Beyond Antibodies 
Event Information
Document Title
Agenda
| Pre-Conference Workshop Monday, July 28, 2008 | PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | | ||||
| Enabling Technologies for Advancing Biologics Toward the Clinic | ||||
| 7:30 | Morning Coffee | |||
| 8:00 | Chairperson's Remarks Gregory Weiss, Ph.D., Associate Professor, U.C. Irvine | |||
| 8:15 | Stability-engineered IgG-like Tetravalent Antibody for Inducing Receptor-mediated Death in Leukemia Cells Cross-linking surface receptors such as BCR and CD20 on B-cell tumor cells and TRAIL-R2 on solid tumors has been observed to contribute to tumor cell death by inducing apoptotic signaling. By increasing antibody valency towards a B cell antigen expressed on human leukemia cells, a tetravalent antibody was proposed to be a more potent cross-linking agent for inducing tumor cell apoptosis. This presentation will discuss technology developed by Biogen Idec for engineering stable single-chain Fv domains that serve as building blocks for constructing IgG-like bispecific and tetravalent antibodies. You will hear how structural and statistical analyses were used to guide a stability engineering strategy resulting in marked improvements in the thermostability of the single-chain Fv moiety enabling high level production of a tetravalent antibody. In vitro studies with the tetravalent antibody that demonstrated enhanced anti-tumor cell activity will also be discussed. Brian Miller, Ph.D., Sr. Scientist, Molecular Engineering, Biogen Idec, Inc. | |||
| 8:45 | Harnessing a Self-Made Phage Library (SMPL) A naturally occurring diversity generating mechanism used by Bordetella bacteriophage allows automatically synthesized, library within library, phage display. The phage-encoded reverse transcriptase generates trillions of mutations across a 44-residue variable region required for phage attachment to its bacterial host. This presentation will explain how harnessing this diversity generating mechanism will access libraries potentially exceeding the diversities of conventional molecular display systems. Gregory Weiss, Ph.D., Associate Professor, U.C. Irvine | |||
| 9:15 | Harnessing Somatic Hypermutation for Antibody Selection and Optimization Somatic hypermutation (SHM) is the natural process of antibody maturation that creates high-affinity antibodies by introducing sequence variation at the IgV (variable) locus via targeted replication mutagenesis catalysed by the nuclear protein activation-induced cytidine deaminase (AID). Anaptys' fully human monoclonal antibody platform based on SHM for optimizing antibody target site and affinity parameters to evolve potent biotherapeutics will be discussed. William J. Boyle, Ph.D., President and Chief Science Officer, Anaptys Biosciences, Inc. | |||
| 9:45 | Networking Refreshment Break | |||
| 10:15 | Affinity Maturation: In Vitro & In Vivo Tools or Molecular Evolution In vitro evolution of antibody variable regions using ribosome display is a powerful tool to improve the potency of antibodies. The benefits of using this technology will be exemplified by data from several in vitro evolution studies. In the drug discovery context, the practice of engineering therapeutic antibodies from nanomolar to picomolar potency is crucial in allowing more candidates to progress into preclinical and clinical studies. Furthermore, sequence hotspot data generated from antibody evolution studies can pinpoint the important structural changes during the evolution process. When taken in conjunction with the mapping of antibody: antigen interaction surfaces it is possible to reveal trends in the structure-activity relationship of candidate drugs. In addition the talk will touch on some more recent work using ribosome display to optimize the potency of agonist antibodies. This model system allows an exploration of the assumption that improving antibody affinity is directly linked to improvements in potency. Ralph Minter, Ph.D., Head of Technology, Research, MedImmune | |||
| 10:45 | Aptamer-based Multiplexed Assays for Biomarker Discovery SomaLogic has developed improved aptamers for use in a multiplexed assay that allows the simultaneous quantification of hundreds to thousands of proteins from a single blood sample at levels below 1pM. The presentation will explain how this assay is being used for biomarker discovery in a number of disease areas, including oncology and cardio vascular diseases. In one lung cancer study, 11 proteins were differentially expressed between cancer and non-cancer samples. Aggregation of these markers into a diagnostic signature resulted in 95% sensitivity and 95% specificity for discriminating between these samples. Marty Stanton, Ph.D., Chief Scientific Officer, SomaLogic | |||
| 11:15 | Structural Analysis of Individual Protein Molecules and Complexes by Protein Tomography™ Protein Tomography™ is a method by which individual protein molecules are visualized. The study of individual protein molecules, not averages of large numbers of molecules, is the key to this technique. This allows the identification of binding epitopes and the determination of the mechanism of inhibition by an antibody or other binding agent. The visualization of individual protein molecules in solution or in the cellular context has been used to identify the site of binding of FAb's and antibodies to the structural epitopes to which they bind. The mechanism of inhibition of a receptor by an antibody was recently deduced using Protein Tomography™. Studies using Protein Tomography™ have consistently shown that antibodies and their targets exhibit a high degree of flexibility leading to a number of conformations, not just one. Michael D. Smith, Ph.D., Field Scientist, Sidec Inc. | |||
| 11:45 | Workshop Ends - Lunch on Your Own | |||
| Main Conference - Day One Monday, July 28, 2008 | PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | | ||||
| 1:15 | Chairperson's Opening Remarks & Keynote Introduction Dimiter S. Dimitrov, Ph.D., ScD, Senior Investigator, Protein Interactions, CCRNP, CCR, NCI-Frederick | |||
| Keynote Address | ||||
| 1:30 | The Good, The Bad, and The Ugly: Drivers for Development of Antibody Alternatives This talk will present how biopharmaceutical and molecular imaging markets are creating a wave of new engineered antibody formats and designed mimetics, including novel protein scaffolds. Enhanced targeting specificity and superior in vivo properties have been designed for a range of diagnostic and therapeutic applications, including conjugation to highly effective "payloads". Human proteomics are discovering novel disease biomarkers which presents an exciting opportunity to develop a wide range of antibody alternatives for therapy and diagnosis. Peter J. Hudson, Ph.D., Research Director, (Neurosciences and Molecular Imaging), CSIRO; Co-chair, HUPO-HAI and SAB Chair, AviPep Pty Ltd. | |||
| Advancements in Next Generation Protein Drug Discovery and Development | ||||
| 2:15 | Engineered Human Antibody Domains as Scaffolds - Nanoantibodies Against HIV and Cancer NCI-Frederick has identified and characterized a highly soluble and stable human VH domain antibody which was used to generate two large (size 2x1010) libraries of high diversity. Several high affinity domain antibodies against HIV and cancer-related proteins were identified and characterized with potential use as therapeutics. NCI-Frederick has also developed engineered human antibody domains as scaffolds which are highly soluble, stable and express at high levels. Based on these new scaffolds, several libraries have been constructed and binders against various antigens are being selected. How these results could be used for generation of "nanoantibodies" will be discussed. Dimiter S. Dimitrov, Ph.D., ScD, Senior Investigator, Protein Interactions, CCRNP, CCR, NCI-Frederick | |||
| 2:45 | Targeting TNF-alpha with ART621—The First Human Framework Domain Antibody to Hit the Clinic This talk will focus on domain antibodies (dAbs), the smallest functional antibody-based units, and how they offer potential for enhanced stability, production yields, tissue penetration and formatting flexibility, and reduced immunogenicity compared with full-size antibodies. Combinatorial methods yielded a potent TNF-alpha-neutralizing dAb which was formatted into a bivalent Fc-linked construct. The resulting molecule, ART621, is only half the size of an IgG, is produced at extremely high yields and is effective in animal models of inflammatory disease. Phase I data suggests the ART621 is generally well tolerated. The candidate is currently entering phase II clinical trials in psoriasis patients. David S. Wilson, Ph.D, Vice President of R&D, USA, Arana Therapeutics Ltd. | |||
| 3:15 | Networking Refreshment Break - Exhibit/Poster Viewing | |||
| 3:45 | Synthetic Biology and Secretion-Capture Display in Protein Engineering This talk will describe advances in construction of extremely high fidelity synthetic libraries, and in selection of target-binding proteins from such libraries. These include large synthetic variant libraries with error rates lower than 1 in 3,000 base pairs, and a novel, secretion-and-capture display method, which allows in-vitro selection of even complex, disulfide-bonded proteins. Dasa Lipovsek, Director of Protein Engineering, Codon Devices, Inc. | |||
| 4:15 |
Antibody fragments such as single-chain antibodies normally lack drug-like properties. Due to a novel and proprietary selection procedure, ESBATech has selected drug-like antibody fragments that qualify for direct therapeutic applications without the need for further protein stabilization. This opens new routes of administration like topical delivery in ophthalmology. A case study will be presented to demonstrate topical delivery via eye drops of an anti TNF antibody fragment to achieve high concentrations in the front as well as the back of the eye. Dominik Escher, Ph.D., CEO, ESBATech AG | |||
| Immunogenicity and Pharmacokinetics | ||||
| 4:45 | Immunogenicity of Biologics: A Regulatory Perspective Immunogenicity testing is a pivotal part of biologic drug development. This presentation will address the regulatory guidance's that apply to immunogenicity testing of biologics, both preclinically and clinically. Risk assessment strategies will differ dependent on the stage of drug development.The regulatory and clinical impact of antibodies to a drug product will be reviewed and discussed. Mary Ellen Cosenza, Ph.D., Executive Director, Regulatory Affairs & Safety, Amgen Inc. | |||
| 5:15 | Strategies to Improve Pharmacokinetics of Small Recombinant Antibody Molecules The therapeutic application of small recombinant antibody molecules and other therapeutic molecules is often limited by a short serum half-life. In order to improve the pharmacokinetic properties we have investigated several strategies including PEGylation, N-glycosylation, fusion to human serum albumin, and fusion to an albumin-binding domain of streptococcal protein G. This comparative study revealed that fusion to albumin or a albumin-binding domain results in a similar increase in circulation time as PEGylation (10-14 fold), while N-glycosylation only moderately increased half-lives (2-3 fold). In summary, these data provide a rational for the modulation of pharmacokinetic properties ranging from a moderate to strong improvement of blood circulation time. Steven J. Swanson, Ph.D., Executive Director Medical Sciences/Clinical Immunology, Amgen, Inc. | |||
| 5:45 | Networking Reception Sponsored by  | |||
| Main Conference - Day Two Tuesday, July 29, 2008 | PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | | ||||
| 7:45 | Morning Coffee | |||
| 8:15 | Chairperson's Remarks Willem 'Pim' Stemmer, Ph.D., CEO & Founder, Amunix | |||
| Protein Scaffolds and Peptides as Therapeutics and Diagnostics | ||||
| 8:30 | Phylomer® Libraries as a Rich Source of Stable Peptides with Biological Activity Against Multiple Target Classes Phylomers® are a new class of peptide derived from genomic fragments of biodiverse archael and bacterial species. These peptides can have high affinity and specificity for targets, even before affinity maturation or optimisation. Phylomer® peptides can also exhibit superior functional hit-rates to randomly encoded peptides, allowing direct phenotypic selections for biological activities. Phylomers® directly selected for binding to microbial cells can have potent antimicrobial activity with minimal toxicity to mammalian cells. Synthetic phylomers® against intracellular targets, have been shown to function in animal models, when fused to a protein transduction domain. Functional phylomers® against a signalling adaptor protein will also be described, together with phylomers® showing specific activity against the extracellular receptor CD40L involved in inflammation. Paul Watt, Ph.D., Vice President, Drug Discovery, Phylogica Ltd | |||
| 9:00 | Microproteins as a Platform for Therapeutics with Optimized Safety, Efficacy, and Manufacturability Amunix has created a platform for design of therapeutics derived from microproteins, which are small protein domains of 20-50AA and 2-4 disulfides that are mostly found in the venoms of snakes, spiders and scorpions. The small size, hydrophilic composition and the disulfide-crosslinked structure make microproteins protease resistant and poorly immunogenic. Amunix creates drugs against the native targets of microproteins (ion channels, integrins, etc) and against well-validated non-native targets (antibody mimetics). The microproteins are used as monomers or as homo- or hetero-multimers, connected by unstructured, hydrophilic sequences which also contribute a long half-life. These modules enable a variety of product formats, allowing us to optimally fit each target's needs. The unstructured, hydrophilic sequences have a larger hydrodynamic radius than typical folded, globular proteins and an apparent molecular weight that is 14-fold their actual molecular weight, and mimic the way PEGylation achieves a long serum secretion half-life. They are therefore called recombinant PEG or 'rPEG'. An example of each different product type will be presented. Willem 'Pim' Stemmer, Ph.D., CEO & Founder, Amunix | |||
| 9:30 | ANTICALINS®: Potent Antagonistic Binding Proteins Derived from Human Lipocalins for Use in Therapy This presentation will explain the many benefits of ANTICALINS® due to their small size, composition of a single polypeptide chain, independence of disulfide bonds or post-translational modification, facile production in microbial host cells. They offer unique opportunities such as dual targeting, pulmonary delivery, and tailored plasma half life. Biochemical, structural, and in vivo data for ANTICALINS® having picomolar affinities for relevant disease targets such as CTLA-4 and VEGF promise high potential as a novel class of biopharmaceuticals. Arne Skerra, Ph.D., Professor of Biological Chemistry, Technical University Munich and PIERIS AG | |||
| 10:00 | Networking Refreshment Break - Exhibit/Poster Viewing | |||
| 10:30 |
Cyclotides are an ultra-stable family of proteins having a cyclic cystine knot motif. The Institute for Molecular Biosciences have used this motif as a molecular template onto which to graft bioactive peptide epitopes and thereby stabilize them. In this presentation this platform technology is exemplified by the grafting of epitopes from myelin oligodendrocyte glycoprotein to generate new leads for the treatment of multiple sclerosis. David Craik, Ph.D., Professor, Institute for Molecular Biosciences, University of Queensland | |||
| 11:00 | The SH3 Domain of Fyn Kinase as a Scaffold for the Generation of New Binding Proteins The generation of novel binding molecules based on non-immunoglobulin protein frameworks ("scaffolds") represents an emerging field in protein engineering. Here, the design, construction, characterization, and use of a novel human Fyn SH3 library will be discussed. In particular, the isolation and in vitro characterization of Fyn SH3 derived proteins binding to mouse serum albumin and to the extra-domain B of fibronectin (EDB), a marker of angiogenesis will be presented. One specific, high-affinity EDB binding clone, named D3, showed a remarkable ability to stain vascular structures in tumor sections. Furthermore, quantitative biodistribution studies in tumor bearing mice revealed the ability of D3 to selectively accumulate in the tumor. Dragan Grabulovski, Ph.D., Chief Scientific Officer, Covagen AG | |||
| Delivery of Antibody Alternatives | ||||
| 11:30 | Pulmonary Delivered Domain Antibodies as Drugs The first dAbs products are now in the clinic and a broad pipeline of additional late stage preclinical assets is following close behind. This talk will review pre-clinical and clinical data of dAb based drugs: monomeric dAbs to cell surface receptors, pulmonary delivered dAbs, AlbudAb fusions and Dual Targeting dAbs. Focus will be placed on the preclinical proof of concept of a novel class of drugs, that is pulmonary delivered dAbs. Pulmonary delivered dAbs offer unique advantages compared to conventional mAb based therapies. GSK-Domantis Group demonstrates superior efficacy using a low dose of pulmonary delivered dAb against the TNF receptor 1 in a mouse model for COPD. This data demonstrates utility of dAbs for treatment of pulmonary disease and validates TNFR1 as a target for tobacco smoke induced disease. Ruud de Wildt, Ph.D., Manager, Biopharm CEDD, GSK-Domantis Group | |||
| 12:00 | Protein Transduction Delivery of Anti-Cancer Peptides & Proteins Delivery across the cell membrane is generally restricted to small molecules less than 500 Daltons in size. However, peptides, proteins, siRNAs are in vast excess to this bioavailability limitation. A lot of attention has been put on delivery by cationic protein transduction domains (PTDs)/cell penetrating peptides (CPPs), such as the TAT peptide. The mechanism that these peptides enter cells has been uncovered, namely macropinocytosis, a specialized form of fluid phase endocytosis, and devised methods to enhance endosomal escape. By using this information, PTD transducible peptides that target cell cycle regulatory proteins to treat mouse models of metastatic ovarian cancer and glioblastoma have been generated and will be discussed. Akiko Eguchi, Ph.D., Howard Hughes Medical Institute, Dept. of Cellular Molecular Medicine, UCSD School of Medicine | |||
| 12:30 | Networking Lunch - Exhibit/Poster Viewing | |||
| Beyond Antibodies Come of Age: Clinical Data | ||||
| 1:45 | Chairperson's Remarks Eric Furfine, Ph.D., Sr. VP, Research & Preclinical Development, Adnexus, a Bristol-Myers Squibb R&D Co. | |||
| 2:00 |
Adnexus is leading the advancement of Adnectins™, a novel, proprietary class of targeted biologics that are derived from human fibronectin, a well-characterized, high-concentration, plasma protein. Adnectin™-based products offer various potential advantages as compared to traditional protein therapeutics, including speed of discovery, ease of manufacturing, and multi-functionality. CT-322 (Angiocept™) is an inhibitor of VEGFR-2, and is the first Adnectin product candidate now in Phase 2 clinical trials. The emerging clinical data from this program will demonstrate the potential of Adnectins™ as a viable new product class to address important unmet medical needs. Eric Furfine, Ph.D., Sr. VP, Research & Preclinical Development, Adnexus, a Bristol-Myers Squibb R&D Co. | |||
| 2:30 |
A case study will be presented by Trubion Pharmaceuticals, a biopharmaceutical company that is creating a pipeline of novel protein therapeutic product candidates to treat autoimmune and inflammatory diseases and cancer. Trubion's current product candidates are novel single-chain protein, or SMIP™, therapeutics, and are designed using its custom drug assembly technology. In addition to its current product candidates, Trubion is also developing product candidates utilizing additional novel technologies. Kendall Mohler, Ph.D., Sr. VP, Research & Development, Trubion Pharmaceuticals | |||
| Technology Workshop | ||||
| 3:00 |  Discovery and Development of Novel Antibody Format and Protein-based Biotherapeutics using Capture Select® Affinity Ligands and Yeast Display Discovery ToolsThe development of novel antibody formats and proteinaceous scaffolds for biotherapeutics requires efficient and generic purification tools to characterize lead molecules. We describe methods of purification for various antibody formats (e.g. Fab, scFv, Fc-fusions), isotypes (e.g., IgA, IgM, IgE), and non-antibody protein scaffolds using CaptureSelect affinity ligands. We further describe our Yeast Display technology as a tool for the affinity maturation of lead molecules. Bruce Dawson, VP, Global Marketing and Sales, BAC, The BioAffinity Company | |||
| 3:30 | Networking Break - Last Chance to View Exhibits/Posters | |||
| 4:00 | Therapeutic Monoclonal Antibodies and Antibody Alternatives-An FDA Perspective Abstract to come. Kathleen Clouse, Ph.D., Director, Division of Monoclonal Antibodies, CBER, FDA | |||
| 4:30 | Panel Discussion: Strategies and Drivers of Mergers & Acquisitions in the Antibody Alternative Space In this panel, hear industry experts discuss:
Larry Gold, Ph.D., CEO & Chairman of the Board, SomoLogic Beth Jacobs, Partner, Bio IB Panelists: Eric Furfine, Ph.D., Sr. VP, Research & Preclinical Development, Adnexus, a Bristol-Myers Squibb R&D Co. Ruud de Wildt Ph.D., Manager, Biopharm CEDD, GSK-Domantis Group Chuck Wilson Ph.D., VP Alliance Management, Technology, Archemix | |||
| 5:30 | End of Conference | |||
Bottom menu
Copyright IBC Life Sciences, a part of Informa Life Sciences Group