Conference Agenda

8:50 am Chair’s Opening Remarks


9:00 am Addressing the Multifaceted Nature of AAV Immunogenicity


  • Immunogenicity of AAV is complex and challenging, involving elements of innate, humoral and cellular immunity that can adversely impact patient eligibility, safety, efficacy, durability of treatment, and ability to re-dose
  • Mitigation strategies should account for all aspects of immunogenicity
  • Discussing data on the effects of ImmTOR tolerogenic nanoparticles on innate, CD8 T cell, and antibody responses to AAV and combination strategies to address high dose toxicity

9:30 am Industry Leaders Panel Discussion: Addressing High Dose AAV Delivery


  • Have we reached the highest dose for gene therapy yet?
  • Exploring dosing strategies: “One and done or Slower and Lower?”
  • What impact would a cumulative vector genome delivery approach have on safety and efficacy?
  • Moving away from one and done: what does best practice look like for dosing strategies?
  • Which role does complement play in the context of high dose gene therapy delivery

10:30 am Speaking Position Reserved for Precision Medicine

11:00 am Speed Networking


This session is the ideal opportunity to get face-to-face time with many of the brightest minds working in the gene therapy field and establish meaningful business relationships to pursue for the rest of the conference

11:30 am Morning Break & Refreshments


The Quest to Source & Leverage Pre-Clinical Models That More Accurately Reflect the Human Immune System

12:00 pm Immune Response to AAV CRISPR Therapy for Duchenne Muscular Dystrophy


  • Examining immunogenicity to AAV based CRISPR therapy
  • Modelling immune response in DMD mode

12:30 pm Immunogenicity Profile in Wild-Type Ferrets After Treatment With SP-101 & Doxorubicin: Inhalation Delivery of AAV Gene Therapy for the Treatment of Cystic Fibrosis

  • Lillian Falese Associate Director - Bioanalytical Development, Spirovant Sciences


  • Sharing the impact of inhalation delivery on the post-dose capsid neutralizing antibody (cell-based assay) profile
  • Implementation of a post-dose capsid total antibody (IgG) response and the decision-making process leading to a screen and titer strategy
  • Evaluation of ferret T-cell responses to the capsid and transgene measured via ELISPOT, the implications of measuring no or low responses


Examining Clinical Manifestations of Immunogenicity

12:00 pm Characterizing the Immunogenicity of AAV8 Empty Capsids in Healthy Volunteers


  • Empty Capsids are immunogenic inducing robust adaptive responses in seronegative healthy volunteers
  • CD4+ T cell help is a major contributor to the overall immune response
  • Empty Capsids can be used as a model antigen to evaluate the efficacy of Immune modulatory strategies in development

12:30 pm Speaking Position Reserved for Certara

1:00 pm Lunch & Networking


Exploring Immune Profiling Methodologies to Better Assess Immunogenicity

2:30 pm Innate Immune Signalling Pathways Leading to Cellular Immune Responses as a Function of Target Organ & AAV Vector Dose

  • Roland Herzog Director - Gene, Cell Therapy Program, Indiana University School of Medicine


  • Understanding innate immune signalling pathways that tigger CD8+ T cell activation
  • What is the role of specific antigen presenting cells in orchestrating the response?
  • Examining the role of target organ and vector dose in the response

3:00 pm Overcoming Innate Immune Barriers That Can Impede AAV Gene Therapy Vectors


  • Overview of innate immune responses in AAV-based gene therapy
  • Discuss the role of complement system in AAV immunogenicity
  • Examining potential immunomodulatory strategies to circumvent AAV related immune responses


Immunogenicity Monitoring in a Clinical Setting

2:30 pm Optimizing AAV Clinical Safety: Evolving Immunomodulation in the Phase 1 Study of RP-A501 (AAV9.LAMP2B) in Danon Disease


  • Overview of immunologic side effects associated with systemic AAV therapy
  • Review of the safety and preliminary efficacy in the adult and pediatric cohorts of the Phase 1 Danon disease study
  • Overview of complement activation and enhancements in the immunomodulatory regimen for the pediatric cohort

3:00 pm Roundtable Discussion: Discussing the Role of Innate Immunity in Clinical Manifestations of Immunogenicity


Immunogenicity of AAV is complex and challenging, involving elements of innate, humoral and cellular immunity that can adversely impact patient eligibility, safety, efficacy, durability of treatment, and ability to re-dose. Innate immunity in widely accepted to be the first in a chain of immune responses but there is still much to be understood. This roundtable will set out to discuss: – – – current understandings of Innate immune responses to the Capsid & Transgene & its impact on long term & short-term efficacy & safety?

3:30 pm Afternoon Refreshments & Networking


4:00 pm Anti-Cas9 Immunity & AAV-CRISPR Gene Editing in the Liver

  • William Lagor Associate Professor - Molecular & Cellular Biology, Baylor College of Medicine


  • Pre-existing immunity to Cas9
  • Understand the consequences of anti-Cas9 immune responses for AAV-CRISPR in the liver
  • Strategies to preserve gene edited hepatocytes

4:30 pm Immune Response to Long-Term CAS9 Expression in Mice & Nhps in the Context of Crispr-Gndm® Mediated Gene Modulation


  • CRISPR/Cas9-mediated in-vivo gene editing offers great potential to treat several genetic disorders
  • Conventional gene editing mediated through DNA strand breaks leads to offtarget gene changes and sometimes cause fatal consequences
  • Our proprietary CRISPR-GNDM® (Guide Nucleotide-Mediated Modulation) platform (aka CRISPRa/i), modulates gene expression without DNA strand breaks has great potential to overcome this hurdle

5:00 pm Engineered Treg Therapy for Tolerance to Anti-Drug Antibody Development


  • Introduction of Tregs and their importance in protein and gene replacement therapy with a few examples
  • Overview of different engineered receptor designs
  • Engineered Tregs for ADA development, using FVIII as an example. Will present published and unpublished information in the