8:00 am Check-In & Coffee Networking
8:55 am Chair’s Opening Remarks
Optimizing Preclinical Development to Accelerate Progression to the Clinic
9:00 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
10:00 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
10:30 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
11:45 am
Addressing Off-Target Toxicity to Improve Vector Efficacy & Safety
12:00 pm Utilizing Payload to Harness Tissue Specificity for CNS Vector Therapies
Synopsis
- Discussing the strategies used to regulate transgene expression cassettes for AAV vectors targeting the CNS
- Exploring how fine-tuning payload expression enhances tissue tropism, safety, and efficacy for CNS indications
- Revealing some of the considerations needed to increase the tissue tropism of viral vectors
12:30 pm Roche | Hosting Partner Position
1:00 pm Lunch Break & Networking
2:00 pm Exploring Enzymatic Conjugation as a Capsid Design Approach to Improve Vector Targeting
Synopsis
- Understanding the approach of enzymatically conjugating chemicals or biologics to the AAV capsid
- Highlighting how this rational design approach can increase tissue tropism and eliminate liver targeting
- Emphasizing how increasing specificity also improves potency and limits toxicity
2:15 pm
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
4:00 pm Evaluating Expression Cassette Composition to Harness Payload Expression
Synopsis
- Understanding the benefits and risks of using elements from various viruses in expression cassette design
- Comparing these benefits and risks to the use of native elements and their respective impacts on vector efficacy and safety
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