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TIDES: Oligonucleotide and Peptide® Technology and Product Development
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TIDES Agenda
Courses: Sunday Morning - Afternoon
Main Conference: Monday | Main Conference: Tuesday | Main Conference: Wednesday
Molecular Diagnostics | Oligonucleotide Therapeutics Discovery | Site Tours
1: Current Topics in Oligonucleotide Manufacturing: Managing the Manufacture of Novel Oligonucleotide Therapeutics
Course Leader: Fran Wincott, Ph.D., President, Wincott & Associates, LLC
This course is focused on addressing current issues that are critical to the successful manufacture of oligonucleotide therapeutics. The emphasis this year is on emerging technologies and the issues that arise as a consequence of the need to produce clinical material for such cutting edge technologies. Establishing a reliable raw material supply chain, impact of novel monomers on synthesis, purification and analytics will be discussed. Learn from those who have been through the challenging process, what worked, what didn't work, and how you can avoid pitfalls and develop your process right the first time.
You will learn:
- What is the key IP around manufacture of oligonucleotides
- How does Safe Harbor impact the manufacture of your oligonucleotide
- Considerations for establishing a novel monomer supply chain
- Considerations for sourcing complex oligonucleotides
- Strategies for cost effective manufacturing of complex oligonucleotides
9:00
Course Introduction
Fran Wincott, Ph.D., President, Wincott & Associates, LLC
Fran Wincott, Ph.D., President, Wincott & Associates, LLC
9:15
Synthesizing Intellectual Property around Manufacture of Oligonucleotides
What is the key intellectual property around manufacture of oligonucleotides? Who needs access to these patents--the manufacturer alone or does the product company need its own rights? What IP legal issues should a therapeutic product company be considering when working with an oligo manufacturer? When does the FDA safe harbor come into play for the oligo manufacturing-related IP, who does the safe harbor protect, and when does the safe harbor protection end, given the need to continue manufacture of an FDA-approved product?
Kathleen M. Williams, Ph.D., J.D., Partner, Intellectual Property, Edwards Angell Palmer & Dodge LLP
What is the key intellectual property around manufacture of oligonucleotides? Who needs access to these patents--the manufacturer alone or does the product company need its own rights? What IP legal issues should a therapeutic product company be considering when working with an oligo manufacturer? When does the FDA safe harbor come into play for the oligo manufacturing-related IP, who does the safe harbor protect, and when does the safe harbor protection end, given the need to continue manufacture of an FDA-approved product?
Kathleen M. Williams, Ph.D., J.D., Partner, Intellectual Property, Edwards Angell Palmer & Dodge LLP
9:50
Outsourcing of L-Configured Nucleoside Phosphoramidites; Establishing a Novel Monomer Supply Chain, from Research to Clinical Supply
Spiegelmers are unnatural L-configured oligonucleotides which are currently being investigated in various clinical studies. A case study for the production of L-configured RNA phosphoramidites required for the manufacturing of Spiegelmers is presented. Different synthetic routes were evaluated during process development from lab- to pilot-scale. Lessons learned during scale-up and process transfer will be discussed.
Stefan Vonhoff, Ph.D., Vice President CMC, NOXXON Pharma AG, Germany
Spiegelmers are unnatural L-configured oligonucleotides which are currently being investigated in various clinical studies. A case study for the production of L-configured RNA phosphoramidites required for the manufacturing of Spiegelmers is presented. Different synthetic routes were evaluated during process development from lab- to pilot-scale. Lessons learned during scale-up and process transfer will be discussed.
Stefan Vonhoff, Ph.D., Vice President CMC, NOXXON Pharma AG, Germany
10:25
Sourcing Novel Constructs from Research to Clinical Supply
Developing novel oligonucleotide therapeutics with higher molecular complexity is challenging. This is especially true for a Virtually Integrated Pharmaceutical Company (VIPCo). This presentation illustrates how a start-up VIPCo and an established CMO work together to solve such a challenge and progress seamlessly from research to clinical supply.
Prof Jian-Sheng Sun, CEO, DNA Therapeutics
Ken Hill, Ph.D., Director, Process Development, Agilent Technologies Inc.
Developing novel oligonucleotide therapeutics with higher molecular complexity is challenging. This is especially true for a Virtually Integrated Pharmaceutical Company (VIPCo). This presentation illustrates how a start-up VIPCo and an established CMO work together to solve such a challenge and progress seamlessly from research to clinical supply.
Prof Jian-Sheng Sun, CEO, DNA Therapeutics
Ken Hill, Ph.D., Director, Process Development, Agilent Technologies Inc.
11:00
Networking Refreshment Break
11:25
Challenges of Manufacturing Morpholino Oligos: Starting from Scratch
Phosphorodiamidate morpholino oligomer (PMO) production borrows only the basics from peptide and oligonucleotide manufacturing. After assuring a supply of high quality monomers, a platform approach for solid phase synthesis, purification, and analysis emerged. The discussion will focus on the monomers, the solid phase synthesis cycle, and the analytical methods.
Dwight Weller, Ph.D., Senior Vice President, Chemistry & Manufacturing, AVI BioPharma, Inc.
Phosphorodiamidate morpholino oligomer (PMO) production borrows only the basics from peptide and oligonucleotide manufacturing. After assuring a supply of high quality monomers, a platform approach for solid phase synthesis, purification, and analysis emerged. The discussion will focus on the monomers, the solid phase synthesis cycle, and the analytical methods.
Dwight Weller, Ph.D., Senior Vice President, Chemistry & Manufacturing, AVI BioPharma, Inc.
12:00
How Does Chemistry Make Novel Oligonucleotides More Affordable?
Telomerase is one of the enzymes responsible for the proliferative immortality of cancer cells. An oligonucleotide N3'-P5'-thio-phosphoramidate conjugate Imetelstat (GRN163L) was recently introduced as telomerase inhibitor. Preparation of this compound required the use of complex multi-step procedures. We have developed a new chemo-enzymatic approach to the nucleoside building blocks, resulting in cost decrease and increase in GRN163L manufacturing efficiency.
Sergei Gryaznov, Ph.D., Director and Senior Research Fellow, Geron Corporation
Telomerase is one of the enzymes responsible for the proliferative immortality of cancer cells. An oligonucleotide N3'-P5'-thio-phosphoramidate conjugate Imetelstat (GRN163L) was recently introduced as telomerase inhibitor. Preparation of this compound required the use of complex multi-step procedures. We have developed a new chemo-enzymatic approach to the nucleoside building blocks, resulting in cost decrease and increase in GRN163L manufacturing efficiency.
Sergei Gryaznov, Ph.D., Director and Senior Research Fellow, Geron Corporation
12:35
Audience Interactive Panel Discussion
2: Bioanalytical Methods for the Determination of Therapeutic Oligonucleotides
Course Leader: Guy A. Tremblay, M.Sc., Research Scientist, Immunochemistry, Charles River Laboratories, Canada
This course reviews bioanalytical techniques for the characterization of peptides and oligonucleotides from biological matrices. The goal is to guide the researcher in the selection of an appropriate set of methods tailored to their own development candidates. Examples are shown to illustrate challenges and pitfalls of peptide and oligonucleotide characterization from plasma and tissues and how the knowledge of basic concepts can be utilized to develop an appropriate set of methods. A comprehensive review of gene arrays in the development of oligonucleotide therapeutics will help the researcher to utilize this new tool.
You will learn:
- How to select the appropriate bioanalytical method
- Fundamentals of hybridization based assays
- Fundamentals of separation based assays
- Advanced mass spectrometry of biomolecules
- How to evaluate requirements for bioanalytical method development
9:00
Introduction to the Course
Guy A. Tremblay, M.Sc., Research Scientist, Immunochemistry, Charles River Laboratories, Canada
Guy A. Tremblay, M.Sc., Research Scientist, Immunochemistry, Charles River Laboratories, Canada
9:15
Oligonucleotide Bioanalytical Assay Development and Validation in a GXP Environment - Comparison of Methodologies
The presentation will focus on a comparison of the different assay approaches evaluated in our laboratories for the bioanalysis of oligonucleotides in plasma, for example hybridisation-fluorescence and competition based immunoassay, using electrochemiluminescene. The challenges and requirements of conducting and validating suitable assays in a GLP/GCP environment will also be discussed.
Victoria Holmes, Ph.D., Senior Research Scientist, Clinical Pharmacology & DMPK, AstraZeneca R&D Charnwood, United Kingdom
The presentation will focus on a comparison of the different assay approaches evaluated in our laboratories for the bioanalysis of oligonucleotides in plasma, for example hybridisation-fluorescence and competition based immunoassay, using electrochemiluminescene. The challenges and requirements of conducting and validating suitable assays in a GLP/GCP environment will also be discussed.
Victoria Holmes, Ph.D., Senior Research Scientist, Clinical Pharmacology & DMPK, AstraZeneca R&D Charnwood, United Kingdom
9:50
Case
Study
Key Considerations when Selecting an Appropriate Bioanalytical Method for Oligonucleotide Quantitation (Focus on CGE and ELISA)Study
Hybridization assays are readily used as bioanalytical tools to support pharmacokinetic, toxicokinetic and animal biodistribution studies for therapeutic oligonucleotide drug programs Reliable, robust and reproducible bioanalytical quantitation is critical in projecting clinical dose treatments. General and critical features of specific quantitative bioanalytical techniques (e.g. CGE, hybridization-based ELISAs) will be discussed, along with a comparison of the relative advantages and limitations of such methods, as well as considerations for their routine application to the various oligonucleotide classes.
Helen Legakis, M.Sc., Research Scientist, Immunochemistry, Charles River Laboratories, Canada
10:25
Analysis of Oligonucleotides and Pegylated Oligonucleotides in Plasma by Ion-Exchange HPLC-UV
An Ion-Exchange HPLC-UV method for oligonucleotides and pegylated-oligonucleotides in plasma following sample preparation by enzymatic digestion will be presented. Resolution of metabolites from the parent compound will be demonstrated and strategies to improve resolution will be presented. Overviews of validations and stability results will also be discussed. Examples of common problems and strategies to overcome them will be presented.
Kurt Moyer, Ph. D., Director of Analytical and Bioanalysis, Analytical and Bioanalytical R&D, Pharmalytica Services
An Ion-Exchange HPLC-UV method for oligonucleotides and pegylated-oligonucleotides in plasma following sample preparation by enzymatic digestion will be presented. Resolution of metabolites from the parent compound will be demonstrated and strategies to improve resolution will be presented. Overviews of validations and stability results will also be discussed. Examples of common problems and strategies to overcome them will be presented.
Kurt Moyer, Ph. D., Director of Analytical and Bioanalysis, Analytical and Bioanalytical R&D, Pharmalytica Services
11:00
Networking Refreshment Break
11:20
Bioanalysis of Oligonucleotides by qPCR
Speaker to be announced
Speaker to be announced
11:55
Innovations in the Preparation and LC/MS Analysis of Oligonucleotide Therapeutics from Biological Matrices
As oligonucleotide therapeutics move into clinical trials there has been a growing need for better bioanalytical methodologies. Extracting oligonucleotides and their metabolites from biological matrices is a unique challenge and emerging high throughput methods will be discussed. LC/MS analysis of isolated oligonucleotides has its own difficulties and studies on improving selectivity and sensitivity via different separation modes will be reviewed.
Michael McGinley, Bioseparations Product Manager, Phenomenex
As oligonucleotide therapeutics move into clinical trials there has been a growing need for better bioanalytical methodologies. Extracting oligonucleotides and their metabolites from biological matrices is a unique challenge and emerging high throughput methods will be discussed. LC/MS analysis of isolated oligonucleotides has its own difficulties and studies on improving selectivity and sensitivity via different separation modes will be reviewed.
Michael McGinley, Bioseparations Product Manager, Phenomenex
12:30
Audience Interactive Panel Discussion
1:00
Lunch on your own
Courses: Sunday Morning - Afternoon
Main Conference: Monday | Main Conference: Tuesday | Main Conference: Wednesday
Molecular Diagnostics | Oligonucleotide Therapeutics Discovery | Site Tours
3: Current Topics in the Analysis of Oligonucleotides in Support of Drug Development
Course Leader: G. Susan Srivatsa, Ph.D., President, ElixinPharma
The course will lead off with a review of US, Canadian and European regulatory expectations for the analysis of oligonucleotides (antisense, siRNA, DNA decoys, aptamers, etc.). Current approaches for sequencing and impurity profile analysis will be discussed. Special topics will include considerations for converting conventional HPLC based methods to UHPLC, analysis of complex oligonucleotide conjugates as well as approaches to assuring quality and stability of oligonucleotides in novel nanoparticle formulations.
You will learn:
- How to select the best method for sequencing an oligonucleotide
- Differences between manual and automated integration of impurity profiles
- Considerations for moving from from HPLC to UHPLC methods
- Approaches for characterization of oligonucleotide conjugates
- Strategies for analysis of oligonucleotides in complex formulations
2:00
Analysis of Complex Oligonucleotides: US, Canadian and European Regulatory Expectations
General review of US, Canadian and European regulatory expectations for the analysis of oligonucleotides (antisense, siRNA, DNA decoys, aptamers, etc.).
G. Susan Srivatsa, Ph.D., President, ElixinPharma
General review of US, Canadian and European regulatory expectations for the analysis of oligonucleotides (antisense, siRNA, DNA decoys, aptamers, etc.).
G. Susan Srivatsa, Ph.D., President, ElixinPharma
2:15
Sequencing Synthetic Oligonucleotides
Sequencing of synthetic oligonucleotides is an important test that is likely to be part of the specification for each batch. Historical techniques may not be well suited to routine quality testing, and newer approaches are now being implemented. Modern approaches to sequencing will be reviewed and the advantages and disadvantages of each will be considered.
James McArdle, Ph.D., President, McArdle and Associates, LLC
Sequencing of synthetic oligonucleotides is an important test that is likely to be part of the specification for each batch. Historical techniques may not be well suited to routine quality testing, and newer approaches are now being implemented. Modern approaches to sequencing will be reviewed and the advantages and disadvantages of each will be considered.
James McArdle, Ph.D., President, McArdle and Associates, LLC
2:50
Manual versus Automated Integration of Oligonucleotides and Related Substances HPLC Impurity Profiles: Regulatory Implications
The separation and reproducible integration of oligonucleotides and related substances is challenging due to their physic-chemical properties, chromatographic limitations and poor resolution. These issues handicap the ability of chromatography data systems to detect and accurately quantitate peaks thus manual rather than automated integration. The regulatory implications of manual versus automated integration, associated analytical variability and potential solutions will be discussed.
Thomas Walker, Ph.D., Associate Director, Quality Control, Agilent Technologies
The separation and reproducible integration of oligonucleotides and related substances is challenging due to their physic-chemical properties, chromatographic limitations and poor resolution. These issues handicap the ability of chromatography data systems to detect and accurately quantitate peaks thus manual rather than automated integration. The regulatory implications of manual versus automated integration, associated analytical variability and potential solutions will be discussed.
Thomas Walker, Ph.D., Associate Director, Quality Control, Agilent Technologies
3:25
Conversion between Conventional HPLC and UHPLC: Theory, Considerations and Challenges
UHPLC technology has been demonstrated to increase peak capacity and decrease analysis time for a variety of separations. Conventional HPLC methods can be converted using a simple mathematical formula that incorporates particle size, column length, and linear velocity. This presentation will focus on the theory, technical details, and practical challenges of converting between HPLC and UHPLC methods.
Jeff Dai, Ph.D., Research Investigator, Analytical R&D, Bristol-Myers Squibb
UHPLC technology has been demonstrated to increase peak capacity and decrease analysis time for a variety of separations. Conventional HPLC methods can be converted using a simple mathematical formula that incorporates particle size, column length, and linear velocity. This presentation will focus on the theory, technical details, and practical challenges of converting between HPLC and UHPLC methods.
Jeff Dai, Ph.D., Research Investigator, Analytical R&D, Bristol-Myers Squibb
4:00
Networking Refreshment Break
4:30
Special Considerations for PEGylated Aptamers
Aptamers are single-stranded, structured oligonucleotides that form stable and specific secondary and tertiary structures. In contrast with other classes of oligonucleotide therapeutics, these structural elements allow this class of therapeutic to effectively bind to their protein target. PEG conjugation is also commonly employed to prolong the circulation half-life of an aptamer. This presentation will focus on challenges, strategies, and the latest technologies for characterization of aptamers and PEGylated aptamers.
YanSheng Wu, Ph.D., Principal Investigator, Analytical Development, Pharmaceutical R&D, Archemix Corp.
Aptamers are single-stranded, structured oligonucleotides that form stable and specific secondary and tertiary structures. In contrast with other classes of oligonucleotide therapeutics, these structural elements allow this class of therapeutic to effectively bind to their protein target. PEG conjugation is also commonly employed to prolong the circulation half-life of an aptamer. This presentation will focus on challenges, strategies, and the latest technologies for characterization of aptamers and PEGylated aptamers.
YanSheng Wu, Ph.D., Principal Investigator, Analytical Development, Pharmaceutical R&D, Archemix Corp.
5:05
Challenges in Assuring Quality and Stability of siRNA in Lipid Nanoparticle Formulations
This presentation will focus on the design and implementation of assays and specification ranges for the control of a complex siRNA drug product, which is currently evaluated in the clinic. Also presented will be results of long term stability studies with the same and similar drug products, . The drug product is a formulation of drug substance comprised of equimolar amounts of two distinct siRNA's, encapsulated as stable nucleic acid lipid particles (SNALP's) for parenteral delivery.
Matthias Kretschmer, Ph.D., Director of Analytical Sciences, Alnylam Pharmaceuticals, Inc.
This presentation will focus on the design and implementation of assays and specification ranges for the control of a complex siRNA drug product, which is currently evaluated in the clinic. Also presented will be results of long term stability studies with the same and similar drug products, . The drug product is a formulation of drug substance comprised of equimolar amounts of two distinct siRNA's, encapsulated as stable nucleic acid lipid particles (SNALP's) for parenteral delivery.
Matthias Kretschmer, Ph.D., Director of Analytical Sciences, Alnylam Pharmaceuticals, Inc.
5:40
Audience Interactive Panel Discussion
4: Managing Analytical Development and Quality Control for Peptides
Course Leader: Gary Musso, Ph.D., President, Musso and Associates LLC
This course covers key topics in the characterization of peptides for product development.. The goal is to provide the participants with case studies and emerging trends in the characterization of peptide therapeutics as part of the control strategy for GMP production.
You will learn:
- New approaches to understanding impurities in peptides using LC-MS and deconvolution software
- Current trends in the impurity limits for peptide therapeutics
- Emerging trends in the regulatory requirements and advanced techniques for analysis of metals in drugs
- Strategies for control and analysis of complex or unstable peptides
- Strategies for assessment of genotoxic impurities in peptides
2:00
Introduction to the Course
Gary Musso, Ph.D., President, Musso and Associates LLC
Gary Musso, Ph.D., President, Musso and Associates LLC
2:15
Therapeutic peptides have to be essentially free of by-product of synthesis. We have utilized accurate LC-MS data independent acquisition for identification of the truncated sequences, additions (synthesis "double hits"), protection groups and combination of all above. Biopharmalynx and PepSeq (sequencer) software were useful for data analysis including identification of diastereomers.
Investigation of Nature of Failed Products in Synthetic Peptides using LC-MS and Dedicated Software
Martin Gilar, Ph.D., Principal Investigator, Waters Corporation
Investigation of Nature of Failed Products in Synthetic Peptides using LC-MS and Dedicated Software
Martin Gilar, Ph.D., Principal Investigator, Waters Corporation
2:50
Regulatory Considerations on Setting Impurity Specifications for Peptide Drug Products
Due to the withdrawal of FDA domestic guidance for synthetic peptide drug products, there have been confusion in recent years regarding the regulatory requirements to assess the impurities levels for synthetic peptides. The presentation will provide an regulatory update on peptide impurities, including:
Due to the withdrawal of FDA domestic guidance for synthetic peptide drug products, there have been confusion in recent years regarding the regulatory requirements to assess the impurities levels for synthetic peptides. The presentation will provide an regulatory update on peptide impurities, including:
- General impurity issues at different stages of drug development
- Unique regulatory and scientific issues of peptide impurities
- Qualification and setting specifications for peptide impurities
- Discussion on the current FDA review practice regarding peptide impurities
3:25
Emerging Trends in the Regulatory Requirements And Icp/icp-ms Applications in Pharmaceutical Research/Peptide Analysis
Metal analysis has become more and more indispensable to drug development, since the determinations of metal contents in pharmaceuticals are at least as critical as other "main stream" analytical tasks. The fundamentals of AA, ICP-OES, and ICP-MS will be introduced, and their applications to pharmaceutical development in general, including their roles in the quantifications of peptides and oligonucleotide through metal analysis will be discussed.
TieBang Wang, Ph.D., Research Fellow, Early Development API Analysis, Merck & Co., Inc.
Metal analysis has become more and more indispensable to drug development, since the determinations of metal contents in pharmaceuticals are at least as critical as other "main stream" analytical tasks. The fundamentals of AA, ICP-OES, and ICP-MS will be introduced, and their applications to pharmaceutical development in general, including their roles in the quantifications of peptides and oligonucleotide through metal analysis will be discussed.
TieBang Wang, Ph.D., Research Fellow, Early Development API Analysis, Merck & Co., Inc.
4:00
Networking Refreshment Break
4:30
Strategies for Control and Analysis of Complex or Unstable Peptides
Speaker to be announced
Speaker to be announced
5:05
Genotoxic Impurities in Peptides: Fact or Fiction
Recently, regulatory characterization and control of peptide impurities has expanded beyond related substance impurities. Aside from residual solvents and metals (palladium) used in peptide manufacture, an assessment of (potential) genotoxic impurities (and control) is now expected for small molecules and increasingly being applied to peptides as part of the control strategy globally. Evaluation and assessment approaches will be discussed.
Gary Musso, Ph.D., President, Musso and Associates LLC
Recently, regulatory characterization and control of peptide impurities has expanded beyond related substance impurities. Aside from residual solvents and metals (palladium) used in peptide manufacture, an assessment of (potential) genotoxic impurities (and control) is now expected for small molecules and increasingly being applied to peptides as part of the control strategy globally. Evaluation and assessment approaches will be discussed.
Gary Musso, Ph.D., President, Musso and Associates LLC
5:40
Audience Interactive Panel Discussion
5: Oligonucleotide Lead Discovery and Candidate Selection
Course Leader: Satya Kuchimanchi, Ph.D., Associate Director, RNAi Lead Development, Alnylam Pharmaceuticals, Inc.
This course will focus on creative strategies for discovering lead molecules and selecting the right oligonucleotide therapeutic candidates for further development. Speakers working on a variety of oligonucleotide classes will present their work on bioinformatics for sequence design, high throughput small scale synthesis, chemical modifications and methods for improving PK and PD. Hear about the unique challenges encountered under each of the above areas, potential solutions, and a case study which will illustrate the integration of these techniques from discovery to IND.
You will learn:
- Sequence design using bioinformatics, different algorithms used and design criteria, targeted species for sequence selection, minimizing off-target effects
- Synthesis of siRNA duplexes - Methods for high throughput synthesis of RNA single strands and duplexes, high throughput QC methods for single strands and duplexes
- Strategies for chemistry selection, effects of chemical modifications on stability and efficacy
- Case study on lead candidate selection of aptamer sequences
- Synthesis, purification and QC methods for single strands and duplexes, discussion on purity criteria for duplexes used in screening experiments
2:00
Introduction to the Course
Satya Kuchimanchi, Ph.D., Associate Director, RNAi Lead Development, Alnylam Pharmaceuticals, Inc.
Satya Kuchimanchi, Ph.D., Associate Director, RNAi Lead Development, Alnylam Pharmaceuticals, Inc.
Sequence Design
2:15
Design of Oligonucleotide Compound Screens: Using Early Design Parameters to Increase Success
Joanne Kamens, Ph.D., Senior Director, Research Alliances, Discovery, RXi Pharmaceuticals
Joanne Kamens, Ph.D., Senior Director, Research Alliances, Discovery, RXi Pharmaceuticals
Library Synthesis
3:00
siRNA Sequences for Lead Selection. High Throughput Synthesis of RNA Single Strands and Duplexes
Satya Kuchimanchi, Ph.D., Associate Director, RNAi Lead Development, Alnylam
Satya Kuchimanchi, Ph.D., Associate Director, RNAi Lead Development, Alnylam
3:45
Refreshment Break
Chemical Modifications
4:05
Integration of Chemical Modifications in RNAi Molecules to Enhance Performance
Devin Leake, Ph.D., Director of R&D, Thermo Scientific Genomics
Devin Leake, Ph.D., Director of R&D, Thermo Scientific Genomics
4:50
Case
Study
Development of an Aptamer Therapeutic - From Discovery to INDStudy
Paul J. Hatala, Ph.D., Associate Director, Chemistry, Archemix Corporation
5:35
Audience Interactive Panel Discussion
6:00 - 7:00 pm
Welcoming Reception for Course Attendees
Sponsored by
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Courses: Sunday Morning - Afternoon
Main Conference: Monday | Main Conference: Tuesday | Main Conference: Wednesday
Molecular Diagnostics | Oligonucleotide Therapeutics Discovery | Site Tours
7:30
Registration and Coffee
8:30
Chairperson's Remarks
Rodney Parsons, Ph.D., Director, Process R&D, Bristol-Myers Squibb
Rodney Parsons, Ph.D., Director, Process R&D, Bristol-Myers Squibb
Keynote Presentations
8:45
Synthetic Biologics: A New Class of Drugs for "Undruggable" TargetsOne of the most vexing problems in life science is that of "undruggability," the difficulty of targeting certain biological macromolecules in vivo using existing drug or ligand discovery technologies. The Verdine laboratory is developing powerful new chemistry-based platform technologies to address undruggable targets. Specifically, the lab is developing "synthetic biologics," molecules that, like biologics, possess the ability to target large flat surfaces, but that, like small molecules, are fully synthetic and hence can be modified at will.
Gregory L. Verdine, Ph.D., Erving Professor of Chemistry, Harvard University
9:30
RNAi: Developing a New Therapeutic PlatformRNAi represents a fundamentally new modality to treat disease. The pace of RNAi drug research and development has been rapid, and offers a possible platform on which to identify potential active drug candidates to any target, including those that are otherwise "undruggable" or not amenable to conventional drugs. Despite the promise, challenges remain, including delivery hurdles and the clear demonstration of efficacy in well-controlled human clinical study, in order to translate the therapeutic potential of RNAi into clinical reality.
John Maraganore, Ph.D., Chief Executive Officer, Alnylam Pharmaceuticals, Inc.
10:15
Non-Coding RNAs as Drug TargetsHigh-throughput genomics efforts by us and others have provided strong evidence that, in contrast to earlier understanding, a great majority of the mammalian genome is transcribed into noncoding RNAs. We have hypothesized the interplay between sets of broadly expressed proteins with large numbers of information carrying RNAs that help recruit these proteins. It follows that targeting of such noncoding RNAs may open novel avenues for highly specific pharmacological interventions.
Claes R. Wahlestedt, M.D., Ph.D., Professor, Director of Neuroscience Discoverys, The Scripps Research Institute - Florida
11:00
Networking Refreshment Break
Featured Presentations
11:30
Deal Trends in Nucleic Acid Based Therapeutics: A Look at Past Deals and Thoughts on the Future
There has been considerable and understandable interest in the world of deal making surrounding the oligonucleotide space over the years. In this session, the history of the deals will be explored and compared with deal making around other therapeutic platforms. Some thoughts about the future of partnerships in this area will be discussed.
Philip McGurk, Ph.D., Senior Director, Business Development, Pfizer Inc.
There has been considerable and understandable interest in the world of deal making surrounding the oligonucleotide space over the years. In this session, the history of the deals will be explored and compared with deal making around other therapeutic platforms. Some thoughts about the future of partnerships in this area will be discussed.
Philip McGurk, Ph.D., Senior Director, Business Development, Pfizer Inc.
12:00
Peptide Therapeutics: New Growth and Directions
Peptides are a growing area of therapeutics due to widespread acceptance of injectable drugs by physicians and patients, and because of technology advances that address issues such as a short half-life and delivery. Data critical to strategic planning, including probabilities of approval success and phase lengths, will be presented, and key aspects of development trends will be discussed.
Janice M. Reichert, Ph.D., Senior Research Fellow, Tufts Center for the Study of Drug Development; Editor-in-Chief, mAbs, Landes Bioscience
Peptides are a growing area of therapeutics due to widespread acceptance of injectable drugs by physicians and patients, and because of technology advances that address issues such as a short half-life and delivery. Data critical to strategic planning, including probabilities of approval success and phase lengths, will be presented, and key aspects of development trends will be discussed.
Janice M. Reichert, Ph.D., Senior Research Fellow, Tufts Center for the Study of Drug Development; Editor-in-Chief, mAbs, Landes Bioscience
12:30
Lunch on your own
Regulatory Updates for Oligonucleotides and Peptides
2:00
Chairperson's Remarks
G. Susan Srivatsa, Ph.D., President, ElixinPharma
G. Susan Srivatsa, Ph.D., President, ElixinPharma
2:15
FDA Perspective on the Development of Peptide-Based Therapeutic Vaccines.
The Office of Tissue, Cell and Gene Therapy, CBER, FDA regulates more than 80 peptide based INDs. Current challenges, CMC deficiencies, and regulatory considerations of peptide therapeutic vaccine development will be discussed in this presentation. Examples of trials and problems that the Office encounters will be demonstrated.
Elena Gubina, Ph.D., Expert Biologist, Office of Tissue, Cell and Gene Therapy, CBER, FDA
The Office of Tissue, Cell and Gene Therapy, CBER, FDA regulates more than 80 peptide based INDs. Current challenges, CMC deficiencies, and regulatory considerations of peptide therapeutic vaccine development will be discussed in this presentation. Examples of trials and problems that the Office encounters will be demonstrated.
Elena Gubina, Ph.D., Expert Biologist, Office of Tissue, Cell and Gene Therapy, CBER, FDA
2:45
Case
Study
Regulatory Experience in Requesting a Biowaiver for Exenatide Once Weekly, a New Therapy for Type 2 DiabetesStudy
Exenatide Once Weekly (EQW) is a long-acting formulation of exenatide BID (twice daily) based on the Medisorb technology from Alkermes, Inc. Several elements of the EQW development program required that bioequivalence documentation be included in the marketing application. This presentation will provide an overview of the approach taken to request a waiver of the requirement for a bioequivalence study based on the establishment of an in vitro/in vivo correlation.
Mark A. Longer, Ph.D., Senior Director, Regulatory Affairs, Amylin Pharmaceuticals, Inc.
3:15
Networking Refreshment Break
3:45
Regulatory Expectations for the Quality of Oligonucleotide and Peptide Products on Applications for Clinical Trials and Market Authorizations in the EU
For regulatory agencies, oligonucleotides and peptides bring about new challenges when establishing their quality profile. The relative complexity of their structure could complicate the characterization of the active substance as well as product related impurities in a way similar to biological products. The regulatory approach taken to establish the quality in relation to the established efficacy and safety profile of oligonucleotides and peptides will be presented.
Axel Ståhlbom, Ph.D., Assessor Biotech, Department of Biotechnology & Pharmacy, Medical Products Agency, Sweden
For regulatory agencies, oligonucleotides and peptides bring about new challenges when establishing their quality profile. The relative complexity of their structure could complicate the characterization of the active substance as well as product related impurities in a way similar to biological products. The regulatory approach taken to establish the quality in relation to the established efficacy and safety profile of oligonucleotides and peptides will be presented.
Axel Ståhlbom, Ph.D., Assessor Biotech, Department of Biotechnology & Pharmacy, Medical Products Agency, Sweden
4:15
Regulatory Expectations for the Safety of Oligonucleotide Products for Clinical Trials and Market Authorizations in Italy and the EU
The regulatory challenge presented with oligonucleotide therapeutics requires early collaboration in drug development and continuing dialogue between sponsors and regulatory authorities to accelerate the transition from non-clinical to early clinical development, particularly regarding planning of how, when and where to conduct the First-in-Man (FIM) study.
Annarita Meneguz, Ph.D., Head of Biochemical Pharmacology and Technical Scientific Advice Coordination Unit, Department of Drug Research and Evaluation, Istituto Superiore di Sanita (Italian Regulatory Authority); Member, CHMP/EMEA/SWP
The regulatory challenge presented with oligonucleotide therapeutics requires early collaboration in drug development and continuing dialogue between sponsors and regulatory authorities to accelerate the transition from non-clinical to early clinical development, particularly regarding planning of how, when and where to conduct the First-in-Man (FIM) study.
Annarita Meneguz, Ph.D., Head of Biochemical Pharmacology and Technical Scientific Advice Coordination Unit, Department of Drug Research and Evaluation, Istituto Superiore di Sanita (Italian Regulatory Authority); Member, CHMP/EMEA/SWP
4:45
Regulatory Considerations in the Development of RNAi Therapeutics
Regulatory issues in the development of small interfering RNA (siRNA) as therapeutics will be discussed from the perspective of toxicology as well as chemistry, manufacturing and controls (CMC). Experience with FDA as well as with European and Canadian authorities in regulatory filings to enable Phase 1 and Phase 2 clinical trials will be shared.
Saraswathy (Sara) V. Nochur, Ph.D., Vice President, Regulatory Affairs, Alnylam Pharmaceuticals, Inc.
Regulatory issues in the development of small interfering RNA (siRNA) as therapeutics will be discussed from the perspective of toxicology as well as chemistry, manufacturing and controls (CMC). Experience with FDA as well as with European and Canadian authorities in regulatory filings to enable Phase 1 and Phase 2 clinical trials will be shared.
Saraswathy (Sara) V. Nochur, Ph.D., Vice President, Regulatory Affairs, Alnylam Pharmaceuticals, Inc.
5:15
Exhibit Hall Opens with Networking Reception and Poster Viewing
Courses: Sunday Morning - Afternoon
Main Conference: Monday | Main Conference: Tuesday | Main Conference: Wednesday
Molecular Diagnostics | Oligonucleotide Therapeutics Discovery | Site Tours
7:00
Registration and Coffee
Innovation Showcase
8:00
Co-Chairpersons' Remarks
Gary Carter, Business Development Manager, Nucleic Acids Solutions Division, Agilent Technologies Inc.
Rodney Lax, Director, Business Development, PolyPeptide Laboratories, Inc.
Hear innovative companies and research groups present their latest data, their business model and their objectives for collaboration. Presenters to be announced. Please visit the Innovative Showcase page for guidelines for submitting applications. Deadline for proposals to present is March 1, 2010; however speaking slots may be committed before that date so please send your proposal as early as possible.
Gary Carter, Business Development Manager, Nucleic Acids Solutions Division, Agilent Technologies Inc.
Rodney Lax, Director, Business Development, PolyPeptide Laboratories, Inc.
Hear innovative companies and research groups present their latest data, their business model and their objectives for collaboration. Presenters to be announced. Please visit the Innovative Showcase page for guidelines for submitting applications. Deadline for proposals to present is March 1, 2010; however speaking slots may be committed before that date so please send your proposal as early as possible.
8:15
Novel and Efficient Method for High Purity Synthetic RNA's and 3'- Conjugates
We have shown that 3'- DMT -5'- CED phosphoramidites lead to step-wise coupling efficiency > 99% in the reverse RNA synthesis (5'à3') with high purity short and long RNA sequences. These new monomers are distinctly superior to the standard 3'- CED -2'-O-TBDMS phosphoramidites used in conventional RNA synthesis (3'à5'). The monomers provide method for synthesis of clean RNA with a wide variety of modifications or labels at the 3'- end of the oligonucleotide.
Suresh C. Srivastava, Ph.D., President, ChemGenes Corp.
We have shown that 3'- DMT -5'- CED phosphoramidites lead to step-wise coupling efficiency > 99% in the reverse RNA synthesis (5'à3') with high purity short and long RNA sequences. These new monomers are distinctly superior to the standard 3'- CED -2'-O-TBDMS phosphoramidites used in conventional RNA synthesis (3'à5'). The monomers provide method for synthesis of clean RNA with a wide variety of modifications or labels at the 3'- end of the oligonucleotide.
Suresh C. Srivastava, Ph.D., President, ChemGenes Corp.
9:00
Sponsored by
Without the Needles: Transdermal Delivery of Peptides and OligonucleotidesTransPharma's ViaDerm system enables safe, reproducible and accurate intradermal and/or transdermal delivery. Microscopic passageways created in the outer layer of the skin allow for delivery of a broad range of active materials, including peptides, proteins and oligonucleotides from a patch or other topical dosage forms. Such is the ViaDerm-hPTH (1-34), a product designed to help osteoporosis patients by eliminating the need for daily painful injections. The product successfully completed a phase 2A clinical study and is jointly developed by TransPharma and Eli Lilly.
Galit Levin, D.Sc., Vice President of R&D Pharma, TransPharma Medical, Israel
Break-Out Discussion Sessions
Regulatory Updates
8:00
Oligonucleotide Therapeutics
Moderator:
Fran Wincott, Ph.D., President, Wincott & Associates, LLC
Panelists:
Elena Gubina, Ph.D., Expert Biologist, Office of Tissue, Cell and Gene Therapy, CBER, FDA
Annarita Meneguz, Ph.D., Head of Biochemical Pharmacology and Technical Scientific Advice Coordination Unit, Department of Drug Research and Evaluation, Istituto Superiore di Sanita (Italian Regulatory Authority); Member, CHMP/EMEA/SWP
Axel Ståhlbom, Ph.D., Assessor Biotech, Department of Biotechnology & Pharmacy, Medical Products Agency, Sweden
Dr. René Thürmer, Deputy Head Unit Pharmaceutical Biotechnology, BfArM - Federal Institute for Drugs and Medical Devices, Germany
Moderator:
Fran Wincott, Ph.D., President, Wincott & Associates, LLC
Panelists:
Elena Gubina, Ph.D., Expert Biologist, Office of Tissue, Cell and Gene Therapy, CBER, FDA
Annarita Meneguz, Ph.D., Head of Biochemical Pharmacology and Technical Scientific Advice Coordination Unit, Department of Drug Research and Evaluation, Istituto Superiore di Sanita (Italian Regulatory Authority); Member, CHMP/EMEA/SWP
Axel Ståhlbom, Ph.D., Assessor Biotech, Department of Biotechnology & Pharmacy, Medical Products Agency, Sweden
Dr. René Thürmer, Deputy Head Unit Pharmaceutical Biotechnology, BfArM - Federal Institute for Drugs and Medical Devices, Germany
8:45
Peptide Vaccines and Peptides Therapeutics
Moderator:
Gary F. Musso, Ph.D., President, Musso and Associates LLC
Panelists:
Elena Gubina, Ph.D., Expert Biologist, Office of Tissue, Cell and Gene Therapy, CBER, FDA
Annarita Meneguz, Ph.D., Head of Biochemical Pharmacology and Technical Scientific Advice Coordination Unit, Department of Drug Research and Evaluation, Istituto Superiore di Sanita (Italian Regulatory Authority); Member, CHMP/EMEA/SWP
Axel Ståhlbom, Ph.D., Assessor Biotech, Department of Biotechnology & Pharmacy, Medical Products Agency, Sweden
Dr. René Thürmer, Deputy Head Unit Pharmaceutical Biotechnology, BfArM - Federal Institute for Drugs and Medical Devices, Germany
Mark A. Longer, Ph.D., Senior Director, Regulatory Affairs, Amylin Pharmaceuticals, Inc.
Peter Larsson, Director of Regulatory Affairs, PolyPeptide Laboratories, Inc.
Moderator:
Gary F. Musso, Ph.D., President, Musso and Associates LLC
Panelists:
Elena Gubina, Ph.D., Expert Biologist, Office of Tissue, Cell and Gene Therapy, CBER, FDA
Annarita Meneguz, Ph.D., Head of Biochemical Pharmacology and Technical Scientific Advice Coordination Unit, Department of Drug Research and Evaluation, Istituto Superiore di Sanita (Italian Regulatory Authority); Member, CHMP/EMEA/SWP
Axel Ståhlbom, Ph.D., Assessor Biotech, Department of Biotechnology & Pharmacy, Medical Products Agency, Sweden
Dr. René Thürmer, Deputy Head Unit Pharmaceutical Biotechnology, BfArM - Federal Institute for Drugs and Medical Devices, Germany
Mark A. Longer, Ph.D., Senior Director, Regulatory Affairs, Amylin Pharmaceuticals, Inc.
Peter Larsson, Director of Regulatory Affairs, PolyPeptide Laboratories, Inc.
9:30
Networking Refreshment Break with Poster and Exhibit Viewing
Sponsored by
Sponsored by
Oligonucleotides
CMC: Manufacturing and Analysis
Sponsored by
10:15
Co-Chairpersons' Remarks
Lubomir Nechev, Ph.D., Director, Process Chemistry, Alnylam Pharmaceuticals, Inc.
Emma Wright, Ph.D., Director, Process Development, Avecia OligoMedicines
Lubomir Nechev, Ph.D., Director, Process Chemistry, Alnylam Pharmaceuticals, Inc.
Emma Wright, Ph.D., Director, Process Development, Avecia OligoMedicines
10:30
Technical Aspects of Building a Commercial Supply Chain for Starting Materials for Oligonucleotides
Developing a commercial supply chain for chemical compounds which are often novel and structurally complicated, involves more than the standard procurement activities associated with materials sourcing. Working both independently as well as with potential vendors on chemical process and analytical R&D activities is often required to ensure quality and meet pricing targets. Various technical issues will be discussed.
Bruce Shutts, M.B.A., Vice President, Technical Strategic Sourcing, Genzyme Corporation
Developing a commercial supply chain for chemical compounds which are often novel and structurally complicated, involves more than the standard procurement activities associated with materials sourcing. Working both independently as well as with potential vendors on chemical process and analytical R&D activities is often required to ensure quality and meet pricing targets. Various technical issues will be discussed.
Bruce Shutts, M.B.A., Vice President, Technical Strategic Sourcing, Genzyme Corporation
11:00
Managing Manufacturing Process Change and Scale-up for the REG1 System
Regado's lead antithrombotic, a direct coagulation Factor IXa inhibitor, provides physicians with the ability to control the therapeutic effect. The manufacturing process of the PEGylated Aptamer was modified and scale increased for clinical requirements. A significant effort was made to characterize and differentiate PEGylatable, non-PEGylatable impurities, and the removal of impurities from the process to understand the manufacturing process capabilities.
Doug Brooks, Ph.D., Executive Director, Chemistry, Regado Biosciences
Regado's lead antithrombotic, a direct coagulation Factor IXa inhibitor, provides physicians with the ability to control the therapeutic effect. The manufacturing process of the PEGylated Aptamer was modified and scale increased for clinical requirements. A significant effort was made to characterize and differentiate PEGylatable, non-PEGylatable impurities, and the removal of impurities from the process to understand the manufacturing process capabilities.
Doug Brooks, Ph.D., Executive Director, Chemistry, Regado Biosciences
Technology Workshop
11:30
Besides phosphoramidites, the solid support is the most critical raw material in the solid-phase synthesis of oligonucleotides. New polystyrene-based supports have been made available recently. Polystyrene supports, in comparison to the classical CPG, provide better chemical inertness but have the inherent deficiency that they are subject to swelling in organic solvents.
Hagen Cramer, Ph.D., Oligonucleotide Process Development Section Head, Girindus America Inc. Member of Solvay Organics
12:00
Scalable Process for RNA Deprotection
The scale-up of RNA deprotection has proven difficult due to the reagents used for cleavage and removal of exocyclic amine and TBDMS protecting groups. Insufficient mixing, inefficient heat control, and ratios of reagents used can all cause deprotection related degradation. A novel scalable solution for the large-scale (>100mMol) deprotection of synthetic RNA is presented allowing Agilent to produce RNA at all scales.
David Macdonald, Director of Chemical Development, Agilent Technologies
The scale-up of RNA deprotection has proven difficult due to the reagents used for cleavage and removal of exocyclic amine and TBDMS protecting groups. Insufficient mixing, inefficient heat control, and ratios of reagents used can all cause deprotection related degradation. A novel scalable solution for the large-scale (>100mMol) deprotection of synthetic RNA is presented allowing Agilent to produce RNA at all scales.
David Macdonald, Director of Chemical Development, Agilent Technologies
12:30
Networking Luncheon in Poster and Exhibit Hall
Sponsored by
Sponsored by
1:45
Pulmonary Delivery of Oligonucleotides: Considerations and Challenges
Oligonucleotides are highly soluble in aqueous formulations making nebulisation an obvious choice for inhaled delivery. However there are several key factors that should be considered before selecting an inhaled drug delivery system. This presentation provides an overview of challenges and choices for inhaled and nasal delivery of oligonucleotides.
Nadim Akhtar, Ph.D., Senior Scientist, AstraZeneca, United Kingdom
Oligonucleotides are highly soluble in aqueous formulations making nebulisation an obvious choice for inhaled delivery. However there are several key factors that should be considered before selecting an inhaled drug delivery system. This presentation provides an overview of challenges and choices for inhaled and nasal delivery of oligonucleotides.
Nadim Akhtar, Ph.D., Senior Scientist, AstraZeneca, United Kingdom
2:15
Case
Study
Late Phase Manufacturing Site TransferStudy
The presentation will describe the transfer of manufacturing site fora late phase product. The steps taken during execution of the transfer will be discussed including risk assessment, small scale process demonstration and subsequent large scale manufacture and the supporting analytical studies.
Emma Wright, Ph.D., Director, Process Development, Avecia OligoMedicines
2:45
Case
Study
A Comprehensive Look at siRNA Impurity Formation as a Function of Melting Temperature, and Is WaterContent a Critical Attribute for siRNA Stability?Study
Double stranded oligonucleotide therapeutics provide a unique challenge with respect to controlling the purity profile of your drug at release and on stability. The combination of non-denaturing and denaturing analytical techniques are used to determine the single strand, double strand, and aggregated impurities profile. A case study investigating the stability of three different siRNA compounds with varying Tm values will be presented.
Daren S. Levin, Ph.D., Investigator, Inhaled Product Development, GlaxoSmithKline
3:15
Networking Refreshment Break with Poster and Exhibit Viewing
Sponsored by
Sponsored by
Technology Workshop
3:45
Confirmation of primary structure (sequence) of oligonucleotide-based Active Pharmaceutical Ingredients is essential for quality control of manufacturing. A semi-automated methodology has been developed for sequence confirmation of any kind of oligonucleotide APIs based on tandem mass spectrometry using novel custom software. Deconvolution of highly complicated, high resolution MS/MS spectra with Agilent Oligonucleotide Sequencer software takes seconds without expertise.
Zoltan Timar, Ph.D., Scientist, Nucleic Acids Solution Division, Agilent Technologies
4:15
Using Differential Scanning Calorimetry (DSC) for the Characterization of siRNA's and Aptamers
This presentation will cover the usage of differential scanning calorimetry (DSC) for the stability and structure characterization of oligonucleotides such as siRNAs and aptamers. DSC data can be used to get an insight into the equilibria that lead to the final target structure. Moreover, the impact of chemical modifications on the stabilization of such molecules is shown.
Hüseyin Aygün, Ph.D., Chief Scientific Officer, BioSpring GmbH, Germany
This presentation will cover the usage of differential scanning calorimetry (DSC) for the stability and structure characterization of oligonucleotides such as siRNAs and aptamers. DSC data can be used to get an insight into the equilibria that lead to the final target structure. Moreover, the impact of chemical modifications on the stabilization of such molecules is shown.
Hüseyin Aygün, Ph.D., Chief Scientific Officer, BioSpring GmbH, Germany
4:45
Validation of Analytical Methods for Oligonucleotides: Unique Challenges and Solutions
Validation of the analytical methods is an integral part of the development of oligonucleotides for preclinical and clinical studies. Application of experience from small molecule analytical validation is not always directly applicable to oligonucleotides. To address oligo-specific problems, new approaches to method validation should be developed. Case studies will be presented to demonstrate practical solutions for execution of accuracy, linearity, specificity, precision, limit of quantitation, and robustness experiments and their application to a variety of oligonucleotides.
Alex Shlyankevich, Ph.D., Senior Director of Analytical Development, Avecia OligoMedicines
Validation of the analytical methods is an integral part of the development of oligonucleotides for preclinical and clinical studies. Application of experience from small molecule analytical validation is not always directly applicable to oligonucleotides. To address oligo-specific problems, new approaches to method validation should be developed. Case studies will be presented to demonstrate practical solutions for execution of accuracy, linearity, specificity, precision, limit of quantitation, and robustness experiments and their application to a variety of oligonucleotides.
Alex Shlyankevich, Ph.D., Senior Director of Analytical Development, Avecia OligoMedicines
5:15
Networking Reception in Poster and Exhibit Hall
Dedicated Poster Viewing - Poster presenters are requested to be available at their posters.
Dedicated Poster Viewing - Poster presenters are requested to be available at their posters.
Peptides
CMC: Manufacturing and Analysis
10:15
Co-Chairpersons' Remarks
Firoz D. Antia, Ph.D., Executive Director, Product Development, Palatin Technologies, Inc.
Derek Maclean, Director, Chemistry, Kai Pharmaceuticals
Firoz D. Antia, Ph.D., Executive Director, Product Development, Palatin Technologies, Inc.
Derek Maclean, Director, Chemistry, Kai Pharmaceuticals
10:30
The Green Synthesis of Peptides Using Enzymes
The formation of a peptide bond by chemical means requires protection and activation of an amino acid building block — a far from "green" sequence of reactions — while enzymatic methods have been curtailed by narrow substrate ranges. Through the use of activating groups that are substrate mimics, enzymatic approaches can now be used to prepare peptides, including those containing D- or nonproteinogenic amino acid units.
David Ager, Ph.D., Principal Scientist, DSM
The formation of a peptide bond by chemical means requires protection and activation of an amino acid building block — a far from "green" sequence of reactions — while enzymatic methods have been curtailed by narrow substrate ranges. Through the use of activating groups that are substrate mimics, enzymatic approaches can now be used to prepare peptides, including those containing D- or nonproteinogenic amino acid units.
David Ager, Ph.D., Principal Scientist, DSM
11:00
Challenges in the GMP Manufacture of Long Peptides
Long chain peptides are increasingly being used as candidates in clinical development programs. The manufacture of long chain peptides poses a unique set of challenges. We will present some examples of the development, production methodology and technical challenges involved in the GMP manufacture of long chain peptides.
Hazel Moncrieff, Ph.D., Senior Group Leader, Peptides, Almac Group, United Kingdom
Long chain peptides are increasingly being used as candidates in clinical development programs. The manufacture of long chain peptides poses a unique set of challenges. We will present some examples of the development, production methodology and technical challenges involved in the GMP manufacture of long chain peptides.
Hazel Moncrieff, Ph.D., Senior Group Leader, Peptides, Almac Group, United Kingdom
11:30
Alternative Approaches for Peptide Isolation
If building your peptide wasn't enough adventure, then there is getting your peptide safely into a form you can handle. Isolation of peptides presents operational and technical challenges, from simple removal of solvents to classical lyophilization to even more complex activities. Alternatives for peptide isolation are out there. Possibilities including precipitation, semi-crystallization and spray drying will be discussed.
Roger Micheli, Ph.D., Director, New Technology and Innovation, Roche Colorado Corporation
If building your peptide wasn't enough adventure, then there is getting your peptide safely into a form you can handle. Isolation of peptides presents operational and technical challenges, from simple removal of solvents to classical lyophilization to even more complex activities. Alternatives for peptide isolation are out there. Possibilities including precipitation, semi-crystallization and spray drying will be discussed.
Roger Micheli, Ph.D., Director, New Technology and Innovation, Roche Colorado Corporation
12:00
Recombinant Manufacturing of Salmon Calcitonin for the Development of Nasal and Oral Calcitonin by a 505 (b)(2) Pathway
A recombinant technology for high level expression and secretion of salmon calcitonin in E. coli has been developed. This technology, which offers certain advantages over traditional chemical synthesis or fusion based recombinant expression, is used to produce calcitonin for a marketed nasal spray product (ForticalTM) as well as an oral tablet calcitonin product in clinical development. The regulatory and production issues in developing these products by a 505(b)(2) regulatory pathway will be presented.
James P. Gilligan, Ph.D, MSIB, Vice President, Product Development, Unigene Laboratories Inc.
A recombinant technology for high level expression and secretion of salmon calcitonin in E. coli has been developed. This technology, which offers certain advantages over traditional chemical synthesis or fusion based recombinant expression, is used to produce calcitonin for a marketed nasal spray product (ForticalTM) as well as an oral tablet calcitonin product in clinical development. The regulatory and production issues in developing these products by a 505(b)(2) regulatory pathway will be presented.
James P. Gilligan, Ph.D, MSIB, Vice President, Product Development, Unigene Laboratories Inc.
12:30
Networking Luncheon in Poster and Exhibit Hall
Sponsored by
Sponsored by
1:45
Case
Study
Site Specific Conjugation of Peptides to Catalytic Antibodies: Development Challenges and Proven CMC StrategiesStudy
Protein-based bioconjugates offer significant advantages over conventional biological drugs. Unique pharmacological effects can be derived from small molecules while pharmacokinetic and other properties may be enhanced by the carrier protein. However, conjugates by their very nature are complex, posing unique challenges in their characterization, process development and manufacture. In this presentation, we will discuss some of the CMC strategies used by Pfizer BioTherapeutics R&D, to successfully develop several bioconjugates.
Olivier Laurent, Ph.D., Associate Director, Formulation and Process Sciences, BioTherapeutics R&D, Pfizer Inc.
Technology Workshop
2:15
Improvements in hardware, software, and instrumentation technology have led to the development of instruments and applications that can be, and are being, deployed in Development operations. In this presentation, a series of Applications of Mass Spectrometry to Development operations will be reviewed and detailed.
Darwin Asa, Ph.D., Marketing Manager, Bruker Daltonics
2:45
Characterization of Impurities Generated during Protein Conjugation
The conjugation of peptides to carrier proteins for the development of biotherapeutic entities often involves the use of heterobifunctional linkers. These reactions may lead to the formation of side reaction products as potential impurities. The characterization of these impurities often requires advanced analytical approaches and techniques, which can provide insight into their formation and control.
James A. Carroll, Ph.D., Research Fellow, BioTherapeutics R&D, Pfizer Inc.
The conjugation of peptides to carrier proteins for the development of biotherapeutic entities often involves the use of heterobifunctional linkers. These reactions may lead to the formation of side reaction products as potential impurities. The characterization of these impurities often requires advanced analytical approaches and techniques, which can provide insight into their formation and control.
James A. Carroll, Ph.D., Research Fellow, BioTherapeutics R&D, Pfizer Inc.
3:15
Networking Refreshment Break with Poster and Exhibit Viewing
Sponsored by
Sponsored by
3:45
Mass Spectrometry: a Universal Tool Built into the Analytical and Process Development of Peptides for Successful Regulatory Filing
In order to support the customized process development of peptides, our strategy is to implement mass spectrometry early in analytical development, with the objective of building product knowledge in parallel to clinical development stages. This presentation will show the success of this approach through a selection of case studies, where peptide structures designed as potential drugs have become increasingly complex (PEGylated, glycosylated, dendrimer peptides).
Jean-Marc Poudrel, Ph.D., Head of Analytical Development, Lonza, Belgium
In order to support the customized process development of peptides, our strategy is to implement mass spectrometry early in analytical development, with the objective of building product knowledge in parallel to clinical development stages. This presentation will show the success of this approach through a selection of case studies, where peptide structures designed as potential drugs have become increasingly complex (PEGylated, glycosylated, dendrimer peptides).
Jean-Marc Poudrel, Ph.D., Head of Analytical Development, Lonza, Belgium
4:15
Manufacturing and Analytical Method Development for Peptide Copolymer Mixtures
PI-2301 is a second-generation peptide copolymer analogous to Copaxone®. The analysis and characterization of PI-2301 represent a great challenge due to the polymeric feature of the product. Specific analytical methods were developed allowing PI-2301 to progress into a clinical Phase 2. Several analytical methods will be presented to demonstrate product characterization and batch-to-batch reproducibility.
Nicolas S. Mourier, Ph.D., Director of Product Development, Peptimmune, Inc.
PI-2301 is a second-generation peptide copolymer analogous to Copaxone®. The analysis and characterization of PI-2301 represent a great challenge due to the polymeric feature of the product. Specific analytical methods were developed allowing PI-2301 to progress into a clinical Phase 2. Several analytical methods will be presented to demonstrate product characterization and batch-to-batch reproducibility.
Nicolas S. Mourier, Ph.D., Director of Product Development, Peptimmune, Inc.
Audience Interactive Panel Discussion
4:45
Follow Up to Critical Industry Issues Raised in CMC Session
Moderator:
Firoz D. Antia, Ph.D., Executive Director, Product Development, Palatin Technologies, Inc.
Panelists:
David Ager, Ph.D., Principal Scientist, DSM
James A. Carroll, Ph.D., Research Fellow, BioTherapeutics R&D, Pfizer Inc.
Olivier Laurent, Ph.D., Associate Director, Formulation and Process Sciences, BioTherapeutics R&D, Pfizer Inc.
Nicolas S. Mourier, Ph.D., Director of Product Development, Peptimmune, Inc.
Jean-Marc Poudrel, Ph.D., Head of Analytical Development, Lonza, Belgium
Moderator:
Firoz D. Antia, Ph.D., Executive Director, Product Development, Palatin Technologies, Inc.
Panelists:
David Ager, Ph.D., Principal Scientist, DSM
James A. Carroll, Ph.D., Research Fellow, BioTherapeutics R&D, Pfizer Inc.
Olivier Laurent, Ph.D., Associate Director, Formulation and Process Sciences, BioTherapeutics R&D, Pfizer Inc.
Nicolas S. Mourier, Ph.D., Director of Product Development, Peptimmune, Inc.
Jean-Marc Poudrel, Ph.D., Head of Analytical Development, Lonza, Belgium
5:15
Networking Reception in Poster and Exhibit Hall
Dedicated Poster Viewing - Poster presenters are requested to be available at their posters.
Dedicated Poster Viewing - Poster presenters are requested to be available at their posters.
Courses: Sunday Morning - Afternoon
Main Conference: Monday | Main Conference: Tuesday | Main Conference: Wednesday
Molecular Diagnostics | Oligonucleotide Therapeutics Discovery | Site Tours
Oligonucleotides
7:30
Coffee
Formulation and Delivery
8:00
Chairperson's Remarks
Bob D. Brown, Ph.D., Senior Vice President, Research, Dicerna Pharmaceuticals, Inc.
Bob D. Brown, Ph.D., Senior Vice President, Research, Dicerna Pharmaceuticals, Inc.
8:15
Delivery of Locked Nucleic Acid (LNA) Oligonucleotide Drugs
Today, close to 20 LNA oligonucleotide drug candidates are at different stages of drug development. Without exception, all LNA oligonucleotides are delivered without encapsulation and formulated in saline. This presentation will focus on the cellular uptake mechanisms and pharmacology of LNA oligonucleotides formulated in saline and the perspectives of LNA drug delivery.
J. Bo Rode Hansen, M.Sc., Ph.D., Director of Technology and Alliance Discovery, Santaris Pharma A/S, Denmark
Today, close to 20 LNA oligonucleotide drug candidates are at different stages of drug development. Without exception, all LNA oligonucleotides are delivered without encapsulation and formulated in saline. This presentation will focus on the cellular uptake mechanisms and pharmacology of LNA oligonucleotides formulated in saline and the perspectives of LNA drug delivery.
J. Bo Rode Hansen, M.Sc., Ph.D., Director of Technology and Alliance Discovery, Santaris Pharma A/S, Denmark
8:45
Optimization of RNAi for Therapeutic Development
Local administration of a new class of RNAi compound, termed self-delivering rxRNA (sd-rxRNA™) results in rapid and efficient cellular uptake and activity in vivo. Data presented will demonstrate the efficacy of locally-administered sd-rxRNAs and support the use of sd-rxRNAs for clinical applications where direct administration to the tissue of interest is possible. The potential preclinical development path of sd-rxRNA™ using intradermal administration will be discussed.
Pamela A. Pavco, Ph.D., Vice President, Pharmaceutical Development, RXi Pharmaceuticals
Local administration of a new class of RNAi compound, termed self-delivering rxRNA (sd-rxRNA™) results in rapid and efficient cellular uptake and activity in vivo. Data presented will demonstrate the efficacy of locally-administered sd-rxRNAs and support the use of sd-rxRNAs for clinical applications where direct administration to the tissue of interest is possible. The potential preclinical development path of sd-rxRNA™ using intradermal administration will be discussed.
Pamela A. Pavco, Ph.D., Vice President, Pharmaceutical Development, RXi Pharmaceuticals
9:15
Improving on a Good Thing - Integrating Preclinical and Clinical Experience in the Development of Next Generation SNALP to Enable RNAi Therapeutics
SNALP, a modular lipid nanoparticle system for the delivery of nucleic acids, are being used to enable the systemic delivery of siRNA in the clinical development of metabolic and oncology therapeutic products. Ongoing formulation development efforts, informed by the clinical experience of Tekmira and our partners, continue to produce SNALP formulations with substantially increased potency and reduced toxicity. Approaches towards the integration of these improvements into new and ongoing product development efforts will be discussed.
Ian MacLachlan, Ph.D., Executive Vice President & Chief Scientific Officer, Tekmira Pharmaceuticals Corp., Canada
SNALP, a modular lipid nanoparticle system for the delivery of nucleic acids, are being used to enable the systemic delivery of siRNA in the clinical development of metabolic and oncology therapeutic products. Ongoing formulation development efforts, informed by the clinical experience of Tekmira and our partners, continue to produce SNALP formulations with substantially increased potency and reduced toxicity. Approaches towards the integration of these improvements into new and ongoing product development efforts will be discussed.
Ian MacLachlan, Ph.D., Executive Vice President & Chief Scientific Officer, Tekmira Pharmaceuticals Corp., Canada
9:45
Networking Refreshment Break with Poster and Exhibit Viewing
Sponsored by
Sponsored by
10:15
Optimizing a Lipid-based Vehicle for siRNA Delivery to Liver
Safe and effective delivery of siRNA remains a significant challenge for fully leveraging its therapeutic potential. A lipid nanoparticle system has been developed for delivery to liver and shown to be safe and potent in rodent and non-human primate. Component SAR, formulation composition, and fabrication process, which impact physical properties and ultimately biological performance, were evaluated systematically. Approaches to further improving delivery efficiency, understanding species variability, and minimizing toxicity are illustrated.
Paul A. Burke, Ph.D., Executive Director, RNAi Therapeutics, Merck & Co., Inc.
Safe and effective delivery of siRNA remains a significant challenge for fully leveraging its therapeutic potential. A lipid nanoparticle system has been developed for delivery to liver and shown to be safe and potent in rodent and non-human primate. Component SAR, formulation composition, and fabrication process, which impact physical properties and ultimately biological performance, were evaluated systematically. Approaches to further improving delivery efficiency, understanding species variability, and minimizing toxicity are illustrated.
Paul A. Burke, Ph.D., Executive Director, RNAi Therapeutics, Merck & Co., Inc.
10:45
Development of an siRNA Therapeutic for Liver Cancer
Alnylam Pharmaceuticals has begun advancing a drug for liver cancer called ALN-VSP that is comprised of two different siRNA's targeting VEGF and kinesin spindle protein delivered in a lipid nanoparticle. This presentation will outline the delivery approach being used for this indication, present the data from a murine orthotopic liver tumor model showing activity against human hepatocellular carcinoma, and discuss the design of the ongoing Phase 1 trial of ALN-VSP in patients with liver cancer.
Jared A. Gollob, M.D., Senior Director, Clinical Research, Alnylam Pharmaceuticals, Inc.
Alnylam Pharmaceuticals has begun advancing a drug for liver cancer called ALN-VSP that is comprised of two different siRNA's targeting VEGF and kinesin spindle protein delivered in a lipid nanoparticle. This presentation will outline the delivery approach being used for this indication, present the data from a murine orthotopic liver tumor model showing activity against human hepatocellular carcinoma, and discuss the design of the ongoing Phase 1 trial of ALN-VSP in patients with liver cancer.
Jared A. Gollob, M.D., Senior Director, Clinical Research, Alnylam Pharmaceuticals, Inc.
11:15
RNAi Therapeutics for Oncology - UsiRNA Construct and DiLA2-based Delivery
UsiRNAs provide potent knockdown of mRNA and reduction in tumor burden when delivered in DiLA2 liposomes in orthotopic models of liver or bladder cancer and systemic or local administration, respectively. Pharmacology and tolerability by these routes in non-human primates provides further evidence for the UsiRNA/DiLA2 platform. This information forms the basis for the design and conduct of clinical trials in oncology.
Michael V. Templin, Ph.D., Vice President, Discovery Research and Pharmaceutical Development, MDRNA Inc.
UsiRNAs provide potent knockdown of mRNA and reduction in tumor burden when delivered in DiLA2 liposomes in orthotopic models of liver or bladder cancer and systemic or local administration, respectively. Pharmacology and tolerability by these routes in non-human primates provides further evidence for the UsiRNA/DiLA2 platform. This information forms the basis for the design and conduct of clinical trials in oncology.
Michael V. Templin, Ph.D., Vice President, Discovery Research and Pharmaceutical Development, MDRNA Inc.
11:45
Case
Study
PROMAXX Antisense Oligonucleotide (ASO) Microspheres for Type 1 Diabetes TreatmentStudy
We produced ASO microspheres by combining 3 phosphorothioated ASOs targeting CD40, CD80 and CD86 dendritic cell costimulatory molecules. RP-HPLC analysis yielded microspheres containing over 70% (wt/wt) nucleic acid. Subcutaneous injection of microspheres prevented and reversed of autoimmune Type-1 diabetes in the NOD mouse. Microspheres accumulated within pancreas and spleen. Spleen dendritic cells exhibited decreased cell-surface costimulatory molecules.
Christian Grant, Ph.D., Research Director, Biomedical Research Models Inc.
12:15
Networking Lunch in Poster and Exhibit Hall
Final Opportunity for Poster and Exhibit Viewing
Final Opportunity for Poster and Exhibit Viewing
Optimization Strategies of Leading Oligo-Based Therapeutics in Preclinical Development
1:30
Chairperson's Remarks
Troels Koch, Ph.D., Vice President and CTO, Santaris Pharma A/S, Denmark
Troels Koch, Ph.D., Vice President and CTO, Santaris Pharma A/S, Denmark
1:45
GED-0301 for the Oral Treatment of Crohn's Disease via the Localized Delivery of a Smad7 Antisense Oligonucleotide: Preclinical and Early Clinical Development
GED-0301 is an antisense oligonucleotide which targets Smad7. An oral dosage form that affords delivery and local activity of GED-0301 in the terminal ileum and right colon is under early clinical development for the treatment of active Crohn's disease. This presentation provides a description of GED-0301 preclinical and clinical development plan.
Salvatore Bellinvia, M.D., Director, Pharma Division, Giuliani S.p.A., Italy
GED-0301 is an antisense oligonucleotide which targets Smad7. An oral dosage form that affords delivery and local activity of GED-0301 in the terminal ileum and right colon is under early clinical development for the treatment of active Crohn's disease. This presentation provides a description of GED-0301 preclinical and clinical development plan.
Salvatore Bellinvia, M.D., Director, Pharma Division, Giuliani S.p.A., Italy
2:15
Advancing Dicer-substrate siRNA (DsiRNA) towards the Clinic
DsiRNAs are highly potent activators of RNAi combined with an extended, flexible medicinal chemistry platform to be used for intracellular delivery and formulations. DsiRNAs enter the RNAi pathway via the enzyme Dicer, mimicking natural miRNAs. At doses sufficient to reduce target gene expression in vivo by greater than 90%, in both tumor and normal tissues, natural miRNA processing is unperturbed. Gene knockdown in vivo using multiple delivery formulations and therapeutic targets will be presented.
Bob D. Brown, Senior Vice President, Research, Dicerna Pharmaceuticals, Inc.
DsiRNAs are highly potent activators of RNAi combined with an extended, flexible medicinal chemistry platform to be used for intracellular delivery and formulations. DsiRNAs enter the RNAi pathway via the enzyme Dicer, mimicking natural miRNAs. At doses sufficient to reduce target gene expression in vivo by greater than 90%, in both tumor and normal tissues, natural miRNA processing is unperturbed. Gene knockdown in vivo using multiple delivery formulations and therapeutic targets will be presented.
Bob D. Brown, Senior Vice President, Research, Dicerna Pharmaceuticals, Inc.
2:45
Promise of Tumor Suppressor miRNAs as Cancer Therapeutics
Mirna Therapeutics is developing miRNA mimics modeled after key tumor suppressor miRNAs that undergo a loss-of-function in cancer. Proof-of-concept experiments demonstrate that systemic administration of these mimics in a novel delivery formulation inhibits the growth and metastasis of established tumors in mice. The formulation was well tolerated and does not induce a non-specific immune response. Examples will be presented.
Paul Lammers, M.D., M.Sc., President and CEO, Mirna Therapeutics
Mirna Therapeutics is developing miRNA mimics modeled after key tumor suppressor miRNAs that undergo a loss-of-function in cancer. Proof-of-concept experiments demonstrate that systemic administration of these mimics in a novel delivery formulation inhibits the growth and metastasis of established tumors in mice. The formulation was well tolerated and does not induce a non-specific immune response. Examples will be presented.
Paul Lammers, M.D., M.Sc., President and CEO, Mirna Therapeutics
3:15
Networking Refreshment Break
Sponsored by
Sponsored by
Development Strategies of Leading Oligo-Based Therapeutics in Clinical Development
Chairperson: Arthur M. Krieg, M.D., Chief Scientific Officer, Research Technology Center, Pfizer Inc.
3:45
The Development of RNA-Modulating Therapies: Prosensa's PRO051 Study Program
Prosensa Therapeutics, a Dutch biopharmaceutical company, is a leader in the development of RNA-modulating treatments for Duchenne Muscular Dystrophy (DMD). PRO051 induces specific exon 51 skipping from the DMD gene transcript. Based upon promising results from two Phase 1/2 studies the compound is moving into Phase 3. We will present the PRO051 development program and Prosensa's approach to its challenges.
Giles Campion, Ph.D., M.D., Chief Medical Officer and Vice President Research and Development, Prosensa Therapeutics B.V., The Netherlands
Prosensa Therapeutics, a Dutch biopharmaceutical company, is a leader in the development of RNA-modulating treatments for Duchenne Muscular Dystrophy (DMD). PRO051 induces specific exon 51 skipping from the DMD gene transcript. Based upon promising results from two Phase 1/2 studies the compound is moving into Phase 3. We will present the PRO051 development program and Prosensa's approach to its challenges.
Giles Campion, Ph.D., M.D., Chief Medical Officer and Vice President Research and Development, Prosensa Therapeutics B.V., The Netherlands
4:15
Evaluation of Locked Nucleic Acid (LNA) mRNA Antagonists as Novel Cancer Therapeutics: The Clinical Perspective
LNA antisense oligonucleotides (LNA-ONs) have high affinity to mRNA, are resistant to degradation, and can silence protein expression in tumor cells even in the absence of transfection. LNA-ONs used in cancer patients, without the use of delivery vehicles, may ultimately inhibit tumor growth. The strategies and clinical evaluation of LNA-ONs against "undruggable" targets in cancer, based on Phase 1 experience, will be discussed.
Aby Buchbinder, M.D., Vice President, Clinical Development, Enzon Pharmaceuticals
LNA antisense oligonucleotides (LNA-ONs) have high affinity to mRNA, are resistant to degradation, and can silence protein expression in tumor cells even in the absence of transfection. LNA-ONs used in cancer patients, without the use of delivery vehicles, may ultimately inhibit tumor growth. The strategies and clinical evaluation of LNA-ONs against "undruggable" targets in cancer, based on Phase 1 experience, will be discussed.
Aby Buchbinder, M.D., Vice President, Clinical Development, Enzon Pharmaceuticals
4:45
Clinical Development of Synthetic siRNAs for Renal and Ophthalmic Indications
Safety data from Phase 1 studies of QPI-1002 (I5NP), a synthetic siRNA for the prevention of ischemia reperfusion injury in the kidney, will be presented. Data will also be presented from nonclinical studies supporting a Phase 1 study of QPI-1007, a synthetic siRNA targeting caspase 2 that is being developed as a neuroprotectant for treating ischemic optic neuropathy and glaucoma.
James D. Thompson, Ph.D., Vice President, Pharmaceutical Development, Quark Pharmaceuticals, Inc.
Safety data from Phase 1 studies of QPI-1002 (I5NP), a synthetic siRNA for the prevention of ischemia reperfusion injury in the kidney, will be presented. Data will also be presented from nonclinical studies supporting a Phase 1 study of QPI-1007, a synthetic siRNA targeting caspase 2 that is being developed as a neuroprotectant for treating ischemic optic neuropathy and glaucoma.
James D. Thompson, Ph.D., Vice President, Pharmaceutical Development, Quark Pharmaceuticals, Inc.
5:15
Close of TIDES®
Peptides
7:30
Coffee
Formulation and Delivery
8:00
Co-Chairpersons' Remarks
Peter Hoffmann, Ph.D., Vice President, New Technology Development, Genzyme Pharmaceuticals
Christopher A. Rhodes, Ph.D., Executive Director, Pharmaceutical Sciences, Amylin Pharmaceuticals, Inc.
Peter Hoffmann, Ph.D., Vice President, New Technology Development, Genzyme Pharmaceuticals
Christopher A. Rhodes, Ph.D., Executive Director, Pharmaceutical Sciences, Amylin Pharmaceuticals, Inc.
8:15
Current Strategies for Developing Sustained Release Peptides and Proteins
Sterile nanosuspensions and self gelling depot systems have become important strategies for the development of sustained release peptide systems. In addition, technologies using mechanical methods (devices) to facilitate administration of sustained release injection dosage forms have, in some cases, become critical to the development of successful peptide sustained release delivery systems. Applications of these technologies to the development of sustained release peptides for the treatment of metabolic and viral diseases will be discussed.
Ralph Tarantino, Ph.D., Research Director, Sterile Dosage Forms, Hoffmann-LaRoche, Inc.
Sterile nanosuspensions and self gelling depot systems have become important strategies for the development of sustained release peptide systems. In addition, technologies using mechanical methods (devices) to facilitate administration of sustained release injection dosage forms have, in some cases, become critical to the development of successful peptide sustained release delivery systems. Applications of these technologies to the development of sustained release peptides for the treatment of metabolic and viral diseases will be discussed.
Ralph Tarantino, Ph.D., Research Director, Sterile Dosage Forms, Hoffmann-LaRoche, Inc.
8:45
MimetibodiesTM, A Platform Technology for the Development of Biologically Active Peptides that Prolongs Half-Life
In the past several decades, hundreds of peptides have been identified which have specific biological activity and are highly potent in in vitro assays but lack the prerequisite pharmacokinetics to become efficacious human therapeutics. We have developed a novel antibody-based platform technology that provides an improved pharmacokinetic profile for biologically active peptides, resulting in a long duration of action.
George A. Heavner, Ph.D., Distinguished Research Fellow, Biologics Research, Centocor, Inc.
In the past several decades, hundreds of peptides have been identified which have specific biological activity and are highly potent in in vitro assays but lack the prerequisite pharmacokinetics to become efficacious human therapeutics. We have developed a novel antibody-based platform technology that provides an improved pharmacokinetic profile for biologically active peptides, resulting in a long duration of action.
George A. Heavner, Ph.D., Distinguished Research Fellow, Biologics Research, Centocor, Inc.
9:15
PuraMatrix Self-Assembling Polypeptides for Therapeutic Delivery Applications
3DM's PuraMatrix™ technology consists a family of synthetic, in situ self-assembling three-dimensional polypeptide hydrogels. The injectable peptide biomaterials assemble or gel upon injection, forming a synthetic nanofiber ECM scaffold. PuraMatrix self-assembling polypeptides have similar physiological properties to the in vivo extracellular matrix, facilitating the delivery of cells, growth factor biologics, or pharmaceuticals.
Lisa Spirio, Ph.D., Co-Founder and Chief Technology Officer, 3DM
3DM's PuraMatrix™ technology consists a family of synthetic, in situ self-assembling three-dimensional polypeptide hydrogels. The injectable peptide biomaterials assemble or gel upon injection, forming a synthetic nanofiber ECM scaffold. PuraMatrix self-assembling polypeptides have similar physiological properties to the in vivo extracellular matrix, facilitating the delivery of cells, growth factor biologics, or pharmaceuticals.
Lisa Spirio, Ph.D., Co-Founder and Chief Technology Officer, 3DM
9:45
Networking Refreshment Break with Poster and Exhibit Viewing
Sponsored by
Sponsored by
Roundtable Discussion on Follow up to Peptide CMC Session Topics
10:15
Enhanced Performance of Peptide and Protein Drugs Using Polysialic Acid (PolyXen®): Clinical Results with Long Acting Insulin and EPO
Polymer based drug delivery with PEG is increasingly being applied to the development of new drugs de novo, in order to ensure adequate longevity in circulation and optimal efficacy. However, PEGylaton has disadvantages that have limited its wider application. The presentation will describe polysialic acid as a ‘next generation' polymer technology that avoids these disadvantages and which has achieved excellent results in Phase 1 studies of long acting forms of insulin and EPO.
Sanjay Jain, Ph.D., Principal Scientist, Lipoxen PLC, United Kingdom
Polymer based drug delivery with PEG is increasingly being applied to the development of new drugs de novo, in order to ensure adequate longevity in circulation and optimal efficacy. However, PEGylaton has disadvantages that have limited its wider application. The presentation will describe polysialic acid as a ‘next generation' polymer technology that avoids these disadvantages and which has achieved excellent results in Phase 1 studies of long acting forms of insulin and EPO.
Sanjay Jain, Ph.D., Principal Scientist, Lipoxen PLC, United Kingdom
10:45
Exenatide Once Weekly: A New Therapy for Type 2 Diabetes
Exenatide Once Weekly (EQW) is a long-acting formulation of exenatide, the active ingredient in Byetta® (exenatide injection) based on the Medisorb technology from Alkermes, Inc. EQW has the potential to be a diabetes therapeutic with superior efficacy, tolerability and patient convenience. This presentation will provide an overview of aspects of drug development including formulation development, scale-up and commercial manufacturing and results of clinical studies.
Steven J. Prestrelski, Ph.D., M.B.A., Vice President, Pharmaceutical R&D, Amylin Pharmaceuticals, Inc.
Exenatide Once Weekly (EQW) is a long-acting formulation of exenatide, the active ingredient in Byetta® (exenatide injection) based on the Medisorb technology from Alkermes, Inc. EQW has the potential to be a diabetes therapeutic with superior efficacy, tolerability and patient convenience. This presentation will provide an overview of aspects of drug development including formulation development, scale-up and commercial manufacturing and results of clinical studies.
Steven J. Prestrelski, Ph.D., M.B.A., Vice President, Pharmaceutical R&D, Amylin Pharmaceuticals, Inc.
11:15
The Technosphere® Inhalation System: Progess in Inhaled Insulin and Inhaled GLP-1
Progress in the development of Technosphere® Insulin (TI) and Technosphere® GLP-1 inhalation products for diabetes treatment will be discussed. The presentation will include clinical data comparing TI, injected rapid acting insulin, and other inhaled insulins; and clinical data comparing GLP-1 Technosphere® with injected Exenatide with respect to insulin and C-peptide induction and gastric emptying. Next generation devices matched to patient treatment needs will also be discussed.
Andrea Leone-Bay, Ph.D., Vice President, Pharmaceutical R&D, MannKind Corporation
Progress in the development of Technosphere® Insulin (TI) and Technosphere® GLP-1 inhalation products for diabetes treatment will be discussed. The presentation will include clinical data comparing TI, injected rapid acting insulin, and other inhaled insulins; and clinical data comparing GLP-1 Technosphere® with injected Exenatide with respect to insulin and C-peptide induction and gastric emptying. Next generation devices matched to patient treatment needs will also be discussed.
Andrea Leone-Bay, Ph.D., Vice President, Pharmaceutical R&D, MannKind Corporation
11:45
Transdermal Delivery of Peptides and Other Biologics Using the PassPort® System
The Altea Therapeutics PassPort System enables the delivery of water-soluble biologics and small drugs transdermally through the creation of aqueous micropores in skin that enable molecules to enter the viable epidermis and systemic circulation. PK/PD results from both preclinical and human clinical studies will be presented to provide an understanding of the capabilities of the system for transdermal biologic delivery.
Frank Tagliaferri, Ph.D., Vice President, Research and Development, Altea Therapeutics
The Altea Therapeutics PassPort System enables the delivery of water-soluble biologics and small drugs transdermally through the creation of aqueous micropores in skin that enable molecules to enter the viable epidermis and systemic circulation. PK/PD results from both preclinical and human clinical studies will be presented to provide an understanding of the capabilities of the system for transdermal biologic delivery.
Frank Tagliaferri, Ph.D., Vice President, Research and Development, Altea Therapeutics
12:15
Networking Lunch in Poster and Exhibit Hall
Final Opportunity for Poster and Exhibit Viewing
Final Opportunity for Poster and Exhibit Viewing
Optimization Strategies of Leading Peptide-Based Therapeutics in Preclinical Development
1:30
Chairperson's Remarks
David Tumelty, Ph.D., Associate Director, Chemistry, Biotherapeutics R&D, Pfizer Inc.
David Tumelty, Ph.D., Associate Director, Chemistry, Biotherapeutics R&D, Pfizer Inc.
1:35
Discovery and Optimization of Novel Agonist Peptides of the Granulocyte Colony-Stimulating Factor (G-CSF) Receptor
G-CSF and its cell surface receptor are responsible for regulating the production of neutrophils. Screening of phage display libraries and subsequent optimization led to the discovery of potent novel peptides that act as functional agonists. This talk will describe our optimization efforts and results of in vitro and in vivo testing of the leads.
Christopher P. Holmes, Ph.D., Executive Director, Affymax, Inc.
G-CSF and its cell surface receptor are responsible for regulating the production of neutrophils. Screening of phage display libraries and subsequent optimization led to the discovery of potent novel peptides that act as functional agonists. This talk will describe our optimization efforts and results of in vitro and in vivo testing of the leads.
Christopher P. Holmes, Ph.D., Executive Director, Affymax, Inc.
2:05
Activation of Glucagon Receptor for the Treatment of Metabolic Disorders
Oxyntomodulin is a GLP-1 receptor (GLP1R)/glucagon receptor (GCGR) dual agonist peptide that reduces body weight in obese subjects. We developed a protease-resistant dual GLP1R/GCGR agonist, DualAG, and a GLP1R agonist, GLPAG, matched for GLP1R agonist potency and pharmacokinetics. The metabolic effects of these two peptides were compared in DIO mice. DualAG exhibits superior weight loss and lipid lowering activity. GLP1R/GCGR agonism is a novel therapeutic approach to the treatment of obesity.
Paul E. Carrington, Ph.D., Research Fellow, Merck Research Laboratories, Merck & Co Inc.
Oxyntomodulin is a GLP-1 receptor (GLP1R)/glucagon receptor (GCGR) dual agonist peptide that reduces body weight in obese subjects. We developed a protease-resistant dual GLP1R/GCGR agonist, DualAG, and a GLP1R agonist, GLPAG, matched for GLP1R agonist potency and pharmacokinetics. The metabolic effects of these two peptides were compared in DIO mice. DualAG exhibits superior weight loss and lipid lowering activity. GLP1R/GCGR agonism is a novel therapeutic approach to the treatment of obesity.
Paul E. Carrington, Ph.D., Research Fellow, Merck Research Laboratories, Merck & Co Inc.
2:35
Case
Study
AL-309: A Preclinical Case Study for Peripheral NeuropathiesStudy
AL-309 is an all D-amino peptide derived from Activity-Dependent Neurotrophic Factor (ADNF). In preclinical models, AL-309 demonstrated protection of peripheral nerve damage after chemotherapy- or diabetes-induced neuropathy as well as an improvement in the pain response which develops in these models. The pharmacology, pharmacokinetics and preliminary toxicology suggest that AL-309 is an interesting drug candidate for the prevention of peripheral neuropathies.
Bruce H. Morimoto, Ph.D., Vice President, Drug Development, Allon Therapeutics Inc., Canada
3:05
Case
Study
Novel Macrocycles as Modulators of the Ghrelin Receptor for the Treatment of Gastrointestinal and Metabolic DisordersStudy
Novel macrocyclic peptidomimetics have been found that differentially modulate the ghrelin receptor. A detailed case study of the discovery of TZP-101, an intravenous ghrelin agonist currently in Phase 3 for the treatment of acute GI dysmotility disorders, will be presented. In addition, insight will be provided into the subtle changes within this structural scaffold that subsequently led to the oral agonist, TZP-102, a Phase 2 compound for chronic GI dysmotility disorders and the antagonist, TZP-301, a preclinical candidate for obesity and diabetes.
Mark L. Peterson, Ph.D., Vice President, IP & Operations, Tranzyme Pharma Inc., Canada
3:30
Networking Refreshment Break
Sponsored by
Sponsored by
Development Strategies of Leading Peptide-Based Therapeutics in Clinical Development
Chairperson: Jesse Z. Dong, Ph.D., Vice President, Chemistry, Ipsen
3:45
Case
Study
BIM-23A760, A Novel Chimeric Molecule for Potential Treatment of Pituitary Adenoma and Neuroendocrine TumorsStudy
BIM23A760 is an innovative first-in-class chimeric compound that contains structural elements of both somatostatin analogue and dopamine agonist, currently in Phase 2 clinical development for the treatment of acromegaly. This molecule targets two of the most common patho-physiological pathways associated with pituitary tumors: growth hormone and prolactin. The design of BIM23A760 is based on a novel concept regarding the amplification of intracellular signaling when simultaneously engaging two receptors with their respective ligands.
Jesse Z. Dong, Ph.D., Vice President, Chemistry, Ipsen
4:15
CVX-060: A Selective Angiopoietin-2 Antagonist CovX-Body
Pfizer BioTherapeutics R&D, has introduced a new class of biotherapeutic agents referred to as CovX-Bodies, which provide an elegant solution to overcome the PK-PD problems of peptides. In this account we describe the synthesis and characterization of CovX-Bodies designed to selectively target Angiopoietin-2, an important angiogenic factor for tumor vasculature.
Abhijit Bhat, Ph.D., Associate Director, Chemistry, BioTherapeutics R&D, Pfizer Inc.
Pfizer BioTherapeutics R&D, has introduced a new class of biotherapeutic agents referred to as CovX-Bodies, which provide an elegant solution to overcome the PK-PD problems of peptides. In this account we describe the synthesis and characterization of CovX-Bodies designed to selectively target Angiopoietin-2, an important angiogenic factor for tumor vasculature.
Abhijit Bhat, Ph.D., Associate Director, Chemistry, BioTherapeutics R&D, Pfizer Inc.
4:45
Case
Study
BA058: A Novel Analog of Human Parathyroid Hormone-related Peptide (hPTHrP)Study
BA058 is a 34-amino acid fragment of hPTHrP and a member of an unique, patented family of (hPTHrP) analogs. BA058 was specifically engineered to optimize bone anabolic potency while reducing hypercalcemia, controlling bone resorption and enhancing product stability, yet maintaining structural and functional distinction from human PTH. BA058 has successfully completed Phase 2 and bears out the development hypotheses.
Louis St.L. O'Dea, MD, FRCP(C), Senior Vice President and Chief Medical Officer, Radius Health, Inc.
5:15
Close of TIDES®
Break-Out Discussion Sessions
8:00
Follow Up Discussion to Oligonucleotide CMC Manufacturing and Analysis Session
This interactive discussion is your opportunity to ask question of the Oligonucleotide CMC Manufacturing and Analysis session chairpersons and speakers.
Moderators:
Lubomir Nechev, Ph.D., Director, Process Chemistry, Alnylam Pharmaceuticals, Inc.
Emma Wright, Ph.D., Director, Process Development, Avecia OligoMedicines
This interactive discussion is your opportunity to ask question of the Oligonucleotide CMC Manufacturing and Analysis session chairpersons and speakers.
Moderators:
Lubomir Nechev, Ph.D., Director, Process Chemistry, Alnylam Pharmaceuticals, Inc.
Emma Wright, Ph.D., Director, Process Development, Avecia OligoMedicines
9:45
Networking Refreshment Break in Exhibit and Poster Hall
Sponsored by
Sponsored by
10:15
Applications of Mass Spectrometry to Synthetic Oligonucleotides
This session will provide the opportunity to bring your questions and points for discussion to the expert panel, who will be prepared to discuss fundamental issues and advanced technology. Among the topics that will be explored are proof of structure, sequencing, impurity identification, mass spectrometry as a test on drug substance or drug product specifications, which technique to apply to which problem, and the limitations that each technique might present.
Moderator:
James V. McArdle, Ph.D., President, McArdle & Associates, LLC
Panelists:
Steven Becht, Ph.D., Senior Research Scientist, PPD
Matthias Kretschmer, Ph.D., Director of Analytical Sciences, Alnylam Pharmaceuticals, Inc.
Zoltan Timar, Ph.D., Scientist, Nucleic Acids Solution Division, Agilent Technologies
This session will provide the opportunity to bring your questions and points for discussion to the expert panel, who will be prepared to discuss fundamental issues and advanced technology. Among the topics that will be explored are proof of structure, sequencing, impurity identification, mass spectrometry as a test on drug substance or drug product specifications, which technique to apply to which problem, and the limitations that each technique might present.
Moderator:
James V. McArdle, Ph.D., President, McArdle & Associates, LLC
Panelists:
Steven Becht, Ph.D., Senior Research Scientist, PPD
Matthias Kretschmer, Ph.D., Director of Analytical Sciences, Alnylam Pharmaceuticals, Inc.
Zoltan Timar, Ph.D., Scientist, Nucleic Acids Solution Division, Agilent Technologies
11:15
Intellectual Property Issues Relating to Therapeutic Oligonucleotides and Peptides
Patents are at the very core of strategic decision-making at therapeutic-based companies, large and small. They impact research and development, commercial products, investor financing, and mergers/acquisitions/IPO's. What is special in protecting inventions relating to therapeutic oligonucleotides and peptides? What freedom to operate issues are particularly relevant?
Co-Moderators:
John P. Iwanicki, M.S., J.D., Attorney, Banner & Witcoff, Ltd.
Kathleen M. Williams, Ph.D., J.D., Partner, Intellectual Property, Edwards Angell Palmer & Dodge LLP
Patents are at the very core of strategic decision-making at therapeutic-based companies, large and small. They impact research and development, commercial products, investor financing, and mergers/acquisitions/IPO's. What is special in protecting inventions relating to therapeutic oligonucleotides and peptides? What freedom to operate issues are particularly relevant?
Co-Moderators:
John P. Iwanicki, M.S., J.D., Attorney, Banner & Witcoff, Ltd.
Kathleen M. Williams, Ph.D., J.D., Partner, Intellectual Property, Edwards Angell Palmer & Dodge LLP
12:15
Networking Lunch in Poster and Exhibit Hall
Final Opportunity for Poster and Exhibit Viewing
Final Opportunity for Poster and Exhibit Viewing
1:30
Peptides: Impurities and their Changing Role in the Global Registration of Peptides
The approach of various regulatory authorities to the impact of ICH impurity limits on peptide specifications will be addressed. Traditional process impurities and degradants seen in peptides will be discussed. In addition the panel will consider the growing importance of non peptide related impurities and potential genotoxic molecules in the registration of API's. The probity of starting materials including TSE certification, and the growing utility of materials from non-traditional pharmaceutical suppliers will also be discussed.
Moderator:
John D. Richards, D. Phil., Vice President, Global Technical Development, The Medicines Company
Panelists:
Firoz D. Antia, Ph.D., Executive Director Product Development, Palatin Technologies, Inc.
Michael S. Verlander, D. Phil., President, PolyPeptide Laboratories San Diego
Additional panelists to be announced.
The approach of various regulatory authorities to the impact of ICH impurity limits on peptide specifications will be addressed. Traditional process impurities and degradants seen in peptides will be discussed. In addition the panel will consider the growing importance of non peptide related impurities and potential genotoxic molecules in the registration of API's. The probity of starting materials including TSE certification, and the growing utility of materials from non-traditional pharmaceutical suppliers will also be discussed.
Moderator:
John D. Richards, D. Phil., Vice President, Global Technical Development, The Medicines Company
Panelists:
Firoz D. Antia, Ph.D., Executive Director Product Development, Palatin Technologies, Inc.
Michael S. Verlander, D. Phil., President, PolyPeptide Laboratories San Diego
Additional panelists to be announced.
Applications of Nucleic Acids Technologies in Molecular Diagnostics
Diagnostics: Tuesday | Diagnostics: Wednesday
TIDES® Main Conference | Oligonucleotide Therapeutics Discovery | Site Tours
7:00
Registration and Coffee
Regulatory Pathways and Quality Strategies
8:00
Chairperson's Remarks
B. Melina Cimler, Ph.D., Senior Vice President, Government Affairs, Beckman-Coulter Inc.
B. Melina Cimler, Ph.D., Senior Vice President, Government Affairs, Beckman-Coulter Inc.
Keynote Presentations
8:10
Commercialization of IVDs Labeled for Research Use Only or Investigational Use OnlyFDA has labeling requirements for diagnostic devices at different stages of development. Failure to comply with the appropriate requirements may put diagnostic device developers at risk for FDA attention. This presentation will explain the meaning of the different requirements, and when to apply different types of labels to devices, and how to avoid making errors in labeling.
Elizabeth Mansfield, Ph.D., Director for Personalized Medicine, OIVD, CDRH, US FDA
8:50
Challenges in Drug and Diagnostic Co-Development -A Diagnostic PerspectiveWe are in a period of much discussed personalized medicine and targeted molecular therapy. While there has been considerable investment in understanding the role molecular assays will play in predicting sensitivity or resistance to new drugs, significant challenges remain. Selecting patients most likely to benefit from these agents has given rise to expanding interest in development of new companion diagnostics. Challenges and practical consideration in the co-development of drugs and diagnostics from a diagnostic regulatory perspective will be discussed.
William Pignato, Global Head, Regulatory Affairs, Novartis Molecular Diagnostics
9:30
Networking Refreshment Break
Sponsored by
Sponsored by
10:15
Case
Study
From Biomarkers to Companion Diagnostics: Opportunities and Challenges of Rx-Dx Co-DevelopmentStudy
One key to success of targeted cancer therapy is appropriate integration of biomarkers into all stages of drug development. Challenges of implementation of biomarker programs reside in understanding cancer pathways, thoughtful selection of testing technology, and constant dialogue throughout the co-development process. Examples will be provided of drug-test co-development to illustrate approaches of streamlining to ensure efficient translation of biomarkers into future companion diagnostics.
Helen Wu, Ph.D., Research Leader, Genomics and Oncology, Roche Molecular Systems, Inc.
10:45
Diagnostic Opportunities in Lung Cancer: Use of a Mass Spectrometry Platform for Identification of Differentially Expressed Peptides in Non Small Cell Lung Cancer Tumor Cells
Biomarkers assays may have considerable value in detection/diagnosis of lung cancer. We have used a mass spectrometry platform to identify candidates for immunoassay biomarker panels. The panels allows one to accurately differentiate malignant disease from controls. including those with benign lung disease. This provides opportunities for disease management of lung cancer at multiple points potentially leading to better outcomes for patients.
Steve Ruben, Ph.D., VP Research, Celera Genomics
Biomarkers assays may have considerable value in detection/diagnosis of lung cancer. We have used a mass spectrometry platform to identify candidates for immunoassay biomarker panels. The panels allows one to accurately differentiate malignant disease from controls. including those with benign lung disease. This provides opportunities for disease management of lung cancer at multiple points potentially leading to better outcomes for patients.
Steve Ruben, Ph.D., VP Research, Celera Genomics
11:15
Reliability & Consistency in the Supply of Oligonucleotides: The Quality System Regulation (QSR) as a Roadmap
The Quality System Regulation (QSR) identifies elements necessary for an effective quality system for medical devices. It provides a roadmap to assure reliable and consistent production of oligonucleotides by establishing good manufacturing processes and specifications by alignment with user needs and intended uses. Additionally, the manufacturer has the flexibility and responsibility to establish criteria that is applicable to its own products.
Fred D. Lasky, Ph.D., Lasky Consulting
The Quality System Regulation (QSR) identifies elements necessary for an effective quality system for medical devices. It provides a roadmap to assure reliable and consistent production of oligonucleotides by establishing good manufacturing processes and specifications by alignment with user needs and intended uses. Additionally, the manufacturer has the flexibility and responsibility to establish criteria that is applicable to its own products.
Fred D. Lasky, Ph.D., Lasky Consulting
Audience Interactive Panel Discussion
11:45
Pathways to Market with Escalating Global Regulatory Expectations
Moderator:
B. Melina Cimler, Ph.D., Senior Vice President, Government Affairs, Beckman-Coulter Inc.
Panelists: all morning speakers
Moderator:
B. Melina Cimler, Ph.D., Senior Vice President, Government Affairs, Beckman-Coulter Inc.
Panelists: all morning speakers
12:30
Networking Luncheon in Poster and Exhibit Hall
Sponsored by
Sponsored by
Manufacturing and Business Considerations for Successful Launch in Clinical Market
1:35
Chairperson's Remarks
Diane Wolfe, General Manager, Eurogentec North America, Inc.
Diane Wolfe, General Manager, Eurogentec North America, Inc.
1:45
Case
Study
PNA Probes: From an Academic Curiosity to In Vitro Diagnostic KitsStudy
A case study on how to bring a nascent molecular technology from proof-of-principle to approved IVD products that improve patient care and management. This presentation will highlight issues and successes on the journey through product development, clinical trials, manufacturing, sales, and marketing.
Henrik Stender, Ph.D., Vice President R&D and Co-Founder, AdvanDx, Inc.
Audience Interactive Panel Discussion
2:15
Intellectual Property so its Intellectual Property: Update on Critical Patents
This presentation will review key patents relating to DNA diagnostics, including PCR. We will highlight certain claims in order to give guidance to kit design so as to avoid freedom-to-operate problems. An audience interactive panel discussion will follow so you can ask your questions to the experts.
Moderator:
Peter G. Carroll, Ph.D., J.D., Founding Partner, Medlen & Carroll, LLP
This presentation will review key patents relating to DNA diagnostics, including PCR. We will highlight certain claims in order to give guidance to kit design so as to avoid freedom-to-operate problems. An audience interactive panel discussion will follow so you can ask your questions to the experts.
Moderator:
Peter G. Carroll, Ph.D., J.D., Founding Partner, Medlen & Carroll, LLP
3:15
Networking Refreshment Break in Poster and Exhibit Hall
Sponsored by
Sponsored by
3:45
What a Commercial Laboratory Needs or How We Both Can Make Money and Improve Health
This presentation will concentrate on the technical requirements, regulatory issues and financial drivers of a commercial lab. Gain guidance from the expert on avoiding common pitfalls encountered by many biotech companies. Reimbursement, technical and clinical validation, positive and negative predictive value, and regulations from CLIA, FDA and New York will be discussed..
Charles Strom, M.D., Ph.D., Medical Director, Genetic Testing Center, Quest Diagnostics, Nichols Institute
This presentation will concentrate on the technical requirements, regulatory issues and financial drivers of a commercial lab. Gain guidance from the expert on avoiding common pitfalls encountered by many biotech companies. Reimbursement, technical and clinical validation, positive and negative predictive value, and regulations from CLIA, FDA and New York will be discussed..
Charles Strom, M.D., Ph.D., Medical Director, Genetic Testing Center, Quest Diagnostics, Nichols Institute
4:15
Primer and Probe Design for Field-Deployable Diagnostic Kits
Field-deployable diagnostics are critical for biodefense, military, and public health applications. As PCR's field use is limited due to multiple constraints, isothermal amplification offers great promise. Several isothermal methods have been developed; all use primers and probes of unique structure and design rules. We will discuss potential solutions to applying automated assay design through web software, with the goal of improving field diagnostics.
Raymond Peterson, Ph.D., Chief Scientific Officer, Celadon Laboratories
Field-deployable diagnostics are critical for biodefense, military, and public health applications. As PCR's field use is limited due to multiple constraints, isothermal amplification offers great promise. Several isothermal methods have been developed; all use primers and probes of unique structure and design rules. We will discuss potential solutions to applying automated assay design through web software, with the goal of improving field diagnostics.
Raymond Peterson, Ph.D., Chief Scientific Officer, Celadon Laboratories
4:45
Case
Study
How to Develop Assays with Limited Resources: Rapid Re-Design and Validation of New Kits for Fungal DetectionStudy
This talk will describe the development of a real-time PCR assay for the detection of fungal pathogens. It will highlight key considerations for design, development, manufacturing and validation and emphasise the benefits of using standard conditions to allow rapid development of multiple products.
Adrian Moody, Ph.D., Director, R&D and Scientific Affairs, Myconostica, United Kingdom
5:15
Networking Reception in Poster and Exhibit Hall
Diagnostics: Tuesday | Diagnostics: Wednesday
TIDES® Main Conference | Oligonucleotide Therapeutics Discovery | Site Tours
7:30
Coffee
Analytical Methods and Validation
8:00
Chairperson's Remarks
Dick Keys, Ph.D., Bioorganic Chemistry, Diagnostics Technology Manager
Dick Keys, Ph.D., Bioorganic Chemistry, Diagnostics Technology Manager
8:15
Development, Implementation, Validation, and Approval of LDT's: The Clinical Laboratory's Role
The presenter will provide contemporaneous information useful to laboratory professionals who are interested in implementing new methods for laboratory developed tests (LDT’s) in a rapidly changing scientific and regulatory environment. Steps required to implement, validate, and offer molecular testing services for LDT’s will be discussed in relation to compliance requirements, including increasing oversight from federal and state agencies based on risk analysis and intended use of the test.
Jan Turczyn, Director, Siemens Clinical Laboratory, Siemens Healthcare Diagnostics
The presenter will provide contemporaneous information useful to laboratory professionals who are interested in implementing new methods for laboratory developed tests (LDT’s) in a rapidly changing scientific and regulatory environment. Steps required to implement, validate, and offer molecular testing services for LDT’s will be discussed in relation to compliance requirements, including increasing oversight from federal and state agencies based on risk analysis and intended use of the test.
Jan Turczyn, Director, Siemens Clinical Laboratory, Siemens Healthcare Diagnostics
8:45
Commutability in Molecular Diagnostics
Inconsistency among laboratories in quantitative measurements of CMV viral load limits interinstitutional comparisons. A critical component of standardization is the use of calibrators that are traceable and commutable. Commutabiilty studies demonstrate that an important goal in the effort to improve healthcare for patients with CMV-related disease is the establishment of traceable and commutable reference materials.
Jerry Boonyaratanakornkit, Research Scientist, Research and Development, AcroMetrix, Inc.
Inconsistency among laboratories in quantitative measurements of CMV viral load limits interinstitutional comparisons. A critical component of standardization is the use of calibrators that are traceable and commutable. Commutabiilty studies demonstrate that an important goal in the effort to improve healthcare for patients with CMV-related disease is the establishment of traceable and commutable reference materials.
Jerry Boonyaratanakornkit, Research Scientist, Research and Development, AcroMetrix, Inc.
9:15
Strategies for Applying Mass Spectrometry for Oligonucleotide Quality Assessment
Mass spectrometry has emerged as a primary characterization technique for oligonucleotide analysis as a proof-of-structure tool with determination of molecular mass as a key indication of product quality in oligo synthesis laboratories. This presentation will highlight the some of the tools that we have been working on to streamline the assessment of product quality for oligonucleotides using electrospray mass spectrometry.
Mark E. Hail, Ph.D., President, Novatia, LLC
Mass spectrometry has emerged as a primary characterization technique for oligonucleotide analysis as a proof-of-structure tool with determination of molecular mass as a key indication of product quality in oligo synthesis laboratories. This presentation will highlight the some of the tools that we have been working on to streamline the assessment of product quality for oligonucleotides using electrospray mass spectrometry.
Mark E. Hail, Ph.D., President, Novatia, LLC
9:45
Networking Refreshment Break in Poster and Exhibit Hall
Sponsored by
Sponsored by
10:15
NIST SRM 2374: A Certified Reference Material to Support Confidence in Gene Expression Measurements
NIST has hosted the External RNA Control Consortium, an industry-initiated ad-hoc standards development effort, to develop materials that can be used to assess the technical performance of gene expression assays. This effort has led to the development of a new certified reference material (CRM), "NIST SRM 2374: DNA Sequence Library for External RNA Controls." This material represents a first-of-its-kind CRM, certified for sequence, with confidence estimates for each of the ~90000 nucleotides. The latest data from the ERCC testing of these materials will be presented, including performance assessment in a variety of applications.
Marc L. Salit, Ph.D., Head of Gene Expression Metrology Team, NIST
NIST has hosted the External RNA Control Consortium, an industry-initiated ad-hoc standards development effort, to develop materials that can be used to assess the technical performance of gene expression assays. This effort has led to the development of a new certified reference material (CRM), "NIST SRM 2374: DNA Sequence Library for External RNA Controls." This material represents a first-of-its-kind CRM, certified for sequence, with confidence estimates for each of the ~90000 nucleotides. The latest data from the ERCC testing of these materials will be presented, including performance assessment in a variety of applications.
Marc L. Salit, Ph.D., Head of Gene Expression Metrology Team, NIST
New Technologies
Chairperson: Marc Lemaitre, Ph.D., CEO, Girindus America Inc. - Member of Solvay Organics
10:45
Case
Study
LNA™ Based Universal RT microRNA PCR SystemStudy
Using a Locked Nucleic Acid (LNA™) based miRNA detection technology we have developed a high throughput QPCR system optimized for detection of miRNAs in clinical paraffin-embedded tissue as well as blood derived plasma or serum. The use of the LNA™ bases adds critical specificity and sensitivity creating a more robust system for more rapid assay development in the clinical and diagnostic assay development.
Adam Baker, Ph.D., Director of Diagnostic Product Development, Exiqon A/S, Denmark
11:15
Universal Transcription-Mediated Amplification (uTMA): A New Assay Format for Quantitative Multiplex Real-Time Analysis
A quantitative multiplex assay format has been developed utilizing a universal TMA approach. In this assay a pair of sequence tags is incorporated into each analyte using a unique, target capture-mediated approach. The assay is sensitive, accurate and precise and displays very low multiplex primer interference. A PCA3/PSA/internal control triplex assay has been developed as a proof of principle.
Norman C. Nelson, Ph.D., Senior Director, Discovery Research, Gen-Probe Incorporated
A quantitative multiplex assay format has been developed utilizing a universal TMA approach. In this assay a pair of sequence tags is incorporated into each analyte using a unique, target capture-mediated approach. The assay is sensitive, accurate and precise and displays very low multiplex primer interference. A PCA3/PSA/internal control triplex assay has been developed as a proof of principle.
Norman C. Nelson, Ph.D., Senior Director, Discovery Research, Gen-Probe Incorporated
11:45
MethylScope and MethylScreen: DNA Methylation-Based Technologies with Wide Applicability to Cancer Personalized Medicine
Epigenetic abnormalities provide a rich source of biomarkers with broad applications in diagnostics and prognostics/theranostics. MethylScope, an oligonucleotide microarray-based technology, generates genome-wide DNA methylation profiles. MethylScreen is a quantitative PCR-based assay platform used for the sensitive and accurate detection of locus-specific DNA methylation states. The use of MethylScreen for biomarker discovery and MethylScreen for efficient biomarker validation and assay development will be presented.
Jared Ordway, Ph.D., Director of Research and Development, Orion Genomics, LLC
Epigenetic abnormalities provide a rich source of biomarkers with broad applications in diagnostics and prognostics/theranostics. MethylScope, an oligonucleotide microarray-based technology, generates genome-wide DNA methylation profiles. MethylScreen is a quantitative PCR-based assay platform used for the sensitive and accurate detection of locus-specific DNA methylation states. The use of MethylScreen for biomarker discovery and MethylScreen for efficient biomarker validation and assay development will be presented.
Jared Ordway, Ph.D., Director of Research and Development, Orion Genomics, LLC
12:15
Networking Lunch in Poster and Exhibit Hall
Final Opportunity for Poster and Exhibit Viewing
Final Opportunity for Poster and Exhibit Viewing
Luncheon Technology Workshop
12:15
1:30
Improvement of the Sensitivity of Molecular Diagnostics Assays by Replacing PCR with Cold-PCR
We describe COLD-PCR, a novel modification of PCR that enables selective amplification of mutant alleles without a-priori information on the position of a mutation. By replacing PCR with COLD-PCR, practically all existing mutation-detection methods (Sanger Sequencing, High resolution melting, dHPLC, and others) increase their sensitivity by ~50-100-fold. COLD-PCR is expected to have diverse applications in the fields of molecular diagnostics, biomarkers, genomic instability, infectious diseases, methylation testing and pre-natal identification of fetal alleles in mother's blood.
G. Mike Makrigiorgos, Ph.D, Associate Professor; Director, Physics and Biophysics Division, Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School
We describe COLD-PCR, a novel modification of PCR that enables selective amplification of mutant alleles without a-priori information on the position of a mutation. By replacing PCR with COLD-PCR, practically all existing mutation-detection methods (Sanger Sequencing, High resolution melting, dHPLC, and others) increase their sensitivity by ~50-100-fold. COLD-PCR is expected to have diverse applications in the fields of molecular diagnostics, biomarkers, genomic instability, infectious diseases, methylation testing and pre-natal identification of fetal alleles in mother's blood.
G. Mike Makrigiorgos, Ph.D, Associate Professor; Director, Physics and Biophysics Division, Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School
2:00
Unnatural Base Pair Systems for Diagnostic Applications
Unnatural base pair systems provide a new technology based on the expansion of the genetic alphabet, enabling the site-specific incorporation of functional components of interest into DNA and RNA. We have developed several unnatural base pairs that function in PCR and transcription with high efficiency and fidelity and are now applying them to new DNA probe and PCR detection techniques for diagnostics.
Ichiro Hirao, Ph.D., Team Leader, Systems and Structural Biology Center (SSBC), RIKEN; President, TagCyx Biotechnologies, Japan
Unnatural base pair systems provide a new technology based on the expansion of the genetic alphabet, enabling the site-specific incorporation of functional components of interest into DNA and RNA. We have developed several unnatural base pairs that function in PCR and transcription with high efficiency and fidelity and are now applying them to new DNA probe and PCR detection techniques for diagnostics.
Ichiro Hirao, Ph.D., Team Leader, Systems and Structural Biology Center (SSBC), RIKEN; President, TagCyx Biotechnologies, Japan
2:30
Zip Nucleic Acids - High Affinity Primers and Probes as Promising Tools for Molecular Diagnostics
Zip Nucleic Acids (ZNAs) are modified oligonucleotides conjugated with cationic units that decrease electrostatic repulsions between nucleic acid strands. The modification increases the melting temperature of the oligonucleotide and accelerates the target recognition. The presentation will describe how ZNAs improve qPCR and reverse-transcription when used as primers or probes.
Nathalie Lenne, Ph.D., Project Leader, R&D, Polyplus-transfection, France
Zip Nucleic Acids (ZNAs) are modified oligonucleotides conjugated with cationic units that decrease electrostatic repulsions between nucleic acid strands. The modification increases the melting temperature of the oligonucleotide and accelerates the target recognition. The presentation will describe how ZNAs improve qPCR and reverse-transcription when used as primers or probes.
Nathalie Lenne, Ph.D., Project Leader, R&D, Polyplus-transfection, France
3:00
Development of a New GMP TAQ Polymerase for Improved PCR Performance
PCR is the method of choice for many diagnostic applications. A new hot-start method was developed that improves the efficiency, specificity, yield and sensitivity of the PCR reaction. HOT Diamond TAQTM is manufactured according to a GMP-Pharma process; resulting in an exhaustively characterized, lot-to-lot reproducible enzyme, with extremely low residual DNA content.
Marie-Claire Beckers, Ph.D., Product Development Manager, Eurogentec S.A., Belgium
PCR is the method of choice for many diagnostic applications. A new hot-start method was developed that improves the efficiency, specificity, yield and sensitivity of the PCR reaction. HOT Diamond TAQTM is manufactured according to a GMP-Pharma process; resulting in an exhaustively characterized, lot-to-lot reproducible enzyme, with extremely low residual DNA content.
Marie-Claire Beckers, Ph.D., Product Development Manager, Eurogentec S.A., Belgium
3:30
Networking Refreshment Break
Sponsored by
Sponsored by
3:45
Novel Approach for Manufacturing DNA Microarrays
Our highly innovative probe printing process generates and transfers nucleic acid molecules from one surface onto another, without loss of spatial resolution, in just three steps. Such process is congenial to longer strands, well above the current industrial standard of 25-60nt. To this purpose new platforms with longmers are being developed to address unique demands of the diagnostic and clinical market.
Andrea Cuppoletti, Ph.D., Chief Technology Officer, Molecular Stamping, Italy
Our highly innovative probe printing process generates and transfers nucleic acid molecules from one surface onto another, without loss of spatial resolution, in just three steps. Such process is congenial to longer strands, well above the current industrial standard of 25-60nt. To this purpose new platforms with longmers are being developed to address unique demands of the diagnostic and clinical market.
Andrea Cuppoletti, Ph.D., Chief Technology Officer, Molecular Stamping, Italy
4:15
SmartFinder: New Real-time PCR platform for Detection of 19 Respiratory Pathogens Simultaneously
Up to now real time PCR detection of infectious agents was limited to 4-5 pathogens. Multiplex approaches using beads detection or capillary electrophoresis are able to detect up to 20 targets. We have developed the SmartFinder technology enabling highly complex realtime PCR assays. The power of this new technology was demonstrated by detection of 19 respiratory pathogens simultaneously.
Guus Simons Ph.D., CEO, PathoFinder BV, The Netherlands
Up to now real time PCR detection of infectious agents was limited to 4-5 pathogens. Multiplex approaches using beads detection or capillary electrophoresis are able to detect up to 20 targets. We have developed the SmartFinder technology enabling highly complex realtime PCR assays. The power of this new technology was demonstrated by detection of 19 respiratory pathogens simultaneously.
Guus Simons Ph.D., CEO, PathoFinder BV, The Netherlands
4 :45
Sample Prep for Next Gen Sequencing
Second generation sequencing technologies are supported by workflows that are relatively complicated and labor intensive, requiring skilled labor and significant hands-on time to prepare samples for each instrument. At Beckman Coulter we have created a simplified automated workflow for the leading second generation sequencing platforms that utilizes the core SPRI™ magnetic particle to create an automated system for sample preparation.
Patrick J. Finn, Director, Product Development Center, Beckman Coulter Genomics
Second generation sequencing technologies are supported by workflows that are relatively complicated and labor intensive, requiring skilled labor and significant hands-on time to prepare samples for each instrument. At Beckman Coulter we have created a simplified automated workflow for the leading second generation sequencing platforms that utilizes the core SPRI™ magnetic particle to create an automated system for sample preparation.
Patrick J. Finn, Director, Product Development Center, Beckman Coulter Genomics
5:15
Close of Applications of Nucleic Acids Technologies in Molecular Diagnostics
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