Accelerating Early Stage Drug Development and the FDA s Critical Path Initiative

Transcription

1 2010 East Coast Symposium Series Accelerating Early Stage Drug Development and the FDA s Critical Path Initiative Sponsored by: TuesdayJune 22, 2010 Boston Cambridge Marriott Two Cambridge Center Cambridge, Massachusetts, USA Tel:

2 AGENDA Tuesday June :00 10:00 am Registration and Refreshments 10:00 10:10 am Opening Remarks, Chris Kemper, Ph.D., Director, Bioanalytical Services, Taylor Technology, a PharmaNet 10:15 10:50 am A Regulatory Overview on FDA s Critical Path Initiative and New Drug Development, Andrew Chang, Ph.D., Executive Director, PharmaNet Consulting 10:50-11:25 am Strategies to Optimize Target Selection, Kathleen Smith, Ph.D., Translational Medicine Consulting 11:25 am 12:00 pm Accelerating Lead Optimization: In vivo Fast PK Studies Using the Exactive Orbitrap, Rohan A. Thakur, Ph.D., Associate Director, Specialized Mass Spectrometry, Taylor Technology, a PharmaNet 12:00-12:45 pm Lunch 12:45 1:20 am Preclinical Data Front-loading: ADMET Perspectives, Sanjeev Thohan, PhD., Senior Research Fellow in Preclinical/Translational Sciences, Novartis Institutes for BioMedical Research 1:20 1:55 pm Strategies to Reduce Immunogenicity of Large Molecules Drugs throughout the Drug Development Process, Robert Dodge, Ph.D., Laboratory Director, Immunochemistry and Cell Biology, Taylor Technology, a PharmaNet 1:55 2:30 pm Application of Dried Blood Spots in the Bioanalytical Laboratory: Advantages and Challenges, Casey Tyrrel, Research Scientist II, Taylor Technology, a PharmaNet 2:30-2:40 pm Closing Remarks and Questions Chris Kemper, Ph.D., Director, Bioanalytical Services, Taylor Technology, a PharmaNet

3 SPEAKER ABSTRACTS A Regulatory Overview on FDA s Critical Path Initiative and New Drug Development Andrew Chang, Ph.D., Executive Director, PharmaNet Consulting The FDA launched the Critical Path Initiative in 2004 in an effort to bridge the gap between basic scientific research and the drug development process. The ultimate goal of this initiative is to modernize and facilitate the development process in order to bring potential human drugs, biological products, or medical devices from discovery to commercialization. The initiative intends to cover many areas of drug development, including: The use of scientific tests and tools to predict whether a product candidate will be safe and effective, to guide the sponsor in choosing an appropriate dose and regimen, The application of scientific tools to manufacture the product at commercial scale and assess the quality of the manufactured product (Quality by Design), The use of biomarkers and disease models as evaluation tools, Streamlining of clinical trials, and Moving manufacturing into the 21st Century. Strategies to Optimize Target Selection Kathleen Smith, Ph.D., Translational Medicine Consulting The use of human tissue samples in pre-clinical development can inform researchers about the potential efficacy of a development candidate prior to testing it in humans. These strategies can facilitate identification of novel drug targets specific for given disease states, aid in the identification of appropriate therapeutic areas for a promising target, and facilitate the exclusion of targets widely expressed in the human body. For antibody therapeutics, screening of candidates for tissue cross-reactivity early in the development process can facilitate the choice of a candidate which can proceed to clinical trials. Proof of concept studies carried out in ex vivo human samples can also provide compelling evidence to support the potential efficacy of drug candidate prior to being tested in clinical trials. Combined, these strategies can aid in selection of candidates more likely to succeed in clinical trials. Examples will be discussed from the therapeutic areas of inflammation and cancer. Accelerating Lead Optimization: In vivo Fast PK studies Using the Exactive Orbitrap Rohan A. Thakur, Ph.D., Associate Director, Specialized Mass Spectrometry, Taylor Technology, a PharmaNet The last decade has seen several strategies employed to increase the throughput of in vivo rodent pharmacokinetic (PK) studies as a means to reduce the attrition rate of new chemical entities. Providing semiquantitative biotransformation data in this first in vivo step could further improve the lead optimization process; the information could be used to optimize the chemical structure or help improve pharmacodynamic properties. This seminar outlines the use of accurate mass, high resolution, mass spectrometry to simultaneously quantify the parent drug and its major biotransformation products during Fast PK bioanalysis in different animal models. Preclinical Data Front-loading: ADMET Perspectives Sanjeev Thohan, Senior Research Fellow in Preclinical/Translational Sciences at the Novartis Institutes for BioMedical Research, Cambridge, MA It is well established that the metabolic disposition of a new chemical entity (NCE) can greatly impact its pharmacological activity profile as well as influence toxicity. Understanding biotransformation and disposition of the parent and metabolites is essential to risk assessment. As we accelerate the drug discovery process, the demands of a detailed understanding of the NCE is being requested earlier and earlier in the research process. In vitro and in vivo profiling of ADMET (Absorption, Distribution, Metabolism, Elimination and Toxicology) parameters is an important of component of the chemical optimization of lead compounds to minimize potential ADME liabilities, drug-drug interactions in the clinical situation. Assays are designed to represent surrogates for critical in vivo ADME properties, including absorption/bioavailability and metabolic stability. This discussion will illustrate the potential of effective ADMET screening as well as some of the caveats and pitfalls to consider.

4 Strategies to Reduce Immunogenicity of Large Molecules Drugs throughout the Drug Development Process Robert Dodge, Ph.D., Laboratory Director, Immunochemistry and Cell Biology, Taylor Technology, a PharmaNet The generation of anti-drug antibodies (immunogenicity) to large molecule drugs has the potential to adversely affect the safety and efficacy of a drug. Numerous methods to decrease the potential for immunogenicity of a large molecule drug exist and these methods may be applied from early drug development, through preclinical studies, and up to when the drug is first introduced into humans. A review of the in silica and ex vivo methods to identify potential immunogenic epitopes and make changes to the drug design prior to in vivo studies is given. Once the drug composition is fixed, factors that have the potential to introduce antibody responses in vivo can be closely linked to product quality. Factors such as host cell protein levels in purified drug substance and product aggregation levels have the ability to affect the immune response of subjects when given the drug. Discussion on when and how to monitor these potential immune responses based on recent FDA draft guidance will be reviewed as well. The Application of Dried Blood Spots in the Bioanalytical Laboratory: Advantages and Challenges Casey Tyrrel, Research Scientist II, Taylor Technology, a PharmaNet Sampling from dried blood spots (DBS) on specialty papers is an innovative methodology in the area of pharmacokinetics and toxicokinetics that serves to replace conventional plasma analysis. The most significant advantage of this technique is reduced blood collection volume, less invasive sampling, and storage and shipping conditions that does not require the use of freezers and dry ice. However this technique presents challenges for the bioanalytical laboratory. This presentation will raise awareness to the DBS technique, highlight the advantages for its use, and present considerations for DBS implementation. SPEAKER BIOGRAPHIES Chris Kemper, Ph.D., Director, Bioanalytical Services, Taylor Technology, a PharmaNet Chris Kemper received his B.Sc. in Chemistry from Rensselaer Polytechnic Institute in 1979 and his Ph.D. in Pharmacology from the University of Louisville School of Medicine in He has held a wide range of positions in the pharmaceutical industry since 1972, including analytical chemist in drug metabolism at Sterling Winthrop, group leader in DMPK at Johnson and Johnson, and business development director at Phoenix International and PharmaNet Development Group. He is currently the director of bioanalytical services at Taylor Technology, a subsidiary of PharmaNet Development Group. Chris was the founding member of the RTP Drug Metabolism Discussion Group (DMDG) and the New England DMDG and past chair of the Delaware Valley DMDG. He has been chair and/or a speaker at over twenty symposia for the RTP and DV DMDGs, the Gordon Conference on Drug Metabolism and Applied Pharmaceutical Software discussion group. He is the author of the bioanalytical chapter in the upcoming book "Early Drug Development: Strategies and Routes to First-in Human Trials", edited by Mitch Cayen and due to be published this summer. Andrew Chang, Ph.D., Executive Director, PharmaNet Consulting Dr. Andrew Chang has more than nineteen years of experience in the development of biologics and pharmaceuticals. At his current capacity as an Executive Director, PharmaNet Consulting, Dr. Chang has advised clients on top-level strategic planning and evaluations related to biological-product development in the US, Europe and Asia on how to efficiently bring products from R&D to market approval. Prior to joining PharmaNet in 2006, Dr. Chang served more than eleven years at the FDA, most recently as an Associate Director for Policy and Regulation and Senior Regulatory Scientist in the Division of Hematology, Office of Blood Research and Review (OBRR), Center for Biologics Evaluation and Research (CBER). He is known

5 nationally and internationally for his significant scientific and regulatory contributions to the development, approval and post market surveillance of recombinant and naturally-derived products. While at FDA, Dr. Chang was known as a leading FDA and CBER spokesperson and has presented the FDA perspective at many national and international meetings. Dr. Chang s formal scientific training includes a Ph.D. in Biochemistry from the State University of New York, and a B.S. in Pharmaceutical Chemistry from the China Pharmaceutical University. Kathleen Smith, Ph.D., Translational Medicine Consulting Dr. Kathleen Smith has over fifteen years experience in the pharmaceutical and diagnostics industries. Recently Dr. Smith was Director, Clinical Validation, at Berkeley HeartLab Inc., a company focused on providing diagnostic and personalized disease management services for patients with or at risk for developing cardiovascular disease. In her role at Berkeley HeartLab, Inc., a subsidiary of Celera, she was responsible for the design and execution of clinical studies to validate the utility of biomarkers tests offered by the company and their disease management program. Dr. Smith has a B.A. in Biochemistry and Genetics from the University of California, Santa Barbara, and a Ph.D. in Immunology from the University of California, San Francisco. Prior to working at Berkeley HeartLab, Inc. Dr. Smith worked for 11 years at Schering Plough Biopharma (formerly DNAX), which focuses on the study of basic mechanisms of inflammation and cancer and transitioning these findings to the clinic. At Schering Plough Biopharma she developed a human tissue bank, which supported pre-clinical research for the entire Schering Plough organization, built a pathology lab which provided services for pre-clinical animal model work and human target validation studies, and initiated and managed a translation medicine program. Dr. Smith has a broad range of scientific expertise which provides her with a unique perspective on the drug development process. Rohan A. Thakur, Ph.D., Associate Director, Specialized Mass Spectrometry, Taylor Technology, a PharmaNet Rohan A. Thakur holds a B.S. in Chemical Engineering and a Ph.D. in chemistry from Kansas State University. He did his Post-Doctoral work at Rutgers University which involved mass spectrometry based approaches in identifying ring opened benzene-dna adducts implicated with leukemia. Rohan began his career with Finnigan MAT in San Jose, CA and has several patents related to his work in mass spectrometry. Currently, Rohan is the Associate Director for specialized mass spectrometry at Taylor Technology in Princeton, NJ. Sanjeev Thohan, Senior Research Fellow in Preclinical/Translational Sciences at the Novartis Institutes for BioMedical Research Sanjeev Thohan is a Senior Research Fellow in Preclinical/Translational Sciences at the Novartis Institutes for BioMedical Research in Cambridge, MA. Prior to this role, he served as the Director of Non-Clinical Discovery/Development at Exelixis Inc in South San Francisco, CA. He holds MS and PhD degrees in Pharmacology and Toxicology from the University of Arizona and University of Maryland with concentrations in interspecies drug metabolism mechanisms, bioactivation, and systems toxicology. His broad background from research units at Walter Reed Army Institute for Research, Covance, AstraZeneca, ViroPharma, and Exelixis allows him a unique vantage point to discovery-development based non-clinical research activities. During his research career, he has facilitated over 16 compounds into clinical trials in the Anti-viral, Oncology, Metabolic and Cardiovascular Diseases therapeutic areas. Robert Dodge, Ph.D., Laboratory Director, Immunochemistry, Taylor Technology, a PharmaNet Robert Dodge, Ph.D. is currently the Laboratory Director, Immunochemistry and Cell Biology, at Taylor Technology, in Princeton NJ, a contract research laboratory specializing in GLP assay development and sample testing. Robert oversees a staff of scientists responsible for the development of assays for drug quantitation, antidrug antibody screening and biomarker detection. He was previously the Laboratory Director at Princeton Bioanalytical Laboratory, a contract research laboratory specializing in cell based assays for protein therapeutics and spent ten years at Bristol-Myers Squibb, starting in the Immunology Department and subsequently holding positions of increasing responsibility in biologic drug development and characterization. Robert has a Ph.D. in chemistry and completed an NIH post-doctoral fellowship at Cornell University.

6 Casey Tyrrel, Research Scientist II, Taylor Technology, a PharmaNet Casey Tyrrel is a Research Scientist II and Principle Investigator with Taylor Technology in Princeton, NJ. She has over ten years experience in method development and bioanalysis for small molecules and has a B.A. in Biology from Thomas Edison State College. Casey is currently involved in adapting dried blood spot techniques for bioanalysis of small molecules and incorporating new technology and automation to improve laboratory efficiency. About PharmaNet Development Group, Inc. PharmaNet Development Group, Inc., a global drug development services company, provides a comprehensive range of services to the pharmaceutical, biotechnology, generic drug and medical device industries. The offers early and late stage consulting, Phase I clinical studies and bioanalytical analyses, and Phase II, III and IV clinical development programs. With approximately 2,300 employees and 41 facilities throughout the world, PharmaNet is a recognized leader in outsourced clinical development. For more information, please visit our website at Exactive and Orbitrap are trademarks of Thermo Fisher Scientific, Inc.