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Drug Discovery & Development of Innovative Therapeutics Japan 2009
Concurrent Sessions
R&D Strategies in a Changing Global Market"Open Innovation" and Global Partnerships in Drug Discovery & Development
8:30
Chairperson's Opening Remarks
8:45
The Development and Commercialization of Dalcetrapib: An Innovative and Successful Partnership between Roche and Japan Tobacco
Roche and Japan Tobacco (JT) established a partnership in 2004 on dalcetrapib (R1658, JTT-705) a first-in-class CETP inhibitor. This collaboration forms one of the cornerstones of Roche's growth strategy in metabolism. JT's and Roche's global R&D capabilities, combined with an excellent working collaboration, have resulted in a successful alliance. The dalcetrapib development plan is on track to bring a potential new treatment option to patients, to reduce cardiovascular morbidity-mortality above and beyond current treatments. Christoph Sarry, Global Alliance Director, F. Hoffmann-La Roche Ltd., Switzerland Yoshinori Inubushi, Ph.D., Vice President, Corporate Licensing & Intellectual Property, Pharmaceutical Division, Japan Tobacco, Inc., Japan
9:15
Trust, Patience and Communication in Partnering to Achieve Alliance Success in Japan: A Case Study of Shionogi, Eli Lilly Japan and Eli Lilly
Eli Lilly and Shionogi have worked together for 100 years (100 year anniversary in 2009). We successfully navigated through a lengthy storming phase of our relationship to formally enter into a strategic partnership around a Lilly neuroscience asset in 2007. This presentation will include alliance health data that illustrates how the alliance has progressed since 2007. Ichiro Okino, Manager, Business Development, Shionogi, Japan Mr. Curtis McManus, Manager, Office of Alliance Management, Eli Lilly and Company, USA
9:45
US Biotech-Japan Pharma Collaboration on a Novel Therapeutic Antibody in Cancer
Hepatocyte growth factor (HGF) and its receptor c-Met are involved in initiation, progression and metastasis of a broad spectrum of cancers. Galaxy Biotech LLC (Cupertino, CA) created a potent anti-HGF mAb, which blocks the HGF/c-Met interaction and shows strong tumor growth inhibition activities in xenograft models. Galaxy gave Takeda Pharmaceutical Company Limited (Osaka, Japan) a global license to develop the mAb. Takeda developed an efficient production process and conducted IND enabling studies in various aspects of translational pharmacology, which are indispensable for successful clinical studies. Toshio Kokubo, Ph.D., Director, Biomedical Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Japan
10:15
Poster and Exhibit Viewing Refreshment Break
Find New Markets & Therapeutic Opportunities: Global R&D Strategies
10:45
GlaxoSmithKline's Strategy for Drug Development in Japan, Asia-Pacific and the Emerging Markets
Judith Hills, Ph.D., Vice President, Asia-Pacific, Japan and Emerging Markets, Worldwide Business Development, GlaxoSmithKline, United Kingdom
11:15
AstraZeneca's Evolving Strategy in Drug Discovery & Development
AstraZeneca has embarked on a series of initiatives to expand its drug pipeline and strengthen its global position as a leading drug development company. The partnership with Bristol-Myers Squibb and acquisitions of Medimmune and Cambridge Antibody Technology are just some examples of our efforts to position ourselves for growth. This presentation will reflect on these experiences and other business and partnership models implemented to enhance our global drug research, development and commercialization efforts. Patrick Keohane, M.D., Vice President and Head of R&D, AstraZeneca KK, Japan
11:45
Networking Luncheon in Poster and Exhibit Hall
Featured Presentations
1:00
Kyowa Hakko Kirin's R&D Strategy for Global Specialty Pharma
Kyowa Hakko Kirin was created as a top-class, R&D based life-science company in Japan on October 1, 2008 by consolidation of Kyowa Hakko and Kirin Pharma. Kyowa Hakko Kirin aims to leverage the respective strengths of two of Japan's leaders in antibody drug technology-centered biotechnology, provide new medical value and compete globally. Kyowa Hakko Kirin has accelerated the overseas clinical development of novel drugs which challenge immense unmet medical needs in cancer therapy. Nobuo Hanai, Ph.D., Vice President, Head, Development Division, Kyowa Hakko Kirin Co., Ltd., Japan
1:30
Chugai's Global R&D Strategy in Antibody and Protein Medicine: Current Status and Future Direction of Next-Generation Biopharmaceuticals
The targeted disease area for antibody drugs extends beyond oncology to intractable disease areas such as rheumatoid arthritis. For second-generation biopharmaceuticals, research is underway on advanced technology-based drugs for innovative therapies. The current status and future of biologics discovery and development will be described. Tatsumi Yamazaki, Ph.D., Executive Vice President, Member of the Board, Chugai Pharmaceutical Co., Ltd., Japan
The Antibody Discovery and Protein Science SummitTutorial: Immunogenicity Prediction of Antibody and Protein TherapeuticsPlease note: Simultaneous translation will not be provided for this tutorial. Tutorial Schedule: This session runs from 8:30 am-2:00 pm. There will be a 30 minute refreshment break at 10:15 and lunch from 11:45 am-12:45 pm.
8:30
Tutorial Leaders' Opening Remarks
One of the great surprises of the biologics revolution has been the discovery that recombinant proteins, including monoclonals of human origin, can cause immune responses when administered to immune-competent subjects. Evaluation of the immunogenicity of biologics has been primarily focused on humoral immune response and as a result, the critical contribution of T cells to the development of anti-monoclonal antibodies (also known as anti-drug antibodies or ADA) has been overlooked. The contributions of effector T cells and regulatory T cells to the development of anti-drug antibodies are relevant to good biologics drug design. This review will focus on the role of T-cell-dependent (Td) immunogenicity assessment in the pre-clinical and clinical phases of drug development. Recent published studies that describe regulatory T-cell epitopes contained in the Fc and CH1 domains of IgG (monoclonals) would suggest that the role of Td immune response deserves greater emphasis in the context of immunogenicity screening and assessment for bioengineered protein therapeutics. Recommendations for Td immunogenicity screening and assessment may contribute to the development of safer protein-based drugs for human use. You will learn about:
Anne S. De Groot, M.D., Adjunct Associate Professor of Medicine, Brown University and Founder, CEO & CSO, EpiVax, Inc., USA Matthew Baker, Ph.D., Chief Scientific Officer and CEO, Antitope Ltd., United Kingdom Additional Speakers/Q&A Panelists:
Immune Responses to Beta Interferon and the Effect on Clinical Efficacy
Michaela Lerner, Senior Manager. Preclinical and Clinical Development Sciences, Biogen Idec, Inc., USA Taruna Arora, Ph.D., Principal Scientist, Protein Science, Amgen, Inc., USA
Current Practice in Clinical Immunogenicity Assessment
Catherine Wang, Ph.D., Manager, Clinical Immunology, Biopharm R&D, GlaxoSmithKline
10:15
Refreshment Break
10:45
Tutorial Continues
11:45
Lunch
12:45
Tutorial Continues
2:00
Close of Tutorial. Start of General Session
General SessionR&D Strategies to Develop Antibody-Based Therapeutics
2:00
The New, New Things in Antibody Technology
The therapeutic antibody market is now well established, mature and growing faster than any other pharmaceutical category. Whether starting a new program, or resurrecting an old one, there is now a wide range of discovery technologies available that need to be evaluated in light of competing, non-antibody drug development approaches. Kevin Johnson, Ph.D., CEO, PanGenetics, United Kingdom
2:30
High Affinity Therapeutic Antibody Leads from Phage Display Libraries
Modern antibody phage display libraries, mined through automated screening approaches, can rapidly generate leads with affinities comparable to those obtained from the secondary immune response. Key aspects of this technology as applied at Dyax Corp will be overviewed, including library design considerations, high throughput methods for affinity determination, and information management challenges and solutions. The success of this technology will be highlighted through several case studies describing rapid discovery of human antibody development candidates. David R. Buckler, Ph.D., Director, Alliance Research, Dyax Corp., USA
3:00
Poster and Exhibit Viewing Refreshment Break
Sponsored by: RR Donnelley
3:30
 The "ADLib® System" is an innovative cellular antibody library technology based on a unique mechanism of antibody diversification and gene conversion. The "ADLib® System" can provide specific antibodies recognizing unique epitopes against very tough antigens such as membrane transfer proteins and evolutionally conserved proteins. Flexible approaches to generate unique antibodies will be discussed with the "ADLib® System". Masa Fujiwara, President & CEO, Chiome Bioscience, Inc., Japan
4:00
Considerations of Quality and Safety in Molecule Design Strategy for Antibody Therapeutics Development
Designing the best therapeutic molecule starts with the end product profile in mind. Next generation antibodies development should take considerations of safety and manufacturability in addition to improving efficacy. Integration of product characteristics and immunogenicity risk assessment into antibody design early on helps minimize potential risks and accelerate timelines for development. Our new approach deploys a number of tools in screening, designing, and selection process of therapeutic antibody candidates. Taruna Arora, Ph.D., Principal Scientist, Protein Science, Amgen, Inc., USA Keynote Presentation
4:30
Keynote Introduction
Osamu Sato, Ph.D., Director, Head of Medical Writing Group, Clinical Data & Biostatistics Dept, R&D Division, Daiichi Sankyo Co., Ltd, Japan
4:35
Eisai Global R&D StrategyEisai has been focusing on the creation of new products in the areas of neuroscience, oncology, vascular, immunology/allergy, and therapeutic antibodies by streamlining the flow of originality and creativity among all of Eisai's discovery functions in global research clusters in Tsukuba/Kobe, Boston/Philadelphia, and London. Recently Eisai has decided to change our activities from research and development to product creation, increasing the emphasis on patient orientation. Kentaro Yoshimatsu, Ph.D., Senior Vice President, Research & Development, Eisai Co., Ltd., Japan
5:10
Networking Reception in Poster and Exhibit Hall
6:10
Close of Day One
General Session
8:30
Chairperson's Welcome and Opening Remarks
Special FDA Presentation
8:35
FDA's Strategy for Predictive Toxicology in New Drug Development: Integrating "Omics" and In Vivo Data into a Regulatory Perspective
The FDA's Division of Systems Toxicology supports the development of new technologies and facilitates integration of data from multiple technology platforms for application to questions associated with the FDA's Critical Path Initiative. The goals of the Division are to identify markers of adverse drug effects and diseases that can be applied in the move toward personalized medicine and to provide technical expertise and guidance for the inclusion of "omics" and in silico data into the review process. The presentation will also provide an overview of the FDA's current priorities from discovery through NDA from a regulatory perspective. Donna L. Mendrick, Ph.D., Director, Division of Systems Toxicology, NCTR, U.S. Food and Drug Administration Audience Interactive Panel Discussion
9:15
Approaches to Predicting and Understanding Drug Liabilities
Ask your questions to the panelists who will address topics including:
Panelist: Yi Wang, M.D., Head, Preclinical Sciences, Alexion Pharmaceuticals, USA
9:45
Poster and Exhibit Viewing Refreshment Break
Concurrent Sessions
Accelerating from Early Discovery to Clinical POCScientific Strategies and Tools in Early Discovery
10:15
Chairperson's Welcome and Opening Remarks
10:20
Locus Pharmaceuticals' Fragment-Based Drug Discovery Engine and Pipeline: Case Study of a Collaboration with Ono Pharmaceuticals
In silico simulation of fragment-protein interactions is expected to extend the already important contribution of fragment-based methods for drug design by increasing the number and diversity of fragments that can be evaluated within a short period of time. This technology is the basis for our own drug discovery pipeline and for a significant drug discovery collaboration with Ono Pharmaceuticals. We will present case studies that the illustrate the application of these methods. Jeff Wiseman, Ph.D., Vice President, Discovery & Chief Technology Officer, Locus Pharmaceuticals, USA
10:45
Rapid Development of An Oncology Pipeline: Case Study of ArQule's Computerized Structure-Based Drug Design Platform
Protein kinases are important signal transducers in normal and malignant cells. The typical Type I kinase inhibitor that binds to the highly conserved ATP-recognition site of these enzymes tend to have poor selectivity, which can translate to substantial off-target toxic side effects. New approaches in computer assisted structure-based drug design have yielded more selective (less toxic) inhibitors that have the potential to treat diseases outside the field of oncology. Thomas Chan, Ph.D., Chief Scientific Officer, ArQule, Inc., USA
11:15
 Traditionally, companies offer segmented research or manufacturing services in the pharmaceutical value chain. Orchid Research Laboratories, the drug discovery subsidiary of Orchid Chemicals & Pharmaceuticals Ltd., offers an integrated Custom Research and Manufacturing Services model that takes New Chemical Entities (NCEs) from discovery stage (milligram level) to launch stage (commercial scale) through various stages. The company has discovery engines in oncology, diabetes, inflammation and anti-infectives. A twin pronged strategy of proprietary drug discovery and collaborative drug discovery enables Orchid to match its capabilities to different partnership needs. CB Rao., Ph.D., Chief Mentor, Orchid Research Laboratories, India
11:45
 Cell-based studies are essential tools in drug discovery. However, the cell lines employed have often been determined by available biological tools and assay technologies, rather than by physiological relevance. Consequently, focus on primary and stem cells that are more phenotypically appropriate models of human disease is rapidly increasing. Critical for this focus is the development of tools, such as transfection technologies, stem cell reagents, transient assay methods, specialized culture reagents, etc, specifically developed for these medically relevant cells. This presentation will highlight the latest advances in such tools. Henry C. Chiou, Ph.D., Principal Scientist, Invitrogen Molecular Biology Reagents Division, Life Technologies, USA
12:15
Networking Luncheon in Poster and Exhibit Hall
1:15
QTempo: A More Sensitive, Accurate Alternative to the hERG Assay Utilizing Pluripotent Stem Cell-derived Beating Cardiomyocytes
Drug-induced QT interval prolongation (DIQTIP) can lead to sudden cardiac death and is a major safety concern for the drug industry and regulating agencies. To reduce the risk of DIQTIP, drug candidates are routinely assayed for in vitro electrophysiological properties using cell-based assays. Here we report the development of QTempo (QT prolongation Examination with Myocardia derived from Pluripotent cell), a significantly improved assay that incorporates beating cardiomyocytes derived from stem cells. Yasuyuki Asai, Ph.D., Chief Technology Officer, ReproCELL, Inc., Japan Technology Workshop
1:45
 The pharmaceutical and biotechnology sectors are under pressure to reduce time and costs for discovery and development of new therapeutic antibodies. This hunt for the right cell candidate is fundamental at both the discovery stage (finding antigen-specific clones from hybridoma fusions) and the cell line development stage (isolating the highest producers from transfections). ClonePix FL is widely used to rapidly find and isolate the best clones from large heterogeneous cell populations for use as therapeutic protein producing cells. The power of this technology lies in its ability to visualize and quantify antibodies secreted from thousands of clones directly in cell culture plates, and to select and isolate only the highest value candidates, thus bypassing the need for high throughput automation. The technology also dramatically increases throughput, shortens timescales and reduces workload. This presentation will highlight applications for 1) finding antigen-specific IgG-secreting clones from hybridoma fusions in as little as 8 days eliminating the need to collect and process large numbers of clones, and 2) rapidly isolating the highest producers from transfected CHO cell lines. Speaker: TBD Accelerating Compounds to the Clinic
2:15
Translational Medicine: Imaging of Serotonin Synthesis in Affective Disorders
To perform imaging of regional brain serotonin (5-HT) synthesis with labelled α-methyl-L-tryptophan [α-MTrp] in the normal and affected brain, studies were performed on laboratory animals using two different rat models of depression. These models showed that antidepressants produce changes in 5-HT synthesis and some 5-HT receptor sites. Some of these correlate with behavioral changes. The evaluation and imaging of regional synthesis, using α-MTrp as a tracer, is an excellent methodology for studying changes in brain 5-HT synthesis and the regional effects of drugs and can help in the discovery new drugs and new treatment modalities. Mirko Diksic, Ph.D., Professor, Department: Neurology and Neurosurgery, McGill University, Canada
2:45
Developing Novel Anti-inflammatory Therapy for Asthma
This presentation will discuss the development of an anti-inflammatory drug that blocks intrapulmonary activation of complement for the treatment of asthma. We will discuss the results of POC studies, the ongoing development program including the results of GLP inhalation toxicology program and the potential strategies of moving forward. Yi Wang, M.D., Head, Preclinical Sciences, Alexion Pharmaceuticals, USA
3:15
Poster and Exhibit Viewing Refreshment Break
3:45
Use of Proteomics and Nanotechnology in Clinical Specimens for Biologically Relevant Target Assessment and Compound Characterization in Oncology
We have developed an approach to measure proteins in clinical specimens at the nanoscale. Using this approach in as few as 25 cells, 5 pgs or 200 nl of specimen we can measure and quantify proteins and their phosphorylation state. This approach enables us to perform detailed proteomic anaylsis on clinical specimens. In particular, we have been able to examine proteomic changes in response to a targeted therapeutic in vivo in human patients. Our general approach can be applied to the development of many types of new therapeutics. Dean W. Felsher, M.D., Ph.D., Associate Professor, Oncology, Stanford University
4:15
Bioventure and Emerging Company Showcase
This session will highlight emerging companies involved in drug discovery and development. Participating companies will present their business plan, technology and applications in drug development. For more information on how to present in this company showcase, please see guidelines on the website or contact Michael Keenan of IBC Lifesciences at mkeenan@ibcusa.com
The Antibody Discovery and Protein Science SummitThe Next Wave of Antibody and Protein-Based Therapeutics
10:15
Chairperson's Welcome and Opening Remarks
Kevin Johnson, Ph.D., CEO, PanGenetics, United Kingdom
10:20
Pharmacology of Antibodies Selected for High ADCC Activity
The generation of monoclonal antibodies with improved effector functions is an area of intensive research. We have established a proprietary technology allowing the selection of antibodies with high contents of non-fucosylated antibodies and enhanced effector activity. In this context, the improved pharmacological properties of a fully human anti-RhD monoclonal antibody and a chimeric monoclonal antibody directed against CD20 will be discussed. Margarita Salcedo Magguilli, Ph.D., Director, Pharmacology and Toxicology Department, LFB Biotechnologies, France
10:45
 This presentation describes a large scale comparison of wildtype and expression-optimized versions of 100 human genes selected from the NCBI Entrez database in mammalian expression systems. In the vast majority of cases, expression optimized constructs outperform their native counterparts in protein yield with unaltered protein functionality, clearly demonstrating the benefits of sequence adaptation to the desired application compared to working with the natural sequence. Applications of this approach in drug discovery research will be discussed. Max Muehlig-Versen, Ph.D., Vice President Asia-Pacific Operations, GENEART AG, Germany
11:15
Human B-lymphocytes as an Excellent Source of High-affinity Antibodies
Evec has a technology to generate fully human antibodies utilizing the growth promoting activity of Epstein-Barr virus (EBV) for B-lymphocytes. The antibodies generated have high affinities ~10-12M, because they are derived from naturally immunized human B-lymphocytes. The EBV technology should become a major technology for antibody generation in the future. Kenzo Takada, M.D., Ph.D., Chairman, Evec, Incorporated, Japan
11:45
Discovery and Production of Human Therapeutic Antibody Mixtures from Single Clonal Cells
Preclinical and clinical evidence indicates that mixtures of therapeutic antibodies (mAbs) provide improved efficacy; however, the developmental and regulatory complexity and manufacturing cost of developing multiple mAbs poses a barrier to their use. To address these issues, we developed the Oligoclonics™ Technology, a platform for the production of mixtures of mAbs by single clonal cell lines. John de Kruif, Ph.D., Chief Scientific Officer, Merus Biopharmaceuticals, The Netherlands
12:15
Networking Luncheon in Poster and Exhibit Hall
1:15
From Pre-clinical to Clinical DARPins
DARPins are a novel class of tailor-made binding proteins with several advantages over monoclonal antibodies. Recent progress with DARPins in pre-clinical programs underlines their potential as therapeutics with optimal PK and low immunogenicity. Michael T. Stumpp, Ph.D., Chief Scientific Officer, Molecular Partners, Switzerland
1:45
Treatment of Cancer by BiTE-activated T cells
Residual tumor cells as are left after standard cancer therapy pose a high risk for relapse and lethal metastasis. Here, we show that this 'minimal residual disease' can be effectively treated with BiTE antibody blinatumomab, which can eliminate residual tumor cells in the bone marrow of patients with acute B-lymphoblastic leukemia. Blinatumomab is also effective in treating bulky disease of patients with non-Hodgkin's lymphoma. Patrick Baeuerle, Ph.D., Chief Scientific Officer, SVP of R&D, Micromet AG, Germany Technology Workshop
2:15
 Sponsored by: Genscript
2:45
Accelerating Drug-Like Antibody Fragments to the Clinic
ESBATech is developing single-chain Fv antibody fragments as therapeutics for topical application. Our platform technology allows us to make drug-like antigen specific fragments against any given target. By using these scaffolds we generated an anti-TNF antibody that is currently in early clinical development for the therapy of acute anterior uveitis by application in eye drops. This case study will show how we generated and improved this anti-TNF scFv with excellent drug-like properties and good efficacy by applying a novel approach in protein engineering. David Urech, Ph.D., Head of Research and Preclinical Development, ESBATech, Switzerland
3:15
Poster and Exhibit Viewing Refreshment Break
3:45
Developing a Novel anti-TNF Therapy Incorporating Domain Antibodies
Domain antibodies (dAbs) are the smallest functional antibody-based units. dAbs offer potential advantages over full-size antibodies including formatting flexibility, reduced immunogenicity and improved production yields and tissue penetration. ART621 is an anti-TNF molecule that contains 2 identical human framework dAbs directed against human TNF linked to a human Fc region. ART621 is the first dAb-based product to enter clinical trials and is currently in Phase II trials for psoriasis and rheumatoid arthritis. The presentation will summarize key pre-clinical and clinical data and the challenges of developing a new type of biologic therapeutic product. David Fuller, M.D., Chief Medical Officer, Arana Therapeutics Ltd., Australia Audience Interactive Panel Discussion
4:15
Antibodies and the Next Wave: Building a Biologics Franchise
Ask your questions to the panelists who will address topics including:
Panelists: Tatsumi Yamazaki, Ph.D., Executive Vice President, Member of the Board, Chugai Pharmaceutical Co., Ltd., Japan Judith Hills, Ph.D., Vice President, Asia-Pacific, Japan and Emerging Markets, Worldwide Business Development, GlaxoSmithKline, United Kingdom Kevin Johnson, Ph.D., CEO, PanGenetics, United Kingdom General SessionFeatured Presentations
4:45
Takeda's Global Business Development Activity: Current and Future
Takeda's global business development strategy for the future is based on acquisitions and research/product alliances in order to maximize Takeda's international presence moving towards 2015 and beyond. This presentation will discuss our experiences to date and strategy for the future. Toshikazu Ban, General Manager, Global Licensing and Business Development, Takeda Pharmaceutical Company Ltd., Japan
5:15
R&D Globalization Strategy: Challenges for Efficiency
To succeed in pharmaceutical development and remain competitive with global mega-pharmas in an environment of decreasing productivity and efficiency in drug development globally, a new strategy is required. Alliance and partnering activities are essential combined with the use of innovative scientific technologies and internal process improvements. This presentation will discuss some of the endeavors currently underway at Shionogi. Takuko Yamada Sawada, Corporate Officer, Executive General Manager, Pharmaceutical Development Division, Shionogi & Co., Ltd., Japan
5:45
Networking Dinner in Tokyo
Join fellow attendees and speakers for an evening out in Tokyo. Space is limited and an additional fee applies. Check box on registration form to sign up. General Session
8:45
Chairperson's Remarks
Dmitry Samarsky, Ph.D., Vice President, Technology Development, RXi Pharmaceuticals, USA Keynote Presentation
9:00
Technical Advancements in Extracting Useful Information from the GenomeAs part of a systems biology approach to studying molecular networks and pathways in differentiating cells, RIKEN scientists use a variety of high-throughput sequencing technologies. We have developed a simple, accurate and rapid DNA amplification scheme called the SMart Amplification Process (SMAP) to address the growing need for molecular diagnostic assays. It has tremendous potential for use in translational medicine from pharmacogenomics-based drug discovery to point-of-care diagnostics. This technology and other scientific innovations from RIKEN's Omics Science Center will be discussed. Yoshihide Hayashizaki, M.D., Ph.D., Director, Omics Science Center, RIKEN, Japan RNAi as a Therapeutic Modality: siRNA and miRNA
9:30
RNAi Therapy: Is it Too Early?
There is no doubt that siRNA is a powerful weapon to down-regulate target genes. We have checked siRNA sequences categorized as siRNA therapy in over 1,000 publications to evaluate siRNA sequence effectiveness to the target gene for potential therapy and to evaluate off-target effects. Prof. K. Saigo and others have made progress on basic science for RNAi mechanism governing its therapy. Their progress lets us challenge RNAi therapy. This presentation will discuss our latest results supported with actual demonstration of siRNA design and selection. Yukikazu Natori, Professor, Tokyo Institute of Technology; Executive Consultant, RNAi Co., Japan
10:00
Development of a Novel RNAi Therapeutics Platform
The design and effective delivery of synthetic RNAi compounds are important factors for therapeutic applications. We will present data obtained with our proprietary rxRNA™ compounds, which can be up to 100 times more potent than conventional siRNAs, demonstrate nuclease resistance, and are potentially more specific for their intended targets. We will also discuss the possible mechanism of incorporation of chemically modified molecules into the RNAi machinery. Dmitry Samarsky, Ph.D., Vice President, Technology Development, RXi Pharmaceuticals, USA
10:30
Networking Refreshment Break
11:00
Atu027, a Liposomal siRNA Formulation Targeting PKN3, Inhibits Cancer Progression
We show that systemic administration of Atu027 by repeated bolus injections or infusions in mice, rats and non-human primates results in specific, RNAi-mediated silencing of PKN3 expression. We demonstrate efficacy of Atu027 in orthotopic mouse models for prostate and pancreas cancer with significant inhibition of tumor growth and lymph node metastasis formation. A prospective, open label, single-centre, dose finding phase I study with Atu027 in subjects with advanced solid tumors will commence in March 2009. Klaus Giese, Ph.D., Chief Scientific Officer and Vice President, R&D, Silence Therapeutics plc, Germany
11:30
Developing Multi-Targeted siRNA Therapeutics with Nanoparticle-Enhanced Delivery
Using siRNA cocktail to silence multiple disease genes is truly realizing the advantage of siRNA-based drugs. We have developed siRNA cocktails using the proprietary algorithm and "Tri-Blocker™" platform, as the active pharmaceutical ingredient (API). Those siRNA cocktails were further tested and validated in several disease relevant animal models using either polymer based or liposome-based nanoparticle delivery systems. Patrick Y. Lu, Ph.D., President and CEO, Sirnaomics, Inc., USA
12:00
Benefits of A Comprehensive Approach to RNAi-Based Therapeutics
Successful RNAi-based therapeutics will require effective oligonucleotide construct and delivery options. MDRNA constructs include Dicer substrate (D-siRNA), meroDuplex (three-stranded) and UNA (unlocked nucleic acid) siRNAs. Constructs tailored to target gene provide high potency while minimizing undesired effects such as off-target events and cytokines. Delivery includes liposomes based on our novel DiLA2 platform, peptide-based formulations, or conjugates. These approaches have proven efficacious for viral, metabolic, and oncology targets. Barry Polisky, Ph.D., Chief Scientific Officer, MDRNA, Inc., USA
12:30
Networking Luncheon
1:30
LNA Oligonucleotides – Within Reach of Potent and Safe Oligonucleotide Therapeutics?
Short, single stranded oligonucleotides based on Locked nucleic acids (LNAs) display unprecedented and long lasting potency in a range of tissues in experimental animals upon intravenous or subcutaneous administration of naked molecules at very low doses. To date 5 different LNA oligonucleotides have completed IND enabling tox against mRNA or miRNA targets and three are currently being examined in human clinical trials. The presentation will provide an update on the unique features of LNA oligonucleotides and their use in human therapeutics. Henrik Ørum, Ph.D., Chief Scientific Officer, Santaris Pharma, Denmark
2:00
Identification and Therapeutic Application of Tumor Suppressor miRNAs
The miR-15/16, miR-34, let-7, and several other miRNAs have been shown to regulate the expression of key oncogenes and the activities of important cancer-related pathways. Reduced expression of these important miRNAs appears to contribute to tumorigenesis and metastasis. We have developed synthetic mimics for six tumor suppressor miRNAs and evaluated the capacity of the small RNAs to inhibit tumor development and metastasis following IV injections in mouse models of cancer. Intriguingly, several of the miRNA mimics have proven to be very effective in restricting the growth and spread of cancer. We are now proceeding with the development of miRNA-based therapies that can be tested for safety and efficacy in advanced animal models. David Brown, Ph.D., Director of Research, Mirna Therapeutics, Inc., USA Panel Discussion
2:30
Is RNAi a Viable Drug Modality?
3:00
Close of Conference
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