Discussion Day - Thursday February 25, 2021

 Is Gene Therapy Really A Cure? Re-Dosing: The Elephant In The Room 

As the quote goes, “by failing to prepare, you are preparing to fail”. Gene therapies have seen incredible progress in recent years, addressing unmet need in a wide variety on indications. One of the key drivers of investment and interest in these therapeutics has been the idea that they will cure patients for life.

However, given the lack of long-term data currently available and possibility that effects will decrease over time, it makes sense to start planning for the eventuality that re-dosing will be required. A whole host of issues, challenges and discussions therefore need to be had about re-dosing and therefore immunogenicity more generally. This is compounded by the fact that many patients are currently excluded from trials because of existing anti-drug antibodies, meaning that progress on the immunogenicity front would have multiple benefits in the short and long term.

This discussion day is solely devoted to tackling these immunogenicity and re-dosing challenges. Engage with experts in the space in an intimate, interactive format and leave with the insights that will prepare you to tackle the future immunogenicity and re dosing challenges you’ll face in the development of your gene therapy pipeline.

9:00 am Chair’s Opening Remarks

Exploring Current Viability of Re-Dosing for Gene Therapies

9:15 am Understanding the Current Challenges of Immunogenicity and Re-Dosing in Gene Therapy


  • Exploring the challenges associated with administering AAV vectors
  • Assessing the need and feasibility of re-dosing with current technologies
  • Understanding the safety of re-dosing

9:45 am Mitigation of Immunogenicity to Enable Re-Dosing of AAV Vectors by Co-Administration with Tolerogenic ImmTOR Nanoparticles


  • Co-administration of ImmTOR nanoparticles with AAV inhibits the formation of anti-AAV antibodies and enables vector re-dosing
  • In addition, admixing of ImmTOR to AAV has a beneficial first dose effect on enhancing transgene expression in the liver
  • Clinical proof-of-concept has been established with ImmTOR combined with a highly immunogenic enzyme therapy

10:15 am Morning Refreshments

Investigating Challenges of Immune Responses

11:00 am A Two-Fold Problem: Investigating Challenges of Immune Responses to Capsids and Transgenes


  • Understanding potential risk of developing immune responses to newly expressed proteins
  • Comparing and contrasting immune responses to capsids and transgenes
  • Exploring the role of Regulatory T cells in suppressing muscle inflammation and immunity.
  • Immunoregulation versus immunosuppression during gene therapy

11:30 am Inhibitors in Hemophilia and Treatment Approaches for Eliminating Antidrug Antibodies with Gene and Immune Therapy


  • AAV liver gene transfer induces transgene tolerance mediated by Treg induction
  • Immune tolerance is dependent on several factors such as AAV vector serotype, antigen expression level, transgene, and genetic background
  • Adjunct immune suppression can complement AAV immune tolerance and prevent AAV capsid Nab

12:00 pm Lunch & Networking

1:00 pm A Proactive Approach to Immunogenicity – Avoiding Immune Response


  • Understanding the importance of selecting the vector and administration route that de-risks immune response upfront
  • Exploring how route of administration affects immunogenicity – is the eye really an ‘immunoprivileged’ organ?

1:30 pm Immunotherapeutic Interventions

  • David Favre Vice President, Translational Medicine , Asklepios BioPharmaceutical


  • Pre-existing vs. naïve anti-AAV immunity require different targeted interventions
  • B-cell and antibody depletion are key for pre-existing immunity but may not be sufficient
  • In naïve subjects: conditioning regimen and B/T -cell mediated immune tolerance induction
  • Advanced immune monitoring strategies and experimental medicine trials are key for progressing immunotherapeutic interventions in patient populations

2:00 pm Afternoon Break

Analyzing the Best Approaches to Increase Likelihood of Successful Re-Dosing

2:30 pm Exploring Immunosuppression as an Approach to Mitigate Immune Response


  • Effect of immunosuppression to prevent immune responses to the AAV capsid and the transgene
  • Effect of immunosuppression to allow for repeated AAV dosing Effect of immunosuppression to manage pre-existing immunity

3:00 pm Panel Discussion: Comparing and Contrasting Immunosuppression and Novel Approaches


  • Discussing the most promising approaches to overcome immunogenicity
  • Investigating which approaches are most applicable to different indications
  • Recognizing the importance of novel technologies in the immunology space

3:45 pm Chair’s Closing Remarks

4:00 pm Close of the Post-Conference Discussion Day