7:30 am Check-In & Coffee Networking
8:25 am Chair’s Opening Remarks
Optimizing Preclinical Development to Accelerate Progression to the Clinic
8:30 am Panel Discussion: Improving Safety & Efficacy Data by Rethinking Large Animal Models
Synopsis
- Outlining the holdbacks of non-human primates from a cost, time, and ethical standpoint
- Emphasizing how utilizing pig models for safety and efficacy tests addresses the challenges presented by non-human primate use
- Highlighting that regulators do not always require the use of non-human primate models
9:30 am Redefining Preclinical Strategy: Leveraging Humanized Mouse Models to Accelerate Regulatory Pathways for CNS Gene Therapies
Synopsis
- Highlighting engineered AAV capsids that effectively cross the blood-brain barrier by targeting human receptors
- Engineering capsids with specificity to a human receptor can render humanized mice highly effective for biodistribution, toxicity, and efficacy studies that are both translationally relevant and cost-efficient
- Streamlining to a single-species preclinical model reduces development time, ethical burden, and barriers to IND submission
10:00 am Building Next Generation Platforms for Gene Therapies: Novel Solutions to Address Common Development Challenges
Synopsis
- Developing and adopting simplified, scalable state-of-the-art platforms to fulfill demand needs for commercial gene therapy manufacturing.
- Evaluating innovative approaches to address the current lack of robust analytics to achieve comprehensive characterization of gene therapy product.
- Introducing potential alternative gene therapy platforms to counter concerns around viral vector safety and toxicity.
10:30 am Morning Refreshment Break & Speed Networking
11:30 am Accelerating Clinical Impact with Novel AAV Vectors Designed for Enhanced Delivery to Eye, Muscle, & CNS
Synopsis
- Applying AI to design AAV capsids with optimized transduction efficiency for eye, muscle, and CNS delivery to facilitate enhanced clinical outcomes
- Validating capsid performance in NHPs to ensure safety, efficacy, and effective translation of novel capsids
- Demonstrating delivery to specific cell populations to motivate accelerated development of more effective treatments for rare and common diseases
Evaluating Factors Impacting Immunogenicity & Dosing to Navigate Safety Concerns
12:00 pm Exploring the Benefits of Direct Administration to Lower Dose & Cost
Synopsis
- Evaluating systemic and direct routes of administration for vector therapy
- Outlining the workflow to implement direct administration for CNS indications
- Elevating the safety and cost benefits of direct administration
12:30 pm Roche | Hosting Partner Position
1:00 pm Lunch Break & Networking
2:00 pm Understanding Immunosuppression for AAV Vectors to Improve Safety
Synopsis
- Exploring modifications to AAV vectors which facilitate immune suppression
- Emphasizing how strategies to eliminate immunogenicity improve vector efficacy
- Highlighting how immunosuppression can also enable a reduction in dose
Identifying & Utilizing Effective Payload Design to Improve Vector Efficacy
2:30 pm Optimizing Overall Vector Efficacy with Promoter Selection & Engineering
Synopsis
- Outlining how promoter engineering enhances transgene expression
- Understanding how promoter strength and vector dose affect the predictability of gene therapy
- Exploring effects of promoters on ON-target versus OFF-target gene expression
3:00 pm Afternoon Break & Networking
3:30 pm Engineering Payload to Increase Expression Durability & Lower Doses
Synopsis
- Highlighting current developments and challenges in AAV gene therapy for Hemophilia A
- Emphasizing how engineering the FVIII protein to generate hyperfunctional mutants could enhance expression durability and improve therapeutic efficacy
- Demonstrating an efficient approach to generate hyperfunctional transgenes, enabling lower therapeutic doses and improved durability compared to firstgeneration AAV gene therapies
4:00 pm Developing Site-Specific Gene Integration Technologies to Reverse Genetic Disorders in a Mutation-Agnostic Manner
Synopsis
- Exploring programmable gene integration technologies to enable mutation-agnostic editing strategies
- Engineering integrases for efficient, site-specific gene integration using phage-assisted continuous evolution and rational protein design
- Optimizing editor components and delivery vectors to enhance the therapeutic potential of gene integration technologies
4:30 pm Exploring How Fine-Tuning Expression Levels Better Addresses Specific Indications
Synopsis
- Understanding that different indications require different transgene expression patterns
- Exploring the possibility of transient but durable expression to treat different indications
- Reviewing design techniques which influence expression levels