*All times are in EDT

9:20 am Chair’s Opening Remarks

DISCOVERING THE FUTURE OF NEXT GENERATION GENE THERAPY VECTORS: WHERE ARE WE HEADING?

9:30 am Developing Next Generation Vectors to Treat Pediatric Patients

  • Nelson Chau VP, Discovery Biology and Translational Research, LogicBio

Synopsis

  • Current vector technologies are not suitable for liver targeted indications in pediatric patients as hepatocyte proliferation results in loss of transgene expression
  • By precisely inserting a corrective transgene into the genome through the GeneRide technology, durable transgene expression can be achieved
  • Highlighting current data on GeneRide as the next generation of gene therapy technologies

10:00 am Delivering Close-Ended DNA for Next-Generation Non-Viral Gene Therapy

Synopsis

  • Utilizing LNPs to deliver gene therapies – POC in mouse disease model, NHP translation
  • Understanding specific disease areas/cell types where ceDNA would offer significant advantages over viral approaches
  • Solving challenges associated with cell-specific targeting using LNPs
  • Non-viral approaches can avoid limitations associated with payload size and immunities of AAVs

 

10:30 am Assessing the Big Pharma Approach to Next Generation AAV Development & Implementation

Synopsis

  •  Understanding the dynamics between big pharma and other key stakeholders when reviewing external opportunities for improved technologies/new modalities
  • Working with external organizations as well as internal efforts in the context of assessing translatability of vectors
  •  What key criteria do big pharma use to assess which vectors to use and progress in gene therapy development?

11:00 am Morning Break & Networking

11:05 am

DEVELOPING TRANSLATABLE VECTORS TO PROGRESS INTO THE CLINIC

11:30 am Characterizing the Proteomic and Epigenomic Landscape of AAV

  • Nicole Paulk Assistant Professor, Biochemistry & Biophyiscs, University of California San Francisco

Synopsis

  • First, publicly available, unbiased ‘omics characterization of AAV
  • Detailed comparison of biochemical differences in AAV by production platform
  • Key insights for choosing a vector production platform

12:00 pm Transcriptome-Based Quantification of AAV Variants with Single- Cell Resolution

  • Leah Byrne Assistant Professor of Ophthalmology, University of Pittsburgh

Synopsis

  • Although the choice of vector is critical for successful clinical translation, accurate and quantitative comparison of AAVs, especially in primates, remains challenging
  • We have developed scAAVengr, a single-cell AAV engineering pipeline to simultaneously quantify and rank efficiency of competing AAV vectors across all cell types in parallel, in the same animals
  • Transcriptome based-quantification of AAV-mediated gene expression allows for precise evaluation of AAV performance and determination of vector tropism, as well as the development of novel AAV vectors for rapid and efficient clinical translation

12:30 pm Lunch & Networking

1:30 pm Virtual Roundtables: Developing Translatable Vectors: Key Considerations

Synopsis

Even if a vector is designed which shows high efficiency and targeting, there are still barriers in translating this effectively to the clinic. Whether thinking about complexity of the vector and therefore ease of manufacturing, or understanding if performance in mouse models is an accurate indicator of performance in humans, several factors influence what will make for a successful vector to proceed into clinical trials. This set of roundtables will explore some of the key considerations when developing not only a specific and effective vector, but a translatable one.

Predicting Translatability Assessing Manufacturability Navigating Regulatory Considerations

 

 

2:30 pm Afternoon Break & Networking

OVERCOMING THE SIZE LIMITATIONS OF AAV VECTORS

3:00 pm Strategies to Tackle Gene Therapy for Large or Alternatively Spliced Genes

  • Hemant Khanna Associate Professor, University of Massachusetts Medical School

Synopsis

  • Current AAV vectors are limited in capacity
  • Several therapeutic targets would require presence of functional genes which are too large for AAV
  • Addressing AAV payload size through developing minigenes is a promising option for several diseases, including Duchenne Muscular Dystrophy

3:30 pm Developing Dual Vector Systems to Deliver Larger Genes to Target Cells

  • Vivian Choi Head of Global Gene Therapy Research, Takeda

Synopsis

  • Dual vector system is an approach to expand the packaging size of AAV vectors by exploiting the natural molecular mechanism of AAV vector genome concatemerization
  • Pros and cons of using a dual AAV vector system versus single AAV vectorsystems and other viral and non-viral delivery systems
  • Approaches that could increase efficiency of dual vector system described in the field
  • Considerations for developing dual vector as a drug product: Product characterization, potency, fill & finish considerations and clinical
    administration

4:00 pm Chair’s Closing Remarks

  • Robert Kotin Adjunct Professor, University of Massachusetts

4:10 pm End of Day Two & Close of Conference