*All times listed are in EST


8:00 am Chair’s Opening Remarks

8:15 am Dorsal Root Ganglia Pathology in AAV Preclinical Studies: Meta-Analysis & Mitigation Strategy

  • Juliette Hordeaux Senior Director, Translational Research & Lysosomal Storage Disease, University of Pennsylvania


• The administration of adeno-associated virus (AAV) vectors to nonhuman primates (NHP) can lead to dorsal root ganglion (DRG) pathology
• A meta-analysis including 256 NHP shows that 83% of animals that were administered AAV through the cerebrospinal fluid (CSF), and 32% of those that received an intravenous (IV) injection developed some DRG pathology and secondary axonopathy
• We developed an efficacious mitigation strategy using DRG-specific microRNA targets

8:35 am Intracisternal AAV9-based Gene Therapy for Lysosomal Storage Diseases: The Clinical Trial Experience


• Intracisternal route of administration in pediatric MPS I and II patients
• Safety and monitoring of intracisternal AAV9 gene therapy
• Biomarker and clinical outcomes assessment challenges in heterogenous phenotypes of MPS II
• Progress and update of the first in human AAV9 gene therapy studies for MPS I and II

8:55 am Q&A Panel Discussion: Overcoming Toxicity & Immunogenicity Challenges


• Does it depend on the disorder?
• What are best preclinical models for toxicology risk assessment?
• Reviewing preclinical data for CNS and systemic toxicity
• How does this translate into humans?
• Discussing immunogenicity concerns for patients

9:15 am Morning Break


10:00 am Lesson From the Clinic & Why AAV Biology Still Matters


• Following the history of AAV administration for CNS disorders
• Discussing the value of AAV biology
• Reviewing clinical data

10:20 am Safety & Efficacy of Intra-Cisternal Administration of AAV Vectors


• Evaluating the intra-cisternal route: pros and cons
• Exploring preclinical studies of toxicity and biodistribution
• Discussing clinical validation

10:40 am Spinal Subpial Vector Delivery for Treatment of Neurological Disorders in Adult Mammals: Maximizing the Therapeutic Potency While Minimizing Toxicity


• Comparing the potency of AAV vectors in infecting spinal cord and brain neuronal pools after intrathecal vs spinal subpial delivery: adult large animal model(s) experience
• Use of subpial AAV delivery for controlled, segment-targeted transgene expression
• Regional pattern of neurodegenerative changes in specific inherited disease as a denominator defining the required route of treatment vector delivery
• Toxicity of intrathecal vs subpial AAV delivery
• Human subpial injection device: preclinical experience in an adult pig

11:00 am Exploring Advances in Devices for Direct Gene Therapy Injection


• Exploring the state-of-the-art technical improvements for gene therapy delivery
• Introducing the latest MRI-friendly cannulas and needles
• Discussing the common challenges with age of patient, tech transfer and scaling

11:20 am Q&A Panel Discussion: Delivery


• Comparing different patient populations for different indications and their suitability for different delivery routes
• Discussing biodistribution vs invasive procedures for delivery to the brain
• Exploring the risk/benefit of different routes of administration, is the data translatable?
• Introducing technology advances for the delivery devices, where is there room for improvement?

12:00 pm Lunch & Networking


12:30 pm Preclinical Model Selection: Understanding the Biology & the Translatability


• Aspects to consider when selection your preclinical model
• Capsid selection and biological relevance
• Translatability to non-human primates

12:50 pm Quantitative PET Imaging Biodistribution of I-124-labeled Adeno-associated Viral Vectors

  • Ronald Crystal Chairman, Department of Genetic Medicine, Weill Cornell Medicine


• Analyzing the biodistribution of AAV gene transfer vectors following in vivo administration
• Using intravenous and intracisternal routes of administration of AAVrh.10 and AAV9 vectors to nonhuman primates in the absence or presence of anti-capsid immunity, we have identified novel insights into initial capsid biodistribution and organ-specific capsid half-life
• Facilitating quantitative in vivo viral vector dosimetry, which can serve as a technique for evaluation of both on and off-target organ biodistribution, and potentially accelerate gene therapy development through rapid prototyping of novel vector designs

1:10 pm Detemining Gene Therapy PKPD

  • Lilly East Director, Clinical Pharmacology & Pharmacometrics, Sarepta Therapeutics


• Clinical translation of AAV-based Gene Therapy
• Dose extrapolation in rare diseases
• Perspectives in clinical pharmacology

1:30 pm Q&A Panel Discussion: Overcoming Translational Challenges

  • Jacinthe Gingras Director of Ophthalmology & Neuroscience, Homology Medicines
  • Ronald Crystal Chairman, Department of Genetic Medicine, Weill Cornell Medicine
  • Lilly East Director, Clinical Pharmacology & Pharmacometrics, Sarepta Therapeutics
  • Holger Patzke Vice President, Neuroscience, Voyager Therapeutics


• Extrapolating dosage data
• Choosing suitable preclinical models
• Seeking translatable biomarkers

2:00 pm Afternoon Break


2:15 pm Clinical Trial Enrolment for Rare Disease Populations & Clinical Endpoints

  • Mark Milton Ophthalmology Therapeutic Area Head, PK Sciences, Novartis


• What level of pre-existing immunity is accepted?
• What level of protein expression is sufficient for different indications?
• What safety biomarkers do you use to understand pathology in man?

2:25 pm Chairs Closing Remarks

2:35 pm Gene Therapy for Spinal Muscular Atrophy: Patient Perspective on Clinical Trials and Impact


• Impact of gene therapy on the SMA patient population
• What really matters? Existing unmet need. How does the risk/benefit ratio differ from developer to patient?
• Informing future gene therapy development and focusing on important metrics

2:55 pm Q&A Panel Discussion: Ethics & Trial Design


• Enrolment criteria for pre-existing immunity titer and how this shifts from company to company
• Forward thinking drug development trial design with the patient in mind
• How has COVID-19 affected gene therapy trials? What can be learned from this for future trial design?

3:30 pm Final Virtual Networking

4:30 pm End of Summit