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
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 Virtual: 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 Mastermind: Developing more Durable Gene Therapies
Synopsis
Gene therapy durability is intrinsically linked to their safety and efficacy. This mastermind 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 Speaking Position Reserved for Beacon Targeted Therapies
10:00 am Virtual: Strategies to Improve the Safety Profile of AAV Mediated Gene Therapies
Synopsis
Talk details to be confirmed
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
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 Virtual: Identifying and Establishing Biomarkers for Complex Rare Diseases
Synopsis
- Validating biomarkers to contribute to defining clinical endpoints
- Balancing standard biomarkers and novel ones – time versus effectiveness
- Predicting real-time efficacy with the patient journey at the centre
2:00 pm Mastermind: 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 mastermind will delve into dosing challenges across:
- Comparative dosing in different animal models
- Systemic vs local dosing
2:45 pm Chair’s Closing Remarks
