CONFERENCE DAY TWO
8.00 Check-In, Coffee & Light Breakfast
8:50 Chair’s Opening Remarks
9:00 Exploring Liposome-Delivered Auger Radioligand Therapy for Target-Agnostic Destruction of Infiltrating Glioblastoma Cells – A First-in-Class Radiopharmaceutical
Synopsis
- Usage of PET/MRI to evaluate nanocarrier biodistribution and Vd/Vi (volume of distribution/volume of infusion) ratios in porcine models by convection-enhanced delivery
- Convection-enhanced delivery of nanocarrier-based Auger radioligand therapy in glioblastoma – presentation of promising pre-clinical data
- How can we incorporate CED therapies in the current treatment of glioblastomas – a neurosurgeon’s perspective
EVALUATING DIFFERENT ROAs IN THE EYES OF THE PATIENT
9:30 Enhancing Quality of Life Without Compromising Efficacy: Lived Experiences of Exploring New Administration Routes for Parkinson’s Medications
Synopsis
- Emphasizing the excitement as a Parkinson's patient in trying new delivery methods that could improve quality of life without risking other symptoms
- Highlighting the balance between risk and reward, and the importance of maintaining efficacy while enhancing patient experience
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
11.30 Screening for Alternative Brain-Penetrant Antibodies for Brain Delivery
Synopsis
- Outlining protein engineering approaches to identify antibodies capable of receptor-mediated transcytosis of the BBB
- Evaluating delivery potential of new antibody candidates
- Implications for future research: could these or other BBB targeting antibodies be utilized for CNS drug delivery?
Track 2: Direct & Local Delivery Chair: Anthony Coston, Principal Engineer, 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
Bruno Godinho, Senior Scientist, Atalanta Therapeutics
2.00 Afternoon Break & Refreshments
EARLY CLINICAL PROGRESS & FUTURE OPPORTUNITIES: WHERE IS THE CNS DRUG DELIVERY LANDSCAPE HEADING NEXT?
2:30 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
3:00 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