8:00 am Coffee & Networking

8:50 am Chairs Opening Remarks

PUSHING THE ENVELOPE: REVOLUTIONIZING NOVEL CAPSID DESIGN FOR SAFETY AND POTENCY

9:00 am Optimizing For On Target Tropism Through Capsid Sequence Design

  • Nerea Zabaleta Instructor, Harvard Medical School and Mass Eye and Ear

Synopsis

• Understanding tropism-related idiosyncrasies of different capsids using ancestral AAV capsid reconstruction.

• De-targeting undesirable tissue tropism to decrease off-site transduction.

• Designing capsid sequences that increase on-target tropism.

9:30 am Solving For AAV Tissue Tropism With The AAVidTM Capsid Discovery Platform

  • David Huss Chief Scientific Officer, Shape Therapeutics Inc.

Synopsis

• The AAVid platform leverages massive diversity libraries to map the AAV landscape directly in NHPs in an unprecedented way

• Machine learning on biological selection data across 48 tissues in 4 NHPs enables identification of sequence features in AAV variants that drive unique tissue tropism profiles

• Tissue tropism profiles (e.g., CNS, heart, CNS + heart, etc.) validation in NHP secondary screening and single-candidate experiments

10:00 am Guiding the Way: Introducing Post-Translational Modifications to Improve On-Target Tropism

Synopsis

• Reviewing the various post-translational chemical modifications for capsids

• Comparing and contrasting different post-translational modifications

• Managing manufacturing issues with chemically modified capsids

10:30 am Developing Organ-Specific Vectors Tailored for A Drug Delivery Medical Device

Synopsis

• Screening for vectors tailored for proprietary medical device

• Aiming for vectors with faster kinetics (i.e. cell entry and expression)

• Expanding technologies to multiple organs

11:00 am Morning Refreshments and Networking

OPTIMIZING THE PAYLOAD FOR ROBUST AND SUSTAINABLE EXPRESSION

11:30 am Development Of Genome Modified Genx, Geny, And Genz AAV Vectors For Improved Transgene Expression

  • Arun Srivastava George H. Kitzman Professor of Genetics and Division Chief, University of Florida

Synopsis

• Single-stranded AAV genome is transcriptionally inactive

• There is no host cell RNA polymerase that can transcribe a single-stranded DNA genome

• Three distinct strategies have been developed to achieve improved transgene expression from ssAAV vectors

12:00 pm Key Design Elements of AAV Cargo Design

  • Sid Kamalakaran Associate Vice President - Genome Engineering & Modeling, Prevail Therapeutics, a wholly owned subsidiary of Eli Lily and Company

Synopsis

• Design of an optimal AAV genome sequence

• Choice of the optimized CDS balancing maximizing potency with other needs such as reducing immunogenicity

• Systems for evaluating potency – in-vitro Vs in-vivo

• Choosing Regulatory elements

• Stuffer sequences for optimally sized AAVs

• NGS tools for characterizing AAV

• Genomes – deploying long read sequencing

12:30 pm Improve The Efficacy And Safety Of AAV-Mediated Gene Silencing And Replacement With Endogenous Promoters

  • Jun Xie Director of Vector Development of Viral Core, Associate Professor, UMass Medical School

Synopsis

• Brief overview of the promoter selection in AAV gene therapy

• Endogenous Human SMN1 Promoter-driven Gene Replacement Improves the Efficacy and Safety of AAV9-mediated Gene Therapy for Spinal Muscular Atrophy

• Astrocyte-restricted Gene Silencing Improves the Safety of AAV9-mediated Gene Therapy for Alexander Disease

1:00 pm Lunch & Networking

2:00 pm More Than Meets the Eye: Designing Mini Genes for Ocular Disorders

Synopsis

• Optimizing for effective transgene delivery to the eye

• Challenges faced during creation of mini genes for ocular disorders

• Showcasing new data in Iveric’s mini-gene portfolio

2:30 pm Engineering the Payload to Control When, Where, and Wow Much We Express

  • Sisi Chen Senior Director of Platform Technologies, Apertura Gene Therapy

Synopsis

• Genetic regulatory elements (GREs) in the payload can be used to target cell types and modulate expression

• Challenges in identifying the target payload profile for a given therapeutic application

• New advances in identifying GREs via high-throughput genetically encoded genomics screens

OVERCOMING REGULATORY AND CMC OBSTACLES FOR A SMOOTH TRANSITION TO DOWNSTREAM

3:00 pm Next-Gen Plasmid Design mAAVRx Achieves High-Yield, High-Quality And Potent AAV Vectors In Scalable Suspension Hek293 Cells

  • Jing Liao Director - Vector Operations, Alexion Pharmaceuticals

Synopsis

• Novel plasmid design mAAVRx enhances the AAV manufacturability by increasing crude harvest titer dramatically

• mAAVRx increases the vector purity with higher non-empty capsid%, lower residual plasmid DNA and non-detectable rcAAV contaminants

• mAAVRx maintains the potency of the vector both in vitro and in vivo

3:30 pm Afternoon Networking Break

4:00 pm Developing Strong Assays and Processes In-House To Ease CMC Costs And Time

  • Aditya Wakankar Vice President - Chemistry, Manufacturing & Controls Strategy Program Management, Sangamo Therapeutics

Synopsis

• Why is it necessary to develop strong pre-CMC assays in-house

• Integration of in-house processes with outsourced manufacturing

• Showcase of manufacturing capabilities

4:30 pm Regulatory Hurdles Faced by Novel Capsid Designs

  • Eduard Ayuso Chief Executive & Technology Officer, DINAQOR

Synopsis

• Understanding the regulatory idiosyncrasies of novel vector designs

• Reviewing regulatory challenges for safety and toxicity for novel vectors

• Examining manufacturing considerations

5:00 pm Chairs Closing Remarks