8:50 am Chairs Opening Remarks

EXPLORING NOVEL VECTORS FOR CNS-CELL SPECIFIC TARGETING

9:00 am Enhancer-AAVs to Express Transgenes in Defined Brain Circuits for Therapeutic Intervention

  • Boaz Levi Associate Investigator - Human Cell Types, Allen Institute

Synopsis

  • Analysis of detailed genomic datasets to reveal enhancers throughout the brain
  • A discovery platform for enhancer-AAV creation and testing
  • New collections of enhancer-AAVs that express transgenes in defined brain circuits
  • Validation of enhancer-AAVs in the multiple species

9:30 am Screening & Selection of the Perfect Vector – An Impossible Challenge

  • Roger Chung Chief Scientific Officer, Celosia Therapeutics

Synopsis

  • Large diversity of research vectors available, but few are clinically approved
  • Importance of well-designed vector screening program
  • Surprising findings from a 60+ vector screen

10:00 am Gene Therapy for Alzheimer’s Disease: The Tale of Two Capsids

  • Anindya Sen Director - Pre-Clinical Research & Development, Prevail Therapeutics

Synopsis

  • Identification of disease relevant, cell type specific capsids for AD gene therapy
  • Mouse efficacy studies for proof of vector
  • Translational path for novel capsid function in NHP and minipigs

10:30 am Morning Refreshments

DISCOVERY & PRECLINICAL TRACK

SEEKING BETTER TRANSLATION OF DOSE SIZE & TRANSDUCTION IN THE PRECLINICAL SETTING

11:30 am Efficacy & Safety of a Tissue-Restricted AAV Vector Encoding Frataxin

  • Edgar Rodriguez Chief Executive Officer & Co-Founder, Lacerta Therapeutics

Synopsis

  • Ubiquitous overexpression of the frataxin protein, which is deficient in Friedreich’s ataxia (FA), can lead to toxicity, negating the potential therapeutic benefit of a gene therapy approach to FA
  • Tissue restricted expression of AAV-delivered frataxin is a viable approach to overcoming toxicities and achieve full therapeutic benefit
  • The efficacy and safety of this approach, from rodent models to NHPs, will be presented and discussed

12:00 pm CRISPR/Cas9 as a Novel Gene Therapy Tool for Dominantly Inherited Forms of Neurodegenerative Disorders

  • Martin Ingelsson Professor & Clinician Scientist, Tanz Centre for Research In Neurodegenerative Diseases, University of Toronto

Synopsis

  • Cell model based assessment of CRISPR/Cas9 as treatment of familial Alzheimer’s disease and Parkinson’s disease
  • Mouse model based assessment of CRISPR/Cas9 as treatment of familial Alzheimer’s disease and Parkinson’s disease
  • Challenges ahead before CRISPR/Cas9 can be assessed in clinical trials on patients with neurodegenerative disorders

TRANSLATIONAL & CLINICAL TRACK

BETTER UNDERSTANDING INNATE & ADAPTIVE MANIFESTATIONS OF IMMUNE RESPONSES IN THE CNS TO BETTER TARGET NEUROLOGICAL DISORDERS

11:30 am Insight into Innate Immune Barriers Against AAV in the Human CNS

Synopsis

  • Relevance of cell intrinsic innate immunity in AAV gene therapy
  • Innate immune sensing and signaling triggered by AAV in cells of the human CNS
  • How innate antiviral restriction factors may impact efficacy of AAV gene therapy

12:00 pm Systemic Administration of Novel Engineered AAV Capsids Facilitates Enhanced Transgene Expression in the Macaque CNS

  • Allie Stanton Phd Candidate - Pardis Sabeti Lab, Harvard Medical School

Synopsis

  • Utilizing an mRNA-based selection strategy to select novel capsids with enhanced tropism for the CNS after intravenous delivery
  • We identified the novel PAL family of capsids which have enhanced CNS targeting and reduced liver tropism in 2 year old cynomolgus macaques
  • We found that a diverse set of capsids potent in the murine CNS were universally ineffective in macaques

12:30 pm Lunch & Networking

DISCOVERY & PRECLINICAL TRACK

LEVERAGING CAPSID ENGINEERING TECHNIQUES TO DEVELOP BETTER NEURONAL TARGETED VECTORS

1:30 pm Utilizing the STRIVE Platform to Engineer Novel CNS AAV Variants

Synopsis

  • Overview of STRIVE, StrideBio’s structure-driven engineering platform
  • Development of STRV5, a novel, neurotropic AAV variant with an improved safety profile
  • Expanding the STRIVE Platform and StrideBio capsid arsenal

2:00 pm Mechanobiological Modulation of the Blood-Brain Barrier by Laser Stimulation of Vascular Targeted Nanoparticles

  • Zhenpeng Qin Associate Professor of Mechanical Engineering, University of Texas at Dallas

Synopsis

  • Reversibly modulating the blood–brain barrier by laser stimulation of molecular-targeted nanoparticles
  • Modulation of blood-brain-tumor barrier permeability enhances drug penetration and treatment efficacy in diverse preclinical glioblastoma models
  • Minimally invasive delivery of peptides to the spinal cord for behavior modulation

TRANSLATIONAL & CLINICAL TRACK

OPTIMIZING CLINICAL TRIAL DESIGN

1:30 pm Comparing & Contrasting Clinical Trial Design for Neurodegenerative & Neurodevelopmental Disorders

  • Heather Lau Executive Director, Ultragenyx Pharmaceutical

Synopsis

  • Focusing on endpoint development
  • How to adapt the interpretation of similar assessments to a degenerative process vs a static encephalopathic process

2:00 pm Genetic Approaches to Parkinson’s Disease: Start Small to Go Big

Synopsis

  • Genetic forms of Parkinson’s disease provide mechanistic insight into idiopathic disease pathogenesis
  • Therapies based on genetic targets can translate into efficacy in the idiopathic population
  • Clinical strategies are streamlined using genetic populations to demonstrate first-in-human POC,
    facilitating demonstration of efficacy in the broader, more heterogeneous population

2:30 pm Afternoon Refreshments & Networking

TACKLING STAKEHOLDER COLLABORATION CHALLENGES TO GET PRODUCTS TO MARKET FASTER

3:00 pm Academic, Biotech, & Pharma Partnerships To Advance Gene Therapy Drug Development for Neurological Disorders

Synopsis

  • Introduction: rare disease landscape
  • How pharma may help to facilitate success in rare diseases through its collaboration with academia, biotech & venture

4:00 pm PANEL: Optimizing Collaboration Across Stakeholder Groups to Expedite Drug Development in the CNS Space for Gene Therapies

  • Kristin Stephenson Director - Strategy & Alliances, St. Jude Children’s Research Hospital
  • Amy Brin Executive Director & CEO, The Child Neurology Foundation
  • Brittany Hernandez Executive Vice President, Crossroad Strategies

Synopsis

  • Hear perspectives and join the discussion about how various stakeholder groups including patient advocacy, researchers and research institutions, and industry cooperate in the development space
  • Where do the current hurdles lie in terms of optimizing collaboration between stakeholder groups?
  • How can stakeholder groups leverage collaboration to get products to the market and patients faster?

5:00 pm Chairs Closing Remarks

5:10 pm End of Conference Day Two