Post-Conference Discussion Day - March 10, 2022

9:15 am - 03:00 pm

Immunogenicity & Durability Discussion Day

9:15 am Chair’s Opening Remarks

Redosing in Gene Therapy: The Potential & The Challenge

9:30 am Effects of ImmTOR Tolerogenic Nanoparticles on Innate, Humoral and Cellular Responses in AAV Gene Therapy and Models of Liver Inflammation

Synopsis

  • ImmTOR nanoparticles encapsulating rapamycin have been shown to mitigate the antibody response to AAV and enable redosing
  • ImmTOR also inhibits hepatic NFkappaB activation, a master regulator of inflammation, in response to high doses of AAV
  • ImmTOR enhances the tolerogenic environment of the liver and is protective in mouse models of liver inflammation

10:00 am Investigating the Promise of Redosing in Gene Therapy with EVADER

Synopsis

  • Moving away from the ‘one and done’ paradigm
  • Understanding of underlying biology of immune response continues to increase
  • Defining optimal dosing regimens with Chameleon’s EVADER technology

10:30 am Morning Refreshments

Minimizing Immunogenic Responses to Viral Vectors

11:00 am Minimizing Immune Response to AAV Gene Therapy

Synopsis

  • Exploring novel immunosuppressive drugs and regimes to reduce immune response
  • Measuring immunogenicity risk and resulting impacts on trial designs & patient eligibility
  • Standardizing immune protocols? Considerations across different disease types and modalities

11:30 am Overcoming AAV Innate Immunity Barriers to Further Gene Therapy Development

  • Manish Muhuri Instructor , University of Massachusetts Medical School

Synopsis

  • Current understanding of AAV innate immune response
  • Exploring the capsid and transgene immune response
  • How can we overcome innate immunity to AAV to ensure development of safer, more efficacious gene therapies?

12:00 pm Lunch & Networking

Developing more Durable Gene Therapies

1:00 pm Addressing Liver-Targeted Gene Therapy Durability in Pediatric Populations

Synopsis

  • Utilising piggyBac integration for stable and durable transgene expression
  • Improving efficiency leading to reduced dosing and lower immunogenicity risk
  • Exploring potential vectors to administer piggyBac

1:30 pm Addressing Paediatric Genetic Diseases Using a Promoterless, Nuclease-Free Gene Insertion Technology to Provide Life-Long Protein Expression

Synopsis

  • Safe and precise genome integration into the albumin gene site provides strong corrective transgene expression from the albumin promoter
  • Many life-altering and life-shortening metabolic diseases result in liver damage. GeneRide-edited hepatocytes are healthier than mutationbearing hepatocytes resulting in selective pressure to repopulate the growing and/or damaged liver with the healthy corrected cells
  • We can monitor selective advantage and expansion of corrected hepatocytes using a circulating technology-related biomarker, and we observe increasing numbers of hepatocytes expressing the corrective gene overtime, leading to reduced disease burden

2:00 pm ROUNDTABLES: Developing more Durable Gene Therapies

Synopsis

Gene therapy durability is intrinsically linked to their safety and efficacy. This roundtable will explore different modalities people are exploring to ensure highly durable, safe gene therapy development, including:

  • Engineering novel vectors for higher overall expression
  • Non-viral delivery for potential redosing

2:30 pm PANEL DISCUSSION: Where are the Biggest Bottlenecks for Gene Therapy Immunogenicity & Which Approaches are Showing Most Promise (and Feasibility)?

Synopsis

  • Actively minimizing immunogenic responses
  • How close are we to redosing?
  • Widening patient eligibility in relation to antibody positivity
  • Exploring innovative vector modifications

3:00 pm Chair’s Closing Remarks

Translational Discussion Day

9:15 am Chair’s Opening Remarks

Addressing Gene Therapy Safety in Translational Development

9:30 am Strategies to Improve the Safety Profile of AAV Mediated Gene Therapies

Synopsis

Talk details to be confirmed

10:00 am Bridging the Gap Between Research & Clinical Development

Synopsis

  • Developing appropriate assays for the purpose of clinical development
  • Defining biomarkers that will be measurable in clinical trials
  • Collating information from different divisions involved in translational development

10:30 am Morning Refreshments

Choosing Appropriate Delivery Methods

11:00 am Development of Lentiviral Vectors for Gene Therapy in Skeletal Dysplasia

Synopsis

  • InnoSkel focuses on gene therapy for inherited skeletal dysplasia
  • Type II collagenopathies (COL2A1 deficiency), such as Spondyloepiphyseal Dysplasia congenita (SEDc) and related, are rare pediatric disease indications with unmet medical needs
  • Systemic delivery of lentiviral vectors (LVV) can efficiently transduce cartilage cells in growth plates of juvenile SEDc disease mouse model and rescue the severe phenotype.
  • Discussing considerations on safety risks and mitigation strategies for the systemic delivery of integrative 3rd generation LVV

11:30 am PANEL DISCUSSION: Choosing Appropriate Delivery Methods for Successful Translation

  • Lisa Stanek VP, Translational Sciences, Affinia Therapeutics

Synopsis

  • Different delivery methods in different animal models impact translatability
  • Setting up for long-term program success, including patient input
  • Comparing between different animal models and capturing data effectively

12:00 pm Lunch & Networking

Determining the Optimal Dose from Preclinical Studies

1:00 pm Strategies for Tackling Cardiovascular Diseases Through Gene Therapy

Synopsis

  • Potential of gene therapy to address rare and prevalent cardiovascular diseases
  • Tenaya’s specific approach to harnessing gene therapy
  • The importance of raising awareness of genetic cardiovascular diseases and the value of early diagnosis

1:30 pm ROUNDTABLES: Determining the Optimal Dose from Preclinical Studies

Synopsis

Accurately extrapolating the correct dose to go on to use in first in human trials is always a challenge in translational development, but in gene therapy the stakes are very high given the ‘one and done’ paradigm behind so many gene therapies and the very low likelihood of redosing. This roundtable will delve into dosing challenges across:

  • Comparative dosing in different animal models
  • Systemic vs local dosing

2:15 pm PANEL DISCUSSION: Comparing Different Preclinical Studies: How can Sharing Knowledge Streamline Translational Development & Contribute to Cost- Effectiveness?

Synopsis

  • Developing more standardized safety and efficacy assays
  • Where can knowledge be shared in translational development whilst protecting proprietary information?
  • Employing a platform-based approach to translational development

3:00 pm Chair’s Closing Remarks