Pre-Conference Workshop Day
December 5, 2023
Systemic Drug Delivery & BBB-Crossing Technologies
Direct Administration Routes & Delivery Devices
7:30 am Registration & Breakfast
8:30 – 10:30 amWorkshop A
Getting Back to Basics: Fundamental Principals of Blood-Brain Barrier Properties Under Normal & Disease Conditions
- Max Nowak Senior Scientist, Viridian Therapeutics
- Sabyasachi Dash Senior Scientist, Alexion-AstraZeneca Rare Disease
Synopsis
Before developing novel therapies in the hope to achieve BBB penetration, it is critical to address fundamental gaps in the understanding of blood-brain barrier biology, permeability, and transcytosis mechanisms.
• How can we evolve knowledge of normal BBB anatomy, receptor expression and functionality before progressing to disease conditions?
• How can we harness in vivo model systems to capture changes in BBB and validate gene expression observations from human samples to understand disease-induced alterations to the BBB?
• What can be learned from past failings to inform future design of carrier systems based on underlying disease processes and biology?
11:00 – 1:00 pmWorkshop C
Searching Beyond Transferrin Receptor 1 for Brain Endothelial Cell-Specific Facilitators of Antibody Delivery Across the Blood-Brain Barrier
- Adem Koksal Scientific Director, Biologics Drug Discovery, Biogen
- Habib Baghirov Scientific Lead, Roche
Synopsis
Ubiquitous expression of TfR1 continues to hold back specific and efficient uptake of antibodies targeting the CNS, therefore enhancing the need for receptors selective for BECs to prevent peripheral toxicity.
• What are the efforts going into identifying new receptors and steering the transcytosis activity of specific receptors to a particular tissue?
• How can we mitigate challenges of peripheral exposure associated with transferrin receptor-mediated delivery?
8:30 – 10:30 amWorkshop B
Unlocking Deeper Brain Targets: Optimizing Intraparenchymal Convection-Enhanced Delivery for Greater Precision & Efficacy
- Stephan Mittermeyer Vice President, Therapeutic Strategies, CNS Gene Therapy, AskBio
- Fergus Quigley Director, Device Development Lead (Early Stage Development), Takeda
- Smrithi Padmakumar Drug Product Development Senior Scientist, Spark Therapeutics
Synopsis
CED shows great promise to combat brain tumors and neurodegenerative disorders by enhancing drug distribution throughout brain parenchyma. Trials must, however, be carefully constructed for widespread clinical adoption.
• What are currently the unmet needs and barriers that prevent large scale translatability of this type of delivery?
• What are the variables to account for when developing protocols for delivering therapeutics directly into the parenchyma?
• How can complications associated with intraparenchymal CNS administration be mitigated to streamline clinical practicalities?
11:00 -1:00 pmWorkshop D
Lost in Translation: Replicating Proof-of-Concept Studies for Intra-CSF Delivery Methods in Clinical Practice
- Jeff Kurz Associate Director, Alnylam Pharmaceuticals
- Darin Falk Chief Scientific Officer, Lacerta Therapeutics
Synopsis
Physiological cross species differences remain a critical barrier to scaling up doses across in vivo intra-CSF studies, therefore emphasizing the need to enhance translatability of rodent and non-human primate models to study CNS drug delivery.
• How can we navigate differences in quality and preparation standards to successfully scale up injection doses from mouse to non-human primate to human?
• How do you determine successful delivery in animal brains and how does this translate to human models displaying different disease properties?
• How can we enhance translatability of imaging studies in animals to visualize drug biodistribution?
1:00 pm Lunch
2:00-4:00 pmWorkshop E
Revolutionizing AAV Delivery Platforms: Minimizing Immunogenicity and Maximizing Biodistribution for Enhanced Brain Targeting
- Kate Henry Senior Scientist in Gene Therapy Accelerator Unit, Biogen
- Christopher Octeau Senior Scientist, Capsida
Synopsis
Despite notable promising efforts to achieve brain-wide transduction in mice and monkeys, developing a BBB-crossing capsid remains an unsolved problem.
• How can we translate successful cases of AAV delivery in vivo into clinical programs and overcome challenges of cross species differences in capsid property requirements?
• Which features of capsid design should be improved to enhance BBB penetration efficiency and frequency of neuronal uptake?
• How do we establish a successful balance between sufficient dose levels and peripheral immunogenicity?
2:00 – 4:00 pmWorkshop F
Enhancing Therapeutic Distribution Beyond Areas Adjacent to the Site of Intra-CSF or Intranasal Administration
- Keri Kasun Associate Medical Director, Biogen
- Aloïse Mabondzo Co-Founder, CERES Brain Therapeutics
- Bryn Martin Vice President of Research, Drug Delivery, and CSF Sciences, Alcyone Therapeutics
Synopsis
To maximize potential of intra-CSF or intranasal delivery, it is important to overcome barriers imposed by neuroanatomy and CSF flow to aid diffusion to deeper brain regions.
• How can we deepen exposure to concentrated regions, such as the mid brain and striatum, following direct dosing into the CSF or nasal cavity?
• Which cases are most beneficial to consider IT, ICV or IN dosing over systemic delivery?