8:00 am Registration & Refreshments
8:20 am Chairs Opening Remarks
ASSESSING DELIVERY OPTIONS FOR CNS & NEURONAL TARGETED GENE THERAPIES
8:30 am PANEL: Assessing the Realities, Challenges & Opportunities of CNS Drug Delivery
Synopsis
- Metanalyses of relevant safety & biodistribution clinical data for delivery options
- Overcoming translational challenges with novel devices to ensure consistency & satisfy regulators
- Uncovering next generation devices for CNS administration
9:00 am AAV-ARSA Mediated Gene Replacement for the Treatment of Metachromatic Leukodystrophy
Synopsis
- AAV delivery strategies for the treatment of MLD
- Capsid and route of administration selection for CNS disorders
9:30 am Optimizing Delivery of CNS Gene Therapies; Considerations for Safety & Efficacy
Synopsis
- Comparison of different delivery devices
- Correlation of brain coverage vs. efficacy
- Discussion of how to minimize local trauma and inflammation after delivery of the AAV
10:00 am Solutions for Delivery of Gene Therapies to the Nonhuman Primate Central Nervous System
Synopsis
- Different routes of administration (CSF vs. parenchymal)
- Surgical workflow options for intracranial delivery in NHPs (OR vs. MRI-based)
- Considerations for anesthesiology, recovery, and behavioral follow up
10:30 am Speed Networking
Synopsis
This session is a great opportunity to introduce yourself to the attendees that you would like to have more in depth conversations with. This session is the ideal opportunity to get face-to-face time with many of the brightest minds working in the Gene Therapy field and establish meaningful business relationships.
11:00 am Morning Refreshments
DISCOVERY & PRECLINICAL TRACK Track Chair: Alison Shottek, Senior Project Manager – Preclinical Programs, Modalis Therapeutics
DEVELOPING NEUROLOGICAL BIOMARKERS IN THE PRECLINICAL SETTING FOR MORE EFFECTIVE MEASURES OF TRANSDUCTION & EFFICACY
11:30 am PANEL: How Do We Know Our Therapy Works?
Synopsis
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- Assessing the preclinical development of biomarkers to demonstrate efficacy and aid clinical translation
- What are key hurdles prohibiting effective assessments of preclinical efficacy for CNS targeted gene therapies and how can biomarkers be leveraged to tackle such challenges?
- How can we leverage technological innovation within the digital biomarkers field to better determine therapeutic response?
12:30 pm Systemic Metachromatic Leukodystrophy Gene Therapy Leading to Disease Prevention in Arsa Ko Mice
Synopsis
- Selection of capsid and route of administration with a strong focus on the CNS
- Biomarker correlation vs. prediction of motor benefit
- Translation to larger species (NHP)
TRANSLATIONAL & CLINICAL TRACK
ASSESSING BIODISTRIBUTION & SAFETY IN THE CLINICAL SETTING
11:30 am A Novel Gene Therapy Targeting APOE4 Associated Alzheimer’s Disease
Synopsis
- The role of APOE in the pathogenesis of Alzheimer’s disease
- The basis of a gene therapy approach in APOE4-associated Alzheimer’s disease
- The Phase 1 clinical trial in APOE4 homozygotes with Alzheimer’s disease
12:00 pm Key Challenges & Considerations in the Transition from Pre-clinical to FIH clinical studies in Neurologic indications
Synopsis
The plan for this expert panel discussion is to focus on the challenges and considerations that companies face as the emerge from Discovery/Pre-clinical work and plan to enter First in Human (FIH) studies requiring support from their GMP manufacturing programs/partners, clinical development, and engagement with patient communities in the planning and early execution of clinical research.
12:30 pm A Phase 1 Clinical Trial of AAV2-BDNF Gene Therapy in Alzheimer’s Disease and MCI
Synopsis
- Prior growth factor gene therapy experience in Alzheimer’s disease
- Preclinical rationale for translation to the clinic
- Clinical update
1:00 pm Lunch & Networking
DISCOVERY & PRECLINICAL TRACK
ASSESSING BIODISTRIBUTION & SAFETY IN THE PRECLINICAL SETTING
2:00 pm Developing a Gene Therapy for the Treatment of Autosomal Dominant Alzheimer’s Disease
Synopsis
- Scientific rationale for a gene replacement approach in ADAD
- Demonstrating preclinical proof-of-concept in mouse models and human cell lines
- Effective CNS biodistribution and safety in nonhuman primates
2:30 pm AAV-Ligand Conjugates for Improved Efficacy & Biodistribution in CNS
Synopsis
- AAV capsids from 1st and last generations limitations (efficiency and safety) are related to the nature of the capsid composition
- Chemical conjugation of AAV capsid alter dramatically the biology of AAV leading to improve bio distribution, transduction and immunological profile
- Chemical conjugation of AAV is a versatile and scalable new capsid technology
TRANSLATIONAL & CLINICAL TRACK
ASSESSING THE EFFICACY OF YOUR PRODUCT IN THE CLINICAL SETTING
2:00 pm Improving Neuronal Gene Transfer to the Brain After CSF Administration of AAV9 in Large Animal Models
Synopsis
- Biodistribution results will be presented from studies carried
out in juvenile NHP and pig models - Comparison of lumbar IT vs ICM delivery routes as well as
constitutive vs neuronal specific promoters in NHP - Optimization of factors such as dose volume, flush volume,
and physical positioning
2:30 pm Strategy for selection of clinical doses for SBT101, a gene therapy for the treatment of adrenomyeloneuropathy (AMN)
Synopsis
- Selection of AAV vector and delivery for AMN
- How target engagement and efficacy studies supported starting dose
- Safety studies further supported dose selection
3:00 pm Afternoon Refreshments & Poster Session
EXPLORING STRATEGIES TO ENHANCE CELL TARGETING & EFFICACY IN THE PRECLINICAL SPACE
3:30 pm TFRC-Targeted GAA Delivered as Gene Therapy Treats CNS & Muscle in Pompe Disease Model Mice
Synopsis
- Design and selection of anti-TFRC antibody fused to GAA
- Delivery of anti-TFRC:GAA as a liver depot gene therapy in Pompe disease Gaa-/- mice results in targeted uptake of GAA protein in need-to-treat tissues, including key cell types in the brain
- Anti-TFRC:GAA rescues glycogen storage in CNS, heart, and skeletal muscle in Gaa-/- mice
4:00 pm Preclinical Development of a Gene Therapy for Frontotemporal Dementia (FTD)
Synopsis
- FTD-GRN and clinical hypothesis
- Preclinical development and efficacy data
- IND enabling and safety data
4:30 pm High Efficiency RNA Editing Gene Therapy for the Treatment of Neurological Disorders
Synopsis
- Redirecting the fully human, endogenous ADAR enzyme enables site-specific RNA editing to correct point mutations, control RNA splicing or modulate protein expression and function. Importantly, this is done without risk of DNA damage or foreign protein immunogenicity
- The RNAfixTM technology platform combines high throughput screening with generative machine learning models to produce highly efficient and specific ADAR-recruiting gRNAs for any clinically-relevant target, including those in sequence contexts that are naturally disfavored by the ADAR enzyme
- Neurological disorders are particularly amenable to an RNA editing therapeutic approach due to high expression of both ADAR1 and ADAR2 enzymes
- Application of the RNAfix technology in Parkinson’s disease will be highlighted
5:00 pm AAVrh10-based Gene Therapy for the Treatment of Frontotemporal Dementia Caused by GRN Mutations
Synopsis
- Dominant mutations in granulin (GRN) gene accounts for up to 10% of frontotemporal dementia (FTD) and results in > 50% reduction of progranulin (PGRN) expression in patients
- Adeno-associated virus (AAV) gene therapy to booster the levels of progranulin may represent a feasible strategy to treat FTD-GRN
- AGTC-601 is an AAV gene therapy to supplement progranulin expression in brain to treat FTD-GRN and shows promising efficacy and safety profile
5:30 pm Chair’s Closing Remarks
5:35 pm Conference Ends
