アジェンダ
言語選択
開催日 : 2008年8月4〜7日
開催地 : 米国 ボストン ワールドトレードセンターボストン & シーポートホテル
アジェンダ
2008年7月7日更新
月曜日
Optional Concurrent Pre-Conference Summits
2008年8月4日（月）
Summit 1
Computational Methods and Informatics Tools to Move Therapeutic Projects Forward
9:00
Chairperson's Opening Remarks
David de Graaf, Ph.D., Director of Systems Biology, Pfizer Research and Technology Center
Tools for Decision-Making and Portfolio Prioritization
9:10
The Coming of Business Intelligence to Drug Discovery and Development
The use of business intelligence (BI) solutions in drug discovery and development offer the capability to reduce risk and make better decisions based on quantitative data gathered from within the organization. This presentation will focus on the emerging opportunity for BI and how both researchers and managers will need to manage change to be successful.
Alan S. Louie, Ph.D., Research Director, Health Industry Insights, An IDC Company
9:40
Using Integrated Data to Drive Better Decision-Making and Portfolio Management in Cancer and Inflammation
Array Biopharma has co-developed a decision support and portfolio management system that aligns project management, financial, clinical, and discovery information. These data are automatically and dynamically obtained from the daily use operations support systems employed by drug discovery, drug development, and clinical trial execution. We will discuss how these tools have impacted Array's oncology and inflammation programs, permitting us to progress projects more efficiently and effectively through the clinic.
Daniel C. Weaver, Ph.D., Associate Director of Scientific Computing, Array Biopharma
10:10
Strategies for Improving Decision Support Within and Between Projects
Today's researcher is faced with a huge wealth and diversity of research information spread over multiple public and proprietary sources. Leveraging these sources of information for more effective decision making requires new innovative software. This session focuses on innovative ways software has been used to solve the researcher's information overload.
Dominic John, Ph.D., Data Access and Decision Support Group Manager, Symyx Technologies
10:40
Networking Refreshment Break
A Systems Biology Approach to Drug Development
11:10
Systems Biology Helps Identify Optimal Properties for Small Molecules and Biotherapeutics
During the late nineties, the genomic revolution provided the pharmaceutical industry with a shot in the arm by delivering many potential targets for a variety of disease areas. Although it was hoped that these targets would rejuvenate product portfolios, it has been challenging to find appropriate drugging strategies for these targets. In this talk, I will provide two approaches to identifying the desired properties of a modality, whether biotherapeutic or small molecule. The approaches are heavily data driven, but provide rapid feedback and testable hypotheses.
David de Graaf, Ph.D., Director of Systems Biology, Pfizer Research and Technology Center
11:40
Using a Systems Approach to Drug R&D
Predicting the best therapeutic approach to cancer pathways before strenuous empirical testing would be very powerful. We have taken a Systems Biology approach to the problem and constructed detailed, mechanistic models of the targeted pathway. Such models may be used to simulate network responses to different targeted therapeutics such as antibodies and small molecule inhibitors. Using growth factor signaling as an example, we will present how computational modeling may predict the best therapeutic strategy with single agents or combinations of targeted inhibitors.
Ulrik Nielsen, Ph.D., Senior Vice President, Research, Merrimack Pharmaceuticals
Panel Discussion
1:20
Quantitative Systems Biology: From Conception to Application
- Applying systems biology in drug development quantitatively
- Finding the common ground between systems biology modelers and users
- Integrating data from the -omics (genomics, proteomics, etc.) and the literature
- Impact of FDA's report on systems biology/biological networks on health and disease
Moderator:
M. Vidyasagar, Ph.D., EVP, Advanced Technology, Tata Consultancy Services, India
Panelists:
David de Graaf, Ph.D., Director of Systems Biology, Pfizer Research and Technology
Ulrik Nielsen, Ph.D., Senior Vice President, Research, Merrimack Pharmaceuticals
Imaging and Translational Medicine
2:30
Building an Enterprise Imaging Gateway and Repository: Lessons Learned and Roadmap Forward
Abstract not available at time of print.
Martin D. Leach, Ph.D., Executive Director, MRL IT Basic Research & Biomarkers, Merck & Co. Inc.
3:00
Achieving Confidence in Mechanism for Drug Discovery and Development
Despite advances in our powers of observation, the ability to determine biological mechanisms from large-scale multi-omic technologies continues to be a major bottleneck. This can be overcome by utilizing computational learning methods that identify directly from the data the circuits and connections between drug-affected molecular constituents and physiological observables. The marriage of multi-omics technologies with reverse engineering approaches can provide missing insights needed to improve drug development success rates.
Iya Khalil, Ph.D., Executive Vice President & Co-Founder, Gene Network Sciences
3:30
Networking Refreshment Break
Tools to Predict Toxicity of Drugs
4:00
Informatics Tools for Cardiosafety Risk Assessment
Cardiosafety is one of the major hurdles clinical drug candidates have to deal with. Some of the risk factors, including blocking hERG potassium ion channels, are now well known. Yet, a significant number of preclinical projects still deal with working out cardiosafety liabilities. The presentation will focus on informatics tools to help project teams mitigate cardiosafety risks during early lead discovery and lead optimization stages.
Dmitri Mikhailov, Ph.D., Labhead, Lead Discovery Informatics, Center for Proteomic Chemistry, Novartis Institutes for Biomedical Research, Inc.
4:30
PepBank Peptide Database: Practical Applications for Development of Novel Therapeutic and Diagnostic Agents
Peptide-based drugs and diagnostics represent a multibillion dollar market. We demonstrate the utility of PepBank, a freely available peptide database, in the development of novel peptide agents. Real-life examples show how sequence similarity searches can save development costs resulting from choosing nonspecific or toxic peptide in screening experiments.
Timur Shtatland, Ph.D., Instructor, Harvard Medical School, Center for Molecular Imaging Research, Massachusetts General Hospital
5:00
Mini-Panel Discussion
5:20
Close of Pre-Conference Summit
Summit 2
The Next Wave of Antibody-Based Therapies
Antibody Combinations, Bispecific Antibodies, Conjugates and Novel Scaffolds
9:00
Chairperson's Opening Remarks
Zhenping Zhu, M.D., Ph.D., Vice President, Antibody Technology, ImClone Systems Incorporated
Combination Antibody Therapies
9:10
Potentiation of Antitumor Efficacy by Antibody Combinations and Bispecific Antibodies
Accumulating evidence indicate that combinations of antitumor antibodies provide greater efficacy than single antibody-based regimen, without adding significant toxicities. With recent progress in antibody engineering technology, BsAb that target simultaneously two tumor-associated molecules are being heralded for their potential to deliver two therapeutic moieties in one molecule.
Zhenping Zhu, M.D., Ph.D., Vice President, Antibody Technology, ImClone Systems Incorporated
9:40
Combination Immunotherapy of NHL With Rituximab (anti-CD20) and Epratuzumab (anti-CD22)
Since both rituximab and epratuzumab have single-agent activity in NHL, two multicenter trials have studied their tolerability and efficacy when combined in full doses. The results show no enhanced toxicity with improved and durable complete responses in indolent and aggressive relapsed/refractory NHL patients.
David M. Goldenberg, Sc.D., M.D., Founder and Chairman, Immunomedics, Inc.
10:10
Networking Refreshment Break
Bispecific and Multispecific Antibody Drugs
10:40
Dual Variable Domain Immunoglobulins (DVD-Ig): A Novel Class of Dual-Specific Biologics
DVD-Igs are constructed using two pre-existing mAbs and retain functions of both mAbs. DVD-Igs target two disease mechanisms simultaneously, are manufactured easily, display good drug-like properties and show efficacy in animal models. DVD-Ig molecules will likely have better efficacy than individual mAbs alone.
Tariq Ghayur, Ph.D., Research Fellow, Abbott
11:05
SEEDbodies: Hybrid Protein Engineering
We engineered human CH3 domains to create analogs called SEEDs (Strand Exchange Engineered Domains). SEEDs can replace the CH3 domains in the Fc. SEED technology allows control in the design of fusion proteins and bispecific antibodies, while simultaneously conferring desirable characteristics including expression levels, purification by protein A, and a favorable PK profile.
Jonathan H. Davis, Ph.D., Senior Scientist, EMD Serono Research Institute
11:30
mAb2™: Multi-specific or Multivalent IgG Antibodies with Engineered Antigen Binding Sites
Constant domains of both heavy and light chain with engineered antigen binding sites (SMIDs: small modular immunoglobulin domains), may be used both as stand alone therapeutic entities (e.g. Fcab™) and as building blocks for mAb2™, which are IgG molecules designed to have e.g. multi specificity, improved avidity, improved effector functions and/or pharmacokinetics compared to their parent monoclonal antibodies.
Geert C. Mudde, Ph.D., CSO, f-star, Austria
11:55
Stability-engineered IgG-like Tetravalent Antibody for Inducing Receptor-mediated Death in Leukemia Cells
We have developed technology for engineering stable single-chain Fv domains that serve as building blocks for constructing IgG-like bispecific and tetravalent antibodies. Structural and statistical analyses were used to guide a stability engineering strategy. In vitro studies with the tetravalent antibody demonstrated that increasing antibody valency resulted in enhanced tumor cell apoptosis.
Scott M. Glaser, Ph.D., Director, Molecular Engineering, Biogen Idec, Inc.
12:20
Mini-Panel Discussion
Improving Antibody Efficacy and Potency
1:45
Antibody-Drug Conjugate Development in Oncology: Preclinical and Clinical Update
The antibody-drug conjugate concept is to use an antibody to deliver a cytotoxic drug selectively to tumors. Such conjugates were shown to enhance the antitumor activity of antibodies and to improve the tumor-to-normal tissue selectivity of chemotherapy. Recent advances in preclinical development and a review of antibody-drug conjugates currently developed in clinical trials for cancer therapy will be presented.
Hans-Peter Gerber, Ph.D., Director, Translational Biology, Seattle Genetics, Inc.
2:20
Antibody-drug Conjugates for the Treatment of Non-Hodgkin's Lymphoma
We are exploring antibody-drug conjugates (ADCs), potent cytotoxic drugs covalently linked to antibodies via chemical linkers, as potential treatments for non-Hodgkin's lymphoma (NHL). We examined potential targets and linker-drug combinations and identified ADCs targeted to CD22 or CD79b that were very effective in xenograft models and have acceptable pre-clinical safety profiles demonstrating their potential as a treatment for NHL.
Andrew Polson, Ph.D., Scientist, Department of Translational Oncology, Genentech, Inc.
2:55
Cancer Therapy by T cell-engaging Antibodies
T cells are considered the most potent killer cells in the organism. With the BiTE format we have managed to design a new antibody class that optimally recruits T cells for elimination of cancer cells. Data will be presented that characterize BiTE antibodies crafted from Herceptin and Erbitux cancer therapies, as well as clinical data from the first BiTE antibody in clinical trials.
Patrick A. Baeuerle, Ph.D., Chief Scientific Officer, Senior Vice President R&D, Micromet, Inc.
3:25
Networking Refreshment Break
Clinical Updates
4:00
Topical Delivery of Fully Human dAbs
Domain Antibodies, or "dAbs", are less than one-tenth the size of conventional antibodies. We believe that dAbs represent the next generation in antibody therapeutics, can be used to go after various targets and can be delivered in ways that are not possible with traditional antibodies.
Ian M. Tomlinson, Ph.D., Vice President, GSK-Domantis Group, Domantis Limited, United Kingdom
4:30
Adnectins™, a Novel Class of Targeted Biologics Generated Using the PROfusion™ Protein Engineering System
Adnectins™ are a novel, proprietary class of targeted biologics, which offer various potential advantages, including speed of discovery, ease of manufacturing, and multi-functionality. Adnectins™ are generated using Adnexus' proprietary protein engineering system, PROfusion™. With PROfusion™, Adnexus scientists can simultaneously engineer trillions of Adnectin™ protein variations at a time in order to efficiently identify, evaluate and optimize product candidates. The presentation outlines Adnexus' success in applying PROfusion™ to multiple programs, including the development of CT-322 (Angiocept™), the first Adnectin™ product candidate now in Phase 2 clinical trials.
Ruchira Das Gupta, Ph.D., Associate Director, Adnexus, a Bristol-Myers Squibb R&D Company
5:00
Mini-Panel Discussion
5:20
Close of Pre-Conference Summit
Summit 3
Global Drug Development and Partnering Strategies
8:50
Chairperson's Opening Remarks
Michael McCully, Director & Senior Analyst, Recombinant Capital, Inc.
Globalizing R&D
9:00
Maximizing the Value of the Evolving R&D Landscape in Asia via Partnership
Multinational corporations are increasingly realizing that Asia isn't just a vast market or a production base - it plays more and more critical role in R&D functions as well. This presentation will discuss our experience in partnering with collaborators in Asia via various different models (functional outsourcing vs integrated research collaboration, exclusive partnership and risk sharing collaboration etc.).
Guoxin Zhu, Ph.D., Director, Discovery Chemistry Research & Technology, Eli Lilly & Company
9:30
Risk Sharing Drug Discovery & Development Alliances: An Emerging Global Partnering Strategy
In addition to outsourcing and CRO type services a new risk-reward sharing pharma R&D business model is fast emerging at the global stage. Recently several companies from Asia including Ranbaxy have established risk sharing R&D partnerships with big western pharma companies. A survey of the current landscape as well as Ranbaxy's experience and opportunities for such alliances will be presented.
Shyam Bishen, Ph.D., MBA, Vice President, Corporate Development, Ranbaxy Inc.
10:00
Leverage Eliminate Anticipate Deliver - An Innovative Business Model for Drug Discovery
Due to various factors including escalating costs, more and more companies are cutting or shrinking discovery efforts to concentrate on clinical stage programs. To address the looming early-stage pipeline shortage, LEAD Therapeutics leads the way in leveraging the best of the US and China to conduct high-quality drug discovery, thereby rendering drug discovery "fundable" today.
Sofie Qiao, Ph.D., President and COO, LEAD Therapeutics, Inc.
10:30
Networking Refreshment Break
11:00
Northern Lights Advanced Solubilization Technologies: A Pfizer/Bend Research Initiative for New Partnership Opportunities
The Pfizer/Bend Research licensing initiative is designed to help companies enhance the bioavailability of poorly soluble compounds using a novel spray-dried dispersion (SDD) technology. This technology has been successfully applied to 20 Pfizer compounds in clinical trials, including Phase 3. Enhancements are typical for compounds with solubilities as low as 1 ng/mL and log P values ranging from 2 to above 8.
Paul R. McGuirk, Ph.D., Executive Director, PGRD/BBC, Pfizer
Jeff T. Gautschi, Ph.D., Director, Technology and Business Development, Bend Research Inc.
Panel Discussion
11:30
New and Evolving Business Models to Leverage the Global R&D Strategies - How Can Small & Medium- sized Companies Reach Out Into the Global Market?
Moderator:
Lorenz Ng, M.D., Managing Partner, Global Ng Associates (GNA) LLC.
Panelists:
Samantha Ying Du, Ph.D., Chief Executive Officer, Hutchison MediPharma Limited, China
Sridhar Mosur, Chief Executive Officer and Managing Director, Jubilant Chemsys, and President, Jubiliant Innovation, India
Guy Miller, M.D., Ph.D., Chairman & CEO, Edison Pharmaceuticals, Inc.
Rabinder Buttar, Ph.D., President & CEO, ClinTec International
Innovative Partnering Strategies and Unique Deal Structures
1:30
The Latest Trends for Biotech Business Development & Finance
If alliance terms are any testament, Biotechs is experiencing a logarithmic growth. The actual dollar terms have gone through the roof over the past two years, and that is without adjusting for the increasing retained rights for commercial opt-ins and codevelopment. Come hear a current overview of alliance, financing, and market performance trends.
Michael McCully, Director & Senior Analyst, Recombinant Capital, Inc.
Panel Discussion
2:00
Venture Outlook in Pharma/Biotech for Next 5 Years
Moderator:
Arthur Klausner, MBA, Partner, Pappas Ventures
Panelists:
Ansbert Gadicke, M.D., Managing Director, MPM Capital
Bruce Booth, Ph.D., Principal, Atlas Venture
Jeffrey Leiden, M.D., Ph.D., Managing Director, Clarus Ventures, LLC.
2:50
Strategic Alliances: A Way to Build A Sustainable Drug Discovery Business
Galapagos signed on GSK, J&J and Lilly, for its therapeutic programs where Galapagos remains in charge of progressing the programs through to clinical POC, and receives success based milestones to offset the costs. In the presentation, we will discuss the rationale for, and structure of the alliances, and share some of the war stories of negotiating these deals.
Onno van de Stolpe, Chief Executive Officer, Galapagos NV, Belgium
3:20
Networking Refreshment Break
3:50
Alnylam Pharmaceuticals: Delivering Innovation with RNAi Therapeutics
The pharma industry is looking to innovation as a way to control the market-based forces driving constraints on drug pricing and reimbursement, and as a way to fill their diminishing pipelines. Alnylam is focused on the discovery, development, and commercialization of RNAi therapeutics, a promising approach for a whole new class of innovative medicines.
John Maraganore, Ph.D., President & CEO, Alnylam Pharmaceuticals
4:20
Structuring a Deal to Enable the Seamless Integration of Research & Development
AVEO's partnership with Schering-Plough to develop and commercialize AV-299, AVEO's novel anti-HGF monoclonal antibody, provides for AVEO to have primary responsibility for translational research and clinical development through proof-of-concept in man, at SP's expense. This deal structure has many potential benefits for both parties.
Elan Z. Ezickson, Chief Business Officer, AVEO Pharmaceuticals, Inc.
4:50
Academic / Industry Collaboration - Closing the Gap
Collaborations between Academia and the Pharmaceutical Industry are historically transactional or individual project oriented. In this presentation, a new model will be introduced to discuss a more systematic and strategic approach to research collaborations that is focused on quality science, efficient and effective delivery and maintaining a long-term scientific relationship.
Kevin R. Webster, Ph.D., Executive Director, Cancer Biosciences, Cancer and Infection Drug Discovery, AstraZeneca R&D Boston
5:20
Close of Pre-Conference Summit
Summit 4
Imaging in Drug Development
8:50
Chairperson's Opening Remarks
Mostafa Analoui, Ph.D., Senior Advisor & Head of Healthcare & Life Science, The Livingston Group; and SVP, Business Development, Charlesson Pharmaceuticals
Molecular Imaging Approaches in Early Discovery
9:00
Early Risk Discharge in CNS Drug Development: The Role Of Molecular Imaging
Molecular imaging with Positron Emission Tomography (PET) plays an increasing role in several stages of CNS drug development. PET studies are involved in target validation, biodistribution and occupancy studies of candidate drugs, and surrogate markers of efficacy. This presentation will focus on new developments in biodistribution and occupancy studies that are, today, the most common application of PET in CNS drug development.
Marc Laruelle, M.D., Vice President, Molecular Imaging, Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, United Kingdom
9:30
Application of PET Technology As A Powerful Tool For Translational Research
PET is a powerful tool for translational research which can provide useful information of PK/PD and biofunction in the living body. We have developed several key technologies of PET including rapid synthesis of tracers and human database. Using the developed technologies, some applications for new drug R&D will be shown.
Shintaro Nishimura, Ph.D., Senior Director, Bioimaging, Applied Pharmacoogical Research Laboratories, Astellas Pharma Inc., Japan
10:00
A High Speed Time-lapse Video Platform for Analyzing Effects of GPCR and Ion Channel Modulators on Cardiomyocyte Contraction
To predict in vivo drug effects on the cardiovascular system, we introduce a unique and sensitive high speed time-lapse imaging platform, and demonstrate quantitative phase-contrast imaging analysis of the effects of multiple GPCR and ion channel modulators on cultured, live, primary rat cardiomyocytes. Video pairs will be presented of the same cells, captured during sequential compound treatments. (Mei Zhang, Mat Holmqvist, Shuzhen Qin, Dan Zhou, Michael Xie, and Jim Barsoum)
Mei Zhang, M.D., Ph.D., Senior Scientist, Department of Biology, Synta Pharmaceuticals
10:30
Networking Refreshment Break
Imaging Disease Areas
11:00
Development of New Cardiovascular Imaging Agents
Non-invasive imaging procedures to identify vascular remodeling in peripheral or coronary vessel are currently limited. A discovery program will be outlined for a novel magnetic resonance imaging agent that selectively targets the arterial wall. MR imaging with a lead agent will be presented.
Simon Robinson, Ph.D., Director, Discovery Biology, Bristol Myers Squibb Medical Imaging
11:30
Mechanistic Neuroimaging Biomarkers in Human Drug Development
Abstract not available at time of print.
Gregory Sorenson, M.D., Director, MGH-HST Center for Biomarkers in Imaging, Massachusetts General Hospital
12:00
Technology Workshop Presentation
For further information on sponsoring a Technology Workshop, please contact Sherry Johnson at sjohnson@ibcusa.com or Kristen Schott at kschott@ibcusa.com
1:30
Structural and Non-Amyloid Functional Imaging Applications in Alzheimer's Disease Drug Development
Structural and functional imaging is being used in Alzheimer's disease drug research to indicate drug action. Structurally, quantitative atrophy assessment will be considered, including its appropriateness for various therapies. Functionally, non-amyloid PET/SPECT methods, e.g., imaging of glucose metabolism, blood flow and neurotransmission, and various MRI/MRS approaches, will also be discussed.
Richard Margolin M.D., Director, Early Clinical Research and Experimental Medicine, Schering-Plough Corporation
2:00
Electrical Impedance Tomography for Breast Cancer Detection: the FEM Modeling
Electrical Impedance Tomography (EIT) has proven effective at detecting cancerous tissue in female breasts. To investigate the efficacies and limitations of EIT in terms of image resolution and sensitivity, a three-dimensional finite element method modeling was conducted. Two models, a baseline model without cancerous tissue and another one with malignant cysts, respectively, were numerically tested with the mono-polar and bi-polar setups in EIT. The model employs a published geometry reported by a research group and generic material properties of breast tissues. The electric potentials measured on the breast surface were compared between the normal and cancerous. Abnormal voltage signature can be detected for the cancerous case.
Leigh Soutter, Ph.D., Physics Logic LLC.
Imaging in Clinical Trials
2:30
MRI in Clinical Trials for Alzheimer's Diseases
The MRI methods used in the ADNI multi-center study are described. Description of the quality control methods, including the ADNI phantom, and development of the imaging protocol is also included. General considerations about the use of 3T versus 1.5T will also be discussed.
Matt Bernstein Ph.D., Professor, Department of Radiology, Mayo Clinic
3:00
Networking Refreshment Break
Imaging in Drug Discovery
3:30
Strategies to Facilitate Translational Imaging in Drug Development
Imaging biomarkers can assist with making go-no go decisions in Phase I/II drug development. An integrated program of preclinical and clinical imaging during the drug development process can facilitate this goal. However, there are important challenges in translational imaging. This talk will discuss important considerations in translating preclinical imaging to the clinical arena so as to assist in making go-no go decisions in the early development of targeted therapies.
Onikepe Adegbola, M.D., Ph.D., Clinical Imaging Physician, Novartis Pharmaceutical Corporation
4:00
Imaging in a Multi-Site Clinical Trial: Role of the Core Lab
The earlier inclusion of imaging end points in drug development trials is increasing, and selecting an image core lab is critical to getting the most value from this activity. This presentation will review the role an imaging core lab should play in managing the imaging component in a drug development trial. Topics will include site selection and qualification, number of readers, and communication plan.
Mark Tengowski, Ph.D., Director, Clinical Affairs, VirtualScopics, Inc.
4:30
Close of Pre-Conference Summit
2008年8月5日（火）
The State-of-the-Art in Different Types of Cancer
8:30
Chairperson's Opening Remarks
Joseph B. Bolen, Ph.D., CSO, Millennium Pharmaceuticals
Hematology
8:40
Oncogenomics to Target the Myeloma Cell in its Bone Marrow Microenvironment
Advances in oncogenomics and increased understanding of the role of the BM in the pathogenesis of MM have provided the framework for a new treatment paradigm targeting the tumor cell and its BM microenvironment to overcome drug resistance and improve patient outcome. Ongoing efforts are aimed at identifying next generation therapies, using oncogenomics to inform the design of combination trials and defining combination therapies to enhance cytotoxicity and overcome drug resistance against MM cells in the BM milieu.
Kenneth C. Anderson, M.D., Kraft Family Professor of Medicine, Dana-Farber Cancer Institute, Harvard Medical School
Lung Cancer
9:25
Treatment Options and Emerging Therapies for Lung Cancer
The treatment of patients with advanced lung cancer has involved two drug combinations of a cytotoxic chemotherapy agent combined with cisplatin or carboplatin for the past two decades, but some subsets of patients now benefit from the use of targeted agents. The targeted agent, bevacizumab, has been introduced into the treatment of some patients with advanced non-small cell lung cancer. This monoclonal antibody is directed against the angiogenic factor, vascular endothelial growth factor. In addition, 4 years have passed since mutations of the tyrosine kinase domain of the epidermal growth factor receptor were discovered in patients with lung cancer who had dramatic clinical responses to treatment with gefitinib and erlotinib. Ongoing trials are testing whether these patients should be treated initially with gefitinib or erlotinib instead of combination chemotherapy. This is the paradigm for further studies to determine if somatic genomic changes can be used to select subsets of lung cancer patients for treatment with different targeted agents.
Bruce E. Johnson, M.D., Director, Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Departments of Medicine, Brigham and Women's Hospital, and Professor of Medicine, Harvard Medical School
Main Conference
Cardio-Metabolic Diseases
8:20
Chairperson's Opening Remarks
Brian Hubbard, Ph.D., Senior Director and Basic Site Lead - Atherosclerosis, Merck Research Laboratories
The Interaction of LDL, Biomarkers and Inflammation with Cardio-Metabolic Risks
Featured Presentation
8:30
LDL Cholesterol Is Still The Most Validated Target For Reducing Cardiovascular Disease Risk
The results of a very small recent trial, ENHANCE led to a number of disproportionately excessive, uniformed and inflammatory remarks from a few cardiologists in the popular press questioning the role of LDL cholesterol lowering in prevention of cardiovascular disease. Those making such comments appear to lack understanding of basic lipid metabolism and the now 5 decades of evidence, especially from clinical event trials, from many mechanisms which reduce LDLc. They also appear to fail to realize that the final pathway by which circulating LDLc is reduced with the three major agents in use, statins, bile acid sequestrants and cholesterol absorption inhibitors is identical via upregulation of the LDL receptor secondary to intracellular cholesterol depletion.
Evan A Stein, M.D., Ph.D., Director, Metabolic & Atherosclerosis Research Center, Director, The Cholesterol Treatment Center
8:55
Discovering Markers of Metabolic Side Effects From Responses To Drugs By Altered Synthesis and Turnover of Fatty Acids and Cholesterol
Altered tissue deposition of fatty acids and cholesterol from [U-13C6]-D-glucose derived acetate via de novo synthesis, turnover and transport are early markers of the developing metabolic syndrome, glucose intolerance and increased futile cycles. Stable isotope-labeled plasma/urine metabolites and the turnover of specific lipoproteins readily reveal metabolic side effects of drugs and response to therapy.
Laszlo G. Boros, M.D., Scientific Advisor, SIDMAP, LLC.
9:20
Role of Inflammation in Diabetic Heart
Chronic inflammation plays an important role in diabetes and its complications. Macrophage infiltration in adipose tissue and elevated cytokine levels are causally associated with insulin resistance in peripheral organs. Our recent findings indicate that macrophage action and local cytokines are involved in metabolic and functional abnormalities associated with diabetic heart.
Jason Kim, Ph.D., Associate Professor, Cellular & Molecular Physiology, Pennsylvania State University College of Medicine
9:45
Fatty Tissues: Getting It In and Storing It Up
We created and studied mice with overexpression or tissue specific knockout of cardiomyocyte lipoprotein lipase (LPL). These mice developed cardiac dysfunction characterized by decreased fractional shortening, and interstitial and perivascular fibrosis. Mice with transgenic overexpression of PPAR gamma in the heart also developed cardiac dysfunction with increased expression of fatty acid uptake and oxidation genes, and GLUT4. Thus, high level of expression of PPAR gamma or other genes that can increase cardiac lipid uptake can cause cardiomyopathy.
Ira J. Goldberg, M.D., Dickinson Richards Professor of Medicine Chief, Division of Preventive Medicine and Nutrition, Columbia University
Main Conference
Anti-Infectives
8:30
Chairperson's Opening Remarks
Donald Moir, Ph.D., CSO, Microbiotix, Inc.
Anti-infective Drug Discovery and Development
8:40
Problems and Prospects of Novel Antibacterial Drug Discovery
Despite significant investment by both small and large pharmaceutical companies, it has proven difficult to identify either new classes of antibacterials or modified versions of existing classes with clinical activity against drug-resistant strains. This talk will review the reasons why antibacterial drug discovery is so challenging and review new approaches being applied to enhance success.
Steven C. Gilman, PhD., CSO, SVP, Discovery & Non-Clinical Development, Cubist Pharmaceuticals, Inc.
New Approaches and Technologies
9:10
Re-designing Beta-lactam Antibiotics
We re-engineer beta-lactams in such a way that they acquire novel properties which render resistant pathogens again susceptible to their action. Examples include ceftobiprole, a first-in-class broad-spectrum cephalosporin to target methicillin-resistant S. aureus (MRSA) and novel beta-lactam/beta-lactamase inhibitor combinations, eg BAL30376, against MDR Enterobacteriaceae and Gram-negative non-fermenters.
Jutta Heim, Ph.D., Chief Scientific Officer, Basilea Pharmaceutica AG, Switzerland
9:30
Combating Antibiotic Efflux Mechanisms
Multidrug-resistance efflux pumps with their unusually high degree of substrate promiscuity significantly restrict the effectiveness of antibacterial therapy. Recent years have heralded remarkable insights into the structure and mechanisms of these fascinating molecular machines. These insights facilitate the ongoing effort to combat antibiotic efflux. Recent advances in the field will be summarized.
Olga Lomovskaya, Ph.D., Senior Director of Biology, Mpex Pharmaceuticals, Inc.
9:50
Strategies to Discover Chemical Biology and Therapeutic Agents in Infectious Disease
In two years the PCMD has completed more than 20 HTS campaigns and several hit-to-lead programs focused on viral, bacterial, fungal, and parasitic pathogens. Examples will be presented from our work leading to the development of novel chemical probes against viral entry into host cells, TB cell wall biosynthesis, fungal biofilms, and malarial parasite invasion of red blood cells.
Andrew Napper, Ph.D., Director of HTS, Penn Center for Molecular Discovery, University of Pennsylvania
Main Conference
Transforming Technologies
8:30
Chairperson's Opening Remarks
Kailash Swarna, Ph.D., Executive Director, sResearch & Development, Amgen, Inc.
Transforming Technologies in Early Discovery
8:40
From Early Discovery to First-in-Human: Realities of The Post-Technology Revolution
Over the last decade, we have witnessed the near-perfect inverse correlation between record levels of technology investments and novel drugs in the clinic. Technology investments are necessary, but drying pipelines are in desperate need more rigor in discovery, and a connection to the clinic. This presentation will explore the value of enabling technologies, the process of target and lead selection, and the priorities that drive the successful launch of therapeutics.
Kailash Swarna, Ph.D., Executive Director, Research & Development, Amgen, Inc., USA
9:10
Cell-free Electrophysiology is Enabling an Efficient Drug Discovery for Ion-transporters
Transporters are an emerging target class in industry and academia. This trend is supported by the development of technologies including IonGate's "cell-free electrophysiology". Presented case studies (NCX, PepT1, neurotransmitter transporters etc.) are illuminating that the technology is accelerating the drug discovery of transporters (covering assay development, screening, pharmacology) and is enabling challenging projects including the measurement of transporters from native tissues (synaptic vesicles, cardiomyocytes) creating a new kind of in-vitro pharmacology.
Henning Vollert, Ph.D., Project Manager, Institute of Pharmacy, University of Kiel, Germany
9:40
Applying Label-Free Technologies to Validate Screening Hits
Label-Free Direct Binding technology is the method of choice for confirming that screening hits bind directly to the target of interest. A number of such technologies are available, such as, NMR, SPR, Thermo-shift and Biolayer Interferometry. A Hit Validation Workflow will be described that takes advantage of the unique properties of each Label-Free technology to confirm the binding of hits to the target proteins. In particular, we will discuss how we have incorporated the ForteBio Octet Red, a fiber optic based biosensor, into our hit validation workflow.
David Mark, Ph.D., Senior Director, Research, Hoffman-La Roche
10:10
Exhibit Hall Opening and Networking Refreshment Break in Exhibit & Poster Hall
Neurological
11:00
Malignant Brain Tumors: Current Challenges and Future Opportunities
Primary brain tumors are rare, but their extremely poor response to available therapies and the short duration of survival following diagnosis have made these tumors an important focus of ongoing research. The extensive characterization of important molecular pathways that mediate key pathologic characteristics of high-grade gliomas has supported the development and evaluation of targeted therapies, including small molecule inhibitors of signaling pathways, antibodies, and novel immunological strategies.
Mark A. Israel, M.D., Director, Norris Cotton Cancer Center and Professor of Pediatrics and of Genetics, Dartmouth Medical School
11:45
Mini-Panel Discussion with Morning Speakers
Main Conference
Cardio-Metabolic Diseases
New Mechanisms & Novel Discoveries
11:00
Endoplasmic Reticulum Stress Factors - Applications in Oncology and Metabolic Diseases
Endoplasmic reticulum (ER) stress results from imbalance between protein load and folding capacity of the ER, which triggers multiple protective pathways to allow cells to adapt to pathological conditions. The novel concept that ER stress factors play critically roles in cancer, obesity and insulin resistance will be discussed.
Amy S. Lee, Ph.D., Professor, Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine
11:30
Osteocalcin: A Novel Potential Treatment for Metabolic Disorders Such As Obesity And Type2 Diabetes
Escoublac is developing human osteocalcin and derivatives thereof as novel treatment for type 2 diabetes and obesity. Osteocalcin has been shown to stimulate cyclinD1 and insulin expression in pancreatic beta-cells and adiponectin expression in adipocytes. In vivo, this peptide hormone can improve glucose tolerance
Nils Bergenhem, Ph.D., Chief Scientific Officer, Escoublac, Inc.
Main Conference
Anti-Infectives
11:00
Using Structure-Based Discovery to Define Novel Antibiotics Targeting the 50S Ribosomal Subunit
Rib-X has merged proprietary high resolution X-ray structural knowledge with customized computational tools and targeted synthetic chemistry to define key regions within the bacterial ribosome. We will illustrate the application of these unique tools to new antibiotic design that overcomes key resistance mechanisms. In particular, we will outline strategies and methodologies that Rib-X has used to identify and refine a new class of antibiotics with efficacy against both community and hospital organisms.
Graham Johnson, Ph.D., Chief Research Officer, Rib-X Pharmaceuticals, Inc.
11:15
Reducing Risk in Preclinical Drug Discovery: Development of Telaprevir (VX-950), a HCV Protease Inhibitor Currently in Phase III Clinical Trials
Effective HCV drugs with fewer side effects and shorter treatment durations are needed. During preclinical development, it is difficult to predict which compound which will be successful in the clinic. The use of preclinical data to select the investigational protease inhibitor telaprevir and successfully predict antiviral activity in patients will be discussed.
Ann D. Kwong, Ph.D., Head of Infectious Diseases, Vertex Pharmaceuticals, Inc.
Panel Discussion
11:30
What Does the Future Hold for Anti-Infective Discovery and Development?
- Why have so many large companies discontinued their anti-infective programs?
- Why do these same large companies remain so interested in agents that are under development in smaller companies?
- What is the risk of infection by a serious community-acquired pathogen such as MRSA?
- What role should the government and granting agencies play in the development of new antibiotics?
- Do pathogenic agents pose a real bioterrorist threat?
Chairperson:
Michael R. Barbachyn, Ph.D., Director, Infection, AstraZeneca Pharmaceuticals
Panelists:
Neil S. Ryder, Ph.D., Executive Director, Infectious Disease, Novartis Institutes for Biomedical Research, Inc.
Steven C. Gilman, PhD., Chief Scientific Officer and Senior Vice President, Discovery & Non-Clinical Development, Cubist Pharmaceuticals, Inc.
Ann D. Kwong, Ph.D., Head of Infectious Diseases, Vertex Pharmaceuticals, Inc.
Donald Moir, Ph.D., Chief Scientific Officer, Microbiotix, Inc
Main Conference
Transforming Technologies
11:00
Cancer Biomarker Discovery and Therapeutic Compound Screening Using ChIP-DSL/Seq Transcriptional Network Mapping
Mapping of Transcriptional Networks using ChIP-Seq and ChIP-DSL Technologies for Rapid Cancer Biomarker Discovery and Therapeutic Compound Screening will be presented. Genome-wide TF mapping of estrogen receptor interactions identified alternative regulatory pathways and prognostic breast cancer biomarkers, while additional studies identified FoxP3-mediated membrane protein targets with T-cell regulatory implications. We also describe promoter-DNA Methylation studies elucidating potential cancer and stem cell differentiation biomarkers, and key elements of the ChIP-DSL/Seq technologies.
Jeffrey Falk, Ph.D., Director of Technology Applications, Aviva Systems Biology
11:30
Biology-driven Discovery of Neuroprotective Drugs
Therapeutic intervention in Alzheimer's and Parkinson's disease by inhibiting protein aggregation-triggered cytotoxicity may represent an effective way of decelerating disease progression. reMYND has set out to discover disease-modifying compounds by unbiased screening of yeast-based models of amyloidogenesis. In this "biology"-driven approach efficacy of compounds is judged on the basis of pharmacologically relevant read-outs (i.e. inhibiting TAU/synuclein-instigated cytotoxicity and misfolding). This screening platform led to the identification of novel chemical entities that counteract neurotoxicity and modulate classical hallmarks of neurodegeneration in animal models of disease.
Gerard Griffioen, Ph.D., CSO, reMYND, Belgium
12:00
Networking Luncheon in Exhibit & Poster Hall
1:00
Dedicated Poster Viewing
1:30
Chairperson's Opening Remarks
Joseph B. Bolen, Ph.D., CSO, Millennium Pharmaceuticals
Breast Cancer
1:35
Inhibiting Signaling in Breast Cancer: Novel Therapeutic Strategies
Abstract not available at time of print.
Neal Rosen, M.D., Ph.D., Head of Developmental Therapeutics, Memorial Sloan-Kettering Cancer Center
Prostate Cancer
2:15
Novel Therapeutic Strategies in Prostate Cancer: Patient Selection and Monitoring
Prostate cancer is a disease with significant heterogeneity in terms of histopathology, molecular alterations and clinical course. Available therapeutic options to date have been scant and have relied primarily on androgen ablation. Importantly, novel therapeutic strategies (e.g. small molecules or antibodies) are being developed to inhibit a variety of oncogenic targets at the molecular level. However, a stratification system to select patients for targeted trials needs to be developed using tissue-based molecular probes. Therapeutic options, criteria for patient selection, the need to obtain tissue biopsies during the course of the trial, and monitoring of adequate molecular targeting will be discussed.
Massimo Loda, M.D., Director, Center for Molecular Oncologic Pathology, Dana Farber Cancer Institute, Brigham & Women's Hospital, Harvard Medical School
2:55
Panel Discussion with Afternoon Speakers
3:35
Networking Refreshment Break in Exhibit & Poster Hall
Main Conference
Cardio-Metabolic Diseases
1:30
Chairperson's Opening Remarks
Brian Hubbard, Ph.D., Senior Director and Basic Site Lead - Atherosclerosis, Merck Research Laboratories
Cardio-Metabolic Targets in Development
1:35
Leveraging Incretin Hormones for the Treatment of Type 2 Diabetes
GLP-1 agonists and DPP-4 inhibitors are significant new additions to the therapeutic armamentarium for type 2 diabetes. This presentation will review the current status of approved products, molecules in development and the long-term prospects of these drugs in the treatment of type 2 diabetes.
Richard E. Pratley, M.D., Professor of Medicine, Director, Diabetes and Metabolism Translational Medicine Unit, University of Vermont College of Medicine
2:05
Targeting HDL: Discovery to Patient Bedside
Novartis is engaged in the discovery of novel HDL modulating medicine and has licensed a functional mimetic peptide of ApoA1 from BruinPharma. The compound promotes the positive functions of HDL and restores endothelial homeostasis. The compound is being evaluated in man for the treatment of cardiovascular complications due to atherosclerosis.
Gene Liau, Ph.D., Research Head, Atherosclerosis, Cardiovascular and Metabolism, Novartis Institutes for Biomedical Research
2:35
CRx-401, A Synergistic Anti-Diabetic Discovered Using A Systems Biology Approach
Using a systems biology approach to diabetes drug discovery, CombinatoRx has identified a pool of novel synergistic combinations that increase glucose uptake in cellular assays. One combination, CRx-401, is a novel mechanism synergistic combination with both PPAR and anti-inflammatory properties. CRx-401 has demonstrated preclinical efficacy in decreasing fasting blood glucose and insulin resistance without promoting weight gain and is currently in a phase 2a clinical trial in Type 2 diabetes.
Margaret S. Lee, Ph.D., Vice President, Therapeutic Area Research, CombinatoRx, Incorporated
3:05
Delivering on the Promise of PDE5 Inhibition: SLx-2101, a Best-In-Class Cardiovascular Agent
1st-generation PDE5 inhibitors have not delivered on their therapeutic promise in cardiovascular diseases, due to inadequate tissue distribution and/or insufficient half-life. Using our Pharmacomer™ Technology Platform we designed SLx-2101 to overcome these shortcomings. Positive Phase II data in uncontrolled hypertensives and in patients with Raynaud's Disease shows SLx-2101's utility in cardiovascular disease.
James L. Ellis, Ph.D., Vice President, Preclinical Research, Surface Logix
3:35
Networking Refreshment Break in Exhibit & Poster Hall
Main Conference
Translational Medicine I
Biomarkers to Confirm Target Engagement
1:30
Chairperson's Opening Remarks
David W. Moskowitz, M.D., Chief Executive Officer, GenoMed, Inc.
1:35
Using SNPs to Lower Cancer Mortality
Genomic variation, including SNPs, causes disease. Genes with disease-associated SNPs operate further upstream in a disease pathway than tissue-expressed genes, so they make better drug targets. SNPs also enable pre-symptomatic diagnosis. In cancer, an early warning system is especially critical. We have found ~5000 SNPs associated with breast, colon, lung, ovary, pancreas, and prostate cancers in whites.
David W. Moskowitz, M.D., Chief Executive Officer, GenoMed, Inc.
2:00
New Perspectives for Disease Modification and Biomarkers for Alzheimer's Disease
To study the complex metabolic consequences of the disease processes and to identify candidates useful as biomarkers for diagnosis and disease progression, information-rich, non-selective but specific analytical approaches are required. Metabolic profiling offer the prospect of efficiently distinguishing individuals with particular disease or toxic states. Here we compare the metabolic profile in human cerebrospinal-fluid (CSF) samples of Alzheimer's disease (AD) patients and age matched healthy controls. With this approach we have identified candidates for biomarkers traced to particular metabolites or pathways specific for AD or the underlying neurodegenerative process.
Christian Czech, Ph.D., Senior Research Scientist, CNS Department, F. Hoffmann-La Roche, Switzerland
2:25
Translational Medicine Approaches in CNS Drug Development: "Buy Down" The Risk And Early Decision-Making
This presentation will illustrate the use of compound biomarkers to demonstrate proof of mechanism; the use of disease biomarkers to demonstrate proof of concept: evidence of modulating underlying neurobiology of the disease; and the use of experimental human models and innovative animal models to bridge the gap between preclinical discovery and clinical development.
Hong Wan, Ph.D., Associate Director, Clinical Translational Medicine, Wyeth Research
2:50
Prediction of Clinical Drug-Drug Interactions from In-Vitro Data
A novel method for the prediction of CYP mediated drug-drug interactions without using the [I] / Ki ratio will be presented. This method uses minimal in vitro data to quantitatively flag potential clinical drug-drug interactions in early drug discovery stage.
Chuang Lu, Ph.D., Senior Scientist II, DMPK, Millennium Pharmaceuticals
3:15
The Role of Biomarkers in the Discovery and Characterization of Sclerostin - A New Therapeutic Target for Treating Low Bone Mass Disorders
We have shown that neutralizing monoclonal antibodies to sclerostin can increase bone formation and bone strength in both rodents and primates. We have recently completed a human Ph I study that indicates that a single dose of an antibody to sclerostin can produce a dose-dependent increase in biomarkers of bone formation and a decrease in biomarkers of bone resorption. This project illustrates how biomarkers can play a key role in the characterization of a disease-causing human mutation as well as helping to identify and progress an antibody for treating low bone mass disorders.
Martyn K Robinson, Ph.D., Inflammation Biology, UCB-Celltech, United Kingdom
3:40
Networking Refreshment Break in Exhibit & Poster Hall
Main Conference
Translational Medicine II
Patient Selection & Stratification
1:30
Chairperson's Opening Remarks
Rose Maciewicz, Ph.D., B.A., M.A., Chief Scientist, Respiratory and Inflammation Research, AstraZeneca
1:35
Genes, Environment and Immunity in the Development of Rheumatoid Arthritis
Rheumatoid arthritis is a common complex disease, where onset, disease course, response to therapy and occurrence of co-morbidities are all dependent on genes, environmental exposures and immune reactions. We describe a Swedish and European translational program where all these parameters are analysed, in the context of genome wide genetic analysis.
Lars Klareskog, Rheumatology Unite, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Sweden
2:00
Increasing Precision in Your Image Analysis to Facilitate Patient Selection for Chronic Degenerative Disease Clinical Trials
Advances in MR imaging techniques will facilitate clinical trials but cannot mitigate failure to detect progression or efficacy of a new therapy if the patient population is heterogeneous. However, increasing the precision of analysis methods using statistical shape modeling enabled a more cost effective interrogation of cross sectional and longitudinal databases of knee osteoarthritis. This has helped to identify the appropriate patient characteristics for 'fast progresses'. Such information will facilitate smaller and possibly shorter proof of concept clinical trials.
Rose Maciewicz, Ph.D., B.A., M.A., Chief Scientist, Respiratory and Inflammation Research, AstraZeneca
2:25
Downstream Oncogenic Signaling Pathway Activation as A Means of Patient Selection
Selection of patients most likely to benefit from targeted therapeutics is a key area of study in oncology. This presentation will describe a case study whereby a previously identified prognostic biomarker was shown to be predictive in the setting of a targeted therapeutic following analysis in a randomized, controlled trial.
Scott Patterson, Ph.D., Executive Director, Medical Sciences, Molecular Sciences, Amgen Inc.
2:50
How Systems Biology Aids In Understanding Molecular Drivers of Safety Endpoints
Adverse events in clinical settings can generally be defined as unexpected efficacy. Because of the unexpected nature of such features we usually lack a cogent molecular hypothesis to prosvide insight and an ability to circumvent the issue. I will exemplify an approach to identify such mechanistic drivers through ongoing projects in the Pfizer portfolio.
David deGraaf, Director, System Biology, Pfizer RTC
3:15
Systems Biology: How to Understand Clinical Responses in the Context Of Specific Patients
Abstract not available at time of print.
Jonathan Swinton, Ph.D., AstraZeneca, United Kingdom
3:40
Networking Refreshment Break in Exhibit & Poster Hall
Keynote Speaker
4:20
Risk-Taking & Innovation in Biotechnology: The MedImmune Success Story
After operating independently for 19 years, MedImmune became part of AstraZeneca plc in June 2007. The new MedImmune - which integrates legacy MedImmune, Cambridge Antibody Technology and AstraZeneca's biologics activities - leverages the independent strengths of each piece of the organization to create a stronger, more diverse discovery engine within a fully |
