Short Courses*

Tuesday, June 14
8:00 - 11:00 am

SC2: Drug Metabolism and Its Impact on Decisions in Lead Discovery - Part 1

This short course will focus on concepts important for those wanting to understand how drug metabolism is applied to drug discovery. Topics will include how drugs are metabolized, what enzymes are involved, common assays for predicting clearance and drug-drug interactions and how drug metabolism concepts are applied during lead optimization. Those scientists involved in medicinal chemistry, pharmacology and drug metabolism will benefit from this overview.

• Enzymes involved in the metabolism of drugs
• Metabolism-based drug-drug interactions
• Understand how drug structure impacts important PK parameters
• Enzyme induction
• Metabolic stability assays

Instructors:
Adrian J. Fretland, Ph.D., Associate Director, DMPK Oncology iScience, AstraZeneca

Mark Grillo, Ph.D., Staff Scientist, Drug Metabolism & Pharmacokinetics, MyoKardia, Inc.

Tuesday, June 14
12:00 - 3:00 pm

SC3: Drug Metabolism and Its Impact on Decisions in Drug Development - Part 2

This short course will focus on concepts important for those wanting to understand how drug metabolism is applied to drug development. Topics will include how drug metabolites are identified in pre-clinical studies and human clinical trials, the role of bioactivation and the growing importance of transporters in drug disposition and safety. Those scientists involved in medicinal chemistry, pharmacology and drug metabolism will benefit from this overview.

• Strategies to identify drug metabolites in preclinical species and humans
• The relation between drug bioactivation and drug toxicity
• Transporters relevant for drug uptake and efflux
• Experimental systems to investigate transporters
• Transporters relevant for drug disposition and adverse effects

Instructors:
Mark Grillo, Ph.D., Staff Scientist, Drug Metabolism & Pharmacokinetics, MyoKardia, Inc.

Mingxiang Liao, Ph.D., Senior Scientist I, DMPK, Takeda Pharmaceutical Intl. Company

SC4: Modern Lead Generation Strategies - Part 1

Lead Generation is where chemical project assets are first created, and as such it is the area of Medicinal Chemistry that most strongly influences timelines and attrition rates. This discipline has undergone significant paradigm changes within recent years as new hit generation techniques have emerged and novel lead characterization methods have been invented. This two part short course will give a comprehensive and up to date review of the field along with many practical examples and is intended for a broader audience ranging from beginner to advanced level.

Part 1 will introduce lead generation and the different hit generation methods available today.

Chairperson:

Joerg Holenz, Ph.D., Director, Discovery and Preclinical Sciences; Project Leader, Neuroscience iMed, AstraZeneca Neuroscience

Instructors:

Tim Cernak, Ph.D., Associate Principal Scientist, Discovery Chemistry, Automation & Capabilities Enhancement, Merck Boston

Rajiah Aldrin Denny, Ph.D., Senior Principal Scientist, Cheminformatics and Computational Chemist, Pfizer, Inc.

Ivan V. Efremov, Ph.D., Senior Principal Scientist, Worldwide Medicinal Chemistry, Pfizer, Inc.

Matthew Clark, Ph.D., Senior Vice President, Research, X-Chem

SC5: Convergence of Immunotherapy and Epigenetics for Cancer Treatment

In recent years the understanding of both the immunotherapy and epigenetics of cancer has increased. This course will provide some details of how immunotherapy and epigenetic pathways interact and how they can be exploited to enhance the efficacy of current cancer treatments. The instructors will review recent scientific evidence and preclinical data that support the development of combination therapies and offer their perspectives on challenges that may have to be tackled along the way.

• Epigenetic regulation of anti-tumor immune responses
• Combinatorial approaches of epigenetic modifiers (HDAC inhibitors, hypomethylating agents) with checkpoint blockade and other emerging immunotherapeutic strategies

Instructors:
Eduardo M. Sotomayor, M.D., Director, GW Cancer Center, Professor, Medicine, Division of Hematology/Oncology, George Washington University

Alejandro Villagra, Ph.D., Assistant Professor, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University

Katherine Bakshian Chiappinelli, Ph.D., Postdoctoral Fellow, Laboratory of Dr. Stephen Baylin, Johns Hopkins University School of Medicine

Javier Pinilla-Ibarz, M.D., Ph.D., Director of Immunotherapy, Malignant Hematology Division, H. Lee Moffitt Cancer Center & Research Institute

Tuesday, June 14
3:30 - 6:30 pm

SC7: Modern Lead Generation Strategies - Part 2

Lead Generation is where chemical project assets are first created, and as such it is the area of Medicinal Chemistry that most strongly influences timelines and attrition rates. This discipline has undergone significant paradigm changes within recent years as new hit generation techniques have emerged and novel lead characterization methods have been invented. This two-part short course will give a comprehensive and up-to-date review of the field along with many practical examples and is intended for a broader audience ranging from beginner to advanced level.

Part 2 will center on how to convert these hits to leads and the most recent trends in lead generation.

Chairperson:

Joerg Holenz, Ph.D., Director, Discovery and Preclinical Sciences; Project Leader, Neuroscience iMed, AstraZeneca Neuroscience

Instructors:

Dean Brown, Ph.D., Director, Discovery and Preclinical Sciences, AstraZeneca

John Mathias, Ph.D., Senior Director, Cystic Fibrosis Program Leader, Pfizer, Inc.

Erin F. DiMauro, Ph.D., Principal Scientist, Medicinal Chemistry, Amgen, Inc.

Ivan Cornella-Taracido, Senior Principal Scientist, Discovery Chemistry, Merck

Jeremy Green, Ph.D., Senior Director, Chemistry, Vertex

SC8: Rational Design of Cancer Combination Therapies

This workshop will focus on the practical aspects of designing first-in-man combination trials, using preclinical data to provide a means for choosing schedules, optimizing drug ratios and escalation schemes. The methodologies presented will integrate hypothesis-driven in vivo pharmacology with in silico modeling as an analytical methodology.

• Why synergy doesn’t help in the design of clinically relevant therapies.
• How to design efficient preclinical combination studies to support early clinical development.
• When and how to address the question of therapeutic potential for a combination in development.

Instructor: Arijit Chakravarty, Ph.D., Director, Modeling & Simulation (DMPK), Takeda Pharmaceutical International Co.

SC9: How to Best Utilize Organotypic 3D Cell Cultures Assays in Oncology>

The course will provide an overview of 3D cell culture models, their strengths and weaknesses. The instructors will share their experiences on the challenges they faced from experimental design to data analysis while developing and optimizing these models for their studies. The focus of their presentations will be in the area of oncology research utilizing either low or high throughput screening approaches.

• Basics of 3D cell culture
• Advantage of 3D models over 2D models in cancer biology
• Developing multi-cellular 3D cell culture models for high throughput screening
• Challenges of data interpretation of high throughput screens utilizing 3D spheroid models

Instructors:
Madhu Lal-Nag, Ph.D., Group Leader, Trans-NIH RNAi Facility, National Center for Advancing Translational Sciences, National Institutes of Health

Geoffrey A. Bartholomeusz, Ph.D., Associate Professor and Director, siRNA Core Facility, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center

Arvind Rao, Ph.D., Assistant Professor, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center

SC10: Molecular Imaging of the Blood-Brain Barrier

In this short course, we will discuss the development and application of molecular imaging techniques for brain research. The course will include introduction of molecular imaging, how to design chemical probes to cross the blood-brain barrier for neuroimaging, the application of novel and existing neuroimaging tools for brain research, and CNS drug discovery.

• An overview various brain imaging techniques such as stimulus- or task-related BOLD fMRI, resting state fMRI, arterial spin labeling, structural imaging, diffusion, spectroscopy
• How these techniques contribute to understanding various pathophysiological elements of pathological states
• Case studies of chronic pain to demonstrate the application of brain imaging to clinical pathology
• An overview of the capabilities and roles of neuroimaging technologies in studies of BBB functions but also drug PK/PD and CNS effects
• Examples of optical, MRI, and PET imaging applications, especially analysis of the brain and molecular exchanges across the BBB in the local environment for effective treatment

Instructors:
Changning Wang, Ph.D., Instructor, Radiology, Massachusetts General Hospital/Harvard Medical School

Marco L. Loggia, Assistant Professor of Radiology, Harvard Medical School, Associate Director, Center for Integrative Pain NeuroImaging, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital

Xiaoyou Ying, Ph.D., Head, Bioimaging, DSAR US, Preclinical Safety, Sanofi US

Thursday, June 16
7:00 - 9:30 pm

SC11: Immunocompetent Murine Models for Preclinical Assessment of Cancer Immunotherapy

Part 1: Humanized Mice as a Tool to Study Human Immunobiology

Instructor: Michael Brehm, Ph.D., Associate Professor, The Robert and Sandra Glass Term Chair in Diabetes, Diabetes Center of Excellence, Program in Molecular Medicine, University of Massachusetts Medical School

The development of severely immunodeficient IL2r null mice that support engraftment of functional human immune systems has enabled the in vivo study of human immunity. This presentation will include a general overview of these humanized mouse models, describing currently available strains, the protocols to generate humanized mice, the strengths of each system and a discussion of the application of these models to study human immunology.

Part 2: Syngeneic Tumor Model

Instructor: Daniela Cipolletta, Ph.D., Investigator II, Exploratory Immuno Oncology, Novartis Institutes for BioMedical Research (NIBR)

We have used murine models to monitor the immune response following perturbation of key oncogenic pathways and immune-checkpoints. This approach has enabled our understanding of tumor induced immune modulation and the identification of novel combinatorial strategies in specific cancer settings.

SC13: A Primer to Gene Editing: Tools and Applications

The course will help the novice understand the basics of how gene editing works, what tools are available for use and how those tools differ from each other. For the expert, this course will offer details on the CRISPR technology, how to set up CRISPR-based screens and complement it with existing RNAi-based screens using proper analysis and follow-up studies. The instructors will also cover the use of gene editing in drug discovery and disease modeling and best practices for design and workflows when working with other model systems, besides mammalian cells.

Instructors:
John Doench, Ph.D., Associate Director, Genetic Perturbation Platform, Broad Institute of Harvard and MIT

Michael Bassik, Ph.D., Assistant Professor, Department of Genetics, Stanford University

Stephanie Mohr, Ph.D., Lecturer, Genetics & Director of the Drosophila RNAi Screening Center, Harvard Medical School

Claire Yanhui Hu, Ph.D., Senior Bioinformatician, Drosophila RNAi Screening Center, Department of Genetics, Harvard Medical School

SC14: Importance of Solubility in Drug Discovery and Development Applications

This short course will cover the importance of solubility in achieving proper concentration, as well as techniques and tools for achieving the desired pharmacological response.

• Solubility and factors influencing solubility
  • Thermodynamic and Kinetic solubility
  • Solubility and lipophilicity
  • Impact of solid-state properties
  • Solubility pH profile
  • Solubility product
  • Super-saturation
   
• Solubility measurement – Kinetic and thermodynamic
• Predicting solubility and parameters that impact solubility
• Solubility diagnosis in discovery
  • Can we identify early what is limiting solubility?
   
• Impact of solubility on absorption and in vitro assays
  • Dissolution and super-saturation
  • Solubility in biological fluids
  • Impact of solubility on oral exposure vs. dose
  • Solubility input parameters for PBPK modeling
  • Assessment of formulation options at the compound selection stage (link back to factors influencing solubility, i.e. lipophilicity, pKa for salt selection)
  • Impact of solubility on in vitro assays
   

Instructors:

Bernard Faller, Director, Discovery ADME, Novartis Institutes for BioMedical Research, Basel

Manuel Sanchez-Felix, Senior Fellow, Chemical & Pharmaceutical Profiling, Novartis Institutes for BioMedical Research, Cambridge

Suzanne Skolnik, Investigator, Analytical Chemistry Group, Novartis Institutes for BioMedical Research, Cambridge

*Separate Registration Required