Continuing Education Courses Schedule
Sunday, June 17 (AM)
CE 1 (Sunday AM) 8:00 AM–12:00 Noon
Clinical Pathology of Biotherapeutics
Co-Chairs: Allison Vitsky, BS, DVM, DACVP, Pfizer Global Research and Development; and Tara P. Arndt, DVM, DACVP, Covance
Biologic drug modalities are rapidly expanding in number and complexity, and this expansion has been accompanied by the observation of equally complex effects, both expected and unexpected, in nonclinical safety studies. The increasing emphasis on immunotherapeutic agents has further complicated matters, such that interpreting clinical pathology data has become a challenging endeavor requiring heightened comprehension of immunology, and a working understanding of responses which may be qualitatively or quantitatively different between species. This session will cover clinical pathology alterations common to various biotherapeutics, using didactic presentations, mechanistic discussions, and case examples to deliver a comprehensive discourse on this challenging topic
Effects of Biologic Drug Modalities on Peripheral Blood Cells
Nancy E. Everds, DVM, DACVP, Seattle Genetics
Immunogenicity and Immune Complex Disease in Preclinical Safety Assessment Studies: Challenges for Assessing Human Safety
John L. Vahle, DVM, PhD, DACVP, Eli Lilly & Company
Complement Activation, Cause and Effect
William Siska, DVM, MS, DACVP, Charles River Laboratories
Immunophenotyping and Cytokines, Considerations and Case Examples
Ellen W. Evans, DVM, PhD, DACVP, Pfizer, Inc.
CE 2 (Sunday AM) 8:00 AM–12:00 Noon
Scientific and Regulatory Considerations in Safety Evaluation of Gene Therapy Products in Preclinical Studies
Co-Chairs: Basel T. Assaf, BVSc, PhD, DACVP, Pfizer, Inc.; and Laurence O. Whiteley, DVM, PhD, Pfizer, Inc.
Progress in understanding the molecular bases of human health and disease in recent decades has flourished the field of Gene Therapy (GT) to offer new possibilities for treating, and even curing, a plethora of medical conditions such as monogenic disorders and metabolic diseases. GT is a therapeutic intervention to genetically alter or modify living cells by means of gene delivery achieved using either viral vectors or non-viral vectors, with the former constituting market share majority. Although gene therapy is conceptually attractive, adverse and even fatal iatrogenic complications have marred the initial enthusiasm of clinical successes. The properties of investigational viral vector-based gene therapy product (VGTP), such as their integration potentials, pose safety concerns unique from those of small molecule drugs and other macromolecule biologics. These products carry risks associated with ectopic or unregulated expression of the transgene, genotoxicity and cell transformation associated with integrative vectors, immunogenicity and inflammatory host tissue responses, long term persistence, and off-target distribution. These risks are generally evaluated in preclinical studies as part of a comprehensive preclinical safety program prior to administration in humans. However, safety assessment for these products can be challenging due to the lack of standardized approaches. A primary goal of this session is to introduce this product class to the toxicologic pathology community and provide a forum for discussion of the scientific and the regulatory considerations in the evaluation of host responses to GT products.
Gene Therapy: From Discovery to Translational Research
Guangping Gao, PhD, University of Massachusetts Medical School
A Pathologist’s Approach to Characterizing the Safety Profile of AAV-Based Gene Therapy
Laurence O. Whiteley, DVM, PhD, DACVP, Pfizer, Inc.
US FDA/CBER Regulatory Considerations in the Preclinical Evaluation of GT Products
Sandhya Sanduja, PhD, US FDA/CBER
Animal Models to Assess the Immunogenicity of AAV Vectors
David Markusic, Indiana University School of Medicine
Advancing GT into the Clinic: In-Depth Experience on the Interaction with Regulatory Agencies and the Advancement to Clinical Trials of GT Products
Katherine A. High, MD, Spark Therapeutics
Sunday, June 17 (PM)
CE 3 (Sunday PM) 1:30 PM–5:30 PM
Toxicologic Pathology of the Peripheral Nervous System
Co-Chairs: Ingrid D. Pardo, DVM, MS, DACVP, Pfizer, Inc.; and Deepa Rao BVSc, MS, PhD, DABT, DACVP, US FDA
Peripheral Nervous System (PNS) toxicity evaluation is relatively less well-defined compared to Central Nervous System (CNS) toxicity evaluation in routine animal toxicology studies. PNS toxicity is often encountered in patients treated with therapeutic agents (e.g., cancer chemotherapeutics), or, following exposure to environmental chemicals (e.g., industrial solvents). Available literature, guidance, and translation between animal studies to human risk assessment is generally limited. This half-day course is designed to familiarize participants with PNS toxicologic histopathology. Topics will include an overview of PNS biology, anatomy, physiology, and biochemistry of the peripheral nervous system (somatic and autonomic nerves and their ganglia); current best practices for PNS sampling, preparation, fixation, and evaluation, commonly observed artifacts and lesions and artifacts in the PNS; as well as examples and mechanisms of agents causing PNS neurotoxicity. A final session of three case studies will conclude into an open platform session with the audience for an engaging discussion with all speakers.
Biology of the PNS
Brad Bolon, DVM, MS, PhD, DACVP, DABT, ATS, FIATP, GEMpath, Inc.
Sampling and Fixation Techniques for Routine and Dedicated Peripheral Nerve and Ganglion Evaluation in Rodents, Dogs, and Primates
Mark Butt, DVM, Tox Path Specialists, LLC
Common Structural Lesions and Artifacts in the PNS
Bernie Jortner, VMD, Virginia Tech
Peripheral Neurotoxicants: Agents and Mechanisms
William M. Valentine, DVM, PhD, DABT, DABVT, Vanderbilt University Medical Center
Electrophysiological Methods for Evaluating the PNS
Joseph C. Arezzo, PhD, Albert Einstein College of Medicine
Case Studies in PNS Neurotoxicity
Ingrid D. Pardo, DVM, MS, DACVP, Pfizer, Inc.; Deepa B. Rao BVSc, MS, PhD, DABT, DACVP, US FDA; and Alok K. Sharma, BVSc, MVSc, MS, PhD, DACVP, DABT, Covance Laboratories Inc.
CE 4 (Sunday PM) 1:30 PM–5:30 PM
The Breakthrough of Oligonucleotide Therapeutics: What Is Happening in between Small and Large Molecules?
Sponsored by the American College of Toxicology (ACT)
Co-Chairs: Sven Korte, PhD, Covance; and Brian Vuillemenot, PhD, DABT, Adverum Biotechnologies, Inc.
The course is aimed for toxicologists and pathologists, but equally provides a great summary for pharmaceutical and regulatory experts. This is a rare chance to get guided through this field by a variety of world leading experts. This CE course will define different classes of oligonucleotide-based therapeutics on the basis of mechanism of action and summarize the history of this compound class. Furthermore, characterization of the pharmacokinetics and toxicology of Antisense Oligonucleotide (ASO) therapeutics will be presented and it will be described how toxicology testing strategies might differ from typical small molecule development. This course will also provide in-depth knowledge to conduct intrathecal screening and chronic lumbar or port catheter studies in juvenile and mature cynomolgus monkeys. Finally, the session will help you to understand the clinical relevance of toxicity findings, pathologic alterations that may be seen in nonhuman primates given repeated subcutaneous or intrathecal doses of single stranded antisense oligonucleotides and discuss recent advancements in the antisense field, allowing a look into the future of this technology platform.
Oligonucleotide Therapeutics: A Historical Perspective
Laurence O. Whiteley, DVM, PhD, DACVP, Pfizer, Inc.
US Regulatory Experience with Oligonucleotide-Based Therapeutics
Ronald L. Wange, BS, PhD, US FDA
Toxicopathology of Single Stranded Antisense Oligonucleotides
Jeffery A. Engelhardt, DVM, PhD, Ionis Pharmaceuticals
Conduct and Design of NHP Studies for First-in-Man Studies
Sven Korte, PhD, Covance Preclinical Services GmbH
When Your Cup Runneth Over: Advances in Antisense Chemistry, Targeting, and Mechanisms
Scott P. Henry, PhD, Ionis Pharmaceuticals
Continuing Education Chair:
Vimala Vemireddi, BVSc, MS, DACVP, DABT, Covance Laboratories, Inc.
Continuing Education Co-Chair:
Gopakumar Gopalakrishnan, DVM, MS, DABT, DACVP, Supernus Pharmaceuticals