Continuing Education Courses

Sunday, June 25

CE1 (Sunday AM) 8:00 AM–12:00 Noon

• Development of Gene Therapies for Ocular Indications: From Concepts to Risk Assessment

  Co-Chairs: Helen S. Booler, BSc (Hons), BVetMed, DECVP, PhD, MRCVS, Novartis; Jacqueline Brassard, DVM, PhD, DACVP, Brassard Toxicologic Pathology Consultancy; and Meg Ferrell Ramos, DVM, PhD, DACVP, AbbVie

  Gene therapy in general has emerged as a research topic of choice in recent years. There has been a resurgence of interest and investment in the field of ocular gene therapy, driven by improved understanding of the genetic basis of ocular disease, advances in viral vector technology and unique anatomic and immunologic properties of the eye. The approval in 2017 of the first ocular gene therapy, indicated for patients with RPE65-associated retinal dystrophies, has provided hope for patients with many previously untreatable inherited retinal dystrophies, and has shifted the way we think about the treatment of ocular diseases more widely. With more ocular gene therapeutics in the pipeline, it is a good time to review the design and development of gene therapy products, with an emphasis on the non-clinical development, common in-life and histopathologic findings, risk assessment and a discussion of the translatability of non-clinical findings and the relevance to patients.

  An Overview of Gene Therapies both General and Specific to Ocular Indications
  Jacqueline Brassard, DVM, PhD, DACVP, Brassard Toxicologic Pathology Consultancy

  Toxicology, Study Design, Emerging Safety Trends, and Regulatory Considerations in the Development of Ocular Gene Therapies
  Brian Short, DVM, PhD, DACVP, Brian Short Consulting, LLC

  Immunological Considerations and Immune-Mediated Pathology in the Development of Ocular Gene Therapies
  Meg Ferrell Ramos, DVM, PhD, DACVP, AbbVie

  In-Life Observations and Pathology of AAV-Based Gene Therapies
  Helen S. Booler, BSc (Hons), BVetMed, DECVP, PhD, MRCVS, Novartis

  An Introduction to Ocular Oligonucleotide Therapies, In-Life Observations, and Associated Pathology
  Krishna Yekkala, BVSc, PhD, DACVP, Janssen Research and Development of Johnson & Johnson

  This program (20-1008492) has been approved for 2.25 hours of continuing education credits in jurisdictions that recognize RACE approval.

  

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CE2 (Sunday PM) 1:30 PM–5:30 PM

• Toxicologic Neuropathology of Novel Therapeutics

  Co-Chairs: Dinesh Bangari, BVSc, MVSc, MS, PhD, DACVP, Sanofi; and Lisa Lanigan, DVM, PhD, DACVP, Charles River Laboratories

  In this half day session, we will present an overview of the mechanisms of action, toxicologic liabilities, and safety risk assessment approaches for novel biotherapeutics for use in treating nervous system disorders and neuromuscular diseases. These modalities include vector-based therapies such as lentiviral and adeno-associated viral vectors (AAVs), cell-based therapies such as stem cells and CAR-T cells, nucleic acid-based therapies such as antisense oligonucleotides (ASOs) and mRNAs, and novel antibody-based therapeutics. The session will begin with an overview of the mechanisms of action for each of these therapeutics, how they can specifically target the nervous system and the unique aspects of safety risk assessment for these novel biotherapeutics. Additionally, there will be a presentation on the methods for investigating biodistribution, pharmacokinetics and pharmacodynamics to enable clinical/human dose prediction of these novel therapeutics. Finally, there will be 2–4 short case studies to demonstrate the importance of an informed safety assessment for novel biotherapeutics that target the nervous system. The goal of this session is to provide a well-rounded overview of the rapidly emerging biopharmaceutical research that is focused on developing novel therapeutics for the treatment of nervous system disorders and neuromuscular diseases.

  Vector-Based and Cell-Based Therapies
  Sarah Cramer, DVM, PhD, DACVP, StageBio

  Case Presentation: Routed by ROA: Effect of Route of Administration on AAV Neuropathology
  Elizabeth Galbreath, DVM, PhD, Takeda Development Center Americas, Inc.

  RNA-Based Therapies
  Jessica Grieves, DVM, PhD, DACVP, Ionis Pharmaceuticals

  Transport Vehicles to Deliver Biologics to the CNS
  Rene Meisner, DVM, DACVP, DABT, Denali Therapeutics

  RNAi Pharmacokinetics and Activity Assessment
  Arlin Rogers, DVM, PhD, Alnylam Pharmaceuticals

  Concept Presentation: Grappling with Gliosis in Assessing Adversity
  Brad Bolon, DVM, MS, PhD, DACVP, DABT, ATS, FIATP, FRCPath, GEMpath, Inc.

  This program (20-1008516) has been approved for 2.50 hours of continuing education credits in jurisdictions that recognize RACE approval.

  

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Virtual Continuing Education Courses

Friday, August 25, 2023, 12:00 Noon–3:45 PM EDT

• Microbiome and Drug Development
  (Sponsored by the American College of Toxicology)

  Session Chairs: Rana Samadfam, Charles River Laboratories, Montreal, QC, Canada; and Alan Hoberman, Charles River Laboratories, Horsham, PA

  The human body is an ecosystem consisting of different communities including human cells with all the complexity of human cell biology, bacteriome, virome, and other microorganisims with both harmless and pathogenic members. There are interactions and competition for resources between members of each community. In this ecosystem, complex interfaces consolidate signals from hosts (bacteria and human) and microbiota (bacterial, phage, virus, etc.) and activate appropriate effector programs to maintain a delicate balance. Failure to maintain this balance contributes to inflammatory disorders, including arthritis, allergies, and colitis. This course will discuss new findings on cross talk between the immune system and the microbiome and how efficacious in treating inflammatory disorders the new therapeutic approaches with microbiome origin are compared with standard of care.

  Human Ecosystem
  Rana Samadfam, Charles River Laboratories, Montreal, QC, Canada

  Preclinical Studies in the Era of the Microbiome
  Rodney R. Dietert, Cornell University, Ithaca, NY

  The Influence of Gut Virome (Phages) and the Immune System on Intestinal Health
  Corinne Maurice, McGill University, Montreal, QC, Canada

  Efficacy of Live Therapeutics in Inflammatory and Autoimmune Conditions
  Samantha Coulson, Coolum Beach, Australia

Friday, September 15, 2023, 12:00 Noon–3:45 PM EDT

• Fluid-Based Biomarkers of the Nervous System and Neurotoxicity

  Co-Chairs: Ingrid D. Pardo, DVM, MS, DACVP, Biogen Inc., Cambridge, MA; and Madhu P. Sirivelu, BVSc, PhD, DACVP, Pfizer, Inc. Cambridge, MA

  There is a critical need to develop non-invasive biomarkers to detect and/or predict nervous system alterations in preclinical species and humans. These can also be used to evaluate efficacy of novel drugs, and to monitor neurologic diseases. In preclinical studies, fluid-based biomarkers for neurotoxicity can be measured in standard samples collected (serum/plasma) or by collecting additional samples such as, urine, ocular fluid, saliva, and CSF (invasive). In 2019, the US FDA authorized marketing of the first blood-based test to aid in the evaluation of traumatic brain injury (TBI) in adults (to assess GFAP [glial fibrillar acidic protein] and UCH-L1 [ubiquitin C-terminal hydrolase L1]) to help health care professionals determine the need for a CT scan in patients suspected of having mild TBI with the purpose of preventing unnecessary neuroimaging and associated radiation exposure to patients (Takala et al., 2015) In addition, the US FDA has authorized the use of NF-L (Neurofilament light chain) to monitor patients with multiple sclerosis (www.fda.gov). The objectives of this course are to update the attendees of the use of fluid-based biomarkers of nervous system in preclinical species, the role pathologists and scientists play in validating and interpreting biomarker data and regulatory aspects of biomarker applications.

  Introduction and the Role of Pathologists in Biomarkers for the Nervous System and Neurotoxicity
  Ingrid D. Pardo, DVM, MS, DACVP, Biogen Inc, Cambridge MA

  Validation of Fluid-Based Neurobiomarkers in Nonclinical Toxicology Species and Their Utility in Gene Therapy Studies
  Madhu P. Sirivelu, DVM, PhD, DACVP, Pfizer Inc., Cambridge, MA

  Fluid-Based Biomarkers of Neurotoxicity with Gene Therapy Toxicity Studies in Nonhuman Primates
  Kelley Penraat, MS, DVM, MVetSc, DACVP, Novartis, Newmarket, NH

  Identification of Translational Biomarkers of Neurotoxicity: HESI’s NeuTox Committee
  Syed Imam, PhD, US FDA HESI, Little Rock, AR

  European Innovative Medicines Initiative (IMI) NeuroDeRisk Strategy: Peripheral Neuropathy in Rats: Biomarkers, Histopathology and IHC Correlation
  Diethilde Theil, DVM, Dr med vet, Hoffmann-La Roche AG, Basel, Switzerland

  Utilizing Fluid-Based Biomarkers for Clinical Trial Decision Making in Neuromuscular Diseases
  Denitza Raitcheva, BS, Biogen Inc, Cambridge, MA

  Development of Biomarkers of Neurotoxicity: Regulatory Perspective
  TBD

Continuing Education Chair:
Maria L. Dagli, DVM, MS, PhD, Universidade de São Paulo, São Paulo, Brazil

Continuing Education Co-Chair:
Melanie Greeley, DVM, PhD, DACVP, Charles River Laboratories, Ashland, OH