Pre Conference Workshop Day - September, 5 2023

7:45 am Registration & Coffee

08:30 – 10:30 am
Workshop A

Clinical Safety Monitoring for AAV Gene Therapies 101

Synopsis

A major objective of early-phase clinical trials is the safety evaluation of a drug candidate. With gene therapies, a complex mixture of difficult-to-predict immediate hypersensitivity and delayed immune reactions can occurs from anywhere between minutes and months of administration. As such, it is vitally important to outline the immune monitoring strategies as part of your clinical safety monitoring strategy ahead of entering the clinic.

Attend this workshop to learn about:

  • Key considerations for measuring the cellular and humoral immune responses to both the vector and transgene
  • How to find out, control, and measure critical assay variables for the cellular response
  • New immune monitoring strategies in the clinic and the rationale behind their selection
  • Exploring some key challenges and limitations (e.g., reproducibility, clinical translatability) of these common assays
  • Should drug sponsors be testing for adaptive cellular immune responses as part of their long-term follow-up plan?
  • Utilising new FDA Type D meetings to help find resolution to safety challenges sooner

11:00 – 13:00 pm
Workshop B

Detecting Pre-Existing Antibodies to AAV Gene Therapies

  • Manuela Braun Senior Scientific Expert - Preclinical Development of Gene & Cell Therapy Products, Bayer
  • Mark Milton Principal, Lake Boon Pharmaceutical Consulting
  • Boris Gorovits Vice President - Preclinical Translational & Bioanalytical, Sana Biotechnology

Synopsis

One of the inherent challenges to effective AAV gene therapy treatment is the prior exposure and neutralizing antibody (NAb) generation in a large number of target populations. The methods used for testing for seropositivity prior to transfer remains a hotly-debated topic, with no universal test or titer currently deployed as an industry standard for detecting anti-AAV antibodies in patients. Whilst this remains the case, having a robust understanding of the NAb vs TAb (Total Antibody) debate – including the practical considerations and rationale behind choosing either/or – is crucial.

Attend this workshop to learn about:

  • Outlining the main differences total antibody (TAb) and transduction inhibition (TI) assays
  • Practical considerations for choosing between the TAb and TI assays
  • Key factors for determining cut-off values
  • Requirements when developing a diagnostic assay for AAV antibody assessments
  • Regulatory insights and planning for diagnostic assay submissions

14:00 – 16:30 pm
Workshop C

Enabling AAV Re-Dosing

Synopsis

The non-replicating nature of AAV vectors gives rise to a key challenge for gene therapy developers – over time, transgene expression will wane. An attractive and traction-gaining method to overcome this durability issue is to re-administer gene therapies, a bucket within which exist a plethora of different novel strategies.

Addressing the Barrier of Memory Cell Reactivity

  • Genine Winslow Founder & Chief Executive Officer, Chameleon Biosciences

Synopsis

  • Outlining the importance of the memory T and B cell response in the formation of anti-AAV antibodies
  • Evaluating the latest immune tolerance approaches to prevent their formation following a priming dose
  • What potential impact does controlling the memory T cell response hold for redosing? 

Can you Re-Dose AAV at High Vector Doses?

Synopsis

  • The ability to administer multiple doses of AAV vector could provide a potential strategy to mitigate toxicities typically associated with vector doses of 1E14 vg/kg or higher
  • However, such a strategy would require the ability to re-dose at vector doses of ~5E13 vg/kg, which presents a considerable immunological challenge
  • Presenting data to investigate combination treatment using ImmTOR tolerogenic nanoparticle to mitigate immune responses to high vector doses

Enhancing the Efficacy of AAV Re-Administration in Liver Gene Therapy

  • Jyoti Rana Assistant Professor - Research, Indiana University School of Medicine

Synopsis

  • Timing of immunosuppression is crucial to prevent immune activation towards AAV vector and transgene product
  • Dose dependent effects on the efficacy of Immunosuppressive treatments
  • Identification of the combination therapy for successful re-administration

Industry Leaders’ Panel: Evaluating Progress of AAV Redosing Developments in 2023

Synopsis

  • Outlining the current state of play between ‘one and done’ and ‘low and slow’ approaches?
  • How is the investment landscape of gene therapies impacting developments in redosing?
  • Where are we making significant progress in the field?