8:15 am Online Registration & Virtual Coffee Networking

8:50 am Chair’s Opening Remarks

UNDERSTANDING IMMUNE RESPONSE TO IMPROVE SAFETY & EFFICACY

9:00 am Links Between Innate & Adaptive Immunity in AAV Gene Transfer

  • Roland Herzog Professor of Pediatrics , Indiana University School of Medicine

Synopsis

• Innate immune sensing of AAV vectors
• Mechanisms leading to immune responses to vector and transgene product
• Blockage of specific pathways to prevent immune responses

9:30 am Immune Management in AAV Gene Therapy to Enhance Safety and Improve Efficacy

  • Barry Byrne Professor & Associate Chairman , University of Florida

Synopsis

• Understanding the mechanisms behind immune response to better inform an immunogenicity mitigation strategy
• Optimizing the process of management formulation to better enhance safety and improve efficacy
• An immune management AAV gene therapy strategy case study

10:00 am Morning Break & Virtual Networking

10:30 am Addressing the Need & Potential Solution for AAV Redosing

Synopsis

• Factors that may contribute to the need for AAV re-dosing include insufficient therapeutic activity of the initial dose, growth of the target organ in pediatric patients, inflammation or tissue injury that causes cell turnover, or desire to split a large vector dose over multiple smaller doses
• ImmTOR technology has been shown to mitigate immune responses to an immunogenetic therapeutic enzyme in humans and to mitigate formation of anti-AAV antibodies and enable vector redosing in animal models
• Specific case examples of applying ImmTOR technology to AAV vector redosing will be discussed

11:00 am Compartmentalization of Immune Response After AAV Gene Therapy

  • Roberto Calcedo Vice President Immunology and Safety, TouchDown Therapeutics

Synopsis

• Blood is not the best surrogate to study T-cell responses to AAV vectors
• T-cell responses can be found in the liver but not in blood after CNS and IV delivery of AAV Vectors
• Discuss whether T-cell responses in the liver are beneficial to induce tolerance in AAV vectors

11:30 am Live Q&A – Ask the speakers your questions

  • Roland Herzog Professor of Pediatrics , Indiana University School of Medicine
  • Barry Byrne Professor & Associate Chairman , University of Florida
  • Takashi Kishimoto Chief Scientific Officer, Selecta Biosciences Inc.
  • Roberto Calcedo Vice President Immunology and Safety, TouchDown Therapeutics

12:00 pm Lunch

IMMUNOGENICITY AT THE POINT OF TRANSLATION

1:00 pm Translational and Clinical Immunogenicity of Valoctocogene Roxaparvovec, & AAV5-Mediated Gene Therapy for Hemophilia A

Synopsis

• Bridging of non-clinical immunogenicity to clinical studies of Valoctocogene Roxaparvovec, an AAV5 mediated gene therapy encoding FVIII for the treatment of Hemophilia A
• The development and characterization of assays used to detect pre-existing AAV5 immunogenicity will be discussed
• Immunogenicity data characterizing the post-dosing humoral and cellular immune responses will be presented

1:30 pm Considerations for Improved Measurement of the AAV-Specific Immune Responses

Synopsis

• How to determine the AAV NAb titers in samples with matrix effect
• Examine if its sufficient to only use IFNg ELISPOT to monitor T-cell activation in AAV-based gene therapy trials
• Discuss whether animal models can predict immunogenicity of AAV in humans

2:00 pm Live Q&A – Ask the speakers your questions

NEXT GENERATION AAV VECTORS: WHAT DOES THE FUTURE HOLD?

2:20 pm Afternoon Break & Virtual Networking

2:50 pm Using Directed Evolution to Avoid AAV Immune Responses

  • Casey Case Senior Vice President Research & Development , 4D Molecular Therapeutics

Synopsis

• Directed evolution has been successfully employed to avoid immune surveillance
• Payload modifications can decrease the response to novel transgenes
• These approaches may ultimately permit redosing

3:20 pm Immunogenicity of Novel AAV Vectors

  • David Favre Vice President Translational Medicine , Asklepios BioPharmaceutical

Synopsis

• Understanding adaptive and innate immunity to AAVs through preclinical models and clinical assessment strategies
• Developing inclusion and exclusion criteria and utilizing in-life monitoring
• What does pre-existing immunity mean for re-dosing and what are the safety considerations?

3:50 pm Next Generation Design of Immune-Evading AAV Vectors

Synopsis

• AAV vectors and the challenge of immune responses
• Drivers of AAV immunogenicity
• Design of AAV vectors that evade immune responses

4:20 pm Live Q&A – Ask the speakers your questions

  • Casey Case Senior Vice President Research & Development , 4D Molecular Therapeutics
  • David Favre Vice President Translational Medicine , Asklepios BioPharmaceutical
  • Ying Kai Chan Chief Scientific Officer , Allyx Therapeutics

4:50 pm Chair’s Closing Remarks