CONFERENCE DAY TWO
8.00 Check-In, Coffee & Light Breakfast
8:50 Chair’s Opening Remarks
EARLY CLINICAL PROGRESS & FUTURE OPPORTUNITIES: WHERE IS THE CNS DRUG DELIVERY LANDSCAPE HEADING NEXT?
9:00 Reviewing Breakthrough Progress of Brainshuttle Platform in 2024: What’s Next for Brainshuttle TM?
Synopsis
- Translational PK/PD framework for “BrainshuttleTM”: Moving molecules into the Clinic
- Update on the clinical development of the Brainshuttle antibody fusion trontinemab
9:30 Biogen/Alycone ThecaFlex for Intrathecal Delivery of Spinraza
Synopsis
- Outlining the story of ThecaFlex, an intrathecal port catheter, for delivering Spinraza to the CSF Showcasing clinical safety data
- Highlighting future directions to transform access to CNS ASO therapies
10:00 Morning Break & Refreshments
Track 1: Systemic Delivery Chair: Yuan Yuan, Associate Scientific Director, Biogen
REVIEWING NOVEL PROGRESS OF CLINICALLY RELEVANT AAV CAPSIDS WITH ENHANCED CNS TROPISM
11.00 Developing Clinically Translatable Capsids with Enhanced CNS Tropism Through Human Receptor-Targeted Engineering
Synopsis
- Outlining the rational design: genetically fusing a TFR1-targeting moiety to an AAV capsid
- Demonstrating efficient CNS transduction specifically in humanized mouse models expressing TFR1
- Highlighting their translatability and clinical applications
ENGINEERING NOVEL THERAPIES WITH ENHANCED BBB-PENETRANCE
Track 2: Direct & Local Delivery Chair: Lisa Shafer, Vice President, Product Development & Reg CMC, Medical Devices & Packaging, Biogen
EXAMINING THE PHYSICAL & CHEMICAL PROPERTIES OF CSF TO OPTIMIZE DRUGS FOR INTRA-CSF INJECTION
11.00 Optimizing the Formulation of CSF-Administered RNA Therapeutics to Prevent Neurotoxicity
Synopsis
- Understanding how CSF formulation differs to plasma formulation
- Considerations for how concentrated the drug formulation can be to avoid localized toxicity in the lumbar spine, cisterna magna or ventricles
- Optimizing the pH to prevent compromising the ionic environment of the CSF
11.30 Roundtable Discussion: Exploring Strategies to Enhance CSF Compatibility
Synopsis
More practical and highly interactive breakout roundtables where attendees can crowd-source solutions and share opinions around pre-assigned topic areas:
Physical chemistry considerations: How can we optimize properties such as viscosity, density, osmolarity, and diffusivity to ensure the drug resides in the target brain region?
How does CSF generation transport and clearance bot facilitate and hinder drug delivery? How can CSF movement rates be optimized for efficient delivery?
Moderator Feedback & Audience Debate
Moderators will be assigned to each roundtable to facilitate discussion and collate the findings. Following the roundtable discussions, they will present back to the entire delegation and open wider audience debate.
12.00 Lunch & Networking
1.00 Roundtable Discussion: Looking Beyond Transferrin for New Receptor-Ligand Pair Opportunities
Synopsis
More practical and highly interactive breakout roundtables where attendees can crowd-source solutions and share opinions around pre-assigned topic areas.
What are the other receptors that could be harnessed for transcytosis across the blood-brain barrier?
How can we overcome species differences in these new receptors of interest?
Which receptors have the greatest potential to be de-risked to reduce peripheral toxicity?
Moderator Feedback & Audience Debate
Moderators will be assigned to each roundtable to facilitate discussion and collate the findings. Following the roundtable discussions, they will present back to the entire delegation and open wider audience debate
DE-RISKING THE TRANSLATIONAL GAP FOR MORE EFFECTIVE CSF ADMINISTRATION
1.00 Applying Learnings from Successful Dose Scaling to Bring New ICV-Administered Therapies to the Clinic
Synopsis
- Reviewing different scaling methods for ICV delivery
- Conducting successful dose scaling across species
- Overcoming the challenges of scaling for intra-CSF delivery routes
1.30 Demonstrating Broad Brain Distribution, Target Engagement & Durability with Di-siRNAs after Intrathecal Administrations in NHPs – Focus on Huntington’s Disease
Synopsis
- Demonstrating how broad distribution results in potent target downregulation throughout the brain, sustained over 6 months
- Showing how RISC-loading assessments support long duration of gene silencing in deep brain regions.
- Leveraging microscopy-based and Mesoscale Discovery assays to evaluate robust distribution in the brain Highlighting how broad, potent, and long-term downregulation of Huntingtin is safe and well-tolerated in NHP
2.00 Afternoon Break & Refreshments
EVALUATING DIFFERENT ROAS IN THE EYES OF THE PATIENT
2:30 Roundtable Discussion: Factoring Patient Feasibility & Comfortability into Your Drug Delivery Discussions
Synopsis
More practical and highly interactive breakout roundtables where attendees can crowd-source solutions and share opinions around pre-assigned topic areas:
From the perspective of the patient, what are the key factors to consider when determining which administration route is optimal in the nearest term?
How do drug delivery considerations vary for aging populations vs pediatric populations?
How do different routes of administration vary in effectiveness and tolerability between patient populations?
Moderator Feedback & Audience Debate
Moderators will be assigned to each roundtable to facilitate discussion and collate the findings. Following the roundtable discussions, they will present back to the entire delegation and open wider audience debate.
EXPLORING INNOVATIVE TECHNOLOGIES TO MEASURE & QUANTIFY DRUG BIODISTRIBUTION IN THE CNS
3:00 Harnessing Radiolabelled Probes to Confidently Quantify the Efficiency of a Systemic Injection to the CNS
Synopsis
- Demonstrating how radioactive labelling can provide deeper quantifications of how much drug is present in the brain regions of interest
- Quantitatively tracking how much drug has crossed the blood-brain barrier and reached a certain compartment
- Comparing the amount of drug present in that particular brain region with the amount initially injected