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
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
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
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
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
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
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
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
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
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
