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Karim Dabbagh Ph.D., Executive Director and Head, External R&D and Innovation Research Units, Pfizer Worldwide R&D

Glen N. Gaulton Ph.D., Professor, Pathology and Laboratory Medicine; Executive Vice Dean and Chief

Scientific Officer, Perelman School of Medicine, University of Pennsylvania

Peter Pitts President and Co-Founder, Center for Medicine in the Public Interest

J. Rick TurnerPhD, PGCE Senior Scientific Director, Clinical Communications, Quintiles & Fellow, Society of

Behavioral Medicine

plEnAry kEynotE pAnEl

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June 4 - 6, 2013 Loews Philadelphia Hotel, Philadelphia, PAWPCCambridge Healthtech Institute’s

World pharmaCongress

Advancing Preclinical Predictions,Faster Clinical Decisions

Celebrating12Years of Preclinical Research

Premier Sponsor

Cancer ModelsChallenging Cancer Heterogeneity with Reproducible and Predictive Preclinical Studies

pain therapeuticsTranslating Success from Preclinical Assays to the Clinic

Formulation & Drug DeliveryImproving Solubility and Bioavailability with Enabling Technologies

predictive Drug SafetyPredicting Drug-Induced Organ Toxicities Using Functional Assays, Models and Markers

preclinical imagingIntegrating Molecular Imaging Technologies to Improve Preclinical Findings

World pharma Congress 2013 l Preclinical efforts targeted

towards discovery, screening, safety and drug delivery

l Attended by biologists, pharmacologists, toxicologists and drug delivery experts

l Active brainstorming and networking opportunity for experts from industry and academia

l Interactive pre-conference short courses taught by experts in an informal setting

l Updates from leading technology and service providers on the latest tools and services

l Informative roundtables, panels, posters, stimulating communication and collaboration

http://www.worldpharmacongress.com

http://www.healthtech.com

http://www.jax.org/

http://www.jax.org/

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Monday pre-Conference Short Courses*tuesday Cancer Models pain therapeutics Formulation &

Drug Deliverypredictive Drug

Safetypreclinical imaging

plenary keynote panel DiscussionWednesday Cancer Models pain therapeutics Formulation &

Drug Deliverypredictive Drug

Safetypreclinical imaging

Breakout DiscussionsDinner Short Courses*

thursday Cancer Models pain therapeutics Formulation & Drug Delivery

predictive Drug Safety

preclinical imaging

About World Pharma CongressAfter a dozen years, covering various topics for the pharmaceutical industry, the World Pharma Congress has found its niche in effectively covering the latest preclinical strategies and technologies for driving better predictions. Building on its experience covering drug targets, high-throughput screening, lead optimization, ADME and drug safety, the event is now primed to move further downstream into early formulations and drug delivery.

plenary keynote panel DiscussionAdvancing Pharma R&D through Communication & Collaborations: Bio-Connectivity at WorkPanelists:

Karim Dabbagh, Ph.D., Executive Director and Head, External R&D and Innovation Research Units, Pfizer Worldwide R&DKarim Dabbagh collaborates with Pfizer WRD leaders to create and draw on global innovative external opportunities in both the biotech and academic space to strengthen Pfizer’s Inflammation and Immunology pipeline via the strategic integration of select assets and technologies. Karim spent 9 years at Roche Palo Alto where he was last Head of Inflammation

Discovery Research prior to becoming the founder of Modus BioMedicine, a start-up biotechnology company aiming to development antibodies for the treatment of transplantation and autoimmune disease. Karim received his Ph.D. in Biochemistry from University College, London and completed postdoctoral fellowships at the Cardiovascular Research Institute at University of California, San Francisco and at Stanford University in the Department of Pediatrics, Division of Immunology.

Glen N. Gaulton, Ph.D., Professor, Pathology and Laboratory Medicine; Executive Vice Dean and Chief Scientific Officer, Perelman School of Medicine, University of PennsylvaniaGlen N. Gaulton, Ph.D. is the Executive Vice Dean and Chief Scientific Officer, and Professor of Pathology and Laboratory of Medicine in the University of Pennsylvania’s Perelman School of Medicine. He received a Ph.D. in biochemistry and molecular biology from the University of California, Santa Barbara. He conducted postgraduate research in immunology at the School

of Public Health and School of Medicine at Harvard University. Dr. Gaulton serves on the Board of Directors of two organizations, is a reviewer for nine scholarly journals, and has been chair of three NIH study sections. He has received numerous awards for teaching and research, including the Dean’s Award for Basic Science Teaching, the Berwick Memorial Teaching Award, the Lindback Award, the Harry Weaver Neuroscience Scholar Award from the National Multiple Sclerosis Society, and the Leukemia Society Scholar Award.

Peter Pitts, President and Co-Founder, Center for Medicine in the Public InterestPeter Pitts is President and co-founder of the Center for Medicine in the Public Interest. Prior to founding CMPI, Pitts was a Senior Fellow for healthcare studies at the Pacific Research Institute. From 2002-2004 Peter was FDA’s Associate Commissioner for External Relations, serving as senior communications and policy adviser to the Commissioner. He supervised FDA’s Office of Public Affairs, Office of the Ombudsman, Office of Special Health Issues, Office of Executive

Secretariat, and Advisory Committee Oversight and Management. He served on the agency’s obesity working group and counterfeit drug taskforce. He has served as an adjunct professor at Indiana University’s School of Public and Environmental Affairs and Butler University.

J. Rick Turner, Ph.D., QuintilesDr J. Rick Turner is Senior Scientific Director of Clinical Communications at Quintiles, in which role he facilitates publications by many colleagues in the peer-reviewed and professional literature. He is an experimental research scientist and clinical trialist, with a particular interest in the development and use of drugs for hypertension and type 2 diabetes mellitus. In the latter capacity he testified before two US Food and Drug Administration Advisory Committees in July

2007 concerning the cardiovascular safety of the thiazolidinedione drug rosiglitazone. Before joining Quintiles, Dr Turner was Chairman of the Department of Clinical Research at Campbell University School of Pharmacy, a Clinical Submissions Scientist at GlaxoSmithKline, and President and Chief Scientific Officer at Turner Medical Communications LLC. In his preceding academic career he conducted experimental clinical research in the field of Cardiovascular Behavioral Medicine, receiving two international research awards (from the American Psychosomatic Society and the Society for Psychophysiological Research) for his ground-breaking research in the field of cardiovascular reactivity: he also published the first student textbook on that topic. Dr Turner has published a total of 14 authored and edited books, and 130 peer-reviewed papers and articles in professional journals. He is also a Fellow of the Society of Behavioral Medicine and a Senior Fellow at the Center for Medicine in the Public Interest.

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Sponsor & Exhibit opportunitiesCHI offers comprehensive sponsorship packages which include presentation opportunities, exhibit space and branding, as well as the use of the pre and post show delegate list. Sponsorship allows you to achieve your objectives before, during, and long after the event. Any sponsorship can be customized to meet your company’s needs and budget. Signing on earlier will allow you to maximize exposure to hard-to-reach decision makers.

Agenda PresentationsShowcase your solutions to a guaranteed, highly-targeted audience. Package includes a 15 or 30-minute podium presentation within the scientific agenda, exhibit space, on-site branding and access to cooperative marketing efforts by CHI.

Breakfast & Luncheon PresentationsOpportunities include a 30-minute podium presentation. Boxed lunches are delivered into the main session room, which guarantees audience attendance and participation. A limited number of presentations are available for sponsorship and they will sell out quickly. Sign on to secure your talk!

Invitation-Only VIP Dinner/Hospitality SuiteSponsors will hand-pick their top prospects from the conference pre-registration list for an evening of networking at the hotel or at a choice local venue. CHI will extend invitations and deliver prospects. Evening will be customized according to sponsor’s objectives (i.e. purely social, focus group, reception style, or plated dinner with specific conversation focus).

Focus GroupsCHI can help you organize and execute a focus group on-site. This exclusive gathering can be useful to conduct market research, gain feedback on a new product idea, and gather marketing intelligence from industry experts on a specific topic. Please inquire for more details.

User Group MeetingCo-locate your user group meeting with the Biotherapeutics Analytics Summit. CHI will help market the event, manage logistical operations, develop agenda, and more. CHI can handle the entirety of the meeting, or aspects of your choice.

Exhibit InformationExhibitors will enjoy facilitated networking opportunities with qualified decision-makers at the World Pharma Congress, making it the perfect platform to launch a new product, collect feedback and generate new leads. Exhibit space sells out quickly, so reserve yours today!

Additional promotional opportunities are available including: • Conference tote bags• Badge lanyards • Tote bag inserts of company literature • Padfolios

• Keynote chair drop of company literature • Session room chair drop of company literature • Program guide sponsor • Poster abstract book sponsor

Looking for additional ways to drive leads to your sales team?CHI can help with custom lead generation programs!

We offer clients numerous options for custom lead generation programs to address their marketing and sales needs. Some of our programs include: live webinars, white papers, market surveys, podcasts, and more!

Benefits of working with CHI for your lead generation needs:

•Your campaign will receive targeted promotion to CHI’s unparalleled database of over 800,000 individuals, all of which are involved in all sectors of the life sciences – lists can be segmented based on geography, research area, title and industry.

•All custom lead generation programs are promoted through our experienced marketing team that will develop and drive targeted campaigns to drive awareness and leads to your lead generation program.

•For our webinar programs, we offer assistance in procuring speakers for your web symposia through our extensive roster of industry recognized speakers across multiple disciplines within life sciences, as well as provide an experienced moderator and dedicated operations team will coordinate all efforts.

• If choosing a white paper program, we can offer editorial experience and provide an industry recognized author to write your white paper.

For additional sponsorship & exhibit information, please contact: Joseph VaccaManager, Business Development781-972-5431 | [email protected]

Corporate SponsorsPremier Sponsor







mailto:jvacca%40healthtech.com?subject=WPC%20Sponsorship%20and%20Exhibit%20Information

http://www.jax.org/

http://www.championsoncology.com/

http://www.chantest.com/

http://www.coriumgroup.com/

http://www.hepregen.com/

http://mirimus.com/

http://www.marshallbio.com/

http://www.maccine.com/index.php

http://www.quintiles.com/

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Short Courses*MONDAY, JUNE 3

Morning Courses | 9:00 am—12:00 pm

SC1: Addressing Safety Concerns for Biologics and Biosimilars Sponsored by

•What are typical biologics safety data and program approaches?•Application of safety studies (Tox, Safety Pharm, Safety Pharm-Reg tox hybrid)•Overview of the current guidance in ICH S6 and the ICH S6 addendum•Unique safety challenges and risk mitigation strategies•Data interpretation and follow-up studies•Overview of biosimilar drug development, including the reduced, but comparative

nonclinical program and the choice of reference productInstructors:Noël Dybdal, Ph.D., D.V.M., Associate Director, Principal Scientist, Safety Assessment, Genentech, Inc.Ulrich Certa, Ph.D., Head, Molecular Toxicology, Non-Clinical Safety, pRED, F. Hoffman-La RocheAnne Ryan, Ph.D., Executive Director, Drug Safety Research and Development, Pfizer, Inc.

SC2: Utilization of Cardiac Contractility Assays for Preclinical Safety Testing•Basics of cardiovascular physiology and definition of myocardial contractility• In vitro and in vivo models and measurements•Assessment of myocardial contractility and ventricular vascular coupling from

pressure-volume loops (“gold” standard) and load dependent methods •Translational challenges: What change in myocardial contractility constitutes a drug

liability? If we do not know, why measure it?•Data interpretation and limitationsInstructors:Robert Hamlin, Ph.D., Professor, Veterinary Biosciences, Ohio State UniversityJonathan Heyen, Principal Scientist, Global Safety Pharmacology, Pfizer Global Research & Development

SC3: Animal Models of Pain: Progress and Challenges•Classical models of acute, tonic and chronic pain•Limitations of these classical models•Refinement of classical models via a consideration of modulatory factors (sex,

genetics, testing environment, social modulation)•Development of new animal models (e.g., operant methods, spontaneous behaviors)Instructor: Jeffrey S. Mogil, Ph.D., E.P. Taylor Professor of Pain Studies, McGill University

SC4: Design and Interpretation of Stability Studies for Product Development

Developing a Line-of-Sight for Product Stability – Forced Stress Testing Through ICH Stability Requirements Robert A. Reed, Ph.D., Vice President, CMC & Technical Operations, Celsion Corp. Best practices have been established for forced stressed degradation studies that allow an accurate prediction of chemical “potential” for a reaction to occur. Furthermore, in-silico prediction software is emerging as a useful tool to fully consider likely reactive pathways that may play an important role in the drug stability. This talk will attempt to provide a high level introduction for best practices to establish degradation potential for a drug substance and some of the pit falls that one may encounter in bridging to ICH stability studies. Case examples will be presented to highlight some of the presented concepts. Overall, the goal is to develop confidence in the predictability and interpretation of early drug development product stability studies for the commercial market.

Controlling Reactive Components in Polymeric Pharmaceutical Excipients for Improving the Stability of APIs Shaukat Ali Ph.D.,Technical Sales Manager, BASF Corp.Excipients play important roles in the stability of APIs in the drug development. The key attributes leading to instability of a drug could vary from the nature of an API and the excipients used in the formulation dosages. Most importantly, the drugs sensitive

to peroxides may have direct implication on the stability of product development. This presentation will cover the understanding of underlying mechanisms for oxidation of drugs and identifying the appropriate measures or safe guards to improve the stability of an API from the excipients’ perspectives.

Integrating mechanistic drug degradation pathways and mathematical modeling in stability assessment and prediction Ajit S. Narang, Ph.D., Sr. Research Investigator, Drug Product Science & Technology, Bristol-Myers Squibb, Co. Predicting the kinetics of drug degradation on storage stability can be challenging. Integrating mechanistic understanding of the drug degradation pathway along with kinetic mathematical modeling of the degradation rate can not only help predict drug product stability, but also quantify the effect of underlying variables and identify mitigation strategies. In this talk, case studies would be presented where mechanistic understanding was combined with mathematical modeling to understand and mitigate stability risks during the manufacturing and stability of an oral solid dosage form.

Afternoon Courses | 2:00—5:00 pm

SC5: Use of Stem Cells for Safety Screening•Types of stem cells being used for drug toxicity testing- What can they offer?•Comparing testing and use of stem cells versus primary cells•Overcoming technical challenges related to working with stem cells•Maintaining and characterizing stem cells for routine predictive safety testing•Regulatory challenges with using stem cellsInstructor: Matthew Peters, Ph.D., Principal Scientist, Safety Assessment, AstraZenecaAdditional Instructors to be Announced

SC6: Introduction to Drug Metabolism and Its Role in Drug Toxicity•Basic concepts of drug metabolism• In vitro tools to investigate drug metabolism•Biotransformation pathways•Understanding the role of reactive metabolites in idiosyncratic drug toxicity•Role of drug transporters in toxicity• In silico tools to aid drug metabolism researchInstructor: John Erve, Ph.D., D.A.B.T., former Principal Scientist, DMPK, Elan Pharmaceuticals, Inc.

SC7: Epigenetic Mechanisms of Pain• Introduction to epigenetic mechanisms• Identifying and validating targets•Unique challenges and opportunities with epigenetic targets•Current state of drug discovery in this areaInstructor: Chas Bountra, Ph.D., Professor of Translational Medicine & Head, Structural Genomics Consortium, University of OxfordAdditional Instructors to be Announced

SC8: Development of Nanotechnology Application into Innovative Therapies•Fundamentals of design, formulation and nanoparticle characterization for

nanotechnology-based therapies•Effective design & utilization of in vivo small and large animal models for preclinical

evaluation of nanomedicine•Challenges for the successful introduction of novel nanomedicine products into

clinical trials and the commercial marketsInstructors:Seungpyo Hong, Ph.D., Assistant Professor of Pharmaceutics and Bioengineering, Department of Biopharmaceutical Sciences, University of Illinois College of PharmacyUma Prabhakar, Ph.D., Consultant, Office of Cancer Nanotechnology Research NCI-NIH

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MONDAY, JUNE 3 (Continued)

Afternoon Courses | 2:00—5:00 pm

SC9: Roadmap for Outsourcing of Preclinical Imaging This complimentary workshop is designed as a one stop shop event for individuals from industry to get a sense of the preclinical imaging CRO landscape. With the recent trend of outsourcing more and more preclinical imaging to CROs, pharma companies are often missing the critical information of imaging and scientific capacities of various imaging CROs. Participants include: Maccine, InviCRO, Molecular Imaging

Processing, Analyzing, Reporting and Archiving Sponsored by Images in Drug Discovery and DevelopmentMatthew Silva, Ph.D., Director, Imaging Research, inviCRO, LLCImprovements in pre-clinical imaging instrumentation over the past decade enabled an increase in novel, translational in vivo imaging applications. While molecular probes and image acquisition protocols have translated well, however, there has not been an analogous translation of image processing protocols. Using case studies, this talk will focus on improving the reproducibility and throughput of pre-clinical image processing protocols across a broad spectrum of applications.

Application of Imaging Technologies to Sponsored by Drug Discovery and Development Studies in Nonhuman PrimatesMahesh Mistry, Ph.D., Executive Director, Business Development, Maccine Pte LtdThe wider application of imaging technologies to preclinical drug efficacy and safety research has the potential to greatly improve prediction of clinical success; especially when applied to non-human primate studies. Herein we describe how PET, CT and MRI imaging modalities are being applied to nonhuman primate efficacy, ADME/PK and safety studies.

Pharmacology Imaging: Molecular Imaging’s Sponsored by Unique Approach to in vivo StudiesPatrick McConville, Ph.D., Chief Operating Officer/CSO, Molecular Imaging, Inc.This is an overview of pharmacoimaging at Molecular Imaging. By combining extensive pharmacological expertise with broad imaging capabilities, our preclinical studies benefit from richer and clinically relevant data enabling better decision making, improved clinical trail design and more confident lead candidate selection.

WEDNEsDAY, JUNE 5

Dinner Short Courses | 6:00 pm—9:00 pm

SC10: Advances in Imaging Quantitation• Image Segmentation – the State-of-the-Art and Applications• Image Registration – the State-of-the-Art and Applications•Multivariate Image AnalysisInstructor: James Gee, PhD, Professor and Director, Penn Image and Computing Science Laboratory, University of PennsylvaniaAdditional Instructors to be Announced

SC11: Genetically Engineered Mouse Models Versus Patient-Derived Xenograft Models: Comparing Strengths and Limitations. Instructors:Serguei Kozlov, Ph.D., Principal Scientist, Center for Advanced Pre-Clinical Research, SAIC-Frederick, Inc.M. Raza Zaidi, Ph.D., Assistant Professor of Biochemistry, Fels Institute for Cancer Research & Molecular Biology, Temple University School of MedicineGwenn Danet-Desnoyers, Ph.D., Director, Stem Cell and Xenograft Core, Adjunct Associate Professor, Hematology-Oncology, University of Pennsylvania School of MedicineDylan Daniel, Ph.D., Investigator III, Oncology Pharmacology, Novartis Institutes for Biomedical ResearchHui Gao, Ph.D., Investigator III, Novartis Institutes for Biomedical Research

*Separate Registration Required

Present a poster and save $50!Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their 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 April 19, 2013. Please see registration page for details.

Reasons you should present your research poster at this conference:•Your poster will be exposed to our international delegation•Receive $50 off your registration•Your poster abstract will be published in our conference materials•Your research will be seen by leaders from top pharmaceutical, biotech, academic

and government institutes

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2nd Annual

predictive preclinical Models in oncologyChallenging Cancer Heterogeneity with Reproducible and Predictive Preclinical Studies

Recommended Short Course* Roadmap for Outsourcing of Preclinical Imaging (Complementary) * Separate registration required; please see page 4 for details

TUEsDAY, JUNE 4

7:45 am Registration and Morning Coffee

»KEYNOTE sEssION

8:30 Chairperson’s Opening Remarks

8:50 Application of Complex Animal Models in Oncology Drug Design and Early DevelopmentNorman M. Greenberg, Ph.D., Vice President, Research and Development, MedImmuneOne of our goals is to establish and strengthen tied with leading investigators at academic, government, biotechnology and pharmaceutical organizations that have expertise in, and access to, complex and robust in vitro and in vivo models for oncology research. This presentation will focus on select programs that leverage our investment and growing expertise in sophisticated model systems to advance important medicines to unmet medical needs.

9:30 Validation of Animal Models of Cancer: It Takes a VillageTerry A. Van Dyke, Ph.D., Head, Mouse Cancer Genetics Program; Program Director, Cancer Pathways and Mechanisms, National Cancer Institute

10:10 Coffee Break

10:40 Pre-Clinical Mouse Models of GliomaEric Holland, M.D., Ph.D., Director, Brain Tumor Center; Vice Chair, Translational Research, Department of Surgery, Emily Tow Jackson Chair in Oncology, Memorial Sloan Kettering Cancer Center.

11:10 Frederick National Laboratory for Cancer Research - New Opportunities.David Heimbrook, Ph.D., CEO, SAIC-Frederick National Laboratory for Cancer Research

11:40 Utilization of Predictive Champions TumorGraft Models Sponsored by to Guide Oncology Drug DevelopmentDavid Sidransky, MD, Chairman & Co-Founder, Champions Oncology, Inc.One of the challenges of oncology drug development is the ability to translate preclinical research into the clinical strategy. By using relevant patient derived xenografts, such as Champions TumorGraft models, oncology drug developers can better guide a compound’s development from the lab to the clinic. Other relevant uses of Champions TumorGraft models are to personalize cancer treatment for patients and facilitate biomarker discovery and validation.

12:10 pm in vivo Complex Chimeric NOG Sponsored by

Mice: Model Development and Use for Preclinical Evaluation of DrugsJean-François Mirjolet, Ph.D., Technology Director, OncodesignMany findings from conventional animal models (i.e. syngeneic or xenogeneic) are not easily translated and do not apply to humans due to the intrinsic differences between species (e.g. immune function…). Complex in vivo chimeric mouse models having human immune function and human tumor target cells were developed. This presentation will focus on human immune reconstitution using NOG mice, engraftment of human tumors within this context and tools to evaluate immune mediated antitumor effects.

1:30 Plenary Keynote Panel Discussion: Advancing Pharma R&D through Communication & Collaborations: Bio-Connectivity at WorkKarim Dabbagh, Ph.D., Executive Director and Head, External R&D and Innovation Research Units, Pfizer Worldwide R&DGlen N. Gaulton, Ph.D., Professor, Pathology and Laboratory Medicine; Executive Vice Dean and CSO, Perelman School of Medicine, University of PennsylvaniaPeter Pitts, President and Co-Founder, Center for Medicine in the Public Interest

3:00 Grand Opening of the Exhibit Hall with Poster Viewing

4:00 The Co-Clinical Trial Paradigm: Improving Predictive Value of Preclinical StudiesDr. Andrew L. Kung, M.D., Ph.D., Director, Pediatric Hematology, Oncology and Stem Cell Transplantation, New York-Presbyterian Morgan Stanley Children’s Hospital/Columbia University Medical CenterConventional mouse studies are poor predictors of efficacy in human clinical trials. The predictive value of preclinical studies may be improved by utilizing newer models that recapitulate the complexity of human disease, along with response criteria that are better aligned with clinical measures of success. The use of genetically engineered mouse models, patient derived xenografts, and molecular imaging will be reviewed in the context of the co-clinical trial paradigm.

4:30 Panel Discussion: Advancing Preclinical Oncology with Better Science and Better CollaborationPanelists: Speakers of Keynote Session

5:00 pm Sponsored Presentation (Opportunity Available)

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

6:30 Close of Day



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WEDNEsDAY, JUNE 5


METASTATIC ANIMAL MODELS AND THEIR APPLICATIONS

8:00 Chairperson’s Remarks

8:10 Modeling Tumor Cell Dormancy in the MouseJeffrey E. Green, M.D. Head, Transgenic Oncogenesis and Genomics Section, Center for Cancer Research, National Cancer InstituteRecurrence of breast cancer as disseminated disease years after the apparently successful treatment of the primary tumor remains a critical aspect of cancer biology that is poorly understood. It is presumed that tumor recurrence results from the metastatic outgrowth of preexisting, dormant tumor cells. The use of in vitro and in vivo models to study the dormant-to-proliferative switch and tumor recurrence, and their potential for preclinical testing will be presented.

8:40 Preclinical Modeling of Melanoma Metastasis and ResistanceGlenn Merlino, Ph.D., Chief, Molecular Genetics Section, Laboratory of Molecular Biology, Division of Basic Science, National Cancer InstitutePost-treatment recurrence and metastasis are the main causes of cancer-related death. This problem is magnified in melanoma, which is highly metastatic and generally chemoresistant. The study of cancer recurrence and metastasis relies on appropriate animal models; however, preclinical models of cancer progression are mostly lacking. We have designed new, and improved on existing, mouse models of progressive melanoma, which we use to study mechanisms associated with drug resistance of recurrent/metastatic BRAF, NRAS and non-BRAF/NRAS melanomas.

9:10 Therapy Model for Advanced Intracerebral B16 Mouse Melanoma Using Radiotherapy Combined with ImmunotherapyHenry Smilowitz, Ph.D., Associate Professor, Cell Biology, University of Connecticut Health CenterA reproducible therapy model for advanced intracerebral B16 melanoma is reported. Implanted tumors (D0), suppressed by a single 15 Gy radiosurgical dose of 100 kVp X-rays (D8) were further suppressed by a single ip injection of a Treg depleting Mab given two days prior to the initiation (D9) of four weekly then eight bi-monthly sc injections of GMCSF-transfected, mitotically disabled B16 cells. The trends of seven independent experiments were similar to the combined result.

9:40 Human Tumor Xenografts in Preclinical Drug Development: Sponsored by Future Trends Towards Improved Model SystemsJulia Schueler, Ph.D., DVM, Oncotest GmbHPatient-derived tumor xenografts (PDX) have played a major role in the development of new cancer therapies and their strengths and weaknesses have gradually been elucidated. The basic model has been refined, leading to models more closely recapitulating human tumor biology. These refinements, coupled with the development of an ex-vivo PDX based 3D assay allowing simultaneous testing of agents in up to 200 PDX, represent an integrated preclinical profiling system and promise to make additional positive contributions to clinical success rates.

10:10 Coffee Break in the Exhibit Hall with Poster Viewing

DESIGNING MODELS FOR PARTICULAR APPLICATIONS

10:40 Building Preclinical Capabilities for ER+ Breast CancerCelina D’Cruz, Ph.D., Principal Scientist I, Oncology Innovative Medicines, R&D, AstraZenecaPreclinical models that represent ER+ and endocrine resistant breast cancer have historically been challenging to create. We have generated and characterized several ER+ xenograft and primary tumor models that represent patient segments of interest. With this platform of models, we have compared standard of care and also selected more targetted drug approaches based on molecular information.

11:10 The Immune Microenvironment and Immunotherapy in Preclinical Models of Melanoma and Breast CancerDylan Daniel, Ph.D., Investigator III, Oncology Pharmacology, Novartis Institutes for Biomedical ResearchModeling therapeutic responses to immune modulating agents in cancer is one of the foremost challenges facing translational researchers today. We have modeled the role of immune cells in tumor progression in autochthonous and allograft GEM models of mammary cancer and melanoma. We will present our findings on the use of targeted agents against specific immune cell types alone and in combination with agents that target tumor cells directly, and thus may indirectly modify the immune microenvironment.

11:40 The JAX Patient Derived Xenograft Sponsored by (PDX) Resource for Clinical AdvancementNeal Goodwin, Ph. D., Senior Fellow & Director, Business Development, in vivo Pharmacology Services, The Jackson LaboratoryA unique program from The Jackson Laboratory (JAX), the UC-Davis Comprehensive Cancer Center and other centers for advancing cancer therapeutic development. Solid and liquid tumors from consenting patients are transplanted into the JAX-NSG immune deficient mouse. These patient derived xenografts (PDX) can be screened with standard and experimental therapeutics to measure and compare tumor response rates. Over 150 PDX tumor models have been established for use in research including co-clinical predictive tumor response studies.

12:10 PDX Models of Acute Myeloid Leukemia for Pre-Clinical Screening of Novel TherapiesMartin Carroll, M.D., Associate Professor, Division of Hematology and Oncology, University of Pennsylvania School of MedicineAcute myeloid leukemia (AML) is a cancer of the blood with a poor prognosis. We describe the use of the immunocompromised mouse models for patient derived xenotransplantation and therapy testing. Although the NSG mouse is the currently most widely used model, NRG mice allow for delivery of a more physiologic dose of chemotherapy and NSGS mice provide more rapid engraftment. Studies in NSG mice with novel therapeutics begin to describe the pro’s and con’s of the NSG model for predicting responses in human trials.

12:40 pm Luncheon Presentation (Opportunity Available)

2nd Annual




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ADDRESSING INTER-PATIENT RESPONSE HETEROGENEITY


2:10 Modeling Inter-Patient Response Heterogeneity Using Patient-Derived Xenograft ModelsHui Gao, Ph.D., Investigator III, Novartis Institutes for Biomedical ResearchNovartis has built a large patient- derived xenograft tumor model bank that contains over 500 models across more than 15 histology subtypes. These models have been extensively used in pre-clinical studies to further characterize genetic targets as well as novel anticancer agents. They are also being used to validate the predictive gene signatures derived from robust in vitro cell line model systems, and have demonstrated high predictive value when compared to clinical studies.

2:40 Novel Tumor Culture System that Retains Primary Tumor PhenotypeTan A. Ince, M.D., Ph.D., Director, Tumor Stem Cell Division, Interdisciplinary Stem Cell Institute and Associate Professor of Pathology, Braman Family Breast Cancer Institute, Miller School of Medicine, University of MiamiCurrently available human tumor cell line panels consist of small number of lines that generally fail to retain the phenotype of the original patient tumor. We developed a cell culture medium that enables routine culture of diverse subtypes of human cancers with >95% efficiency. Importantly, these cell lines retain the genomic landscape, histopathology, and molecular features of the original tumors. Furthermore, the molecular profile and drug response of these cell lines correlate with distinct groups of primary tumors with different outcomes. Thus, tumor cell lines derived using this new methodology represent a significantly improved new platform to study human tumor biology {Feeley, 2001 #15} and treatment.

3:10 RNAi Mouse Models for Drug Discovery Research Sponsored by

Prem K. Premsrirut, Ph.D., CEO, Mirimus, Inc.Mirimus’ creates the most advanced RNA interference (RNAi) tools for drug discovery research. We provide innovative RNAi mice with reversible gene silencing capabilities that enable researchers to adopt novel approaches and obtain high-quality, preclinical scientific validation of targets and toxicology assessment prior to advancing into expensive clinical trials.

3:25 LION, PUMA and the Tumour Sponsored by

Microenvironment: Building Clinically Relevant PDX models for Oncology Drug DiscoveryAaron Cranston, Ph.D., Head, in vivo Services, PRECOS Ltd. Clinically relevant preclinical models that represent tumour-specific subsets which better recapitulate the complexity & heterogeneity of human cancers can interrogate novel agents more appropriately. Unique models of acquired resistance (PUMA) derived from our focused lung PDX subset panel (LION) will be presented & their advantages in preclinical testing discussed.

3:40 Refreshment Break in the Exhibit Hall with Poster Viewing

4:10 Using Genetically Engineered Mouse Models to Study Circulating Tumor CellsAndrew Rhim, M.D., Instructor of Medicine, Gastroenterology/Medicine, University of PennsylvaniaCirculating tumor cells have recently become a robust and popular topic of study. However, major questions remain unanswered regarding the nature of this important cell population; for example, what is the role of EMT in generating these cells? How heterogeneous are CTCs? When do CTCs arise during cancer progression? Do CTCs

display stem cell capabilities? In this talk, the use of genetically engineered mouse models to answer these questions will be reviewed. Finally, translation of these lessons to actual clinical applications will be summarized.

4:10 Breakout Discussion Groups

5:40 Close of Day

6:00 Recommended Short Course*

Genetically Engineered Mouse Models Versus Patient-Derived Xenograft Models: Comparing Strengths and Limitations. Instructors:Serguei Kozlov, Ph.D., Principal Scientist, Center for Advanced Pre-Clinical Research, SAIC-Frederick, Inc.M. Raza Zaidi, Ph.D., Assistant Professor of Biochemistry, Fels Institute for Cancer Research & Molecular Biology, Temple University School of MedicineGwenn Danet-Desnoyers, Ph.D., Director, Stem Cell and Xenograft Core, Adjunct Associate Professor, Hematology-Oncology, University of Pennsylvania School of MedicineDylan Daniel, Ph.D., Investigator III, Oncology Pharmacology, Novartis Institutes for Biomedical ResearchHui Gao, Ph.D., Investigator III, Novartis Institutes for Biomedical Research

ThUrsDAY, JUNE 6


IMAGING IN CANCER DRUG DEVELOPMENT


8:40 Molecular Imaging in Preclinical Oncology Models: From Concepts to PracticePeter King, Ph.D., Senior Scientist, Molecular Imaging (Oncology), Janssen, Pharmaceutical Companies of Johnson and JohnsonAn escalating number of research programs within the oncology field are focusing on the tumor microenvironment and biomarkers. By incorporating the use of novel non-invasive molecular imaging techniques to look at drug target expression, tumor-host interactions, and pharmacokinetic and pharmacodynamics of the drug within these humanized pre-clinical oncology models, it will enable us to interrogate our drugs in more human reflective systems. This in turn can accelerate the pace of drug development both in preclinical research and early clinical-translation.

9:10 Characterization and Preclinical Application of a Therapeutic Monoclonal Antibody-Based PET TracerCharles Glaus, Ph.D., Scientist, Research Imaging Sciences, AmgenCancer immunotherapy harnesses the cytotoxic capabilities of the immune system and directs it towards the destruction of tumor cells. The development of novel molecules that induce tumor-specific immune responses has tremendous potential for patients and is an area of focus in biopharmaceutical industry. The aim of this study was to quantify the in vivo distribution of a radiolabeled immunotherapeutic in a syngeneic tumor model using SPECT/CT imaging and organ biodistribution.

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9:40 Predicting Response to Folate-Targeted Drug Therapy Using the Companion Imaging Agent, 99mTc-etarfolatideChristopher P. Leamon, Ph.D., Vice President, Research Endocyte, IncVintafolide is a potent folate-targeted vinca alkaloid conjugate that is currently being evaluated in global phase 3 trials. Response to vintafolide and other folate-targeted drugs is dependent on folate receptor (FR) expression, which can be anatomically assessed in a non-invasive, real-time format using the folate-targeted companion diagnostic agent, 99mTc-etarfolatide. This novel and personalized approach may allow for the identification of pati


10:40 Application of in vivo and ex vivo Imaging for Assessing PK and PD in Preclinical Cancer Models: Optimizing Discovery to DeliveryWerner Scheuer, Research Leader, Pharma Research and Early Development, Discovery Oncology; Roche Diagnostics GmbHApplication of different imaging modalities to monitor the efficacy of new compounds on primary tumor growth, metastasis and angiogenesis. Verification of in vivo imaging data by multispectral fluorescenec histology of explanted tumor tissue.

11:10 Smart Nanoparticle Approaches for Targeted Diagnosis and Therapy of CancerWillem Mulder, Ph.D., Associate Professor of Radiology, Director, Nanomedicine Program, Translational and Molecular Imaging Institute, Mount Sinai School of MedicineMicrofluidics-based nanoparticle synthesis technology allows the creation of complex multifunctional nanoparticles. Such complex formulations permit the integration of several agents/materials and functionalities as well as smart coatings. In the context of cancer such nanoparticle platforms serve as valuable tools in preclinical research and may enable improved diagnosis and treatment for patients in the future.

11:40 Panel Discussion: Imaging End Points in Preclinical Cancer ResearchPanelists: Speakers of the SessionModerator: Werner Scheuer, Research Leader, Pharma Research and Early Development, Discovery Oncology; Roche Diagnostics GmbH


PRECLINICAL TUMOR MODELS FOR TARGETED CANCER THERAPIES


1:40 Derive Response Biomarker for Oncology Drug Using Preclinical ModelsTheresa Zhang, Ph.D., Associate Director, Merck Research LaboratoriesPreclinical models are widely used to discover sensitivity and resistance biomarkers for oncology drugs. This talk will use examples to discuss the best practices to design and implement preclinical studies for biomarker discovery, focusing on how to select appropriate models that best represent the human tumors of interest, and how to power the discovery and validation studies sufficiently to improve the possibility of success of the biomarker in clinic.

2:10 Preclinical Development of LGX818: A Highly Potent and Selective RAF kinase InhibitorDarrin Stuart, Senior Research Investigator II, Novartis Institutes for Biomedical ResearchSelective RAF kinase inhibitors have demonstrated dramatic efficacy in melanoma patients whose tumors express BRAFV600E. However, the majority of patients relapse within 6 months. LGX818 was developed with the hypothesis that a more potent inhibitor with optimal pharmacological properties would improve the rate and durability of anti-tumor response in melanoma patients. This presentation will focus on the preclinical development and differentiation of LGX818 with emphasis on preventing or delaying resistance.

2:40 Targeting Tumor Re-Initiating Cells to Prevent Therapeutic Resistance and Disease RelapseErica Jackson, Ph.D., Scientist, Research Group Leader, Genentech

3:10 Outlier Kinases Identified by RNA-Seq Provide Personalized Therapeutic TargetChandan Kumar-Sinha, Ph.D., Research Assistant Professor, Pathology, University of MichiganAnalyzing a compendium of RNA-Seq data from diverse cancers, we shortlisted the kinases displaying the highest levels of absolute expression among all the kinases expressed within a sample that also displayed the highest levels of differential expression relative to all the samples in our compendium of 485 samples. Next, examining a panel of breast and pancreatic cancer cell lines by RNA knockdown and/or pharmacological inhibition, we observed a profound dependence on “sample-specific outlier kinases”. Our results suggest that sample-specific outlier kinases represent personalized therapeutic targets that could help improve combinatorial therapy options in a wider cohort of cancers than currently realized.

3:40 Close of Conference

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targeting pain with novel therapeuticsTranslating Success from Preclinical Assays to the Clinic

MONDAY, JUNE 3

Recommended Short Course*

9:00-12:00 pm Animal Models of Pain: Progress and Challenges* Separate registration required; please see page 4 for details

TUEsDAY, JUNE 4


COLLABORATION & OPEN INNOVATION--A WAY FORWARD FOR PAIN


8:40 We Must Work Together to Discover New AnalgesicsChas Bountra, Ph.D., Professor of Translational Medicine & Head, Structural Genomics Consortium, University of OxfordPatients need new analgesics, the industry is struggling and the costs of R&D are rising. The only solution is to pool the resources and capabilities ofpublic and private funders, academics, patient groups and regulators. A pre-competitive partnership with rapid dissemination of reagents and data, will reduce the current wastage and needless exposure of patients to molecules destined for failure.

9:25 Virtual Discovery at AstraZenecaStephen Zicha, Ph.D., Project Director, Sciences, AstraZeneca Neuroscience Research & DevelopmentNeuroscience drug discovery has experienced one of the highest failure rates in terms of bringing novel medicines to the patients who need them compared to other research areas, and no therapeutic targeting a novel mechanism has been approved for analgesic use in the past decade. One strategy to overcome this drought is to work collaboratively with multiple external groups to help accelerate the drug discovery process while benefitting from access to the world’s best and newest scientific innovations. Some case studies highlighting this approach will be presented, with a particular focus on improving the translation of pre-clinical discoveries into successful clinical development.

ION CHANNELS

9:40 Accelerating Pain Drug Discovery Targeting Ion Channels Sponsored by by Partnering with ChanTestEmir Duzic, Ph.D., Senior Director, Discovery Services, ChanTest

10:10 Coffee Break

10:40 Discovery and Preclinical Validation of Novel Voltage-Gated Sodium and Calcium Channel Blockers with Analgesic PotentialMichael F. Jarvis, Ph.D., Volwiler Senior Research Fellow & Associate Director, Early Discovery, Pain, AbbVie, Inc.The complexities associated with effective pain control are manifest by variations in underlying disease etiologies, functional interactions and redundancies in sensory pathways and low efficacy and/or poor tolerability for current analgesics. Voltage-gated sodium and calcium channels serve as final common modulators of neuronal membrane excitability and neurotransmitter release, respectively. Emerging genetic validation and biophysical data coupled with improved screening technologies have led to renewed interest in the discovery of novel blockers of these channels for pain management. The development of channel isoform selective blockers will be highlighted in this presentation.

11:10 Panel Discussion: Novel Approaches to Discovery and Development

State-Dependent Calcium Channel Blockers for PainMargaret S. Lee, Ph.D., Vice President, Research & Translational Medicine, Zalicus, Inc.With prolonged excitation, such as during chronic pain signaling, the relative proportion of voltage gated calcium channel inactivation increases. Specifically targeting the inactivated state offers an opportunity for pharmacological selectivity that may broaden therapeutic window, minimize adverse effects and increase efficacy. We have discovered novel, first-in-class calcium channel blockers that demonstrate enhanced potency for the inactivated state. Z160 and Z944, selective, state-dependent, N- and T-type calcium channel blockers respectively, demonstrate potent effects in nonclinical pain models. Both are currently in clinical development for pain indications.

TARGETING PAIN WITH NEW TARGETS, NEW APPROACHES

11:40 A New Selective Sigma-1 Receptor Antagonist (S1RA; E-52862) for the Treatment of PainJosé Miguel Vela, Ph.D., Drug Discovery & Preclinical Development, EsteveSigma 1 receptor (σ1 receptor) is a unique ligand-regulated molecular chaperone which is activated under stress or pathological conditions and modulates the function of several neurotransmitter receptors and ion channels. Preclinical data obtained in sigma-1 receptor knockout mice and using several sigma-1 receptor ligands, particularly the σ1 receptor antagonist S1RA (E-52862), are consistent with a role for σ1 receptor in central sensitization and pain hypersensitivity and supports a potential therapeutic use of σ1 receptor antagonists for the management of neuropathic pain. Moreover, data support their use in opioid adjuvant therapy: combination of S1RA with opioids results in potentiation of opioid analgesia, without significant increases in opioid-related unwanted effects. Results from clinical trials are thus eagerly awaited to ascertain the potential of σ1 receptor modulation in pain therapy.

12:10 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:30 Plenary Keynote Panel Discussion: Advancing Pharma R&D through Communication & Collaborations: Bio-Connectivity at WorkKarim Dabbagh, Ph.D., Executive Director and Head, External R&D and Innovation Research Units, Pfizer Worldwide R&DGlen N. Gaulton, Ph.D., Professor, Pathology and Laboratory Medicine; Executive Vice Dean and Chief Scientific Officer, Perelman School of Medicine, University of PennsylvaniaPeter Pitts, President and Co-Founder, Center for Medicine in the Public Interest

2:10 Using Rodent Visceral Pain Models as a “Higher-Throughput” Activity Screen in Preclinical Drug DiscoveryMichele Hummel, Ph.D., R.Ph., Principal Investigator, Discovery Research, Purdue Pharma L.P.Overall, many challenges confront the drug discovery process. The discovery of novel therapeutics to treat chronic painful conditions is not without exception. Despite the progress the pain field has made in the last two decades, much criticism still remains around the utility of existing animal models. In this regard, our group affirms the use of two rodent visceral pain models as a “higher-throughput” means of assessing compound activity in vivo. This presentation will describe these models as well as highlight their value in pain research. More importantly, we will provide evidence showing how activity in these models will provide an early and likely gauge of subsequent preclinical in vivo efficacy in more complex rat models. We will also demonstrate how these models and data have been used toadvance some candidate molecules on several of our company’s Target Teams.



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4:00 AYX1 Drug Candidate For Preventing Post-Surgical Pain and Improving Functional RecoveryJulien Mamet, Ph.D., Founder & CSO, Adynxx, Inc.AYX1 is a DNA decoy compound designed to prevent pain and facilitate functional recovery following surgery. Administered as a single intrathecal injection, AYX1 inhibits the activity of the transcription factor EGR1 focally in the spinal cord. Pharmacological studies demonstrate that AYX1 prevents mechanical hypersensitivity in preclinical models of neuropathic, incisional and inflammatory pain and improves functional recovery in models of spontaneous post-operative pain. AYX1 is under active clinical development.

4:30 Activation of Group II Metabotropic Glutamate (mGlu2/3) Receptors as a Treatment Strategy for Chronic PainMichael P. Johnson, Ph.D., Research Advisor, Pain/Migraine DHT, Neuroscience Discovery, Eli Lilly & Co.The Group II metabotropic glutamate receptors (mGlu2 and mGlu3) are plasma-membrane associated G-protein-coupled proteins that function via presynaptic, postsynaptic and glial mechanisms to negatively modulate neuronal excitability. Within the pre-synaptic element, Group II mGlu receptors (primarily mGlu2) reside outside the synaptic zone where their activity appears to be dependent on an extrasynaptic, non-vesicular pool of glutamate. In addition, mGlu3 receptors are found within glial cells that are closely associate with neuronal synapses, and regulate sensitivity of synaptic transmission by controlling glutamate transporters and release of paracrine factors such as TGFβ. Activation of mGlu2/3 receptors by glutamate or by other exogenous agonists, such as LY379268, leads to the inhibition of synaptic glutamate release, thereby dampening downstream post-synaptic excitation. Thus, mGlu2/3 receptor agonists are efficacious in multiple animal models associated with hyper-glutamatergic tone including chronic pain [neuropathic, visceral and inflammatory pain models]. The relative importance of mGlu2 and mGlu3, as well as the novel epigenetic mechanism of some analgesic compounds will be discussed.

5:00 Development of a Phenotypic Pain Assay for Identification of Modulators of Excitability in Native Sensory NeuronsPaul Karila, Ph.D., Head, Discovery Services, Cellectricon ABWe have developed an enabling assay platform for chronic pain based on electric stimulation of primary DRG neuronal cultures. The biological relevance of the assay in combination with its ability to characterize a medium throughput screening libraryenables identification compounds for treatment of chronic pain early in the project lifecycle. Therefore, the platform is addingtrue value to the decision-making process. In addition, our phenotypic approach provides the possibility to address previously unknown targets within disease-relevant pathways.


6:30 Close of Day

WEDNEsDAY, JUNE 5


NOVEL APPROACHES FOR OPIOID ANALGESICS

8:30 Chairperson’s RemarksEdward Bilsky, Ph.D., Professor, Pharmacology & Director, Center of Excellence in the Neurosciences, University of New England

8:40 Dual Targeting μ Agonist/δ Antagonist Opioid AnalgesicsEdward Bilsky, Ph.D., Professor, Pharmacology & Director, Center of Excellence in the Neurosciences, University of New England

9:10 Oral Inhalation of Peripherally-Restricted KOR Agonists Produces Rapid Antinociception in Multiple Pain Models without Opioid LiabilitiesAndrea Leone-Bay, Ph.D., Vice President, Pharmaceutical Research & Development, MannKind CorporationSelf-administered, rapid-acting pain medicines without opioid side effects, like addiction and respiratory depression, remain an unmet medical need. We have identified a series novel small peptide peripherally-restricted kappa opioid agonists that meet this need. These new drugs have been combined with a non-invasive, oral inhalation delivery system that provides a very rapid (5 minutes or less), dose-dependent onset of pain relief in several nonclinical pain models.

9:40 GPCR Biased Ligands as Improved Analgesics: Promise and ProgressJonathan D. Violin, Ph.D., Head of Biology and Co-Founder, Trevena, Inc.GPCR biased ligands selectively engage a subset of the intracellular signals stimulated by full agonists, suggesting an opportunity to solve “on-target” adverse events. This concept has been demonstrated in vitro and in vivo with several molecules targeting opioid receptors, including TRV130, a G protein-biased ligand targeting the mu opioid receptor. TRV130 was potently analgesic with reduced respiratory depression and constipation compared to morphine in preclinical studies, and is now in clinical development.


IMAGING IN PAIN THERAPEUTICS DEVELOPMENT

10:40 Imaging Pain and AnalgesicsDavid Borsook, M.D., Ph.D., Director, Center for Pain and the Brain, Harvard Medical School

11:10 The Utility of Nonhuman Primates in Pain Research Sponsored by

David Hygate, Team Leader, Neurobiology & CNS Safety, Maccine Pte Ltd Herein we describe the development of a non-human primate neuropathic pain model as well as the use of fMRI in an inflammatory pain model as drug discovery tools with the potential for translation to early clinical studies.

11:40 Pharmacologic Modulation of Brain Mechanisms Operative in Humans with Chronic PainRichard Harris, Ph.D., Assistant Professor, Anesthesiology, University of MichiganBrain imaging studies implicate disruption of central chemistry and function in chronic pain patients. Demonstration of changes in these outcomes to pharmacologic intervention is needed. I will present data on altered brain neurochemical and connectivity patterns during pharmacologic treatment of chronic pain patients diagnosed with fibromyalgia. These data point towards the future development of personalized analgesic therapies using neuroimaging.


INNOVATIVE TRIAL DESIGN FOR EARLY CLINICAL ASSESSMENT

2:10 Efficient POC Studies in Pain: From Withdrawal to ConnoisseurTony W. Ho, M.D., Vice President, Clinical Innovative Medicine, AstraZeneca



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2:40 The Impact of Study Design and Study Conduct on Assay Sensitivity: Scientific Review and Proposed SolutionsNathaniel Katz, M.D., MS, President & CEO, Analgesic Solutions; Tufts University School of MedicineJeremiah Trudeau, Ph.D., Director, Outcomes and Psychometrics, Analgesic SolutionsThe historical view that the observed effect of a drug is produced only by the drug itself, with superimposed random variation from study to study, can no longer be sustained. The observed effect size is in fact not only determined by the intrinsic effect of a drug at a specific regimen and in a specific population, but also by the study design, and also by study conduct: an “assay sensitivity tripod.” Failed studies have become routine in an era where the drug is expected to shoulder all the burden of assay sensitivity with little regard for optimizing study design and conduct. While the science of clinical research methods is just emerging, several study design factors have been shown to impact observed drug effects, including concomitant and rescue medication, study structure (e.g. crossover vs. parallel), patient selection criteria, randomization ratio, etc. Perhaps even more important is study conduct, where factors such as the manner in which research staff influence patient expectation of benefit, number of sites, patient pain reporting capability, and central review of eligibility have been shown to impact outcome. In this talk we will provide a rational framework for considering these factors, review the current state of the science of clinical pain research, and offer practical solutions for the major pitfalls in study design and conduct.

3:10 A Novel Target for Chronic Migraine Therapy: Clinical Demonstration of Nasal Oxytocin Efficacy and SafetyDavid C. Yeomans, Ph.D., Founder and Chief Scientist, Trigemina; Professor and Director of Pain Research, Stanford UniversityChronic migraine affects more than 6 million people in the US alone. Pain in these patients is thought to be mediated by activity in the trigeminal nerve. We have demonstrated that there are receptors for the peptide hormone/neurotransmitter oxytocin on pain-sensing (CGRP positive) trigeminal neurons, including those that innervate the dura. We have shown that nasal application of radiolabelled oxytocin in rats preferentially concentrates this peptide throughout the trigeminal system, potentially allowing access to oxytocin receptors on those neurons and producing a trigeminal - selective analgesic effect. In rats, this is seen in that nasal oxytocin is highly analgesic for the face and head, but ineffective for non-craniofacial pain, and that this analgesia is greatly enhanced by prior inflammation, suggesting that nasal oxytocin may be useful in treating human pain states wherein there has been pre-existing inflammation. To test this, we performed a Phase IIa, double-blinded, placebo controlled trial in 40 chronic migraineurs.



5:40 Close of Day

ThUrsDAY, JUNE 6


PRECLINICAL ASSAYS: NOVEL MOUSE MODELS AND BEYOND


8:40 Use of Operant Measures for High-Throughput Drug ScreeningJohn K. Neubert, D.D.S., Ph.D., Associate Professor, University of FloridaPreclinical analgesic testing has traditionally relied on reflex-based outcome measures. Recent developments using operant assays provide for novel assessments of pain and analgesia and allow for evaluation of nociceptive processing and modulation throughout the neuraxis. Advantages of operant assays will be provided, including generation of comprehensive data sets, providing clinically-relevant outcomes, and highlighting the high-throughput aspects for pain testing.

9:10 Expression, Neurobiology and Treatment of Pain-Related Behavioral Depression in RatsS. Stevens Negus, Ph.D., Professor, Department of Pharmacology and Toxicology, Virginia Commonwealth UniversityPain is often associated with clinically relevant depression of behavior and mood, and relief of pain-related depression is a common goal of treatment in both human and veterinary medicine. Intracranial self-stimulation (ICSS) is a type of operant conditioning procedure that has been widely used to study the neurobiology of motivated behavior, and it can also be used to generate stable behavioral baselines for studies of pain-related behavioral depression. This talk will review recent research on the expression, neurobiology and pharmacological modulation of pain-related depression of ICSS in rats. Results suggest that assays of pain-depressed ICSS may provide new insights into mechanisms of pain-related depression and serve as a useful tool to improve translation of preclinical to clinical results in analgesic drug development.

9:40 Animal Models of Pain - “Back Translation” for Neck and Back PainBeth A. Winkelstein, Ph.D., Professor, Departments of Bioengineering and Neurosurgery, University of Pennsylvania


11:10 Panel Discussion: Better Models for Better Predictive Validity



1:40 Novel Readouts for the Analysis of Spontaneous Pain in AnimalsWolfgang Schröder, Ph.D., Scientific Director, Pain Pharmacology, Grünenthal GmbH

2:10 Talk Title to be AnnouncedMichele Hummel, Ph.D., R.Ph., Principal Investigator, Discovery Research, Purdue Pharma L.P.

2:40 Targeted Neurotoxin Studies in Companion Dogs: Bridging the Gap between Mice and MenDorothy Cimino Brown, D.V.M., Chair, Department of Clinical Studies, School of Veterinary Medicine, University of PennsylvaniaWhen naturally occurring diseases that cause pain in companion animals (pets) mimic the same conditions in people, studying new treatments in these animals can provide valuable insight into pharmaceutical efficacy. This presentation will detail how studies in companion dogs with bone cancer played a pivotal role in moving a TRPV1 agonist from laboratory animal studies to phase I/II clinical trials.

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MONDAY, JUNE 3

Recommended Short Courses*Development of Nanotechnology Application into Innovative TherapiesDesign and Interpretation of Stability Studies for Difficult Drugs* Separate registration required; please see page 4 for details

TUEsDAY, JUNE 4


THE EVOLVING NEEDS OF DELIVERING DIFFICULT-TO-DELIVER DRUGS: OPPORTUNITIES AND CHALLENGES

8:30 Chairperson’s Opening RemarksBobby Singh, Ph.D., Chief Technology Officer, Corium International, Inc.

8:40 Nanomaterial for Drug Delivery: Opportunities, Challenges and Lessons LearnedAnil K. Patri, Ph.D., Deputy Director, Nanotechnology Characterization Laboratory, Advanced Technology Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer ResearchAdvances in nanotechnology research are bringing about radical changes in early disease diagnosis and therapy. Nanotechnology based delivery systems can improve the delivery of approved therapeutics for better efficacy, and resurrect failed drugs by solving solubility, toxicity, and bioavailability issues. This talk will highlight the resources available for preclinical assessment, advances in nanomaterial technologies for cancer therapy, and the challenges in translation of nanomedicinie.

»9:10 FEATUrED PrEsENTATION: Nanopreparations for Delivery of Non-Deliverable Pharmaceuticals

Vladimir Torchilin, Ph.D., D.Sc., University Distinguished Professor, Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern UniversityPoorly soluble or highly unstable substances often represent promising drug candidates, however problems with their delivery and bioavailable dosage forms frequently prevents them from becoming real drugs. Various formulation strategies based on the use of nanocarrier systems to overcome poor solubility and instability of many drugs, including anticancer agents and siRNA, have been suggested, such as non-targeted and targeted polymeric micelles and layer-by-layer nanoparticles.

9:40 Accelerating the Translation of Nanotechnology Platform in Cancer through Public-Private PartnershipsUma Prabhakar, Ph.D., Consultant, Office of Cancer Nanotechnology Research NCI-NIHThe Alliance for Nanotechnology in Cancer of the NCI initiated a public private industry partnership called TONIC to evaluate promising nanotechnology platforms for drug delivery, imaging and monitoring and, facilitate their successful translation from bench to bedside, to help, timely, effective and novel diagnosis and treatment options for cancer patients. The interactions with government, academia, patient advocacy groups and industry in advancing the translation of the will be discussed.

10:10 Coffee Break

NOVEL PREFORMULATION: REDUCING THE RISK OF DRUG FAILURE EARLY ON

10:40 Proven Predictive Models in Drug Development to Anticipate Clinical OutcomesTycho Heimbach, Ph.D., Associate Director & Senior Investigator II, Biomedical Research, Novartis Pharmaceuticals CorporationSeveral case examples will be presented on predictive physiologically-based pharmacokinetics (PBPK) and PK/PD models to anticipate FIH and other clinical trials across all BCS/BDDCS class drugs. Successful integration preclinical and clinical data and application of custom (PBPK) software which significantly improved the accuracy of drug absorption and exposure prediction in humans will be discussed. In addition, examples where PBPK as a tool has impacted drug development will be shared.

11:10 Role of Pharmaceutics and Enabling Technologies in Discovery of Novel Acute Care TherapiesAkash Jain, Ph.D., Senior Scientist I, Discovery Pharmaceutics, Cubist Pharmaceuticals, Inc.Presentation will focus on the applications of modeling and simulation, automation and novel delivery technologies during early drug discovery to enable selection of candidates with optimal developable profile for acute care therapies. Case studies will be discussed to highlight the role of early intervention of pharmaceutics in discovery to enable candidate selection and identifying novel delivery approaches to maximize a NCE’s therapeutic potential and its fit with intended clinical use.

11:40 Improving the Bioavailability of Poorly Soluble Compounds Sponsored by with Hybrid Nanoparticle FormulationsPer Andersson, Ph.D., CEO, XSpray


1:30 Plenary Keynote Panel Discussion: Advancing Pharma R&D through Communication & Collaborations: Bio-Connectivity at WorkKarim Dabbagh, Ph.D., Executive Director and Head, External R&D and Innovation Research Units, Pfizer Worldwide R&DGlen N. Gaulton, Ph.D., Professor, Pathology and Laboratory Medicine; Executive Vice Dean and Chief Scientific Officer, Perelman School of Medicine, University of PennsylvaniaPeter Pitts, President and Co-Founder, Center for Medicine in the Public Interest


4:00 Native-State Solubility and Thermal Stability Studies for Selecting De-Risked Drug Lead Candidates in DiscoveryAaron Yamniuk, Ph.D, Senior Investigator, Protein Science and Structure, Bristol-Myers Squibb Co.Solubility is a key attribute of protein therapeutics that influences the ease with which they are discovered and developed. This presentation will describe a novel method for rank-ordering native-state solubilities of drug candidates, and how this information is applied in combination with thermal stability analyses to select drug candidates that have improved biophysical behavior.



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4:30 Difficult DVD-Immunoglobulins: Lessons Learned from Early Screening towards Faster Formulation DevelopmentVineet Kumar, Ph.D., Senior Research Scientist II, Department of Pharmaceutics, AbbVieThe importance of preformulation work during the early screening of molecules will be discussed. Lessons learned from various DVDs were used in the adaptation of a suitable screening funnel. The screening necessitates an early interdepartmental collaboration between the different groups including PK, formulations, analytics and others. Case studies and the screening approach used will be discussed.

5:00 Talk Title to be AnnouncedAjit S. Narang, Ph.D., Sr. Research Investigator, Drug Product Science & Technology, Bristol-Myers Squibb, Co.


6:30 Close of Day

WEDNEsDAY, JUNE 5


NOVEL DELIVERY STRATEGIES IN DRUG TARGETING

8:30 Chairperson’s RemarksVladimir Torchilin, Ph.D., D.Sc., University Distinguished Professor, Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University

8:40 FEATURED PRESENTATION: Principles of Ligand-Targeted Drug DesignPhilip S. Low, Ph.D., Ralph C. Corley Distinguished Professor, Department of Chemistry, Purdue UniversityBecause targeted therapeutics treat pathologic cells without damaging normal cells, they will likely dominate the drug market of the future. In this presentation, I will discuss the basic principles underlying the successful design of ligand-targeted therapeutics, using multiple examples of ligand-targeted drugs currently in the clinic or late preclinical development to illustrate each major principle.

9:10 Centyrins: A Novel Scaffold for New TherapeuticsKaryn O’Neil, Ph.D., Chief Scientific Officer, Centyrex Venture, Johnson & JohnsonAlternative scaffolds share properties with antibodies in terms of their specificity and potency and with small molecules in terms of simplicity and size. The Centyrin platform, a consensus fibronectin domain, has been optimized to enable selection of Centyrins that inhibit multiple classes of proteins. We will describe how the biophysical properties of Centyrins make them ideal for novel therapeutic applications including drug conjugates and targeted nanoparticles.

9:40 Development of Novel Targeted Cancer Therapies with BIND Accurins™Jeff Hrkach, Ph.D., Senior Vice President, Technology Research & Development, BIND BiosciencesAccurins™ are a new class of highly selective targeted therapeutics, precisely engineered to have long circulation half-lives, high drug loading levels, finely tuned pharmacokinetics and surface-bound targeting ligands that bind selectively to cell-surface receptors on diseased cells. Accurins achieve high and prolonged concentrations creating optimal therapeutic indices. BIND is developing Accurin targeted therapeutics, primarily focused on oncology.


10:40 NanomAbs: New Leap in Antibody-Drug ConjugatesStephane E Allard, Ph.D., CMO, EpiCept Corp.NanomAbs platform is a conjugate of a targeting moiety to chemotherapeutic drug loaded polymeric nanoparticles. Development of Immune’s linker technology enabled the optimized drug to mAb ratio using the mAb as a targeting moiety. Extensive preclinical research recently showed improved anti-cancer effect in several cancer models and beneficial safety profile. Leveraging the technology for targeted combo cancer drug delivery is underway showing synergistic effects in advanced tumors.

11:10 Addressing the Delivery Challenge for siRNA TherapeuticsMarian Gindy, Ph.D., Director, Pharmaceutical Sciences, Merck Research LaboratoriessiRNA represents a promising therapeutic strategy, with potential to access molecular targets considered undruggable by small molecule and protein therapeutics. Challenge toward realizing this technology is the safe and effective delivery of siRNA to target tissues. siRNAs properties prevent diffusion across most cell membranes, requiring the use of delivery systems to confer intracellular access. Presentation will illustrate the development of such oligonucleotide delivery technologies.

11:40 Nanopharmaceutical Delivery of Toxic and Biodegradable Drugs: Case Studies of Camptothecin and siRNASonke Svenson, Ph.D., Director, Research, Cerulean Pharma, Inc.Cerulean’s nanopharmaceutical technology consists of polymeric nanoparticles carrying drug molecules conjugated to the constituent polymers. Encapsulation protects the body from toxic drugs, and protects biodegradable drugs from enzymatic or hydrolytic metabolism inside the body. Chemical conjugation of drug molecules to the carrier prevents burst release in favor of controlled drug release from the nanopharmaceuticals.


IMAGING & ADVANCED CHARACTERIZATION TOOLS IN DRUG DELIVERY RESEARCH


2:10 Visualizing Targeted Delivery of Polymer-Drug ConjugatesBan-An Khaw, Ph.D., George D. Behrakis Professor of Pharmaceutical Sciences, Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern UniversityMost chemotherapeutic agents are not target specific. They can be made target specific by antibody-drug conjugate technology. To improve targeting ability and highly efficient delivery of drugs, bispecific antibody complex pretargeting and targeting with polymer-drug conjugates (PDC) was developed. Targeting with radioisotope labeled or chemotherapeutic PDCs enabled visualization of very small cancer lesions, and therapy was as efficient as free drug but has no non-target toxicity respectively.



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2:40 PET Imaging of Antibodies for Evaluation of Distribution, Clearance and PK in vivoVania Kenanova, Ph.D., Head, Preclinical PET/SPECT/CT Imaging Laboratory, Global Imaging Group, Novartis Institute for Biomedical ResearchQuantitative PET imaging is routinely used for evaluation of antibodies in vivo. This involves radiolabeling of the antibody either by attaching radionuclide directly (I-124 to Tyr) or via a chelate (NODAGA [Cu-64], desferal [Zr-89]). The PET image is a result of the catabolism and clearance of the protein, chelate and radiolabel. This talk will go over the distribution and clearance of radiolabel alone, radiolabel-chelate and radiolabel-(chelate)-protein for PK analysis.

3:10 Sponsored Presentation (Opportunity Available)


4:10 Nanoscale Evaluation of Novel Dendritic Nanocarriers for Cancer TargetingSeungpyo Hong, Ph.D., Assistant Professor of Pharmaceutics and Bioengineering, Department of Biopharmaceutical Sciences, University of Illinois College of PharmacyAlthough a myriad of promising nanocarriers have been recently developed, targeted drug delivery to cancerous regions still remains a tremendous challenge. This presentation will focus on new drug delivery platforms based on dendritic structures to take advantage of multivalent binding and enhanced self-assembly. Fundamental understanding as well as biological testing of those novel nanocarriers will be discussed.


When and Where to Introduce Delivery into the Product Development PipelineBobby Singh, Ph.D., Chief Technology Officer, Corium International, Inc.

Bringing Down the Silos•Technology and strategy selection and implementation•Collaboration to innovate and improve preclinical to clinical translation•The Science of Particle Size Analysis and its Impact on Translational Performance

Moderator to be Announced

Effect of Particle Shape, Size and Density on a Nanoparticle’s Tendency to Escape•Why do several successful preclinical technologies fail in clinic•Tools and technologies for characterization and data interpretation•Working with a Very Small Amount of API: Pros and Cons of Miniaturization

Moderator to be Announced

Working with a Small Amount of API: Pros and Cons of MiniaturizationWeiguo Dai, Ph.D., Scientific Director, Fellow, Drug Product Development, Johnson & Johnson•Advantages and disadvantages of miniaturization and automation in

drug development•Data correlation between early development and late development studies and how

it can hasten or delay product development timelines•Evolving role of preformulation in faster development

5:40 Close of Day

ThUrsDAY, JUNE 6


NEXT-GENERATION DELIVERY TECHNOLOGIES


8:40 Breaching the Blood-Brain Barrier: Novel Drug Delivery Strategies for the CNSPankaj Karande, Ph.D., Assistant Professor, Department of Chemical & Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic InstituteDrug delivery to the brain has been a long-standing challenge in the treatment of neurological and neurodegenerative disorders due to the formidable blood-brain barrier (BBB). I will specifically discuss the design and discovery of peptides that bind to one such protein, transferrin, as a way of chaperoning drugs from systemic circulation into the brain. Peptide-mediated delivery is an efficient and significantly less invasive alternative to current methods of CNS delivery.

9:10 Next-Generation Transdermal Technologies for Needle-Free Delivery of BiologicsBobby Singh, Ph.D., Chief Technology Officer, Corium International, Inc.Despite the increasing patient acceptance and market success of biologic drugs, significant challenges remain with their mode of administration and commercial distribution. This presentation will provide an overview of transdermal technologies capable of overcoming a number of challenges associated with needle-based liquid injections.

9:40 Developing Next Generation Anticancer Drugs Using NVIGEN Sponsored by Nanoparticle-Imaging-Delivery Platform Aihua Fu, Ph.D., CEO, NVIGEN Inc.NVIGEN Inc developed a unique nanoparticle-imaging-delivery platform utilizing pricisely engineered nanoparticle properties. Our nanoparticles demonstrated extremely enhanced permeability and retention effect with over 30 days cancer region retention following single intravenous injection, controllable pharmacokinetics, and superior magnetic, fluorescent and cancer targeting properties. How to leverage such powerful platform for next generation anticancer drug development will be discussed.


OVERCOMING CHALLENGES IN THE DELIVERY OF POORLY SOLUBLE DRUGS

10:40 FEATURED PRESENTATION: Oral Delivery of Poorly Water-Soluble Drugs: Approaches to Overcome the Solubility Limitation to Enable a Successful Drug Product DevelopmentMunir Hussain, Ph.D., Distinguished Research Fellow, Drug Product Science & Technology, Bristol-Myers Squibb Co.Early identification of the underlying factors for low oral absorption of a drug candidate is critical to successful product development. Factors affecting oral absorption of poorly water-soluble drugs, including the role of poor wetting/solvation vs. crystal lattice energy will be addressed. Approaches used to enhance absorption according to the underlying mechanism for poor absorption will be discussed together with case studies that illustrate application of the various approaches.



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11:10 Novel Amorphous Nanoparticle Technology: Successes and ChallengesWeiguo Dai, Ph.D., Scientific Director, Fellow, Drug Product Development, Johnson & JohnsonAmorphous nanoparticle delivery technology has emerged to improve oral availability of poorly water soluble compounds. It exhibits the behavior of nanoparticles and amorphous formulation approach, and therefore increases solubility and dissolution rate, leading to an improvement in oral absorption of such compounds. The presentation will discuss the recent progresses and key challenges in an amorphous nanoparticle approach from preclinical to commercialization.

11:40 “Hot Melt Extrusion” as Enabling Technology for Development of Poorly Soluble DrugAnjali Agrawal, Ph.D., Senior Principal Scientist, Pharmaceutical R&D, Boehringer Ingelheim Pharmaceuticals, Inc.Hot melt extrusion is an efficient technology involving intensive mixing of a drug with a carrier at elevated temperature in continuous mode to create amorphous solid dispersion with enhanced bioavailability potential for poorly soluble drug. The applicability of HME technology will be illustrated in this talk through a case study focusing on systematic approach to develop solid dispersion by HME process, performance assessment of HME dispersion, and scale up considerations.



1:40 Prediction of the Potential Issues of Bioperformance in Human: Stories of Difficult MoleculesKung-I Feng, Ph.D., Principal Scientist, Basic Pharmaceutical Sciences, Merck Sharp & Dohme Corp.Prediction of the potential issues of bioperformance in human at the early stage is critical to success in development. Issues including drug-drug-interaction, insufficient oral absorption, food effect, and PK variability could lead to failure in development. The underlying factors contributing to these issues will be discussed. Case studies will be presented to demonstrate the correlations between the underlying factors to bioperformance.

2:10 Overcoming Bioavailability Hurdles for Poorly Soluble Clinical Candidates Using Non-Conventional DeliveryChitra Telang, Ph.D., Principal Scientist, Pharmaceutical R&D, Boehringer Ingelheim Pharmaceuticals, Inc.Solubilizing drug candidates for delivery to clinic continues to pose challenges. High dose demands for certain therapeutic areas warrants use of non-conventional technologies and a departure from crystalline dosage forms. It is important to fit an appropriate solubilization technology to the drug substance based on physicochemical considerations. This presentation will highlight case studies spanning solubilization approaches of prodrugs, lipid-based emulsions and amorphous dispersions.

2:40 Facile Production of Multifunctional Nanoparticles for Hydrophobic Therapeutics by Block-Copolymer-Directed Rapid PrecipitationRobert K. Prud’homme, Ph.D., Professor, Department of Chemical & Biological Engineering, Princeton UniversityA process, Flash NanoPrecipitation, involving rapid precipitation with block copolymer-directed assembly produces highly loaded nanoparticles, with multifunctional capabilities in a single step. The PEG layer creates long-circulating time and the PEG chain with terminal ligands enables targeting. The use of hydrolytically unstable linkers enables the controlled release of drug(s) from particles to create “drug cocktails” in a way that has not been possible before.

3:10 From Nanoparticle Shapes to A Minimal ‘Self’ Peptide That Inhibits Clearance and Enhances DeliveryDennis E. Discher, Ph.D., Robert D. Bent Chaired Professor, Department of Chemical and Biomolecular Engineering, University of PennsylvaniaNanoparticles of diverse shapes have emerged as carriers of some potential for delivery of soluble and insoluble compounds. However, all foreign particles are cleared by phagocytes that also must recognize and avoid clearance of “self” cells. CD47 is reportedly a “marker of self”, and we have reduced it to synthetic peptides.


Inaugural




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integrated Drug Safety risk AssessmentsPredicting Drug-Induced Organ Toxicities Using Functional Assays, Models and Markers

TUEsDAY, JUNE 4


EFFECTIVENESS OF AN INTEGRATED APPROACH TO SAFETY


8:40 FEATURED PRESENTATION: Is Drug Safety Really a Problem in 2013?Paul B. Watkins, M.D., Director, Hamner-UNC Institute for Drug Safety Sciences, University of North Carolina at Chapel HillData from 2008-2010 suggest that safety, including unfavorable risk to benefit ratio, account for only about 20% of clinical development failures. In addition, no drugs approved for marketing in the last 5 years have been permanently withdrawn from the market due to safety concerns. It is not correct to interpret these data as the result of great advances in preclinical safety testing or clinical safety signal detection. Concerns about safety have dramatically altered the drug development landscape such that important new drugs are never advanced into the clinic, doses used in clinical trials are too low to be efficacious, and the size, duration and costs of clinical drug development have ballooned. Concerns about drug safety remain the major bottleneck in the delivery of affordable new drugs to the patients who need them.

9:10 Endothelin-A Receptor Antagonists and Liver Toxicity: A Focus on SitaxentanJohn Erve, Ph.D., D.A.B.T., Former Principal Scientist, DMPK, Elan Pharmaceuticals, Inc.Sitaxentan (Thelin™) an endothelin-A receptor antagonist (ERA) marketed for pulmonary arterial hypertension and considered to be less toxic than the ERA Bosentan (Tracleer™) was withdrawn in 2010 due to eight deaths from severe liver toxicity. Ambrisentan (Letaris™), the newest ERA, is a propanoic acid and has a lower risk of liver toxicity than either bosentan or sitaxentan which are sulfonamides. Studies to better understand the mechanisms of ERA hepatotoxicity are currently underway.

9:40 Opportunities for Integrated Safety Assessment - Early and OftenSanjeev Thohan, Ph.D., Senior Research Fellow, Preclinical and Translational Sciences, Novartis Institute for Biomedical ResearchAs an industry, we have established comprehensive in vitro/in silico approaches for generating “on and off target” profiles for our drug candidates. An often overlooked opportunity to evaluate safety endpoints are the early pharmacology and efficacy studies. These studies often entail substantial dose escalations and can be effectively leveraged to understand the early changes with not only tissue histology but also biomarkers without compromise to study endpoints.

10:10 Coffee Break

10:40 A More Holistic Approach to Drug Design Concepts in Minimizing Cell-Based Target Organ ToxicityMichael Aleo, Ph.D., Research Fellow, Investigative Toxicology, Pfizer Global Research & DevelopmentYvonne Will, Ph.D., Associate Research Fellow, Compound Safety Prediction, Pfizer Global Research & DevelopmentMany mechanisms such as mitochondrial dysfunction, ER stress, inflammation, HERG have been identified as contributors to such toxicities. However, it has become evident that none of these mechanisms alone will accurately predict a particular organ toxicity or severity of toxicity and that only a risk matrix approach could potentially provide advancement to this dilemma. Here, we provide examples of such a risk matrix approach and how it can change upon exposure projection.

11:40 Quintiles CardioCheck: Multi-Parameter Sponsored by Preclinical Profiling for Potential Cardiotoxicity of Drug CompoundsKimberly Doherty, Principal Research Associate, QuintilesHigh drug attrition rates are often due to toxic effects on the heart. Earlier preclinical assessment can reduce costly drug withdrawals and improve patient safety. Current methods of assessing cardiotoxicity are limited since they only assess a single mechanism or are done in less predictive animal models. Quintiles’ CardioCheck provides a comprehensive means of estimating cardiotoxic potential by assessing multiple parameters that are important in cardiac health and function in a human cardiomyocyte model.

11:55 pm Sponsored Presentation (Opportunity Available)

12:10 pm 12:10 pm Use of Micropatterned Cocultures (MPCC) to Sponsored by

Detect Compounds That Cause Drug-Induced Liver Injury in HumansYvonne Will, Ph.D., Associate Research Fellow, Compound Safety Prediction, Pfizer Global Research & DevelopmentClinical DILI can be predicted with a sensitivity of ~50% and a false positive (FP) rate of ~5% using 24-h cultures of sandwich-cultured primary human hepatocytes and imaging of four cell injury endpoints (Xu et al., 2008). We hypothesized that long-term drug dosing in a functionally stable model of primary hepatocytes could provide for increased predictivity over short-term dosing paradigms.


1:30 PLENARY KEYNOTE PANEL DISCUSSION: Advancing Pharma R&D through Communication & Collaborations: Bio-Connectivity at Work


NEW MODELS FOR PREDICTING DRUG SAFETY

3:55 Chairperson’s Opening RemarksYvonne Will, Ph.D., Associate Research Fellow, Compound Safety Prediction, Pfizer Global Research & Development

4:00 Systematic Approaches to Organ Specific Toxicities Using ZebrafishCalum MacRae, M.D., Ph.D., Physician-Scientist, Department of Medicine, Cardiovascular Research Center, Brigham and Women’s Hospital; Associate Professor, Harvard Medical SchoolMany drug effects are a result of complex phenomena; using the larval zebrafish it is possible to model much of drug efficacy and toxicity in a native context and at throughputs compatible with discovery phase screening. We have exploited a range of assay approaches to move towards a ‘TOX’ reporter zebrafish line capable of the interrogation of core organ specific toxicities in a manner that ultimately may allow balancing of efficacy and toxicity during the early phases of drug discovery.

4:30 Organs-on-Chips for Predicting Drug Toxicity and EfficacyDanilo Tagle, Ph.D., Associate Director for Special Initiatives, National Center for Advancing Translational Sciences, National Institutes of HealthOrgans-on-chips are bio-engineered microdevices that represent functional units of human organs such as, the lung, liver and heart, modeling both cell architecture and physiology. This unique platform could ensure that safe and effective therapeutics are identified sooner, and ineffective or toxic ones are rejected early in the development process. To accomplish this goal, the NIH has partnered with DARPA and FDA to improve the process for predicting whether drugs will be safe in humans.



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5:00 Janus Faces of Safety & Efficacy Sponsored by

Arthur M. Brown, Ph.D., President & CEO, ChanTest Corporation


6:30 Close of Day

WEDNEsDAY, JUNE 5


EARLY DE-RISKING: WHAT TO EXPECT FROM PREDICTIVE TESTING?


8:40 FEATURED PRESENTATION: Safety Pharmacology at the CrossRoadsGary Gintant, Ph.D., Research Fellow, Department of Integrative Pharmacology, Global Pharmaceutical Research & Development, AbbVieSafety Pharmacology is facing evolutionary pressures as climates change within the industry. Safety studies now demand efforts across a wider spectrum of drug discovery efforts, from early compound selection to possible post-marketing follow-up studies. Mechanistic understandings of important safety liabilities, flexible “just in time” assays, and understanding assay limitations are essential in choosing the correct approaches and managing expectations for a successful transformation.

9:10 Integrating Cardiovascular Safety Pharmacology and ToxicologyJonathan Heyen, Principal Scientist, Global Safety Pharmacology, Pfizer Global Research & DevelopmentCardiovascular attrition continues to be a challenge in advancing compounds. In an effort to better understand potential cardiovascular liabilities of novel compounds, there has been an integration of cardiovascular endpoints into multiple safety and efficacy studies. Various in vitro strategies coupled with jacketed telemetry and imaging technologies have helped to shape the integration of safety pharmacology into these studies and have proven useful in decision-making and compound advancement.

9:40 Cellular Impedance Measures of Cardiomyocyte Cultures for Screening Kinase InhibitorsMatthew Peters, Ph.D., Principal Scientist, Safety Assessment, AstrazenecaThere is an urgent need for novel in vitro assays that enable earlier and broader testing for cardiovascular activity. Data obtained using label-free impedance assays with primary and stem cell-derived cardiomyocytes reveal a novel combination of features, including sensitivity to contractile activity, versatile data analysis, robust/translatable data, and sufficient throughput to be a valuable addition to the cardiovascular screening arsenal, with particular value for kinase inhibitors.


10:40 Organs on Chips: Advances and Potential Application in Pharmacology, DMPK, Drug Safety and EfficacyAnthony Bahinski, Ph.D., MBA, FAHA, Lead Senior Staff Scientist, Advanced Technology Team, Wyss Institute for Biologically Inspired Engineering, Harvard University Center for Life SciencesBiomimetic ‘Organ-on-Chip’ microsystems technologies that recapitulate organ-level functions offer exciting new approaches to attack fundamental questions in biology, create novel disease models, and develop in vitro surrogates for regulatory sciences. These engineered cell culture microenvironments utilize human cells and go beyond conventional 3D in vitro models by recapitulating the tissue-tissue interfaces, spatiotemporal chemical gradients, and mechanical microenvironments of living organs.

11:10 Prediction of P450 Inhibition, Metabolic Stability and Isoform Selectivity with a Newly Derived in silico TechnologyEmanuele Carosati, Ph.D., Researcher, Department of Chemistry, University of Perugia, ItalyIn the framework of the Human Cytochrome P450 Consortium, aimed at solving important problems in the predictive metabolism of potential drug candidates, we developed a novel in silico technology to model P450 inhibition, stability and isoform selectivity. This technology encodes xenobiotics’ orientations within the catalytic site into newly derived, P450-dedicated, molecular descriptors, core of quantitative models that can be easily trained with in-house data.

11:40 Role of Electrostatic Potential in the In Silico Prediction of Molecular Bioactivation and MutagenesisKevin Ford, Ph.D., MRSC, DABT, Safety Assessment, Genentech, Inc. Electrostatic potential (ESP) is a useful physicochemical property of a molecule that provides insights into inter- and intra-molecular associations, as well as prediction of likely sites of electrophilic and nucleophilic metabolic attack. Knowledge of sites of metabolic attack is of importance in DMPK research since drugs frequently fail in clinical trials due to the formation of bioactivated metabolites which are often difficult to measure experimentally due to their reactive nature and relatively short half-lives. Computational chemistry methods have proven invaluable in recent years as a means to predict and study bioactivated metabolites without the need for chemical syntheses, or testing on experimental animals. Additional molecular properties (heat of formation, heat of solvation and ELUMO - EHOMO) will be discussed as complementary indicators of the behavior of metabolites in vivo. Five diverse examples will be presented (acetaminophen, aniline/phenylamines, imidacloprid, Nefazodone and vinyl chloride) which illustrate the utility of this multi-dimensional approach in predicting bioactivation, and in each case the predicted data agreed with experimental data described in the scientific literature. A further example of the usefulness of ESP is provided by an examination of the use of this parameter in providing an explanation for the sites of attack of the nucleic acid cytosine. Exploration of sites of attack of nucleic acids is important as adducts of DNA are frequently

12:10 pm Organotypic 3D Co-Culture models - Sponsored by From Hepatic Models Towards a Complete 3D Toxicology PanelJan Lichtenberg, Ph.D., CEO, InSphero Inc.Long-term, repeat dose and inflammation-mediated toxicity are new applications enabled by multi-cell-type 3D microtissues. Examples will be discussed where the physiological relevance of hepatocyte co-cultures allows picking up toxicity where monolayers fail. In addition, the characterization of new 3D microtissues based on HepaRG and iPS cardiomyocytes is presented.

12:25 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

TRANSLATIONAL CHALLENGES: CAN WE TRULY BRIDGE THE GAP?


2:10 FEATURED PRESENTATION: Predicting, Minimizing and Avoiding Human Adverse Drug ReactionsGerry Kenna, Ph.D., Independent Consultant; Former Principal Scientist, Hepatic Target Organ Strategy Lead, Safety Assessment, Molecular Toxicology, AstraZenecaThere is an unmet need for approaches that can be used in drug discovery and development to design and select compounds that have minimal propensity to cause toxicity, and also for approaches that enable prediction and early detection of at risk individuals. Historically, these enormous challenges have been tackled by individual research groups which have tended to work in isolation and have lacked the volume and breadth of expertise needed to make substantial progress. A more promising way



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forwards is via pre-competitive consortia that involve leading academic and industrial scientists and are funded jointly by the public and private sectors. The potential opportunity provided by this new approach will be highlighted.

2:40 Practical Applications of DILIsym™, a Mechanistic Model of Drug-Induced Liver InjuryYuching Yang, Ph.D., Research Scientist, The Hamner-UNC Institute for Drug Safety SciencesDILIsym™ is a mechanistic, multi-scale, mathematical model developed to assist in the safety characterization of compounds in clinical development. The primary goals for the model include understanding how in vitro toxicity assay results translate to preclinical animal models, the relevance of preclinical results for humans, and how biomarker results translate to patient safety. Practical uses for DILIsym™ in drug development and in communications with regulator agencies will be presented.

3:10 Nonclinical Safety Assessment of Biologics: Sponsored by Species Selection Beyond the Standard ApproachJoerg Bluemel, Ph.D., Director, Toxicology, Biologics Safety Assessment/Translational Sciences, MedImmune LLCThe growth of biologics in drug development has lead to increased demand for non-clinical safety assessment studies of biologics. However, there is increased public and regulatory scrutiny, and difficulties regarding the use of non-human primates. Therefore, there is an urgent need to investigate the suitability of alternative species, like the minipig, for non-clinical safety assessment of biologics. This presentation will highlight the current status of research on alternative test species, as well as current gaps.


4:10 Gaps and Opportunities in Nonclinical Safety Pharmacology TestingWendy Halpern, D.V.M., Ph.D., DACVP, Senior Scientist/Pathologist, Genentech, Inc.


Effective Utilization of Predictive Models for Safety AssessmentsModerators: Gary Gintant, Ph.D., Research Fellow, Department of Integrative Pharmacology, Global Pharmaceutical Research & Development, AbbVieJonathan Heyen, Ph.D., Principal Scientist, Global Safety Pharmacology, Pfizer Global Research & Development

Safety Concerns Surrounding Biologics Drug DevelopmentModerators: Noël Dybdal, D.V.M., Ph.D., DACVP, Director, Safety Assessment, Genentech, Inc.Joerg Bluemel, Ph.D., Director, Toxicology, Biologics Safety Assessment/Translational Sciences, MedImmune LLC

Tackling Translational Challenges in Drug Safety TestingModerators: Gerry Kenna, Ph.D., Independent Consultant; Former Principal Scientist, Hepatic Target Organ Strategy Lead, Safety Assessment, Molecular Toxicology, AstraZenecaPaul B. Watkins, M.D., Director, Hamner-UNC Institute for Drug Safety Sciences, University of North Carolina at Chapel Hill

5:40 Close of Day

ThUrsDAY, JUNE 6


HOW MUCH OF A SAFETY CONCERN IS POSED BY BIOLOGICS?


8:40 FEATURED PRESENTATION: Challenges to Safety Assessment and Toxicity with New Generation of Oncology BiologicsRakesh Dixit, Ph.D., DABT, Vice President, Research & Development; Global Head, Biologics Safety Assessment, Pathology & LAR, MedImmuneKathleen McKeever, Ph.D., DABT, Director, Biologics Safety Assessment, MedImmuneTargeted biologics including antibody-drug conjugates and immunotherapeutics have revolutionized the treatment options and improved survival rates for cancer patients. While the benefits from these next generation of oncology molecules are unprecedented, there is recognition of new unique toxicities to immune system, endocrine, hepatic and gastrointestinal toxicities that must be carefully managed. Case studies will discuss these emerging safety concerns and ways to manage them.

9:10 Addressing Challenges and Embracing Opportunities in the Safety Assessment of BiologicsNoël Dybdal, D.V.M., Ph.D., DACVP, Director, Safety Assessment, Genentech, Inc.The biology and pharmacology of biologics require openness to case-by-case evaluation in developing a successful preclinical development program, and can demand willingness to diverge from traditional toxicology design. This approach has fostered opportunities for refining and improving preclinical development. Today’s presentation will explore examples of some areas of biologic preclinical development that continue to attract debate, including species selection and immunogenicity assessment.



11:40 Nonclinical Safety Assessment of Two Proposed Biosimilar Monoclonal AntibodiesAnne Ryan, Ph.D., Executive Director, Drug Safety Research and Development, Pfizer, Inc.The nonclinical study design, based upon available biosimilar guidances, regulatory input and available innovator data, for two proposed biosimilar antibodies will be presented. In addition, study data for each molecule will be presented and compared with that of the marketed innovator products.

12:10 PANEL DISCUSSION: Safety Testing for Biologics: Where are the Gaps?Participants: Session Speakers


USE OF MOLECULAR IMAGING FOR DRUG SAFETY ASSESSMENTS




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1:40 FEATURED PRESENTATION: Noninvasive Traditional and Novel Methods to Assess Chemotherapy-Related Cardiac DysfunctionEugene Storozynsky, M.D., Ph.D., Assistant Professor of Medicine, Program in Heart Failure and Transplantation Division of Cardiology, University of Rochester Medical CenterThere are close to 25 chemotherapeutic agents that have been associated with chemotherapy-induced cardiotoxicity. Early recognition of chemotherapy-induced cardiotoxicity is important to prevent development of irreversible cardiomyopathy. I will discuss surveillance methods including electrocardiographic, echocardiographic, and nuclear imaging to monitor for preclinical development of LV dysfunction. I will also discuss possible treatment strategies to prevent progression.

2:10 Development of Non-Invasive Neurotoxicity Biomarkers Using in vivo Magnetic Resonance Imaging (MRI)Serguei Liachenko, Ph.D., Director, Bio-Imaging, National Center for Toxicological Research, Food and Drug AdministrationCurrent approaches in the analysis of neuropathology in support of new drug submissions to the FDA (the use of several arbitrary histology slices) can sometimes result in false-negative findings, meaning that small localized lesions can easily be missed. Non-invasive MRI can provide unique information about the structure and function of the whole brain in vivo with high resolution and contrast and serve as the basis of the translatable neurotoxicity biomarkers.

2:40 In vivo Evaluation of Drug Effects in the Kidney and Liver Using Intravital Multiphoton MicroscopyKenneth Dunn, Ph.D., Associate Professor of Medicine and Biochemistry, Indiana UniversityCostly drug failures due to unforeseen toxicity highlight the need to understand the mechanisms of drug actions in vivo. Since conventional readouts of in vivo toxicity seldom provide clues as to the initiating events and sequence of injury processes, mechanistic studies are conducted in cultured cells, systems that incompletely represent the relevant in vivo environment of drug actions. We use intravital microscopy to analyze the acute effects of drugs on the liver and kidney.

3:10 High-Throughput Toxicity Screening with Silicon Microelectrode Arrays and Lens-Free Imaging SolutionsDries Braeken, Ph.D., Research & Development Team Leader, Bio-Nano-Electronics, Imec, BelgiumWe present a new silicon microelectrode array platform that makes it feasible to record intracellular action potentials from thousands of cells in a non-invasive manner. This assay yields information about ion channel activity with high precision and in an automated fashion. We also present a lens-free imaging method that can be integrated and is significantly cheaper than conventional microscopy, while providing detailed information and a large field of view.


6th Annual


Lead Sponsoring Publications

Sponsoring Publications Media Partner

Sponsoring Organization

Drug Safety Executive CouncilSafer Medicines. Faster.

™

Web Partners



http://www.ondrugdelivery.com

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Molecular imaging in Drug Discovery and DevelopmentIntegrating Molecular Imaging Technologies to Improve Preclinical Findings

Recommended Short Course* Roadmap for Outsourcing of Preclinical Imaging (Complementary) * Separate registration required; please see page 4 for details

TUEsDAY, JUNE 4


LATEST TECHNOLOGICAL ADVANCES


8:40 The Power of Imaging in Drug DiscoveryThomas Bocan, Ph.D., Senior Director, Preclinical Imaging, Pharmatherapeutics Precision Medicine, Worldwide Research & Development, Pfizer, Inc.

9:10 New Developments in CT Imaging: Novel, Nanoparticle Contrast Media, Multi-Energy Scanners and Iterative ReconstructionDavid Cormode, Ph.D., Assistant Professor, Radiology, University of PennsylvaniaIn the past five years the field of nanoparticle CT contrast agents has rapidly grown. This is starting to allow molecular imaging with CT. In addition, CT scanner technology is improving to allow specific and sensitive detection of contrast media. This presentation will cover the recent advances in the field and offer a perspective on future developments.

9:40 Molecular and Cellular MRIErik M. Shapiro, Ph.D., Research Director, Department of Radiology, Michigan State UniversityThis presentation will cover: MRI contrast agents for Molecular and Cellular MRI; Strategies for using targeted contrast agents for Molecular MRI of cancer and other pathologies; Magnetic cell labeling and MRI-based cell tracking; Quantification schemes for Molecular and Cellular MRI; A path towards clinical translation for experimental Molecular and Cellular MRI paradigms.

10:10 Coffee Break

10:40 Emerging Technologies in Imaging QuantitationJames Gee, Ph.D., Professor and Director, Penn Image and Computing Science Laboratory, University of PennsylvaniaAdditional Instructors to be Announced

11:10 Nature-Derived Nanoparticles for Targeted Diagnosis and TherapyWillem Mulder, Ph.D., Associate Professor of Radiology, Director, Nanomedicine Program, Translational and Molecular Imaging Institute, Mount Sinai School of MedicineLipoproteins, natural nanoparticles that function as fat transporters in the human body, can be used as models to create multifunctional nanoparticles that inherently have specificity for atherosclerosis. Chemical modifications can be introduced to alter their specificity and reroute such nanoparticles to other epitopes and diseases of interest. The payload of lipoprotein-derived nanoparticles may vary from small hydrophobic or amphiphilic molecules to hydrophobically coated nanocrystals, to introduce diagnostic and/or therapeutic features.



1:30 Plenary Keynote Panel Discussion: Advancing Pharma R&D through Communication & Collaborations: Bio-Connectivity at WorkKarim Dabbagh, Ph.D., Executive Director and Head, External R&D and Innovation Research Units, Pfizer Worldwide R&DGlen N. Gaulton, Ph.D., Professor, Pathology and Laboratory Medicine; Executive Vice Dean and CSO, Perelman School of Medicine, University of PennsylvaniaPeter Pitts, President and Co-Founder, Center for Medicine in the Public Interest


4:00 Fluorine-18 Chemistry Fuel the Discovery of Novel PET TracersScott Edwards, Ph.D., Vice President and General Manager, R&D, SciFluor Life Sciences, LLCInnovative methodologies aimed at improving the selectivity and yield for the incorporation of F-18 into small molecules, peptides, and small proteins are thus an active area of research, including: metal-assisted electrophilic fluorination; “Click” chemistry, and fluorophilic bifunctional chelators for directly labeling biologics. This presentation will review the new F-18 methodologies and provide perspective on their application in the synthesis of new tracers as translational research and development tools.

4:30 Panel Discussion: The Future of Molecular Imaging in Drug Discovery and Development Moderator: Erik M. Shapiro, Ph.D., Research Director, Department of Radiology, Michigan State University



6:30 Close of Day

WEDNEsDAY, JUNE 5


APPLICATIONS OF MOLECULAR IMAGING


8:40 Centyrins, a Novel Protein Scaffold with Ideal Properties for Molecular Imaging ApplicationsJeannie Rojas, Ph.D., Director, Janssen R&DCentryrin’s are a novel class of alternative scaffold proteins developed to be the next generation of biological therapeutic molecules. However, Centyrin molecules have biophysical properties which are ideally suited for molecular imaging applications. In this presentation, both in vivo and in vitro data will be presented to showcase the highly desirable biophysical properties of the Centyrin molecule, which make this platform ideal for imaging applications.

9:10 The Importance of Molecular Imaging and Correlative Studies in the Evaluation of Biologicals for the Treatment and Diagnosis of Visceral AmyloidosisJonathan Wall Ph.D., Professor of Medicine, Human Immunology and Cancer Program, Director, Amyloid and Preclinical Molecular Imaging Laboratory, University of Tennessee Graduate School of MedicineThis talk will describe the use of molecular imaging and correlative studies in the development of novel biological agents for the treatment and detection of visceral amyloid disease. Specifically, this talk will discuss the preclinical development of peptide radiotracers and clinical evaluation of a therapeutic monoclonal antibody for amlyoidosis of the visceral organs.



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9:40 Characterization of H3 Receptor Occupancy for Bavisant (JNJ-31001074) Using PET ImagingMichael A. Letavic, Scientific Director and Fellow, Neuroscience, Janssen Research and Development, LLCThe pre-clinical characterization of the potent and selective histamine H3 antagonist Bavisant (JNJ-31001074) will be presented emphasizing the use of imaging techniques to assess drug levels required for target engagement and to assist in human dose predictions. Human PK and PET imaging data that corroborate the predicted human PK profile and demonstrate robust target engagement in human will also be discussed.


IMAGING IN PAIN THERAPEUTICS DEVELOPMENT

10:40 Imaging Pain and AnalgesicsDavid Borsook, M.D., Ph.D., Director, Center for Pain and the Brain, Harvard Medical School

11:10 The Utility of Nonhuman Primates in Pain Research Sponsored by

David Hygate, Team Leader, Neurobiology & CNS Safety, Maccine Pte Ltd Herein we describe the development of a non-human primate neuropathic pain model as well as the use of fMRI in an inflammatory pain model as drug discovery tools with the potential for translation to early clinical studies.

11:40 Pharmacologic Modulation of Brain Mechanisms Operative in Humans with Chronic PainRichard Harris, Ph.D., Assistant Professor, Anesthesiology, University of MichiganBrain imaging studies implicate disruption of central chemistry and function in chronic pain patients. Demonstration of changes in these outcomes to pharmacologic intervention is needed. I will present data on altered brain neurochemical and connectivity patterns during pharmacologic treatment of chronic pain patients diagnosed with fibromyalgia. These data point towards the future development of personalized analgesic therapies using neuroimaging.


IMAGING & ADVANCED CHARACTERIZATION TOOLS IN DRUG DELIVERY RESEARCH


2:10 Visualizing Targeted Delivery of Polymer-Drug-ConjugatesBan-An Khaw, Ph.D., George D. Behrakis Professor of Pharmaceutical Sciences, Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern UniversityMost chemotherapeutic agents are not target specific. They can be made target specific by antibody-drug- conjugate technology. To improve targeting ability and highly efficient delivery of drugs, bispecific antibody complex pretargeting and targeting with polymer-drug conjugates (PDC) was developed. Targeting with radioisotope labeled or chemotherapeutic PDCs enabled visualization of very small cancer lesions, and therapy was as efficient as free drug but has no non-target toxicity respectivel

2:40 PET Imaging of Antibodies for Evaluation of Distribution, Clearance and PK in vivoVania Kenanova, Ph.D., Head, Pre-clinical PET/ SPECT/CT Imaging Laboratory, Global Imaging Group, Novartis Institute for Biomedical ResearchQuantitative PET imaging is routinely used for evaluation of antibodies in vivo. This involves radiolabeling of the antibody either by attaching radionuclide directly (I-124 to Tyr) or via a chelate (NODAGA [Cu-64], desferal [Zr-89]). The PET image is a result of the catabolism and clearance of the protein, chelate and radiolabel. This talk will go over the distribution and clearance of radiolabel alone, radiolabel-chelate and radiolabel-(chelate)-protein for PK analysis.



4:10 Nanoscale Evaluation of Novel Dendritic Nanocarriers for Cancer TargetingSeungpyo Hong, Ph.D., Assistant Professor of Pharmaceutics and Bioengineering, Department of Biopharmaceutical Sciences, University of Illinois College of PharmacyAlthough a myriad of promising nanocarriers have been recently developed, targeted drug delivery to cancerous regions still remains a tremendous challenge. This presentation will focus on new drug delivery platforms based on dendritic structures to take advantage of multivalent binding and enhanced self-assembly. Fundamental understanding as well as biological testing of those novel nanocarriers will be discussed.


5:40 Close of Day

ThUrsDAY, JUNE 6


IMAGING IN CANCER DRUG DEVELOPMENT

8:30 Chairperson’s RemarksLawrence de Garavilla, M.S., Ph.D., Research Fellow, Head, Imaging and PK/PD, Immunology Therapeutic Area, Janssen Pharmaceutical

8:40 Molecular Imaging in Preclinical Oncology Models: From Concepts to PracticePeter King, Ph.D., Senior Scientist, Molecular Imaging (Oncology), Janssen, Pharmaceutical Companies of Johnson and JohnsonAn escalating number of research programs within the oncology field are focusing on the tumor microenvironment and biomarkers. By incorporating the use of novel non-invasive molecular imaging techniques to look at drug target expression, tumor-host interactions, and pharmacokinetic and pharmacodynamics of the drug within these humanized pre-clinical oncology models, it will enable us to interrogate our drugs in more human reflective systems. This in turn can accelerate the pace of drug development both in pre-clinical research and early clinical-translation.

9:10 Predicting Response to Folate-Targeted Drug Therapy Using the Companion Imaging Agent, 99mTc-etarfolatideChristopher P. Leamon, Ph.D., Vice President, Research Endocyte, IncVintafolide is a potent folate-targeted vinca alkaloid conjugate that is currently being evaluated in global phase 3 trials. Response to vintafolide and other folate-targeted drugs is dependent on folate receptor (FR) expression, which can be anatomically assessed in a non-invasive, real-time format using the folate-targeted companion diagnostic agent, 99mTc-etarfolatide. This novel and personalized approach may allow for the identification of patients who would most likely benefit from FR-targeted therapy.

9:40 Application of in vivo and ex vivo Imaging for Assessing PK and PD in Preclinical Cancer Models: Optimizing Discovery to DeliveryWerner Scheuer, Research Leader, Pharma Research and Early Development, Discovery Oncology; Roche Diagnostics GmbHApplication of different imaging modalities to monitor the efficacy of new compounds on primary tumor growth, metastasis and angiogenesis. Verification of in vivo imaging data by multispectral fluorescenec histology of explanted tumor tissue.




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10:40 Smart Nanoparticle Approaches for Targeted Diagnosis and Therapy of CancerWillem Mulder, Ph.D., Associate Professor of Radiology, Director Nanomedicine Program, Translational and Molecular Imaging Institute, Mount Sinai School of MedicineMicrofluidics-based nanoparticle synthesis technology allows the creation of complex multifunctional nanoparticles. Such complex formulations permit the integration of several agents/materials and functionalities as well as smart coatings. In the context of cancer such nanoparticle platforms serve as valuable tools in preclinical research and may enable improved diagnosis and treatment for patients in the future

11:10 Pathways for the Translation of Preclinical Imaging into Clinical TrialsRonald L. Korn, M.D., Ph.D., Founder & CEO, Imaging EndpointsPreclinical imaging plays a vital role in drug development. However, translation of methodologies and knowledge into clinical trials is not always possible. Thus, new strategies are needed to translate and observe imaging changes in humans. We will outline the bidirectional translational approach taken at Imaging Endpoints to achieve this objective.

11:25 pm Panel Discussion: Imaging End Points in Preclinical Cancer ResearchModerator: Lawrence de Garavilla, M.S., Ph.D., Research Fellow, Head, Imaging and PK/PD, Immunology Therapeutic Area, Janssen Pharmaceutical Panelists: Speakers of the Session

12:10 Luncheon Presentation (Opportunity Available)

USE OF MOLECULAR IMAGING FOR DRUG SAFETY ASSESSMENTS


1:40 FEATURED PRESENTATION: Noninvasive Traditional and Novel Methods to Assess Chemotherapy-Related Cardiac DysfunctionEugene Storozynsky, M.D., Ph.D., Assistant Professor of Medicine, Program in Heart Failure and Transplantation Division of Cardiology, University of Rochester Medical CenterThere are close to 25 chemotherapeutic agents that have been associated with chemotherapy-induced cardiotoxicity. Early recognition of chemotherapy-induced cardiotoxicity is important to prevent development of irreversible cardiomyopathy. I will discuss surveillance methods including electrocardiographic, echocardiographic, and nuclear imaging to monitor for preclinical development of LV dysfunction. I will also discuss possible treatment strategies to prevent progression.

2:10 Development of Non-Invasive Neurotoxicity Biomarkers Using in vivo Magnetic Resonance Imaging (MRI)Serguei Liachenko, Ph.D., Director, Bio-Imaging, National Center for Toxicological Research, Food and Drug AdministrationCurrent approaches in the analysis of neuropathology in support of new drug submissions to the FDA (the use of several arbitrary histology slices) can sometimes result in false-negative findings, meaning that small localized lesions can easily be missed. Non-invasive MRI can provide unique information about the structure and function of the whole brain in vivo with high resolution and contrast and serve as the basis of the translatable neurotoxicity biomarkers.

2:40 In vivo Evaluation of Drug Effects in the Kidney and Liver Using Intravital Multiphoton MicroscopyKenneth Dunn, Ph.D., Associate Professor of Medicine and Biochemistry, Indiana UniversityCostly drug failures due to unforeseen toxicity highlight the need to understand the mechanisms of drug actions in vivo. Since conventional readouts of in vivo toxicity seldom provide clues as to the initiating events and sequence of injury processes, mechanistic studies are conducted in cultured cells, systems that incompletely represent the relevant in vivo environment of drug actions. We use intravital microscopy to analyze the acute effects of drugs on the liver and kidney.

3:10 High-Throughput Toxicity Screening with Silicon Microelectrode Arrays and Lens-Free Imaging SolutionsDries Braeken, Ph.D., Research & Development Team Leader, Bio-Nano-Electronics, Imec, BelgiumWe present a new silicon microelectrode array platform that makes it feasible to record intracellular action potentials from thousands of cells in a non-invasive manner. This assay yields information about ion channel activity with high precision and in an automated fashion. We also present a lens-free imaging method that can be integrated and is significantly cheaper than conventional microscopy, while providing detailed information and a large field of view.




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Conference Hotel: Loews Philadelphia Hotel1200 Market StreetPhiladelphia, PA 19107Phone: 215.627.1200www.loewsphiladelphia.com

Discounted Room Rate: $215.00 s/dDiscounted Room Rate Cut-off Date: May 7, 2013

Please visit our conference website to make your reservations online or call the hotel directly to reserve your sleeping accommodations. You will need to identify yourself as a Cambridge Healthtech Institute conference attendee to receive the discounted room rate with the host hotel. Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted on a space- and rate-availability basis. Rooms are limited, so please book early.

Top Reasons to Stay at The Loews Philadelphia •Minutes from Amtrak 30th Street Station and 20 minutes from Philadelphia Airport•Complimentary wireless internet in your guest room •Close to many of Philadelphia’s historical sites, including the Liberty Bell and

Independence Hall•Steps from Reading Terminal Market, which offers an exhilarating selection of baked

goods, meats, poultry, seafood, produce, flowers, and more•Nearby world-class dining•Located in the historic PSFS Building: A 20th Century Masterpiece

We understand that you have many choices when making your travel arrangements. Please understand that reserving your room in the CHI room block at the conference hotel allows you to take full advantage of the conference sessions, events and networking opportunities, and ensures that our staff will be available to help should you have any issues with your accommodations.

Flight Discounts: Special discounts have been established with American Airlines for this conference. •Call American Airlines 1-800-433-1790 and use Conference code 4463BU.•Go to www.aa.com/group and enter Conference code 4463BU in promotion

discount box.•Contact our dedicated travel agent, Wendy Levine at 1-877-559-5549 or wendy.

[email protected].

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Rail Discounts: Amtrak Offers a 10% discount off the best available rail fare to Philadelphia, PA between June 1, 2013 and June 9, 2013. To book your reservation, call Amtrak at 1-800-872-7245 or contact your local travel agent.

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and SAVE!AdditionAl registrAtion detAilsEach registration includes all conference sessions, posters and exhibits, food functions, and access to the conference proceedings link.Handicapped Equal Access: In accordance with the ADA, Cambridge Healthtech 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 least 30 days prior to the start of the meeting.to view our substitutions/Cancellations Policy, go to http://www.healthtech.com/regdetailsVideo and or audio recording of any kind is prohibited onsite at all CHI events.

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A series of diverse reports designed to keep life science professionals informed of the salient trends in pharmaceutical technology, business, clinical development, and therapeutic disease markets.For a detailed list of reports, visit InsightPharmaReports.com, or contact Rose LaRaia, [email protected], +1-781-972-5444.

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CONFERENCE PRICING

Commercial Academic, Government, Hospital-affiliated

Single short course $695 $395Two short courses $995 $695Three short courses $1195 $895

Event Pricing BEST VALUE! (Includes access to all conference days, plus two short courses.)

Registrations after April 19, 2013, and on-site $3175 $1645

Single Conference Pricing (Includes access to all conference days. Excludes short courses.)

Registrations after April 19, 2013, and on-site $2345 $1095

SHORT COURSES

CONFERENCE DISCOUNTS POSTER DISCOUNT ($50 Off) Poster abstracts are due by April 19, 2013. Once your registration has been fully processed, we will send an email containing a 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 to publish your poster title and abstract in various marketing materials and products.

DRUG SAFETY EXECUTIVE COUNCIL (DSEC) MEMBERS: CHI is pleased to offer all DSEC Members a 25% discount to attend. Records must indicate you are a DSEC member at time of registration. Please Note - Discounts may not be combined.

REGISTER 3 - 4th IS FREE: Individuals must register for the same conference or conference combination and submit completed registration form together for discount to apply.

ALUMNI DISCOUNT: Cambridge Healthtech Institute (CHI) appreciates your past participation at World Pharma Congress. As a result of the great loyalty you have shown us, we are pleased to extend to you the exclusive opportunity to save an additional 20% off the registration rate.

GROUP DISCOUNTS: Discounts are available for multiple attendees from the same organization. For more information on group rates con-tact David Cunningham at +1-781-972-5472

Alumni and register 3 - 4th is free discounts cannot be combined.

June 4-6

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How to Register: [email protected] • P: 781.972.5400 or Toll-free in the U.S. 888.999.6288

Please use keycode WPC F when registering

Monday, June 3, Morning Courses | 9:00 am—12:00 pm Monday, June 3, Afternoon Courses | 2:00—5:00 pmSC1: Addressing Safety Concerns for Biologics and Biosimilars SC5: Use of Stem Cells for Safety Screening

SC2: Utilization of Cardiac Contractility Assays for Preclinical Safety Testing SC6: Introduction to Drug Metabolism and Its Role in Drug ToxicitySC3: Animal Models of Pain: Progress and Challenges SC7: Epigenetic Mechanisms of PainSC4: Design and Interpretation of Stability Studies for Product Development SC8: Development of Nanotechnology Application into Innovative Therapies

SC9: Roadmap for Outsourcing of Preclinical Imaging

Wednesday, June 5, Dinner Courses | 6:00 pm—9:00 pmSC10: Advances in Imaging Quantitation

SC11: Genetically Engineered Mouse Models Versus Patient-Derived Xenograft Models: Comparing Strengths and Limitations

Short Course is Cancelled



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