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6th Assay & Drug Discovery Technologies

 
  May 10, 2011  
     
 
GTC, Hyatt at Fisherman's Wharf, San Francisco, CA
July 07-08, 2011


Day 1Day 2
 
Day 1 - Thursday, July 7, 2011
  
7:00Registration & Continental Breakfast
  
7:55Welcome & Opening Remarks
  
  
 KEYNOTE PRESENTATION
8:00Single Cell and Tissue Proteomic with QFIA
  
 George P. Hemstreet III, M.D. Ph.D.
Chief and Professor
Urologic Surgery
University of Nebraska Medical Center
  
 Innumerable biomarkers have been investigated and include DNA, mRNA, microRNA, and proteins. Thus, there are multiple approaches for classifying biomarkers as they relate to the pathogenesis of human disease. Quantitative Fluorescence Image Analysis (QFIA), is a microscope system approach whereby proteins can be precisely quantified in the context of the micro ecosystem of the cellular compartments. Critical to the success of quantification is appropriate sample collection, fixation, instrument calibration, specificity of reagents and etc. Recent advances in optical imaging fluorescent standards and antibody reagents, stable light sources have led to the development of QFIA methodology to study the fundamental events occurring in the cellular actin associated with premalignant and malignant changes associated with human carcinogenesis. The precision of protein measurements has also served to elucidate and confirm the concept of biochemical field disease. Longitudinal studies of workers at risk for bladder cancer have clarified the concept of premalignant field disease and can predict individuals at risk for malignancy years in advance of clinically manifest cancer. The opportunity exists to incorporate this methodology in studying individuals at risk for malignancy and defining specified treatment regimens for the notification of individualized risk assessment, prevention, and therapy. Fundamental concepts of QFIA will be presented for the clinical and research utility of this system.
  
  
Session I: Cell Based Assays
 
  
8:45Robert Damoiseaux, Ph.D., Scientific Director, Molecular Shared Screening Resources at the California Nano Systems Institute, UCLA
  
9:10James Herrington, Ph.D., Scientist, Genentech
  
9:35High-Throughput in vivo Vertebrate Screening at Cellular Resolution
 M. Fatih Yanik, Ph.D., Lab Director, High Throughput Neurotechnology Group, Massacheusetts Institute of Technology
  
10:00Networking & Refreshment Break
  
10:30Microfluidics 2.0: Cell-based Discovery
 Cristian Ionescu-Zanetti, Ph.D., Chief Technology Officer, Fluxion Biosciences
  
10:55Chaohong Sun, Ph.D., Group Leader, Fragment Screening and Lead Characterization, Abbott
  
11:20Flori Sassano, Ph.D., Research Associate, Bryan Roth Lab (GPCR), University of North Carolina, Chapel Hill
  
Session II: Assays for Biotherapeutics and Beyond
 
  
11:45Using Label-free Assays to Improve Efficiency in Drug Discovery
 Fredrik Sundberg, Global Director, Strategic Market Development, GE Healthcare
  
 Enabling technology solutions can impact discoveries in basic research, as well as critical stages of drug discovery and product development, improving both drug candidate quality and overall productivity by reducing safety risks and improving efficacy. The use of disruptive technologies, such as label-free and high-content cellular analysis, can rapidly eliminate false-positive hits in screening and drive lead optimization to improve the probability of success in later clinical stages. For example, the implementation of rapid SPR biosensor assays and ultra-sensitive calorimetry provide more information faster on protein interactions that can be used in both hit validation as well as biomarker related assays, such as clinical immunogenicity testing. Combined with scalable purification solutions and cell-based bioassays, label-free technology solutions improve overall productivity all the way from research to QC. It targets key applications for most therapeutic strategies and opens future opportunities for pairing therapeutics and diagnostics.

Main topics covered include:
• Market overview and introduction to label-free technologies
• Key application areas in screening and hit validation
• Fragment-based screening using SPR biosensors
• Protein stability and biomarker analysis
• Future vision on label-free approaches
  
12:10Lunch On Your Own
  
1:30[Oral Presentations from Exemplary Submitted Abstracts]
 To be considered for an oral presentation, please submit an abstract here.
  
1:55Darren Kamikura, Ph.D., Research Scientist, Bioassays, Eli Lilly
  
Session III: Advanced Methods in Drug Discovery
 
  
2:20Mass Spectrometry – Pros and Cons in its Application in High Throughput ADME Profiling
 Sean Xiang Wu, Ph.D., Associate Director, New Lead Discovery, Exelixis
  
 Early assessment of ADME (Absorption, Distribution, Metabolism, and Excretion) properties of drug candidates has become an essential component of modern drug discovery. ADME characterizations are important in identifying compounds that are likely to fail in clinical development, meanwhile prioritizing candidates that are more likely to have good human pharmacokinetic properties and to avoid or minimize potential drug-drug interactions. At Exelixis we have established a capability to profile compounds (>100 compounds/week) in a panel of ADME assays in parallel with biochemical and cellular characterizations. Traditionally, LC-MS has been used to analyze ADME samples. Even after extensive optimization to shorten its run time, LC-MS method still couldn’t handle the rapidly increasing number of ADME samples from CYP450 inhibition and metabolic stability assays. Recently we integrated a RapidFire system with an ABI4000 mass spectrometer to increase our sample analysis throughput by over 20-fold. This system has enabled a real-time and quantitative measurement of large number of ADME samples. For example, RapidFire system permitted us to test a large number of compounds for seven cytochrome P450 (CYP450) inhibition studies in a dose-response evaluation, comparing with a capacity of only single point evaluation supported by LC-MS. Thus, RapidFire system provided us with a rapid and robust evaluation of clinically important drug-drug interaction potential information. The assay development process, benefits, and potential drawbacks of the RapidFire system will be presented.

Benefits: 
Main topics covered include:
• What is RapidFire system and how is it being integrated in the lab?
• What are the major benefits of RapidFire mass spectrometry (RF-MS) comparing to LC-MS?
• Is the signal quality sacrificed to gain the speed on the RF-MS?
• What are the potential drawbacks of the RF-MS?
  
2:45Lynn Yieh, Ph.D., Project Leader, Bioinformatics, Johnson & Johnson
  
3:10Networking & Refreshment Break
  
3:40Remote Open Access – The Lab2Lab™ Advantage
 Brian Everatt, Ph.D., Research Scientist III, Novartis
  
 Currently, open access submission of chemical and biological samples to analytical equipment such as HPLC and LC-MS requires substantial manual investment. Typically medicinal chemistry samples are submitted for reaction monitoring, purity confirmation and final compound analysis; processes which can be a time consuming, error prone and inefficient. Lab2Lab™ from TTP LabTech is a novel approach to submitting and transporting samples for analysis across an entire site. Sample vials are registered and methods selected, an ELN reference is assigned and the sample is placed into the “Sender”. The system then transports the samples using low pressure compressed air and directs them to the most appropriate analytical instrumentation available. The analytical results are then automatically returned to the originators ELN. 

This presentation will describe the system recently installed at Novartis, Horsham (UK) and demonstrate the typical throughput capability and time savings this introduces to the users, in addition to showing how it is possible to rationalize expensive equipment, reducing the cost of maintenance and support whilst increasing availability. It will show how the system can cope with failure of the analytical instrumentation by being able to redirect samples to working equipment, and the potential for future expansion.
  
4:05David Ferrick, Ph.D., Chief Scientific Officer, Seahorse Bioscience
  
  
 FEATURED PRESENTATION
4:30Implementation of Relevant Cellular In Vitro Assays in Support of Preclinical Candidate Nominations
  
 Ilona Kariv, Ph.D.
Director and Lead
In Vitro and Cellular Pharmacology
Merck
  
 Recent advances in translational medicine and better understanding of patient stratification strategies in the clinic enable the selection of improved preclinical candidates. However, identification of novel chemotypes with the desired in vivo activity profile early during the drug discovery process still remains difficult. The major challenge during lead optimization is to generate pharmacologically predictive results to identify high quality leads, enhancing the probability of success by aligning in vitro testing of compound activity with clinical biomarker measurements. Because many hits can be quickly identified during primary HTS campaigns, prioritization and optimization of the target-specific chemical entities becomes the next critical step. This presentation will provide examples of designing specific decision-making screening funnels focusing on the incorporation of cellular assay platforms, and will highlight advantages of the increased sophistication of compound testing in biologically relevant assays that monitor complex functional systems. Implementation of the cell-based predictive assays in conjunction with advanced high throughput automation and data analysis not only allow for the identification of relevant lead chemotypes, but also serve as a basis for shortening the cycle time in support of nomination of preclinical candidates with the desired functional activity.
  
  
5:05Networking Reception & Poster Session
  

Day 1Day 2
 
Day 2 - Friday, July 8, 2011
  
7:30Continental Breakfast
  
  
 FEATURED PRESENTATION
8:00The Impact of Screening on Drug Discovery at Bristol-Myers Squibb
  
 Martyn Banks, Ph.D.
Executive Director
Molecular Sciences and Candidate Optimization
Bristol-Myers Squibb
  
 For the size of the company Bristol Myers Squibb has one of the most innovative drug discovery pipelines in the industry and the screening infrastructure has played an important part in this success.

This talk will highlight how this screening success was achieved from a scientific, technological and most importantly the cultural perspective. Each of these domains of success will be described and the talk will focus on examples of success and lessons learned. The talk will also describe small vignettes from compounds that are in clinical trials or those that are now used to treat patients. The audience will hear how not only innovative science was enabled but how the complex interplay of drug discovery disciplines worked together toward a common goal with a holistic approach to the use of technology.
  
  
Session IV: Label Free Technologies
 
  
8:35HTS Hits Validation Using Multiple Label-Free Technologies: Biacore, ITC and Thermal Shift
 Lin Gao, Ph.D., Senior Principal Scientist, Roche Discovery Technologies
  
 High throughput screening is a well established paradigm for lead generation in the drug discovery process. One of the most important decisions we make after processing >1 million compounds is hit validation. Typically, hit confirmation is performed by single-point repeats or by titration experiments in the original HTS assay format. However, many pitfalls face traditional HTS technologies, including fluorescence interfering compounds, assay format-related false positives. In order to overcome these challenges, we have integrated several label-free technologies into our hit validation workflow. These affinity-based methods provide an orthogonal approach to further validate and ensure the quality of the hits we deliver to the chemists.

I will present a case study in which following the HTS campaign, we investigated the hits using SRP, thermal shift assays as well as isothermal titration calorimetry. Results from these studies will be compared with conventional biochemical assay data. In addition, I will discuss the advantages and disadvantages of each label-free technology. The benefits of this approach include:
• Drastically reduce false positive hits due to biochemical assay interference and compound interference
• Take advantage of the throughput of certain label-free technology can offer
• Multiple orthogonal technologies reduce false positives as well as false negatives
  
9:00High-Throughput, Label-Free Screening Small Molecule Compound Libraries for Protein-Ligands Using Combination of Small Molecule Microarrays and a Special Ellipsometry-Based Optical Scanner
 Xiangdong Zhu, Ph.D., Professor, Physics, UC Davis
  
 Small-molecule compounds including natural products and peptides remain a major source of therapeutic and preventative drugs. The initial steps in developing new small-molecule compound drugs or novel applications of existing drugs against a protein target often involve screening large libraries of small molecules with diverse structures and compositions for the few that exhibit sufficiently high affinity to the target and have a suitable orthosteric or allosteric effect before further structural optimization and other developmental work. Since the number of small molecule compounds in a library is large, from tens of thousands (from NCI Open Repository, or commercial vendors, or NIH Molecular Libraries Small Molecule Repository) to millions (privately developed and owned by major Pharmaceutical companies), high-throughput affinity screening (HTS) methods are needed. Small-molecule microarrays (SMM) supported on a solid substrate surface in combination with a high-throughput binding assay detection platform are among the viable HTS options.

By detecting small molecule microarrays with a high-speed oblique-incidence-reflectivity-difference (OIRD)- based optical scanner, we demonstrate the capability of screening, by binding affinity constants, 10,000 immobilized targets on a functionalized glass slide for ligands of a protein probe without fluorescence labeling. We report our recent development of such a binding assay platform that enables screening 40,000 ~ 50,000 small molecule compounds in a day with a single scanner, or 120,000 compounds with 3 such scanners. This binding assay platform, when combined with robust high-throughput microarray fabrication technology, promises to be the most efficient approach for small molecule compound screening for protein ligand discovery and protein captures.
  
9:25Expediting Kinetic Characterization, Epitope Binning and Epitope Mapping of Antibodies Using Label-free Biosensors
 Yasmina N. Abdiche, Ph.D., Senior Principal Scientist, Rinat-Pfizer
  
 Advances in label-free biosensor instrumentation have increased both the number of interactions that can be monitored simultaneously and the flexibility with which assays can be configured. Methods will be presented on how to increase throughput in various assays for characterizing antibodies in drug discovery, drawing from data generated on three commercial biosensor platforms.
  
9:50Networking & Refreshment Break
  
10:30Meeting the Expectations of Label-Free Platforms for Cell Based Assays in Drug Discovery and Development
 Lance Laing, Ph.D., Executive Director, Therapeutics and Platform Technologies, ACEA Biosciences
  
 Label-free technologies have been variously described for many different drug discovery and development applications. Plate-based label-free cell assays employing refractive index or impedance based platforms have been recently described as a black box result requiring much assay development time whose output is tedious to decipher. Dr. Laing will describe assays and results for label-free cell applications that are useful and unambiguous. In addition, further description will provide insight into where new developments are allowing more challenging targets to be approached using photonic crystal or impedance plate-based formats for cell assays.
  
10:55David A. Lowe, Chief Scientific Officer and Executive Vice President, Research & Development, Psychogenics
  
11:20[Oral Presentations for Exemplary Submitted Abstracts]
 To be considered for an oral presentation, please submit an abstract here.
  
11:50Lunch
  
Session V: Novel Assay and Screening Technologies
 
  
1:00Small-Molecule Microarrays (SMM): A Novel Approach to Drug Discovery for Challenging Protein Targets
 Patrick Kleyn, Ph.D., President and Chief Scientific Officer, Ligon Discovery
  
 Ligon's Small-Molecule Microarray (SMM) technology is a massively-parallel, high-throughput screening technology that identifies small-molecule protein ligands. Diverse small-molecule libraries of any source are printed onto glass slides using a proprietary covalent attachment chemistry that allows them to interact with protein targets in solution. Specific protein-ligand interactions are detected via an antibody to the protein or to an epitope tag. A major benefit of SMM is the ability to use complex mixtures of proteins such as cell lysates for screening as well as purified proteins. As such, SMM are particularly well-suited to challenging target classes such as protein-protein interactions, transcription factors where purifying a single protein from its natural complex may be inappropriate. The speed and scale of SMM also enable rapid parallel screening of multiple members of a protein family or cellular pathways to identify ligands with highly selective profiles. I will present an overview of the SMM technology as well as examples of discoveries made using SMM at Ligon including small-molecule inhibitors of challenging protein targets such as transcription factors.
  
1:25High Content Screening of Parasitic Organisms
 Michelle Arkin, Ph.D., Associate Director, Small Molecule Discovery Center, UCSF
  
 The Small Molecule Discovery Center (SMDC) at UCSF offers researchers access to drug-discovery technologies, including HTS, fragment-based ligand discovery, and medicinal chemistry. This talk will summarize recent projects in neglected tropical diseases done in collaboration with the Sandler Center for Drug Discovery and will touch on the expanding roles of academic centers in driving innovation in drug discovery.

With tropical diseases, academics have an important opportunity to develop technologies and evaluate new therapeutic targets. Schistosomiasis is an example of a parasitic disease that infects hundreds of millions of people, yet is widely neglected by the drug-discovery world. We have taken a high-content imaging approach to screen for compounds that kill the causative agent of Schistosomiasis. In developing this imaging technology, we have solved problems with automating sample preparation and data collection, and we are developing a suite of image analysis tools that define helminth phenotypes based on shape and motion descriptors. These tools have allowed us to increase our throughput for drug screening and to deepen our understanding of the mechanism of action of anti-helminth compounds. This project is supported by NIH (R01AI089896-01).
  
1:50HTS Hit Triage: Lead Identification using Biophysical Tools
 Kartik Narayan, Ph.D., Senior Research Biochemist, Merck
  
2:15Simon Thomas, Ph.D., Head, Scientific Computing, Cyprotex Discovery
  
2:40Ji-Hu Zhang, Ph.D., Senior Research Investigator, Assay Development and High Throughput Screening, Novartis
  
3:05TBA
  
3:30Conference Concludes
  
Day 1Day 2
 
 
 
Organized by: GTC Conference
Invited Speakers:
KEYNOTE SPEAKER
George P. Hemstreet III, M.D., Ph.D.
Chief and Professor
Urologic Surgery
University of Nebraska Medical Center
 
FEATURED SPEAKERFEATURED SPEAKER
Martyn Banks, Ph.D.
Executive Director
Molecular Sciences and Candidate Optimization
Bristol-Myers Squibb
Ilona Kariv, Ph.D.
Director and Lead
In Vitro and Cellular Pharmacology
Merck
 
 
DISTINGUISHED SPEAKERS
 
Yasmina Abdiche, Ph.D.
Senior Principal Scientist
Pfizer
 
Michelle Arkin, Ph.D.
Associate Director, Small Molecule Discovery Center
University of California, San Francisco
 
Robert Damoiseaux, Ph.D.
Scientific Director, Molecular Shared Screening Resources at the California Nano Systems Institute
University of California, Los Angeles
 
Brian Everatt, Ph.D.
Research Scientist III
Novartis
 
David Ferrick, Ph.D.
Chief Scientific Officer
Seashorse Bioscience
 
Lin Gao, Ph.D.
Senior Principal Scientist
Roche Discovery Technologies
 
James Herrington, Ph.D.
Scientist
Genentech
 
Cristian Ionescu-Zanetti, Ph.D. 
Chief Technology Officer
Fluxion Biosciences
 
Darren Kamikura, Ph.D.
Research Scientist, Bioassays
Eli Lilly
 
Patrick Kleyn, Ph.D.
President and Chief Scientific Officer
Ligon Discovery
 
Lance Laing, Ph.D.
Executive Director, Therapeutics and Platform Technologies
ACEA Biosciences
 
Kartik Narayan, Ph.D.
Senior Research Biochemist
Merck
 
Flori Sassano, Ph.D.
Research Associate, Bryan Roth Lab (GPCR)
University of North Carolina, Chapel Hill
 
Chaohong Sun, Ph.D.
Group Leader, Fragment Screening and Lead Characterization
Abbott
 
Fredrik Sundberg
Global Director, Strategic Market Development
GE Healthcare
 
Simon Thomas
Head, Scientific Computing
Cyprotex Discovery
 
Sean Xiang Wu, Ph.D.
Associate Director, New Lead Discovery
Exelixis
 
M. Fatih Yanik, Ph.D.
Lab Director, Highthroughput Neurotechnology Group
Massachusetts Institute of Technology
 
Lynn Yieh, Ph.D.
Project Leader, Bioinformatics
Johnson & Johnson
 
Ji-Hu Zhang, Ph.D.
Senior Research Investigator, Assay Development and High Throughput Screening 
Novartis
 
Xiangdong Zhu, Ph.D.
Professor, Physics
University of California, Davis
 
Deadline for Abstracts: June 7, 2011
 
Registration: https://www.gtcbio.com/component/register/?cn=6th+Assay+&+Drug+Discovery+Technologies&cid=31
 
   
 
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