*All times listed are in EST

Targeting Adult Neurodegenerative Disorders

8:00 am Start of Day

8:30 am Gene Therapy for Parkinson’s Disease: Bridge to the Future

Synopsis

  • Past approaches for Parkinson’s Disease gene therapy: dopamine enhancement, neuromodulation, and neuroprotection
  • An ongoing journey: what we have learned from prior studies and how changes are being implemented in current Parkinson’s Disease gene therapy studies
  • Role of gene therapy as standard of care for patients with Parkinson’s Disease: a vision for how to achieve approvals and beyond

8:50 am Targeting APOE4 to Tackle Alzheimer’s Disease with Gene Therapy

  • Ronald Crystal Founder & Chief Scientific Advisor, Lexeo Therapeutics

Synopsis

  • Exploring the vectors used to target hereditary neurologic disorders
  • Assessing the delivery methods and challenges for AAV
  • Evaluating gene therapy for CLN2 disease and APOE4 Alzheimer’s disease

9:10 am Clinical Trial Update: AAV2-BDNF Gene Therapy in Alzheimer’s Disease

  • Mark Tuszynski Professor & Director, Translational, Neuroscience Institute, UC San Diego School of Medicine

Synopsis

  • Showcasing how BDNF prevents neuronal death, stimulates neuronal function, and builds new synapses in animal models of Alzheimer’s disease
  • Highlighting the AAV2-BDNF gene therapy as the only potential therapy for Alzheimer’s disease that might improve memory by building new synapses
  • Evaluating the administration of AAV2-BDNF under MRI guidance to humans

9:30 am Panel Discussion: Targeting Adult Patient Populations with Neurodegenerative Disorders

  • Amber Van Laar Vice President, Clinical Development , AskBio
  • Ronald Crystal Founder & Chief Scientific Advisor, Lexeo Therapeutics
  • Mark Tuszynski Professor & Director, Translational, Neuroscience Institute, UC San Diego School of Medicine

10:00 am Structured Networking

10:45 am Morning Break

Next Generation Vectors For Improved Cell-Specificity & CNS Tropism

11:15 am Evaluating AAV Delivery for Neuroscience Gene Therapy

  • Junghae Suh Vice President, Gene Therapy Accelerator Unit , Biogen

Synopsis

  • Gene therapy for neuroscience continues to be challenging
  • Discussing AAV capsid considerations for neurological disorders
  • Discovering AAV capsid innovations for improved CNS specificity and tropism

11:15 am Discovery of New AAV Capsids using Barcoded Ancestral Libraries

Synopsis

  • AAV gene therapy is limited by the availability of capsids
  • Identifying divergent capsids by random mutagenesis and structural hypotheses has yielded very few new capsids
  • Affinia uses capsid libraries based on ancestral sequence reconstruction to create libraries with high sequence divergence and high functionality
  • Discussing results of screening barcoded, ancestral libraries

11:55 am Machine Guided AAV Capsid Engineering for Improved CNS Delivery

  • Eric Kelsic Founder & Chief Executive Officer, Dyno Therapeutics

Synopsis

  • Machine-guided capsid engineering represents a new approach to overcome the current challenges of in vivo gene delivery
  • This approach combines three advanced technologies:
    • Next-gen library synthesis
    • Next-gen sequencing
    • Machine learning
  • With this workflow the search for improved capsids can be dramatically accelerated

12:15 pm Panel Discussion: Vector Discovery for Improved CNS Delivery

  • Melissa Kotterman Vice President, Head of Discovery & Engineering, 4D Molecular Therapeutics
  • Junghae Suh Vice President, Gene Therapy Accelerator Unit , Biogen
  • Eric Kelsic Founder & Chief Executive Officer, Dyno Therapeutics
  • Charles Albright Chief Scientific Officer, Affinia Therapeutics

Optimizing Translational Strategies of Doses

11:15 am Considerations for Translational Dose Selection for Gene Therapies

  • Sergey Aksenov Senior, Preclinical & Early Development Pharmacometrics, Novartis Institutes for BioMedical Research (NIBR)

Synopsis

  • Reviewing pharmacological concepts for gene therapy and outline a preclinical dose selection research program for gene therapy programs (i.e what needs to be measured in what species NHP vs other species, what are objectives of NHP biodistribution studies)
  • Describing a mathematical model approach to analyzing data from biodistribution studies, with the goal of informing first-in-human gene therapy dose range
  • Illustrating the modeling approach with NHP data

11:35 am Determining Optimal Dose & Considering Disease Progression for Time of Intervention

Synopsis

  • Determining the dose for first-in-human gene therapy studies
  • Considering the best route of administration
  • Understanding disease progression to optimize the timing of intervention

11:55 am Clinical Trial Strategies in the Rare Neurodevelopmental Disorders: Challenges & Opportunities

Synopsis

  • Summarizing latest thoughts on clinical trial approaches in RNDDs (including Angelman Syndrome, Dup15q Sydrome, Dravet syndrome, Rett Syndrome, Tuberous Sclerosis Complex, CDKL5-deficiency disorder and Fragile X Syndrome)
  • Sharing insights from both industry and academic perspectives on the future of translational medicine for the next generation of therapies in this field
  • Considering not only broader clinical trial design elements relevant to these populations but also of emerging commonalities and opportunities specific to RNDDs more broadly

12:45 pm Lunch Break

Enhancing Preclinical Model Value

1:45 pm Leveraging the Use of Computational Modelling for Biodistribution Studies

  • Bryn Martin Vice President, Research, Precision Delivery, & CSF Sciences, Alcyone Therapeutics

Synopsis

  • Talk details to follow

2:00 pm Optimizing Preclinical Models to Determine Gene Therapy Safety & Efficacy

  • Monica Bennett Head of Gene Therapy Unit, Neuroscience, Novartis Institutes for BioMedical Research (NIBR)

Synopsis

  • Preclinical development of AAV gene therapies for neurological disorders
  • Considerations for the development of AAV gene therapies
  • Preclinical development of AAV gene therapies

2:25 pm Efficacy of Gene Therapy Using a Dual Route of Administration in a Large Animal Model of Batten Disease

  • Jennifer Daily Executive Director, Preclinical Development, Neurogene

Synopsis

  • A large animal model of disease is more clinically translational due to the brain structure and size and CSF flow
  • Selecting the right delivery route is critical for efficacy in alarge animal model
  • A dual route of administration was essential for targeting the major phenotypes characteristic of CLN5 Batten disease

2:45 pm Panel Discussion: Optimizing Preclinical Predictions for CNS Gene Therapies

  • Bryn Martin Vice President, Research, Precision Delivery, & CSF Sciences, Alcyone Therapeutics
  • Monica Bennett Head of Gene Therapy Unit, Neuroscience, Novartis Institutes for BioMedical Research (NIBR)
  • Jennifer Daily Executive Director, Preclinical Development, Neurogene

Approaching the Clinic: Trial Design

1:45 pm The Multiple Ethical Challenges of Designing Pivotal Clinical Trials for Pediatric Rare Neurological Disorders

Synopsis

  • Limitations of randomized controlled trials
  • Limitations of single-arm trials
  • The potential of biomarkers and composite endpoints in rare
    disease

2:00 pm International, Multi-Center, Gene Therapy Trials in Rare Neurological Diseases: Opportunities & Challenges

Synopsis

  • Complex study designs pose operational challenges
  • Regulatory scrutiny of gene therapy trials introduces operational burden
  • Rare conditions and young populations require creative solutions and attention to patient experience

2:45 pm Panel Discussion: Clinical Challenges for Neurological Gene Therapies

3:15 pm Afternoon Break & Networking

Gene Therapy For Neurological Disorders: Toxicity & Safety

4:00 pm Addressing Disease Progression in CNS: Moving from Rare to Common Disorders

  • Gavin Corcoran Chief Research & Development Officer , Sio Gene Therapies

Synopsis

  • How are development paths for more common disease best managed?
  • Key areas of challenge with conducting trials
  • Are endpoints for gene therapies the same as endpoints for small molecules?

4:20 pm Showcasing the Latest CNS Toxicity Knowledge After Direct Parenchymal Administration

Synopsis

  • Assessing the delivery procedure: risks and improvements
  • Exploring local toxicity and AAV capsids, and transgene expression
  • MRI follow-up and evaluation of local tolerance: experience from large animals studies and patients
  • Evaluating the immune reaction and redosing strategies
  • Next steps: disease selection and protocol design

4:40 pm CNS Immunogenicity & Toxicity Panel

Synopsis

  • Discussing the latest CNS immunogenicity data
  • Debating DRG toxicity
  • Translation of toxicity research into the clinic

5:10 pm Biotech Quick-Fire Round

Synopsis

As the gene therapy landscape expands and more companies target the CNS, this session will showcase the latest companies to join the scene with a series of short presentations from the conference attendees.

5:40 pm Chair’s Closing Remarks

6:00 pm Scientific Poster Session

Synopsis

Once the presentations finish, join your colleagues to share your latest neurological research and view your fellow attendees gene therapy progress, to forge new connections and catch up with familiar faces over a drink.

7:00 pm End of Day