increasing abundance of clinical interventional data the product is a medical food, dietary supplement »» Target Identification and from experience with fecal microbiota transplantation, or prescription drug. Microbiome-based products Validation - Part 1 & Part 2 7:30 Interactive Breakfast Breakout there is an opportunity to develop therapeutic insights are novel and available guidelines are open to »» Antibacterial Discovery and Discussion Groups directly from clinical observations. Finch Therapeutics interpretation. In this talk, I will walk through the Development Grab a cup of coffee and join a breakout discussion identifies microbial therapies by observing patterns of process of bringing a microbiome-based therapeutic »» Targeting Gram-Negative group. These are informal, moderated discussions microbial engraftment that drive clinical responses. to the clinic, with emphasis on key considerations, Pathogens with brainstorming and interactive problem solving, We plan to use the patterns to develop a new hurdles and challenges that must be factored into the »» NASH and Fibrosis allowing participants from diverse backgrounds generation of rationally selected microbiota therapies development process. »» Targeting the Microbiome to exchange ideas and experiences and develop for Inflammatory Bowel Disease. 11:45 Sponsored Presentation (Opportunity Available) »» Antibody Discovery Forum - future collaborations around a focused topic. Details 9:35 NOD2, Innate Immunity and the Microbiome 12:15 pm Session Break Part 1 & Part 2 on the topics and moderators are available on the Klare Lazor, Graduate Student, Laboratory of Catherine »» Antibodies Against Membrane conference website. Grimes, Department of Chemistry and Biochemistry, 12:25 Luncheon Presentation (Sponsorship Protein Targets - Part 1 & Part 2 University of Delaware Opportunity Available) or Enjoy Lunch on Your Own 1:15 Refreshment Break in the Exhibit Hall with Hotel & Travel 10:05 Coffee Break in the Exhibit Hall with Poster TARGETING THE MICROBIOME Viewing and Poster Competition Winner Announced Poster Viewing IN AUTOIMMUNITY AND Registration Information MICROBIOME MARKET, INFLAMMATORY BOWEL DISEASE DEVELOPMENT & INVESTMENT Click Here to Register 8:30 Chairperson’s Remarks DiscoveryOnTarget.com Thomas Sundberg, PhD, Senior Research Scientist I, OPPORTUNITIES Center for Development of Therapeutics, Broad Institute 1:55 Chairperson’s Remarks of MIT and Harvard Keith F. Batchelder, MD, CEO and Founder, Genomic Healthcare Strategies

A Division of Cambridge Innovation Institute Targeting the Microbiome DiscoveryOnTarget.com • 59 HOT & EMERGING Final Weeks to Register

Cover 2:00 Human Microbiome Growth Opportunities and Predictions Conference Madhumitha Rangesa, Department of Chemical and At-A-Glance BioMolecular Engineering, NYU: Tandon School of Sponsorship & Exhibit Engineering; (formerly Senior Analyst, Frost & Sullivan) This presentation focuses on recent development Short Courses in the areas of microbiome-driven therapeutics. An Symposia overview of key research groups, disease focus areas and trends will be provided. The discussion will Training Seminar encompass a review of select technologies, markets Plenary Keynotes and products as well. Agenda »» Small Molecules for Cancer 2:30 PANEL DISCUSSION: From Microbiome to Market: Exploring Business Development Immunotherapy Opportunities and Investment Models »» Autoimmune and Inflammation Keith F. Batchelder, MD, CEO and Founder, Genomic Drug Targets Healthcare Strategies (Moderator) »» NK Cell-Based Cancer David Donabedian, PhD, Venture Partner, Longwood Immunotherapy Fund; CEO and Co-Founder of Longwood portfolio »» Targeting Tumor Myeloid Cells Company Axial Biotherapeutics, Inc. »» Targeting the Ubiquitin- Gail H. Javitt, JD, Member of the Firm, Health Care and Proteasome System Life Sciences Practice, Epstein Becker Green »» Kinase Inhibitor Discovery Jeannie Rojas, PhD, MBA, Portfolio Leader, Research »» CNS and Neurodegenerative and Development, Janssen R&D Targets This panel discussion is appropriate for you if you »» GPCR-Based Drug Discovery are working in research, science or industry and »» Constrained Peptides and have questions about translation opportunities or Macrocyclics the kinds of business and financial models that »» Lead Generation Strategies investors find attractive. We will discuss the areas »» Target Identification and of the microbiome investors are looking at and why. Validation - Part 1 & Part 2 We will explore the global scope of microbiome »» Antibacterial Discovery and and successful collaboration, reimbursement, and Development business investment models between science, »» Targeting Gram-Negative business, healthcare, and government in bringing live Pathogens microbial products to market. We will also discuss »» NASH and Fibrosis balancing venture activities, external R&D, and long- »» Targeting the Microbiome term market opportunities. Join us for a lively and »» Antibody Discovery Forum - interactive discussion. Part 1 & Part 2 »» Antibodies Against Membrane 4:00 Close of Conference Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Targeting the Microbiome DiscoveryOnTarget.com • 60 ANTIBODIES Final Weeks to Register Inaugural | September 26-27 Antibody Discovery Forum Part 1 Cover Discovery Technologies and Methods Conference At-A-Glance Sponsorship & Exhibit

Short Courses Discovery on Target’s new Antibody Discovery Forum conference offers research scientists working at the R&D generation transgenic animals and recent case studies Symposia stage the opportunity to participate in a novel meeting format that will encourage discussion and the exchange of will be discussed. information on the application of new science and technology for the discovery of new biotherapeutics. Training Seminar 9:40 Grand Opening Coffee Break in the Exhibit Hall Part 1 will focus on the discovery workflow, and explore best practices for identifying and using new and legacy with Poster Viewing Plenary Keynotes technologies to discover novel and functional drug candidates in an environment where speed and efficiency is now a mandate. The meeting will consider new approaches to the essential steps in the discovery process and 10:25 Applying Fully Automated Antibody Discovery Agenda how to make these more efficient by selectively and intelligently integrating the many new tools now available Workflows for Finding the Needle in the Haystack »» Small Molecules for Cancer on the market. A key focus of the agenda will be a discussion of methods used to discover well-performing Stefan Zahn, PhD, Principal Scientist, Antibody Immunotherapy candidates and leads as early as possible – and to accomplish this goal at the lowest possible cost needed to Technology, Novo Nordisk AS, Denmark »» Autoimmune and Inflammation achieve a high-quality outcome. The discovery of therapeutic antibodies depends on Drug Targets finding the right antibody with proper functionality, »» NK Cell-Based Cancer affinity and developability within a highly diverse RECOMMENDED ALL ACCESS produce since they have to maintain secondary and B-cell repertoire. In vivo antibody platforms have Immunotherapy tertiary structures to maintain functionality. Here we »» Targeting Tumor Myeloid Cells PACKAGE: Choose 2 Short Courses proven to efficiently deliver on these parameters. We describe the design and production of a challenging will present a highly automated antibody discovery »» Targeting the Ubiquitin- or 1 Symposium and 2 Conferences/ antigen and strategies we have set up to increase Proteasome System workflow based on traditional hybridoma technology throughput to support our discovery workflow. and discuss emerging technologies for deeper mining »» Kinase Inhibitor Discovery Training Seminars 8:40 Meeting the Needs of Antibody Discovery and of the B-cell repertoire providing eventually greater and »» CNS and Neurodegenerative • September 25 Short Course 8: Targeting of Ion Engineering Campaigns with Automated Workflows faster success. Targets Channels with Monoclonal Antibodies Avinash Gill, PhD, Senior Scientific Manager, Genentech »» GPCR-Based Drug Discovery • September 26-27 Conference: Antibody 10:55 Enhancing Antibody Discovery Methods and An increasing need for high-throughput (HTP) Maximizing Throughput in the Absence of Automation »» Constrained Peptides and Discovery Forum - Part 1 processes to rapidly produce large numbers of Macrocyclics Colby Souders, PhD, Senior Scientist - Antibody and • September 27-28 Conference: Antibody antibodies has accompanied the rising scale and Protein Engineering, Kanyos »» Lead Generation Strategies Discovery Forum - Part 2 complexity of antibody discovery and engineering. »» Target Identification and The way in which therapeutic antibodies are • September 27 Short Course 13: GPCR Automated HTP workflows have been put in discovered has rapidly progressed in the past Validation - Part 1 & Part 2 Structure-Based Drug Discovery place to combine highly productive small-scale decade. New methods allow us to find potent human »» Antibacterial Discovery and mammalian expression and purification platforms for clinical candidates at an accelerated pace; however, Development generating antibodies and other therapeutic formats. proprietary technology and fully automated platforms »» Targeting Gram-Negative Wednesday, September 26 The availability of purified material has enabled are not available for every campaign to facilitate Pathogens unambiguous identification of “hits” in biological and 7:00 am Registration Open and Morning Coffee discovery efforts. Here we address ways of finding »» NASH and Fibrosis functional screening assays. the optimal drug candidate by exploring multiple » Sponsored by » Targeting the Microbiome OPTIMIZING THE 9:10 Optimizing Therapeutic Antibody discovery techniques and integrating the most current »» Antibody Discovery Forum - Discovery with OmniAb technology available to every researcher, such as Part 1 & Part 2 DISCOVERY WORKFLOW Bill Harriman, PhD, MBA, Vice President, single B-cell sorting and next-generation sequencing. »» Antibodies Against Membrane 8:00 Welcome Remarks Antibody Discovery Services Ligand Protein Targets - Part 1 & Part 2 Kent Simmons, Senior Conference Director, Cambridge Shelley Izquierdo, PhD, Director, Antibody 11:25 INTERACTIVE PANEL AND AUDIENCE Healthtech Institute Discovery, Ligand Hotel & Travel DISCUSSION: Best Practices for Improving the 8:05 Chairperson’s Opening Remarks The OmniAb® portfolio of transgenics leverages 3 Discovery Workflow species to generate the OmniMouse®, OmniRat® Registration Information Avinash Gill, PhD, Senior Scientific Manager, Genentech Avainash Gill, PhD, Senior Scientific Manager, and OmniChicken™ antibody discovery platforms, 8:10 High Throughput Generation of Genentech (Moderator) enhancing the diversity of immunological responses Colby Souders, PhD, Senior Scientist - Antibody and Click Here to Register Challenging Antigens to therapeutically relevant targets and potentially Medha Tomlinson, PhD, Principal Research Protein Engineering, Kanyos Bio DiscoveryOnTarget.com uncovering novel epitopes for improved biological Medha Tomlinson, PhD, Principal Research Scientist, Scientist, AbbVie activity. Due to precise transgene design and effective Generation of proprietary therapeutics in disease AbbVie Bioresearch Center in vivo affinity maturation, typical programs yield large Stefan Zahn, PhD, Principal Scientist, Antibody requires recombinant protein antigen or a cell-based cohorts of developable antibody candidates. Next immunogen. Target antigens are challenging to Technology, Novo Nordisk AS, Denmark

A Division of Cambridge Innovation Institute Antibody Discovery Forum - Part 1 DiscoveryOnTarget.com • 61 ANTIBODIES Final Weeks to Register

Cover 12:25 pm Session Break 3:25 Refreshment Break in the Exhibit Hall with Poster 8:35 Developments in Computational-Based Methods Viewing and Poster Competition Winner Announced for Antibody Design Conference 12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own Andrew Wollacott, PhD, Principal Scientist, Visterra, Inc. At-A-Glance Over the last decade, there have been notable 1:15 Refreshment Break in the Exhibit Hall with 4:05 PANEL DISCUSSION: Best Practices for Sponsorship & Exhibit developments in computational protein design Poster Viewing Phenotypic and Functional Antibody Screening Andrew Bradbury, PhD, MB BS (MD), CSO, Specifica, Inc. methods, high throughput protein characterization, Short Courses and availability of antibody repertoire data. The SCREENING AND SELECTION (Moderator) Symposia Andrew Nixon, PhD, Vice President, Biotherapeutics convergence of these methods has led to significant 1:50 Chairperson’s Remarks advances in structure-guided design and antibody Training Seminar Molecule Discovery, Boehringer Ingelheim Andrew Bradbury, PhD, MB BS (MD), CSO, Specifica, Inc. Sai Reddy, PhD, Assistant Professor, Biosystems engineering. Here we provide an overview of recent Plenary Keynotes 1:55 Best Practices for Evolving in House Screening Science and Engineering, ETH Zurich, Switzerland developments and applications in the field of protein design and offer our perspective on best practices for Agenda Libraries and Discovery Platforms applying these tools for antibody discovery. »» Small Molecules for Cancer Andrew Nixon, PhD, Vice President, Biotherapeutics Molecule Discovery, Boehringer Ingelheim 9:05 Sponsored Presentation (Opportunity Available) Immunotherapy 5:05 Interactive Breakout Discussion Groups The choices that we make early in the discovery »» Autoimmune and Inflammation Join a breakout discussion group. These are informal, 9:35 Coffee Break in the Exhibit Hall with process have a profound impact on the quality of Drug Targets moderated discussions with brainstorming and Poster Viewing the antibodies that are advanced into development »» NK Cell-Based Cancer interactive problem solving, allowing participants 10:20 Engineering Cells at the Protein Level with and the subsequent speed to the clinic. Here we will from diverse backgrounds to exchange ideas and Immunotherapy discuss how to approach and iterate during the early Intracellular Antibodies »» Targeting Tumor Myeloid Cells experiences and develop future collaborations around Andrea Marschall, PhD, Postdoctoral Researcher, screening stages to ensure successful identification of a focused topic. Details on the topics and moderators »» Targeting the Ubiquitin- therapeutic candidates. Biochemistry, Brandeis University Proteasome System are available on the conference website. Intracellular antibodies (intrabodies) can knock down 2:25 How Can NGS Support Library Production, »» Kinase Inhibitor Discovery functions by acting at the protein level and allow Selection and Screening? »» CNS and Neurodegenerative 6:05 Welcome Reception in the Exhibit Sponsored by gradual quantitative tuning of membrane-receptors. Bradbury_AndrewAndrew Bradbury, PhD, MB BS (MD), Targets Hall with Poster Viewing We demonstrated gradual reductions of vascular CSO, Specifica, Inc. »» GPCR-Based Drug Discovery 7:10 Close of Day adhesion molecule 1 (VCAM1) in vitro. In the world’s The use of next-generation sequencing (NGS) as first transgenic intrabody mouse that we generated, »» Constrained Peptides and a routine tool during antibody library generation, Macrocyclics Thursday, September 27 ablation of VCAM1 by an intracellular antibody selection and screening provides deep understanding resulted in aberrant localization of B cells in adult »» Lead Generation Strategies of all aspects of in vitro antibody generation. »» Target Identification and 7:30 am Registration Open and Morning Coffee animals. Intrabody mice were viable although genetic NGS analysis of the PCR products generated by knockouts of VCAM1 are lethal. Validation - Part 1 & Part 2 primers used to create a naive antibody library from IMPLEMENTING EMERGING »» Antibacterial Discovery and lymphocytes, for example, revealed that primers are 10:50 Best Practices for Evaluation and Implementing Development far more promiscuous than anticipated and amplify DISCOVERY TECHNOLOGIES New Technology Platforms »» Targeting Gram-Negative many other V genes, even when the primers have been 8:00 Chairperson’s Remarks Shiv Krishnan, PhD, Head, Business Development & Pathogens designed to be V gene or family specific. This talk will Jane Seagal, PhD, Senior Scientist, Biologics Generation Licensing, Technology Platforms, Sanofi »» NASH and Fibrosis discuss other insights gained from the routine use of Group, AbbVie Bioresearch Center Access to cutting edge technologies is critical for sustaining innovation and productivity in drug »» Targeting the Microbiome NGS in antibody library production and selection. 8:05 High-Throughput Antibody Engineering in »» Antibody Discovery Forum - discovery. The advent of high throughput technologies 2:55 Leveraging Computational Sponsored by Mammalian Cells by CRISPR/Cas9-Mediated powered by miniaturization and computation has Part 1 & Part 2 Modeling Methods to De-Risk the Homology-Directed Mutagenesis increased access to a large variety of molecular »» Antibodies Against Membrane Development of Biologics Sai Reddy, PhD, Assistant Professor, Biosystems Science modalities. With the large variety of options in the Protein Targets - Part 1 & Part 2 Hubert Li, PhD, Senior Scientist, Schrödinger and Engineering, ETH Zurich, Switzerland marketplace, the objective selection of the right Computational approaches applied upstream can Homology-directed mutagenesis (HDM) extends Hotel & Travel technologies is a major challenge. This presentation play vital complementary roles in reducing failure the concept of CRISPR/Cas9-mediated homology- covers strategies and methodologies used for rates, development delays, and the cost of advancing directed repair to generate site-directed mutagenesis Registration Information identifying, evaluating and implementing technologies biologic drug candidates. We present in silico methods libraries in mammalian cells. Following cleavage by for drug discovery and development. for detecting protein liabilities early in the discovery the Cas9 protein, single-stranded oligonucleotides Click Here to Register phase and describe how to integrate these approaches containing degenerate codons serve as the repair 11:20 Luncheon Presentation (Sponsorship DiscoveryOnTarget.com to screen and mitigate common issues like instability template, providing integration of sequence diversity Opportunity Available) or Enjoy Lunch on Your Own and aggregation propensity. These approaches into the genome. We used HDM to generate libraries 11:50 Conference Registration Open are designed to guide experimentalists in making in the antibody CDRH3 and combined this with triage decisions by identifying classes of hits for a mammalian surface display platform for high- continued exploration. throughput screening.

A Division of Cambridge Innovation Institute Antibody Discovery Forum - Part 1 DiscoveryOnTarget.com • 62 ANTIBODIES Final Weeks to Register

Cover 12:20 pm Plenary Keynote Program Click here for details. Conference At-A-Glance 2:00 Refreshment Break in the Exhibit Hall with Sponsorship & Exhibit Poster Viewing Short Courses 2:45 Close of Conference Symposia Training Seminar Plenary Keynotes Agenda »» Small Molecules for Cancer Immunotherapy »» Autoimmune and Inflammation Drug Targets »» NK Cell-Based Cancer Immunotherapy »» Targeting Tumor Myeloid Cells »» Targeting the Ubiquitin- Proteasome System »» Kinase Inhibitor Discovery »» CNS and Neurodegenerative Targets »» GPCR-Based Drug Discovery »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Antibody Discovery Forum - Part 1 DiscoveryOnTarget.com • 63 ANTIBODIES Final Weeks to Register Inaugural | September 27-28 Antibody Discovery Forum Part 2 Cover Discovery of Novel Cancer Immunotherapies Conference At-A-Glance Sponsorship & Exhibit

Short Courses The second part of the program will address the challenging circumstance of identifying novel approaches 3:55 Agonist Bispecific Antibodies Delivering the Next Symposia that can be used to enter the thriving immune-oncology space. The meeting will begin with a broad look at Immuno-Oncology Breakthrough current understandings of the biology of immune-oncology and what has been learned from the many recent John Haurum, PhD, CEO, F-Star, United Kingdom Training Seminar clinical studies in the space – and then explore specific opportunities related to new and underexplored targets, Targeting T cells via TNFRSF costimulatory pathways Plenary Keynotes improvements in target selectivity and unmet medical needs. Special consideration will also be given to the has the potential to strongly activate the immune translation of academic and clinical stage findings into commercial development programs. A discussion format system due to broad expression across multiple Agenda will offer those in attendance a novel opportunity to explore strategies in this space with colleagues. immune cells. However, FcR-mediated crosslinking »» Small Molecules for Cancer is often required for optimal activity, limiting clinical Immunotherapy 2:55 KEYNOTE PRESENTATION: efficiency, due to low affinity of Fc:FcR interactions »» Autoimmune and Inflammation RECOMMENDED ALL ACCESS Diverse Biologics Modalities and ADCC-mediated T cell depletion. We will present Drug Targets PACKAGE: Choose 2 Short Courses Underpin ‘Third Wave’ Cancer novel bispecific programmes that do not bind to FcR, »» NK Cell-Based Cancer or 1 Symposium and 2 Conferences/ Immunology Therapeutics but instead crosslink their two targets, resulting in a Immunotherapy potent and controlled T cell activation. Training Seminars Jonathon Sedgwick, PhD, Vice »» Targeting Tumor Myeloid Cells President and Global Head, Cancer Immunology 4:25 Refreshment Break in the Exhibit Hall with »» Targeting the Ubiquitin- • September 25 Short Course 8: Targeting of Ion and Immune Modulation, Boehringer Ingelheim Poster Viewing Proteasome System Channels with Monoclonal Antibodies Pharmaceuticals »» Kinase Inhibitor Discovery • September 26-27 Conference: Antibody Despite over a century of research, it has OPPORTUNITIES IN NEW TARGET »» CNS and Neurodegenerative Discovery Forum - Part 1 only been in the current decade that using DISCOVERY Targets • September 27-28 Conference: Antibody the patient’s own immune system to attack »» GPCR-Based Drug Discovery 5:00 Droplet-Microfluidics as a Powerful Tool for Discovery Forum - Part 2 and remove cancer as a reliable and effective »» Constrained Peptides and therapeutic approach has succeeded, through Cancer Immunotherapy Macrocyclics • September 27 Short Course 13: GPCR use of so-called “checkpoint inhibitor” Christoph Merten, PhD, Group Leader, Microfluidics, »» Lead Generation Strategies Structure-Based Drug Discovery monoclonal antibodies. Additional approaches European Molecular Biology Laboratory »» Target Identification and to enable the immune system to recognize and (EMBL), Germany Droplet-microfluidics allows assays to be carried out Validation - Part 1 & Part 2 kill cancer cells are being investigated. Diverse Thursday, September 27 at high throughput, using minute amounts of sample »» Antibacterial Discovery and biologics modalities dominate the field, and material (e.g., patient biopsies). In this talk, I will show Development 11:50 am Conference Registration Open these will be discussed. how these conceptual advantages can be exploited »» Targeting Gram-Negative in cancer immunology, e.g., for the discovery of Pathogens 12:20 pm Plenary Keynote Program 3:25 Emerging Technologies for Personalizing tumor-associated antigens (TAAs) and personalized »» NASH and Fibrosis Click here for details. Cancer Immunotherapy therapy approaches. »» Targeting the Microbiome Aaron Goldman, PhD, Instructor in Medicine, Harvard »» Antibody Discovery Forum - 5:30 Antibody Discovery for Novel Multi-Targeting 2:00 Refreshment Break in the Exhibit Hall with Medical School Strategy in Immuno-Oncology Part 1 & Part 2 Poster Viewing The ability to predict whether a patient will respond to Thomas Bouquin, PhD, Head, Biologics Research, »» Antibodies Against Membrane treatment is a ‘holy grail’ for oncologists. The vision Sanofi, France Protein Targets - Part 1 & Part 2 FUTURE DIRECTIONS FOR CANCER and strategy for the 21st century treatment of cancer Targeting the first generation of immune checkpoints calls for a personalized approach in which therapy Hotel & Travel IMMUNOTHERAPY pathways has revolutionized cancer treatment selection is designed for each individual patient. Here, leading to durable responses in previously not curable 2:45 Welcome Remarks we profile emerging models, systems and platforms Registration Information patients. However, many patients and cancer types Kent Simmons, Senior Conference Director, Cambridge that seek to harness the complexity of the tumor do not respond to these treatments, prompting the Healthtech Institute microenvironment to provide solutions for the clinic. discovery of new classes of immunotherapies. The Click Here to Register 2:50 Chairperson’s Opening Remarks presentation will focus on our strategy to discover DiscoveryOnTarget.com Thomas Bouquin, PhD, Head, Biologics Research, antibodies against next-generation targets in the Sanofi, France immune oncology space and their combination in our proprietary multi-specific format.

A Division of Cambridge Innovation Institute Antibody Discovery Forum - Part 2 DiscoveryOnTarget.com • 64 ANTIBODIES Final Weeks to Register

Cover 6:00 Genome-Wide Networks of Stem Cell-Associated has been demonstrated in models of head and neck, survival from malaria. LD01 has broad utility as a Retroviral Sequences Define Novel Diagnostic and ovarian, breast cancer and mesothelioma. Phase I stand-alone immunotherapeutic and as a genetically Conference Therapeutic Targets in Clinically Lethal Malignancies clinical evaluation is now ongoing in patients with engineered component of other therapies. At-A-Glance Gennadi V. Glinsky, MD, PhD, Research Scientist, Institute locally advanced or recurrent head and neck cancer, 11:15 T-DM1-Resistant Cells Gain High Metastatic Sponsorship & Exhibit of Engineering in Medicine, University of California, employing intra-tumoral delivery to minimize toxicity. Potential: Identifying Novel Therapeutic Targets for San Diego Short Courses 9:05 Development of DART and TRIDENT Molecules the Treatment of T-DM1-Resistant Disease Stem cell-associated retroviral sequences (SCARS) to Target Costimulatory and Checkpoint Receptors for Wen Jin Wu, MD, PhD, Senior Investigator, Office of Symposia define thousands of genetic regulatory elements that Immuno-Oncology Applications Biotechnology Products, Center for Drug Evaluation and emerged during human genomes’ evolution from Training Seminar Gundo Diedrich, PhD, Director, Antibody Engineering, Research, FDA endogenous retroviruses, and genome-wide, SCARS MacroGenics T-DM1 is an ADC approved to treat trastuzumab- Plenary Keynotes shaped the evolution of human-specific genomic Bispecific molecules offer unique opportunities for resistant breast cancers. Despite initial favorable regulatory networks (GRNs). Experimental and clinical Agenda the treatment of cancer that cannot be replicated outcomes, most patients eventually progress evidence documenting the critical role of SCARS »» Small Molecules for Cancer with monospecific antibodies. The development of disease due to development of acquired resistance and associated GRNs in pathogenesis of clinically bispecific DART and TRIDENT molecules for dual to T-DM1. We found that T-DM1-resistant cells gain Immunotherapy intractable human malignancies will be reported with checkpoint inhibition (PD-1 x LAG3, PD-1 x CTLA4) and high metastatic potential with significantly increased »» Autoimmune and Inflammation an emphasis on molecular and genetic definitions of tumor localized immune cell agonism (HER2 x CD137) cell motility and invasion and that integrin proteins Drug Targets novel diagnostic and therapeutic targets. will be presented. A synthesis of how these novel play critical roles in the regulation of cell invasion. »» NK Cell-Based Cancer 6:30 Dinner Short Course Registration agents can be combined with other cancer treatments We proposed that targeting integrins may be a novel Immunotherapy Click here for details on short courses offered. in an integrated immune stimulatory approach therapeutic approach to treat T-DM1-resistant disease. »» Targeting Tumor Myeloid Cells will be discussed. »» Targeting the Ubiquitin- 9:30 Close of Day 11:45 Completing the Immunity Cycle by Developing Proteasome System 9:35 Targeting the Innate Immune System to Improve Myeloid Immunotherapies the Outcomes of PD-1/PD-L1 Therapy Tatiana Novobrantseva, PhD, Co-Founder, Head, »» Kinase Inhibitor Discovery Friday, September 28 Kathleen M. Mahoney, M.D., Ph.D., Clinical Instructor, Research and Development, Verseau Therapeutics »» CNS and Neurodegenerative 7:00 am Registration Open Beth Israel Deaconess Medical Center; Research Macrophages/DCs are biologically optimized to either Targets Associate, Dana Farber Cancer Institute induce or suppress an immune response. Targeting »» GPCR-Based Drug Discovery 7:30 Interactive Breakfast Breakout Blocking either the PD-1 receptor or its ligand PD-L1 pro-tumorigenic macrophages has been repeatedly »» Constrained Peptides and Discussion Groups has improved overall survival in Phase III trials in identified as a very important next step of development Macrocyclics Grab a cup of coffee and join a breakout discussion patients across tumor types. While some tumors fail to for the field of immuno-oncology. Similarly, myeloid »» Lead Generation Strategies group. These are informal, moderated discussions response due to a lack of immune cells infiltrating the cell suppression has been long realized to be fueling »» Target Identification and with brainstorming and interactive problem solving, tumor, others fail despite immune cells in the tumor. the vicious cycle of the autoimmune disease. The talk Validation - Part 1 & Part 2 allowing participants from diverse backgrounds The microenvironment of many “hot” tumors is hostile will describe Verseau Therapeutics approaches to »» Antibacterial Discovery and to exchange ideas and experiences and develop to antitumor lymphocyte activity, in part due to the tweaking myeloid cell functionality in human disease. Development future collaborations around a focused topic. Details myeloid cell population, including tumor-associated 12:15 pm Session Break »» Targeting Gram-Negative on the topics and moderators are available on the macrophage and myeloid-derived suppressor cells. Pathogens conference website. By targeting these innate immune cells via pathways 12:25 Luncheon Presentation (Sponsorship »» NASH and Fibrosis such as CSFR1 or VISTA, we may be able to improve Opportunity Available) or Enjoy Lunch on Your Own »» Targeting the Microbiome the responses and durable outcomes of PD-1/PD-L1 1:15 Refreshment Break in the Exhibit Hall with »» Antibody Discovery Forum - OPPORTUNITIES IN IMPROVED therapy for patients with these “hot” tumors. Poster Viewing Part 1 & Part 2 TARGETING AND SPECIFICITY 10:05 Coffee Break in the Exhibit Hall with Poster »» Antibodies Against Membrane TRANSLATIONAL RESEARCH 8:30 Chairperson’s Remarks Viewing and Poster Competition Winner Announced Protein Targets - Part 1 & Part 2 Joseph Rucker, PhD, Vice President, Research and 10:45 A Microbiome-Derived Dual Checkpoint 1:55 Chairperson’s Remarks Development, Integral Molecular, Inc. Inhibitor with Anti PD-1 Activity Enhances T Cell Kris F. Sachsenmeier, PhD, Associate Director, Hotel & Travel Translational Science, AstraZeneca 8:35 ErbB Targeted CAR-T Cell Immunotherapy of Activation and Antitumor Immunity Registration Information Head and Neck Cancer: T4 Immunotherapy Marc Mansour, PhD, Senior Consultant, Leidos Health 2:00 The TGFb Pathway as a Resistance Mechanism John Maher, PhD, Clinical Senior Lecturer in LD01, is a microbiome-derived small peptide with of Immune-Checkpoint Inhibitors and Novel Targets in Immunology, Kings College London, United Kingdom dual checkpoint activity against PD1 and one other the TGFb Pathway Click Here to Register synergistic receptor. LD01 increases T cell proliferation Kuldeep Neote, PhD, Senior Director, New Ventures/ DiscoveryOnTarget.com T4 immunotherapy consists of a CD28+CD3 zeta- based chimeric antigen receptor (CAR), targeted in the presence of PDL-1. In challenge models, Scout J&J Innovation Center Boston against the extended ErbB network, and which is systemic LD01 reduced B16-F10 lung metastases, The hallmarks of resistance to PD-1/PD-L1 blockade co-expressed with an IL-4 responsive chimeric protected animals from sepsis, and enhanced vaccine- is a low mutational burden, T cell exclusion or a cytokine receptor. Preclinical efficacy and safety induced malaria specific T cells leading to enhanced TGFb activated stroma. TGFb has been shown as an

A Division of Cambridge Innovation Institute Antibody Discovery Forum - Part 2 DiscoveryOnTarget.com • 65 ANTIBODIES Final Weeks to Register

Cover important driver of checkpoint blockade re-sistance and changes in tumor HLA status and antigen tissue matrix. Lead products targeting Muc1 and in metastatic melanoma and urothelial cancers, but presentation. Theoretical means of addressing each Muc16 for a range of indications are discussed. Conference development of TGFb antagonist-based therapies has resistance mechanism will also be reviewed within the At-A-Glance 3:30 Selection of Antibody-Drug Conjugate Targets been hampered by systemic toxicity. The presentation current context of preclinical and clinical experience. Using Expression Data, Glycoproteomics, and Sponsorship & Exhibit discusses strategies to neutralize TGFb in the tumor 3:00 Indirect Immunization with Antigen-Specific Functional Screens microenvironment that have the potential of limiting Short Courses Monoclonal IgG & IgE: Schedule-Dependent Jennifer J. Hill, PhD, Team Lead, MS & NMR Analytics, systemic toxicity and reverse immune evasion typified Interactions with Cytotoxic Agents and National Research Council Canada Symposia by a T cell exclusion phenotype. Immune Modulators Antibody-drug conjugates (ADCs) are a promising Training Seminar 2:30 Overcoming Specific Mechanisms of Resistance Christopher F. NIcodemus, MD, Chairman, Clinical & therapeutic class for cancer therapy. We describe our to Immuno-Oncology Therapies Scientific Advisory Board, OncoQuest, Inc., Canada approach to identify new ADC targets, incorporating Plenary Keynotes Kris F. Sachsenmeier, PhD, Associate Director, We examined the properties of Fc-gamma and gene expression data mining and glycoproteomic Agenda Translational Science, AstraZeneca Fc-epsilon constructs and identified molecules to profiling, followed byin vitro screening through a »» Small Molecules for Cancer As the clinical use of immunotherapies increases, initiate CD8 T cell Immunity that translates into surrogate ADC assay. Based on these target selection knowledge of specific mechanisms of resistance are promising preclinical and clinical antitumor activity in methods, we are producing thousands of monoclonal Immunotherapy coming into focus. A review will be presented which a schedule-dependent fashion linked to administration and single-domain antibodies generated against a »» Autoimmune and Inflammation summarizes a number of widely-accepted immuno- of cytotoxic and select immune adjuvants. IgE shows variety of cancer-associated targets and screening Drug Targets oncology resistance mechanisms, including tumor additional promise in mobilizing NK cell activity at low them for ADC activity, in vitro and in vivo. »» NK Cell-Based Cancer micro-environmental immunosuppression, activation doses and influencing tissue perfusion of solid tumor 4:00 Close of Conference Immunotherapy or inactivation of specific signaling pathways »» Targeting Tumor Myeloid Cells »» Targeting the Ubiquitin- Proteasome System »» Kinase Inhibitor Discovery »» CNS and Neurodegenerative Targets »» GPCR-Based Drug Discovery »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Antibody Discovery Forum - Part 2 DiscoveryOnTarget.com • 66 ANTIBODIES Final Weeks to Register 6th Annual | September 26-27 Antibodies Against Membrane Protein Targets Part 1 Cover Characterization and Structural Biology; The Development of Conference Biotherapeutics for Ion Channel and GPCR Targets At-A-Glance Sponsorship & Exhibit

Short Courses Part 1 surveys solutions to research and development challenges specific to the ion channel and GPCR target families 9:40 Grand Opening Coffee Break in the Exhibit Hall Symposia and offers presentations of biotherapeutics now advancing through development and clinical studies. The segment with Poster Viewing also includes an in-depth session focusing on new ion channel and GPCR structures, new tools for structural biology Training Seminar 10:25 Exploration of New Methods to Improve and the key characterization assays used to understand binding and functional activity in these targets. and Streamline Expression of Difficult to Express Plenary Keynotes Membrane Proteins to Support Drug Discovery Agenda RECOMMENDED ALL ACCESS generated. Furthermore, multivalent engineering Pravien Abeywickrema, Senior Scientist, Target Protein »» Small Molecules for Cancer demonstrated that electrophysiological profiles can be Design, Janssen Research & Development PACKAGE: Choose 2 Short Courses improved and combined into new modes of action. Integral membrane proteins represent more than Immunotherapy 60% of current drug targets. Despite the clinical »» Autoimmune and Inflammation or 1 Symposium and 2 Conferences/ 8:40 Discovery of Functional Monoclonal Antibodies significance, therapeutic agents that target Drug Targets Training Seminars Targeting Ion Channels: Challenges and Solutions membrane proteins have been difficult to develop. »» NK Cell-Based Cancer • September 25 Short Course 8: Targeting of Ion Trevor Wilkinson, PhD, Associate Director, Antibody Discovery and Protein Engineering, MedImmune Ltd., Poor expression in recombinant systems is the most Immunotherapy Channels with Monoclonal Antibodies critical challenge to producing functional membrane »» Targeting Tumor Myeloid Cells United Kingdom • September 26-27 Conference: Antibodies Complex multi-spanning membrane proteins, such proteins for antibody discovery, structural and »» Targeting the Ubiquitin- Against Membrane Protein Targets - Part 1 functional studies. The results from the exploration Proteasome System as GPCRs and ion channels, are attractive targets • September 27-28 Conference: Antibodies for therapeutics. Discovery of functional monoclonal of different technologies for streamlined, efficient »» Kinase Inhibitor Discovery Against Membrane Protein Targets - Part 2 antibodies targeting these proteins is challenging stable cell-line generation and transient expression in »» CNS and Neurodegenerative although advances in this area are being realized. mammalian cells for several GPCRs and ion channels Targets • September 27 Short Course 18: Practical We will review the challenges in targeting ion will be presented. »» GPCR-Based Drug Discovery Phenotypic Screening channels with antibodies and provide an overview 10:55 A Multiplatform Strategy for the Discovery of »» Constrained Peptides and of the solutions being developed. We will illustrate Conventional Monoclonal Antibodies that Inhibit the Macrocyclics Wednesday, September 26 progress in this field with case studies of ion channel Voltage-Gated Potassium Channel Kv1.3 »» Lead Generation Strategies antibody discovery. Paul Colussi, PhD, Vice President, Research, »» Target Identification and 7:00 am Registration Open and Morning Coffee TetraGenetics Validation - Part 1 & Part 2 9:10 KEYNOTE PRESENTATION: The We have isolated conventional antibodies that »» Antibacterial Discovery and ION CHANNEL TARGETS High-Resolution Crystal Structure of potently and selectively block the activity of Kv1.3, a Development 8:00 Welcome Remarks the NavMs Sodium Channel voltage-gated potassium channel widely recognized »» Targeting Gram-Negative Kent Simmons, Senior Conference Director, Cambridge Provides Information on Drug as a therapeutic target for a variety of autoimmune Pathogens Healthtech Institute Binding and Mutations Associated diseases. We developed a general strategy to »» NASH and Fibrosis 8:05 Chairperson’s Opening Remarks with Human Diseases achieve our goals by combining high-level expression »» Targeting the Microbiome Pravien Abeywickrema, Senior Scientist, Target Protein Bonnie Ann Wallace, PhD, Professor, Institute of of recombinant voltage-gated ion channels in »» Antibody Discovery Forum - Design, Janssen Research & Development Structural and Molecular Biology, Birkbeck College, Tetrahymena thermophila with immunization of Part 1 & Part 2 phylogenetically diverse species and screening tools 8:10 Nanobodies to Ion Channel Targets; What Do We United Kingdom »» Antibodies Against Membrane that allow deep-mining of the immune repertoire. Know and Where Do We Want to Go? Our high resolution crystal structures Protein Targets - Part 1 & Part 2 Diane Van Hoorick, PhD, Senior Project Leader, of Nav mutations, along with molecular 11:25 Exploiting TRP Channels for dynamics and spectroscopic, mutational and Targeted Drug Entry Hotel & Travel Ablynx, Belgium Nanobodies, based on single-domain antibody electrophysiology studies of the channel, have Bruce P. Bean, PhD, Professor, Neurobiology, Harvard enabled visualization of the binding sites of Medical School Registration Information fragments, retain target selectivity of full-length antibodies and in addition are easily engineered into channel-blocking drugs and the transmembrane Many neurons mediating pain express TRPV1 or multi-valents and multi-specifics. Based on these fenestrations that enable drug ingress into the TRPA1 channels or both. The pores formed by these Click Here to Register aspects, Nanobodies are ideal biologics for flexible channel, the changes in the voltage sensor channels are unusual in allowing entry of very large DiscoveryOnTarget.com targets such as ion channels. Multiple functionally and the channel gate associated with ion cations, up to 450 Daltons. This property can be active Nanobodies modifying particular conformational transport and the channel opening and closing, exploited to deliver cationic drug molecules into the and functional states in different channels were and the roles of mutations associated with neurons. This mechanism can be used to produce human diseases. long-lasting inhibition of pain, and can also be used to

A Division of Cambridge Innovation Institute Antibodies Against Membrane Protein Targets - Part 1 DiscoveryOnTarget.com • 67 ANTIBODIES Final Weeks to Register

Cover inhibit itch, cough, and inflammation involving release 1:15 Refreshment Break in the Exhibit Hall with such as GPCRs and ion channels. We have obtained of inflammatory neuropeptides. Poster Viewing a panel of high affinity single domain antibodies Conference Sponsored by specific for the chemokine receptor CXCR4 which is a At-A-Glance 11:55 Efficient Membrane Protein Targeting Antibodies Discovery Using GPCR TARGETS therapeutic target in fibrosis. The lead i-body AD-114 Sponsorship & Exhibit Synthetic Antibody Libraries 1:50 Chairperson’s Remarks blocked SDF-1-induced leukocyte recruitment in an air pouch model of inflammation and the recruitment Short Courses and CIS Display Catherine Hutchings, PhD, Independent Consultant, Guy Hermans, PhD, CSO, Isogenica Ltd. United Kingdom of fibrocytes into the lungs of mice with bleomycin Symposia induced pulmonary fibrosis. 12:25 pm Session Break 1:55 Pipeline Update on GPCR and Ion Training Seminar 2:55 Overcoming Tolerance by Deep 12:35 Luncheon Presentation: Sponsored by Channel Antibodies Catherine Hutchings, PhD, Independent Consultant, Mining of Natural Immune Repertoires Plenary Keynotes Discovery of Highly Specific Claudin 6 Kevin Heyries, PhD, Co-Founder, Business Development Antibodies for Targeting Cancer United Kingdom Agenda and Strategy Lead, AbCellera Joseph Rucker, Vice President, Research G protein-coupled receptors (GPCRs) and ion channels »» Small Molecules for Cancer represent some of the most important target classes Antibodies from natural immune responses are widely and Development, Integral Molecular regarded as superior to those generated by display Immunotherapy for therapeutic drug discovery across a wide range Oncology target Claudin 6 is upregulated in cancer and technologies; however, immune tolerance poses a »» Autoimmune and Inflammation of diseases. The progress made by antibody-based is not expressed in normal human tissue, unlike its serious challenge for targets with high inter-species Drug Targets therapeutics directed to these target classes will closely related homolog Claudin 9. Integral Molecular homology. Insoluble and poorly immunogenic targets »» NK Cell-Based Cancer be reviewed outlining the breadth and diversity of has discovered specific Claudin 6 antibodies using such as membrane proteins exacerbate this challenge. Immunotherapy its MPS Antibody Discovery Engine. High-resolution antibody molecules, target opportunities in R&D and the clinical pipeline, including recent development to We show how AbCellera’s ultra-deep screening »» Targeting Tumor Myeloid Cells epitope mapping, together with specificity analysis technology overcomes these challenges, producing »» Targeting the Ubiquitin- using the Membrane Proteome Array allowed the expansion of opportunities afforded by next- generation modalities. hundreds of diverse rodent antibodies against targets Proteasome System selection of lead candidates mAbs. These mAbs with 100% rodent-human homology, including G »» Kinase Inhibitor Discovery bind unique residues on Claudin 6, creating novel 2:25 i-bodies against the Chemokine Receptor CXCR4 protein-coupled receptors. »» CNS and Neurodegenerative intellectual property, and lack reactivity for other cell as a Treatment for Fibrosis Targets surface proteins. Mick Foley, PhD, CSO, AdAlta, Australia 3:25 Refreshment Break in the Exhibit Hall with Poster »» GPCR-Based Drug Discovery i-bodies are small, stable, human scaffolds containing Viewing and Poster Competition Winner Announced »» Constrained Peptides and a long CDR3 that enable better access to proteins Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 STUDENT FELLOWSHIP Full-time graduate students and PhD candidates are encouraged to apply for the »» Antibacterial Discovery and Discovery on Target Student Fellowship. Applications are due by August 10, 2018. More information available at DiscoveryOnTarget.com [ ] Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis • Full-time graduate and PhD candidates qualify for a student rate. Students are »» Targeting the Microbiome encouraged to present a research poster and receive an additional $50 off their »» Antibody Discovery Forum - registration fee. Students with a research poster will be recognized as a student Part 1 & Part 2 fellow at the event. »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2 • Student rates cannot be combined with any other discount offers. Students must present a valid/current student ID to qualify for the student rate. Limited to the Hotel & Travel first 100 students that apply. Registration Information • The deadline to submit a poster is Friday, August 10, 2018. Those who submit a poster after this date will not receive recognition in the conference materials. The Click Here to Register DiscoveryOnTarget.com final deadline to register as a student fellow is Friday, August 10, 2018.

A Division of Cambridge Innovation Institute Antibodies Against Membrane Protein Targets - Part 1 DiscoveryOnTarget.com • 68 ANTIBODIES Final Weeks to Register

Cover 4:05 Targeting Membrane Proteins in their 7:10 Close of Day 9:35 Coffee Break in the Exhibit Hall with Native Context Poster Viewing Conference Iwan Zimmermann, PhD, Postdoctoral Fellow, Institute of Thursday, September 27 10:20 Conformation-Specific Antibodies to Study At-A-Glance Medical Microbiology, University of Zurich, Switzerland 7:30 am Registration Open and Morning Coffee GPCR Signaling Sponsorship & Exhibit Antibody generation against native conformations Mariana Lemos-Duarte, PhD, Postdoctoral Researcher, of membrane proteins remains challenging and Short Courses CHARACTERIZATION AND Icahn School of Medicine at Mount Sinai suffers from poor translation to binding in the native Activation of G-protein-coupled receptors Symposia membrane context. We have established an in vitro STRUCTURAL BIOLOGY such as opioid receptors lead to initiation of selection procedure using three differently shaped Training Seminar 8:00 Chairperson’s Remarks signaling cascades resulting in enhanced protein synthetic nanobody libraries called sybodies. This Mariana Lemos-Duarte, PhD, Postdoctoral Researcher, phosphorylation. Among the various kinases, protein Plenary Keynotes enabled us to rapidly generate conformation-selective Icahn School of Medicine at Mount Sinai kinase C is thought to play a crucial role in the high affinity binders against challenging membrane Agenda desensitization of opioid receptors. To explore this, I protein targets. Furthermore, we have developed 8:05 Confobody Enabled Structure »» Small Molecules for Cancer Based Drug Discovery: Locking GPCRs in am using conformation-sensitive antibodies as unique NestLink, a selection/screening hybrid technology tools to explore the role of protein kinase C in opioid Immunotherapy Functional Conformations centred on barcoding peptides that allows for deep receptor desensitization. »» Autoimmune and Inflammation mining of binder pools directly on cells. Sarah Triest, PhD, Scientist, Confo Therapeutics, Belgium Drug Targets Camelid single domain antibodies are excellent tools 10:50 Characterization of Targeted Engineered 4:35 Structural Insights into the Extracellular »» NK Cell-Based Cancer to stabilize conformational states of GPCRs. Confo Toxin Bodies (ETBs), Designed to Provide a Novel Recognition of the Human Serotonin 2B Receptor Therapeutics uses such conformation sensitive Mechanism of Action in Oncology Immunotherapy by an Antibody »» Targeting Tumor Myeloid Cells antibodies (Confobodies) to constrain GPCRs in the Erin Willert, PhD, Senior Vice President, R&D, Molecular Andrii Ishchenko, PhD, Senior Research Associate, desired disease-linked conformer as a starting point Templates »» Targeting the Ubiquitin- Structural Biology, USC Proteasome System for drug discovery. The Confobody technology allows Molecular Templates, a clinical stage Given the importance of G protein-coupled receptors fragment screening of conformer-selective agonists biopharmaceutical company, develops highly potent, »» Kinase Inhibitor Discovery (GPCRs) as pharmaceutical targets, there has been with the desired efficacy profile and potency. A case specific, next-generation immunotoxins. Engineered »» CNS and Neurodegenerative an immense interest in therapeutic mAbs that act study will be shown for the µ-opioid receptor. Toxin Bodies (ETBs) destroy cancer cells by enzymatic Targets on GPCRs. We present the structure of a complex inactivation of ribosomes, a mechanism of action »» GPCR-Based Drug Discovery between the human 5-HT2B receptor and a Fab 8:35 Novel Uses of FT-ICR for Membrane Protein, Nanodisc, mAb and ADC Analysis distinct from other therapeutics, facilitating activity »» Constrained Peptides and fragment bound to the extracellular side of the in the refractory/relapsed setting and in combination Macrocyclics receptor and highlight the structural determinants Iain D. G. Campuzano, Principal Scientist, Discovery Attribute Sciences, Amgen with other treatment modalities. Molecular Templates’ »» Lead Generation Strategies of Fab binding. The structure sheds light on the pipeline ETBs, proprietarily de-immunized to avoid »» Target Identification and mechanism of selectivity in extracellular recognition of Membrane proteins make up approximately 50% of possible “druggable” targets, making them very both innate and adaptive immune recognition, target Validation - Part 1 & Part 2 GPCRs by mAbs. attractive molecules for many research groups. cell surface receptors expressed on hematological »» Antibacterial Discovery and Native-MS analyses for accurate antibody, protein and solid tumors. Development 5:05 Interactive Breakout Discussion Groups and nanodisc MW and drug-to-antibody ratio (DAR) 11:20 Luncheon Presentation (Sponsorship »» Targeting Gram-Negative Join a breakout discussion group. These are informal, confirmation have traditionally been performed Opportunity Available) or Enjoy Lunch on Your Own Pathogens moderated discussions with brainstorming and using oa-ToF instrumentation and more recently 11:50 Conference Registration Open »» NASH and Fibrosis interactive problem solving, allowing participants the extended mass range Orbitrap analyser with »» Targeting the Microbiome from diverse backgrounds to exchange ideas and incremental improvements in data quality. Herein »» Antibody Discovery Forum - experiences and develop future collaborations around we present the analysis of mAbs, ADCs, nanodiscs 12:20 pm Plenary Keynote Program Part 1 & Part 2 a focused topic. Details on the topics and moderators and PEGylated biotherapeutics using FT-ICR MS, Click here for details. »» Antibodies Against Membrane are available on the conference website. with a specific focus for enabling membrane protein Protein Targets - Part 1 & Part 2 characterization. 2:00 Refreshment Break in the Exhibit Hall with 6:05 Welcome Reception in the Exhibit Sponsored by 9:05 Sponsored Presentation (Opportunity Available) Poster Viewing Hotel & Travel Hall with Poster Viewing 2:45 Close of Conference Registration Information

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A Division of Cambridge Innovation Institute Antibodies Against Membrane Protein Targets - Part 1 DiscoveryOnTarget.com • 69 ANTIBODIES Final Weeks to Register 6th Annual | September 27-28 Antibodies Against Membrane Protein Targets Part 2 Cover Antigen and Antibody Generation, Discovery of Functional Antibodies Conference At-A-Glance Sponsorship & Exhibit

Short Courses Part 2 offers an examination of state-of-the-art approaches for the expression of high quality membrane protein explore large panels of antibodies and select lead Symposia antigens and antibody generation, then explores selection and screening strategies that can be applied to candidates with specific properties for development. discover binders with functional activity against GPCR and ion channel targets. Training Seminar 4:10 Sponsored Presentation (Opportunity Available) Plenary Keynotes 2:55 Droplet-Microfluidics for the Discovery of 4:25 Refreshment Break in the Exhibit Hall with RECOMMENDED ALL ACCESS Poster Viewing Agenda Antibodies Binding or Modulating Receptors PACKAGE: Choose 2 Short Courses »» Small Molecules for Cancer on Target Cells 5:00 Conformational Display Selection of Functional Christoph Merten, PhD, Group Leader, Microfluidics, Antibodies against GPCRs Immunotherapy or 1 Symposium and 2 Conferences/ European Molecular Biology Laboratory John Burg, PhD, Head, Biochemistry, Ab Initio »» Autoimmune and Inflammation Training Seminars (EMBL), Germany Biotherapeutics Drug Targets • September 25 Short Course 8: Targeting of Ion Droplet microfluidics has become a powerful tool for G protein-coupled receptors (GPCRs) are critical »» NK Cell-Based Cancer Channels with Monoclonal Antibodies antibody screening. After giving a general overview on signaling mediators for both endogenous ligands and Immunotherapy • September 26-27 Conference: Antibodies the technology, I will introduce our new 2-cell platform, therapeutics. By combining next-generation synthetic »» Targeting Tumor Myeloid Cells Against Membrane Protein Targets - Part 1 facilitating assays involving two different cell types. antibody libraries with novel selection techniques, »» Targeting the Ubiquitin- This allows screening hybridoma cells or even primary we have enabled the facile discovery of functional Proteasome System • September 27-28 Conference: Antibodies Against Membrane Protein Targets - Part 2 plasma cells (from mice and humans) for the secretion antibodies against GPCRs. Our selections have »» Kinase Inhibitor Discovery of antibodies binding or modulating membrane yielded antibodies that recognize native extracellular »» CNS and Neurodegenerative • September 27 Short Course 18: Practical receptors on specific target cells. Approximately GPCR epitopes, with the ability to modulate receptor Targets Phenotypic Screening 100,000 antibodies can be screened in a single signaling. Our technology opens the door to routine »» GPCR-Based Drug Discovery experiment in less than 24 hours. discovery in this important new class of biologics. »» Constrained Peptides and Thursday, September 27 3:25 Strategies for Antibody Discovery to Integral 5:30 Generation of Positive Allosteric Modulators of Macrocyclics Membrane Proteins TRPV1 Using Affimer Reagents »» Lead Generation Strategies 11:50 am Conference Registration Open Robert Pejchal, PhD, Associate Director, Antibody Darren Tomlinson, PhD, Associate Professor, University »» Target Identification and Discovery, Adimab LLC of Leeds, United Kingdom Validation - Part 1 & Part 2 12:20 pm Plenary Keynote Program Discovery of antibodies that target integral membrane Affimers are scaffolding proteins that constrain »» Antibacterial Discovery and Click here for details. proteins at the cell surface represent a unique variable regions for molecular recognition and Development challenge. Using yeast presentation of large synthetic can be used as alternatives to antibodies in many »» Targeting Gram-Negative human antibody libraries, Adimab has developed applications. In this talk, I will focus on the isolation Pathogens 2:00 Refreshment Break in the Exhibit Hall with methods for isolation of target specific binders of Affimer reagents against TRPV1, an ion channel »» NASH and Fibrosis Poster Viewing utilizing whole cells selection, NGS, and high- implicated in pain disorders. The reagents act as »» Targeting the Microbiome throughput screening. Considerations for utilization of positive allosteric modulators, and we have mimicked »» Antibody Discovery Forum - DISCOVERY OF FUNCTIONAL solubilized protein are also discussed. the interaction with small molecules through in silico Part 1 & Part 2 ANTIBODIES 3:55 Integrating New Visualization and drug design based on a co-crystal structure. »» Antibodies Against Membrane 2:45 Welcome Remarks Analysis Tools for Large Antibody Datasets from 6:00 Interrogation of Surface Ig-Bearing Protein Targets - Part 1 & Part 2 Kent Simmons, Senior Conference Director, Cambridge Single-Cell Screening and Ig-Secreting Cells using Fluorescence Healthtech Institute Maia Smith, MSc, Data Visualization Lead, AbCellera Activated Cell Sorting Hotel & Travel 2:50 Chairperson’s Opening Remarks High throughput discovery technologies enable John S. Kenney, PhD, President, Antibody Solutions the rapid generation of large panels of antibody Surface immunoglobulin (SIg)-bearing B cells and Registration Information Iain D. G. Campuzano, Principal Scientist, Discovery Attribute Sciences, Amgen candidates. The resulting volume of data is complex antibody secreting cells (ASCs) e.g., plasmablasts and multidimensional, making it exceedingly difficult to or plasmacytes, are two populations within the Click Here to Register analyze with conventional workflows in order to select germinal center for isolating high-affinity, antigen DiscoveryOnTarget.com leads. We will show how AbCellera’s pipeline integrates specific antibodies. Using Fluorescence-activated a dynamic, interactive visualization software to easily Cell Sorting (FACS), SIg cells may be identified by

A Division of Cambridge Innovation Institute Antibodies Against Membrane Protein Targets - Part 2 DiscoveryOnTarget.com • 70 ANTIBODIES Final Weeks to Register

Cover Ag-staining of SIg, whereas, ASCs require capture of targets of function-modifying antibodies. We present 12:15 pm Session Break antibody secreted by the cell prior to Ag-staining. I’ll case studies describing strategies to discover Conference 12:25 Luncheon Presentation (Sponsorship demonstrate the utility of a FACS-based approach for antibodies to these targets, focusing on antigen Opportunity Available) or Enjoy Lunch on Your Own At-A-Glance isolating cells from either population. engineering, generation of large and diverse antibody 1:15 Refreshment Break in the Exhibit Hall with Sponsorship & Exhibit repertoires and high throughput screening. 6:30 Dinner Short Course Registration Poster Viewing Short Courses Click here for details on short courses offered. 9:35 Improving Antibody Discovery against 9:30 Close of Day Challenging Targets GENERATION AND OPTIMIZATION Symposia Rajesh Vij, Senior Scientific Researcher, Antibody OF MEMBRANE PROTEIN ANTIGENS Training Seminar Friday, September 28 Engineering, Genentech The generation of large and diverse panels of 1:55 Chairperson’s Remarks Plenary Keynotes 7:00 am Registration Open monoclonal antibodies against multi-transmembrane Dan Rohrer, PhD, Senior Director, Biologics Discovery, Agenda or integral membrane proteins has proven challenging, Bristol-Myers Squibb »» Small Molecules for Cancer 7:30 Interactive Breakfast Breakout thus hindering the discovery of rare functional clones. 2:00 Advances in Target Expression and Display for Focusing on a case study, we will discuss how antigen Immunotherapy Discussion Groups Discovery of Biological Therapeutics format, immunization scheme, and downstream »» Autoimmune and Inflammation Grab a cup of coffee and join a breakout discussion Ivan Correia, MBA, PhD, Research Fellow, Head, Global expression and screening strategies can be optimized Drug Targets group. These are informal, moderated discussions Protein Sciences, AbbVie Bioresearch Center to identify antibodies with novel activities. »» NK Cell-Based Cancer with brainstorming and interactive problem solving, Generation of specific immune response to a target Immunotherapy allowing participants from diverse backgrounds 10:05 Coffee Break in the Exhibit Hall with Poster protein is dependent on correct fold and conformation »» Targeting Tumor Myeloid Cells to exchange ideas and experiences and develop Viewing and Poster Competition Winner Announced state of the antigen and must represent its natural »» Targeting the Ubiquitin- future collaborations around a focused topic. Details 10:45 Cell Membrane Preparation to Enable state in vivo. Other important considerations Proteasome System on the topics and moderators are available on the Immunization, Antigen-Specific B-Cell Sorting and include post-translational modifications and genetic conference website. polymorphism. Progress is continuously being »» Kinase Inhibitor Discovery Screening for Antibodies against Cell Surface Targets made, and in this presentation, we introduce new »» CNS and Neurodegenerative Habtom Hapte, PhD, Principal Scientist, Biotherapeutics perspectives and advances. We highlight many options Targets Discovery, Boehringer Ingelheim ANTIBODY GENERATION available and successfully applied to a large number of »» GPCR-Based Drug Discovery Here we report a strategy that resulted in identification target proteins. »» Constrained Peptides and 8:30 Chairperson’s Remarks of antigen-specific B cells using membrane prep Macrocyclics Christopher Murawsky, PhD, Principal Scientist, Amgen as bait and a membrane prep based Meso-Scale 2:30 Beyond Detergents: Nanoencapsulation of »» Lead Generation Strategies 8:35 Tag-on-Demand – Exploiting ‘Switchable’ Discovery (MSD) screening. Single B-cell sorting using Membrane Proteins for Drug Discovery »» Target Identification and Expression Technology for the Enrichment of High- membrane prep as bait generated 118 target-1-specific Tim Dafforn, PhD, Professor, Biotechnology, University of hits. This strategy will enable us to generate immune Birmingham, United Kingdom Validation - Part 1 & Part 2 Expressing Membrane Protein Cell Lines responses against targets that are difficult to express For more than 40 years, the only way to extract »» Antibacterial Discovery and Zachary T. Britton, PhD, Scientist, Antibody Discovery and and purify using membrane prep based immunization, membrane proteins from cells was to use a detergent. Development Protein Engineering, MedImmune, LLC sort and screen. However, this approach was far from successful, »» Targeting Gram-Negative Poor expression and detection of membrane protein therapeutic targets have hampered drug discovery 11:15 So Long Llamas: Rapid Discovery of Synthetic producing samples with low stability and activity. The Pathogens recent emergence of nanoencapsulation systems »» NASH and Fibrosis and screening efforts. To address this issue, we have GPCR-Targeted Nanobodies developed a “Tag-on-Demand” approach to exploit Conor McMahon, PhD, Postdoctoral Fellow, Biological like MSP and SMALP now provide membrane »» Targeting the Microbiome protein samples with high stability. In this talk, I will »» Antibody Discovery Forum - ‘switchable’ expression of ‘tagged’ membrane proteins Chemistry and Molecular Pharmacology, Harvard for detection and selection steps that can be turned Medical School summarize these approaches and new developments Part 1 & Part 2 off for ‘untagged’ expression of native proteins and Single-domain camelid antibody fragments that have occurred in the SMALP field. »» Antibodies Against Membrane used directly in whole-cell drug discovery efforts. (‘nanobodies’) are broadly used as tools for biological 3:00 Expression and Screening of Human Integral Protein Targets - Part 1 & Part 2 Validation of this approach using model membrane research and have therapeutic potential. However, Membrane Protein Targets Hotel & Travel proteins will be presented. nanobody discovery typically requires animal Nicola Burgess-Brown, PhD, Principal Investigator, 9:05 Antibody Generation for Membrane Proteins and immunization, presenting a host of barriers to their Structural Genomics Consortium, University of Oxford, Registration Information Complex Epitopes production. We developed a fully synthetic yeast United Kingdom Christopher Murawsky, PhD, Principal Scientist, Amgen displayed nanobody library, which circumvents The SGC promotes research advancement through Many of the most therapeutically interesting targets animal immunization and also allows rapid isolation our open access policy, and in the absence of IP. Click Here to Register of conformation-specific binders. From this library, Globally, we have solved more than 2000 human DiscoveryOnTarget.com are multi-pass or multi-subunit membrane proteins that have nominal surface area exposed that can serve we generated a range of functional nanobodies protein structures and 10 novel integral membrane as epitopes for antibody binding. The extracellular targeting GPCRs, including conformational proteins (IMPs). Although we have made a regions may interact to form complex, non-linear stabilizers and ligands. significant contribution to structural biology and epitopes that are required for activity and are the 11:45 Sponsored Presentation (Opportunity Available) protein production for functional studies, IMPs and

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Cover protein-protein complexes still remain a challenge to produce. Here, I present our established approaches Conference for eukaryotic expression and screening IMPs using At-A-Glance baculovirus/insect cells and BacMam technology. Sponsorship & Exhibit 3:30 Emerging Strategies for Membrane Protein Short Courses Presentation in Antibody Discovery Pawel Dominik, PhD, Senior Scientist, Cancer Symposia Immunology Discovery, Pfizer Training Seminar Phage display enables the discovery of high affinity antibodies to a variety of antigens. While discovering Plenary Keynotes antibodies has become routine for most proteins, Agenda it is still challenging for transmembrane proteins. »» Small Molecules for Cancer Nanodiscs have emerged as powerful tools to study membrane proteins in a more natural lipid Immunotherapy environment. By combining phage display and »» Autoimmune and Inflammation nanodiscs, we improved our ability to discover Drug Targets antibodies to multi-pass transmembrane proteins. This »» NK Cell-Based Cancer approach expands the toolbox for the rapid discovery Immunotherapy of therapeutic antibodies. »» Targeting Tumor Myeloid Cells »» Targeting the Ubiquitin- 4:00 Close of Conference Proteasome System »» Kinase Inhibitor Discovery »» CNS and Neurodegenerative Targets »» GPCR-Based Drug Discovery »» Constrained Peptides and Macrocyclics »» Lead Generation Strategies »» Target Identification and Validation - Part 1 & Part 2 »» Antibacterial Discovery and Development »» Targeting Gram-Negative Pathogens »» NASH and Fibrosis »» Targeting the Microbiome »» Antibody Discovery Forum - Part 1 & Part 2 »» Antibodies Against Membrane Protein Targets - Part 1 & Part 2

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A Division of Cambridge Innovation Institute Antibodies Against Membrane Protein Targets - Part 2 DiscoveryOnTarget.com • 72 Final Weeks to Register Pricing & Registration Information All access (Choose 2 Short Courses or 1 Symposium and 2 Conferences/Training Seminars) Conference Discounts Academic, Government, Register 3 – 4th is FREE: Individuals must register for the same conference or Cover Commercial Hospital-Affiliated conference combination and submit completed registration form together for discount to apply. Conference Registrations After August 31, 2018 and On-Site $3,399 $2,049 Group Discounts: Special rates are available for multiple attendees from the same At-A-Glance organization and for NIH/Government employees. For more information on group and government discounts contact Elizabeth Lemelin at 781-972-5488. Sponsorship & Exhibit Standard Package (Choose 2 Conferences/Training Seminars, excludes Short Courses and Symposia) Alumni Discount – SAVE 20%: CHI appreciates your past participation at Discovery On Target. As a result of the great loyalty you have shown us, we are pleased to extend to Short Courses Registrations After August 31, 2018 and On-Site $3,049 $1,429 you the exclusive opportunity to save an additional 20% off the registration rate. Symposia Poster Submission - Discount ($50 Off): Poster abstracts are due by August 10, 2018. Once your registration has been fully processed, we will send an email containing a Training Seminar Single Conference Pricing (Choose 1 Conference/Training Seminar, excludes Short Courses and/or Symposia) unique link allowing you to submit your poster abstract. If you do not receive your link within 5 business days, please contact [email protected]. *CHI reserves the right Plenary Keynotes Registrations After August 31, 2018 and On-Site $1,999 $1,099 to publish your poster title and abstract in various marketing materials and products.

Agenda *Alumni, Twitter, LinkedIN, Facebook or any other promotional discounts cannot be »» Small Molecules for Cancer Symposia Pricing combined. Discounts not applicable on Event Short Courses. Immunotherapy One Symposium $999 $699 If you are unable to attend but would like to purchase the Discovery on Target CD »» Autoimmune and Inflammation for $750 (plus shipping), please visit DiscoveryOnTarget.com. Massachusetts Drug Targets delivery will include sales tax. »» NK Cell-Based Cancer Short Course Pricing Immunotherapy ADDITIONAL REGISTRATION DETAILS »» Targeting Tumor Myeloid Cells One Short Course $699 $399 Each registration includes all conference sessions, posters and exhibits, food functions, and access to the conference proceedings link. »» Targeting the Ubiquitin- Two Short Courses $999 $699 Handicapped Equal Access: In accordance with the ADA, Cambridge Healthtech Proteasome System Institute is pleased to arrange special accommodations for attendees with special needs. All requests for such assistance must be submitted in writing to CHI at »» Kinase Inhibitor Discovery Three Short Courses $1,199 $899 least 30 days prior to the start of the meeting. »» CNS and Neurodegenerative To view our Substitutions/Cancellations Policy, go to healthtech.com/regdetails. Targets Video and or audio recording of any kind is prohibited onsite at all CHI events. »» GPCR-Based Drug Discovery »» Constrained Peptides and Conference Programs Macrocyclics »» Lead Generation Strategies Symposia Antibodies Short Courses »» Target Identification and Target-Based Discovery & Validation Validation - Part 1 & Part 2 September 25 September 26–27 September 26–27 September 25 »» Antibacterial Discovery and S1: Antivirals: Targeting HBV and Beyond C2A: Targeting the Ubiquitin-Proteasome System C9A: Antibody Discovery Forum - Part 1 SC1: Introduction to GPCR-Based Drug Discovery Development S2: Targeting Autophagy C3A: CNS and Neurodegenerative Targets C10A: Antibodies Against Membrane Protein Targets SC2: Drug Metabolism and Its Role in Discovery and »» Targeting Gram-Negative C4A: Constrained Peptides and Macrocyclics - Part 1 Drug Development C5A: Target Identification and Validation - Part 1 SC3: How to Best Utilize 3D Cells, Spheroids, and PDX Pathogens Immunotherapy September 27–28 Models in Oncology »» NASH and Fibrosis September 27–28 C9B: Antibody Discovery Forum - Part 2 SC8: Targeting of Ion Channels with »» Targeting the Microbiome September 26–27 C2B: Kinase Inhibitor Discovery C10B: Antibodies Against Membrane Protein Targets Monoclonal Antibodies - Part 2 SC9: CNS Translational Strategies »» Antibody Discovery Forum - C7A: Small Molecules for Cancer Immunotherapy C3B: GPCR-Based Drug Discovery C8A: NK Cell-Based Cancer C4B: Lead Generation Strategies SC10: Applications of Artificial Intelligence and Part 1 & Part 2 Machine Learning in Drug Discovery and Development Immunotherapy C5B: Target Identification and Validation - Part 2 Training Seminars »» Antibodies Against Membrane SC11: Mechanistic Understanding of Pharmacological September 27–28 Probes for the Ubiquitin-Proteasome System Protein Targets - Part 1 & Part 2 September 27–28 C7B: Autoimmune and Inflammation Drug Targets Hot & Emerging September 27 C8B: Targeting Tumor Myeloid Cells TS2: Introduction to Small Molecule Drug Discovery SC13: GPCR Structure-Based Drug Discovery Hotel & Travel September 26–27 and Development SC14: Advancing Tools and Technologies for Registration Information C6A: Antibacterial Discovery and Development Fragment-Based Design C1A: NASH and Fibrosis SC15: Introduction to Targeted Covalent Inhibitors SC16: Immunology Basics September 27–28 Click Here to Register SC17: Technologies to Assess Permeability and Efflux C6B: Targeting Gram-Negative Pathogens in Gram-Negative Bacterial Pathogens DiscoveryOnTarget.com C1B: Targeting the Microbiome SC18: Practical Phenotypic Screening

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