DAY TWO - Thursday July 18, 2024
8:00 am Morning Networking Coffee
8:50 am Chair’s Opening Remarks
ESTABLISHING CRITICAL UPFRONT CONSIDERATIONS FOR EFFECTIVE POTENCY ASSAY DESIGN TO STRENGTHEN REGULATORY SUBMISSIONS
9:00 am Designing Activity Assays for Non-Enzymatic/Structural Protein Products to Confidently & Robustly Measure Potency
Synopsis
- Generating a release assay for measuring downstream protein effects to supplement binding assays and prove potency
- What kind of in vitro assays are acceptable? Assessing and clarifying agency expectations on binding assay data versus gene-knockdown versus true activity assays
- Establishing alternative assays to prove that binding studies are meaningful and indicative of potency
9:30 am (NEW DATA) Designing a Potency Assay for a Product with a Complex or Unknown Mechanism of Action to Mimic In Vivo Function & Satisfy Regulators
Synopsis
- Brainstorming approaches for developing a functional potency assay for proteins with a complicated or unknown function in vivo
- How many protein read-outs are necessary for products undergoing posttranslational modifications or other structural changes?
- Determining the stage of development from which multiple protein assays are required to anticipate and overcome the regulatory challenge
10:00 am Enhancing Cell-Based Potency Assay Sensitivity to Overcome Limited Viral Vector Quantity
Synopsis
- Enhance the transduction efficiency to improve transgene expression
- Evaluate the impact of full/partial/empty vector on potency
- Using potency assays to facilitate the process development optimization
10:30 am ROUNDTABLE: Overcoming Limited Viral Vector Quantity to Create Appropriate Reference Standards Upfront
Synopsis
Roundtable discussions include a larger focus on group discussion. A moderator will introduce the session topic and attendees then split into groups to discuss a series of predetermined agenda points. At the end, all groups report back on their discussions, and findings are collated.
This roundtable will cover:
- Balancing quality with quantity of reference standards – How do you ensure sufficient quantity of viral vectors for clinical supply?
- Selecting appropriate cell lines in the generation of reference materials
- Establishing protocols for dealing with small batches of reference standards and low sample numbers
11:15 am Morning Refreshments & Networking
MINIMIZING VARIABILITY & INCREASING SENSITIVTY TO ENHANCE CELL-BASED POTENCY ASSAYS
12:00 pm Development of Potency Assays for AAV Encoded Transgenes Under the Control of Tissue-Specific Promoters
Synopsis
- Dual reporter-gene assay, highly specific
- Frozen assay-ready format, low variability, large dynamic range
- No need for adeno helper virus
12:20 pm ROUNDTABLE: Selecting Appropriate Cell Lines During Potency Assay Development to Maintain Biological Relevance & Reflect Potency In Vivo
Synopsis
Roundtable discussions include a larger focus on group discussion. A moderator will introduce the session topic and attendees then split into groups to discuss a series of predetermined agenda points. At the end, all groups report back on their discussions, and findings are collated.
This roundtable will cover:
- Discussing the factors influencing the appropriate selection of transducible cell lines for batch testing
- Comparing the relative advantages and disadvantages of working with immortalized versus primary cell lines for potency testing
- Overcoming limitations associated with utilizing vectors with high specificities in their tropism
- Understanding the importance of measuring transduction efficiency on your selected cell line to determine biological relevance
1:00 pm Networking Lunch
2:00 pm Human 3D Tissue Models for Functional Potency
Synopsis
- Advantages of human 3D tissue models for functional potency assessment
- Biomarkers aren’t enough anymore: enter clinically translational functional assays
- Best practices for implementing these technologies
2:30 pm (NEW DATA) Develop MoA-Based Potency Assay for a Highly Glycosylated Structure Protein
Synopsis
- Developing a quantitative and high throughput functional potency assay for a highly glycosylated structure protein
- Overcoming limitations associated with vectors with muscle-specific promoter
- Enhancing assay signal windows to facilitate assay development
2:50 pm Insight, Improvement, and Qualification for Infectivity Assay for AAV products
Synopsis
- The importance of ITA assay in AAV product characterization and the assay design
- Improvements to solve commonly faced issues affecting infectivity assays with high throughput approaches
- Method Qualification: strategy, parameters and results
3:20 pm Afternoon Networking Break
DESIGNING POTENCY ASSAYS FOR NOVEL GENE THERAPY MODALITIES
3:50 pm Outlining the Key Considerations for Developing Potency Assays for Arenavirus-Based Gene Therapy Products Meet Regulatory Demands
Synopsis
- Outlining the emergence of gene therapy modalities beyond traditional AAV approaches
- Evaluation of appropriate potency assays to reflect the Mode of action of arenaviral therapeutics
- Why T cells matter – challenges in the development of CD8+ T cell activation assays
4:20 pm Developing a Potency Assays Strategy for a Novel Human Bocavirusbased Gene Therapy
Synopsis
- What is human bocavirus and why is it is suitable vector for gene therapies against Cystic Fibrosis?
- Utilising an Ussing chamber chloride ion current as a novel functional assay to assess potency
- Reflecting on the lessons and learnings from using a novel vector approach to overcome developmental hurdles upfront