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 Session Reserved for Expertise Partners: Clearpoint

Synopsis

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

DEVELOPING NEUROLOGICAL BIOMARKERS IN THE PRECLINICAL SETTING FOR MORE EFFECTIVE MEASURES OF TRANSDUCTION & EFFICACY

11:30 am Session Reserved For Meeting Partners PPD

Synopsis

PPD Sponsor

12:00 pm PANEL: How Do We Know Our Therapy Works?

Synopsis

  • 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?

TRANSLATIONAL & CLINICAL TRACK

ASSESSING BIODISTRIBUTION & SAFETY IN THE CLINICAL SETTING

11:30 am A Novel Gene Therapy Targeting APOE4 Associated Alzheimer’s Disease

  • Jay Barth Chief Medical Officer, Lexeo Therapeutics

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 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

12:30 pm A Phase 1 Clinical Trial of AAV2-BDNF Gene Therapy in Alzheimer’s Disease and MCI

  • Mark Tuszynski Professor, University of California, School of Medicine

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 Systemic Metachromatic Leukodystrophy Gene Therapy Leading to Disease Prevention in Arsa Ko Mice

  • Jacinthe Gingras Senior Director - Ophthalmology & Neurology, Homology Medicines

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)

  • Karen Kozarsky Founder Chief Scientific Officer, Swan Bio Therapeutics

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 & Networking

EXPLORING STRATEGIES TO ENHANCE CELL TARGETING & EFFICACY IN THE PRECLINICAL SPACE

3:30 pm Session Reserved for Meeting Partners: PackGene

Synopsis

3:40 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

4:10 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

4:40 pm High Efficiency RNA Editing Gene Therapy for the Treatment of Neurological Disorders

  • David Huss Chief Scientific Officer, Shape Therapeutics

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

5:10 pm AAVrh10-based Gene Therapy for the Treatment of Frontotemporal Dementia Caused by GRN Mutations

  • Lingzhi Zhao Senior Director - Gene Therapy & Transnational Discovery, AGTC

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

5:40 pm Chair’s Closing Remarks

5:50 pm End of Conference Day One