Thursday, May 1
1:00-2:00 Conference Registration
1:55-2:00 Chairperson’s Opening Remarks
2:00-2:25 Fifteen Years of Personalized Medicine: Looking Back and into the Future
Eric Lai, Ph.D., Senior Vice President and Head, Pharmacogenomics, Takeda Pharmaceuticals International
The completion of the Human Genome Project, the International HapMap Project and the development and application of new molecular technologies, especially high-throughput DNA sequencing, have provided critical knowledge for understanding human diseases and have promised to greatly improve healthcare. Despite these advances, the clinical application of personalized medicine is still limited. This presentation will discuss other potential ways of applying pharmacogenomics to drug development and the use of big research datasets to address unmet medical needs and patient stratification strategies for personalized medicine.
2:25-2:50 Human Genetics for Patient Stratification in Neuroscience: Challenges and Opportunities
Jens R. Wendland, M.D., Director and Head, Neuroscience Genetics, Pfizer Worldwide R&D
Many pharma clinical trials in neuroscience target subpopulations of patients based on, for example, incomplete overall response to standard of care (treatment-resistant depression) or categorical non-response of specific psychopathological phenomena (negative symptoms in schizophrenia). Biomarkers that robustly enable stratification would therefore be highly valuable, yet they remain scarce – and therefore, most efforts are focused on exploratory biomarker analyses. We will present challenges and opportunities of using state of the art human genetics for exploratory neuroscience biomarker analyses in clinical trials.
2:50-3:20 Sponsored Presentations (Opportunities available)
3:20-4:15 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15-4:40 Making Decisions about Conducting Efficacy Pharmacogenetic Studies
Liling Warren, Ph.D., Senior Scientific Investigator, GlaxoSmithKline
Efficacy pharmacogenetic (PGx) studies conducted during clinical development have the potential to identify predictive markers that may have translational impact to aid medicine development and subsequently to inform clinical decisions. When the overall trial fails to demonstrate efficacy, there is often particular interest to investigate whether PGx can identify a subset of patients who may benefit from the medicine. Through theoretical and simulation work, we quantify chances of success for efficacy PGx studies during clinical development. Our work suggests that it is generally unlikely that PGx can "rescue" a trial that fails for efficacy. When a trial demonstrates overall efficacy, opportunities for well-powered PGx efficacy studies will increase. Nevertheless, for nearly all studies there will be some range of marker frequencies and effects, however small, that are well powered even at a genome-wide scale. As the cost of genotyping continues to decline and the recognition of the potential value a predictive marker may bring to medicine development and ultimately patient outcome, a strategy to routinely screen for predictive PGx markers in clinical trials may eventually be justified.
4:40-5:05 Biomarkers and Patient Selection: The Theory and the Practice
Tarek Sahmoud, M.D., Ph.D., Corporate Vice President, Clinical Research and Development, Celgene Corporation
Development of targeted therapy in oncology is one of the most promising avenues for future therapies. Such development raises specific questions in term of methodological and regulatory aspects associated with the validation of the target being most challenging. We will first discuss the methodology of such trials, realistic estimation of the magnitude of the expected effect, proportion of sensitive patients, selection of the appropriate patient population, choice of the primary endpoint, sample size calculations, and whether stratification is needed. We will also discuss the use of pharmacokinetics and pharmacodynamics as an integral component of development of targeted agents.
5:05-5:30 Personalized Medicine and Pharmacogenomics: Biomarker Strategies to Optimize Drug R&D
Iris Grossman, Ph.D., Global Head, Personalized Medicine and Pharmacogenomics, Teva Pharmaceutical
Shifting away from the traditional "trial-and-error" approach to clinical practice requires a tailored approach early on in drug R&D. Teva's Personalized Medicine and Pharmacogenomics (PMP) unit applies state-of-the-art biomarker strategies to optimize the benefit-risk profile of its drugs and ultimately drive global improvement in patient care. PMP activities span the R&D pipeline, from the discovery phase through to late-stage development and patient stratification for marketed drugs. This presentation will review PMP's global strategy, supported by key examples.
5:30-5:55 Predictive Modeling for the Discovery of Efficacy Markers Towards Patient Selection
Nirmala Nanguneri, Ph.D., Director and Head, Biomarker Analysis and Informatics, Novartis Institutes for Biomedical Research
6:00-9:00 Dinner Courses*
- Next-Generation Sequencing as a Clinical Test
- Laboratory-Developed Tests
(*Separate registration required)
Friday, May 2
7:30-8:15 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee
8:25-8:30 Chairperson’s Opening Remarks
8:30-8:55 Exploring Tumor Somatic Mutations to Further Refine the Responding Patient Population
Scott D. Patterson, Ph.D., Executive Director, Medical Sciences, Amgen
Rigorous hypothesis testing is a key final element in demonstrating the clinical validity of a biomarker. But to get to that stage, a sufficient level of evidence has to be generated to gain the confidence of key stakeholders to test a given biomarker hypothesis. Further, as the implementation of a therapeutic is usually intended to be global in nature, considerations for global diagnostic implementation should be taken into account. Biomarkers of the EGFR pathway will be described in this context.
8:55-9:20 Talk Title to be Announced
Xiaolan Hu, Ph.D., Head, Clinical Genetics, Bristol-Myers Squibb
9:20-9:45 Utilization of Point-of-Care Genotyping Technologies to Actively Recruit into a Genotype-Stratified Three Period Crossover Experimental Medicine Trial
Charles J. Cox, Ph.D., Head, Genetics Experiment Design and Delivery, GlaxoSmithKline
9:45-10:00 Sponsored Presentation (Opportunity Available)
10:00-10:50 Coffee Break in the Exhibit Hall with Poster Viewing
10:50-11:15 Molecular Diagnostics of Cancer for Precision Medicine: Strategies and Challenges for Improving Clinical Outcome
Towia Libermann, Ph.D., Associate Professor, Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School; Director, BIDMC Genomics, Proteomics, Bioinformatics, and Systems Biology Center and DF/HCC Cancer Proteomics Core
Advances in NGS are unraveling cancer mutations, providing opportunities for developing precision medicine diagnostics. Growing understanding of cancer pathways combined with innovative targeted therapies enable discovery of actionable mutations in individual patients. Strategies to tailor therapy based on each patient’s genetic characteristics are postulated to change the course of cancer. While an attractive concept, tumor heterogeneity and clinical trial complexities are major challenges for improving clinical outcome. Advances and challenges in cancer diagnostics for precision medicine will be discussed.
11:15-11:40 Next-Generation Sequencing Strategies for Selecting Patients Who May Benefit from PARP Inhibitor Therapy
Mitch Raponi, Ph.D., Senior Director, Molecular Diagnostics, Clovis Oncology
The discussion will address the following questions: What biomarkers should we be focusing on to identify appropriate patients who will likely benefit from PARP inhibitors? How can we apply next-generation sequencing technologies to identify all patients who will respond to the PARP inhibitor rucaparib? What regulatory challenges are we faced with for approval of NGS companion diagnostics?
11:40-12:05 pm Talk Title to be Announced
Saumya Pant, Ph.D., Research Fellow, Merck
12:05-12:30 The Use of Targeted NGS Assays to Identify Tumor Molecular Defects and Support Treatment Selection in NCI-Sponsored Clinical Trials
P. Mickey Williams, Ph.D., Director, Molecular Characterization Laboratory, Frederick National Laboratory for Cancer Research (tentative)
12:30 Close of Conference