Explore the Agenda
8:00 am Check-In, Coffee & Light Breakfast
8:55 am Chair’s Opening Remarks
Turning Brain Delivery Breakthroughs into Sustainable CNS Pipeline Growth
9:00 am Keynote: Why is it so much Harder to Deliver Oligonucleotides to the Brain Compared to Other Organs?
- Exploring that the rate-limiting step for oligonucleotides targeted for CNS indications is release of oligonucleotides from lysosome and brain tissue
- Evaluating novel delivery technologies across LNPs, ultrasound, viral particles and routes of administration in delivering oligonucleotides to the brain without compromising on potency, distribution, affinity or efficacy
- Reviewing the next step to optimizing structural design to ensure delivery to the cytoplasm and nucleus
9:30 am Bispecific TfR1/Target Antibody Shuttles (e.g. Anti-Aβ Trontinemab): Latest Preclinical & Clinical Insights
- Assess how bispecific constructs couple transport and therapeutic domains to enable BBB crossing while maintaining target engagement in the brain parenchyma
- Evaluate dose-dependent saturation of TfR1 transport pathways and its effect on nonlinear brain uptake
- Characterize intrabrain distribution patterns (capillary-associated vs parenchymal delivery) to assess true tissue penetration versus vascular trapping
- Compare clinical biomarker strategies (e.g. PET imaging, CSF biomarkers) for demonstrating CNS target engagement
10:00 am Fireside Chat: Building the Next Generation of CNS Pipelines Through Brain Delivery & Modality Innovation
- Determining which brain delivery technologies and therapeutic modalities warrant integration into long-term neuroscience portfolios
- Establishing evidence thresholds for advancing CNS delivery platforms from discovery-stage innovation into clinical development
- Balancing investments across internal R&D, platform partnerships, licensing opportunities, and external innovation ecosystems
- Identifying the biological, translational, and regulatory advances most likely to unlock the next wave of CNS therapeutic development
10:30 am Speed Networking
A prime chance to make the most of in-person networking and forge new connections as new companies enter, and existing ones broaden their presence within the CNS drug delivery space. Designed to maximize your introduction to numerous new individuals and serve as a catalyst for ongoing discussions during the Summit.
11:00 am Morning Break & Refreshments
Track 1: Technology & Platform Development
Designed for:
Drug delivery, platform, biologics, antibody, oligonucleotide, vector, protein engineering and chemistry teams developing the next generation of CNS delivery technologies.
Explore the engineering, chemistry and design principles underpinning brain shuttles, capsids, conjugates and device-enabled delivery systems to improve BBB transport, brain exposure and delivery efficiency.
Chaired by –
Capsid & Vector Engineering for Efficient Gene Therapy Delivery Across the BBB
11:00 am Translating ALPL-Mediated BBB Transport into the Clinic: Next-Generation Capsid Engineering for CNS Gene Therapy
- Translate ALPL-mediated BBB transport from platform discovery into clinical reality, supported by early human data and safety readouts
- Position ALPL as a differentiated, cross-species BBB target with improved translational relevance beyond legacy approaches such as TfR1
- Demonstrate how strong NHP validation of ALPL-targeting capsids enables progression into clinical CNS programs, including tau knockdown in Alzheimer’s disease
- Showcase next-generation capsid engineering strategies that enhance brain-wide transduction, reduce off-target effects, and improve systemic gene therapy delivery
11:30 am Advancing Chronic Intrathecal Delivery via Implantable Port-Catheter Systems to Improve CNS Therapeutic Access & Patient Experience
- Introducing the design and functionality of implantable intrathecal port‑catheter systems enabling repeat access to cerebrospinal fluid for CNS therapeutic delivery
- Evaluating how device-enabled delivery can reduce reliance on repeated lumbar punctures and improve patient experience adherence and long-term feasibility
- Sharing clinical progress and learnings from ongoing studies assessing safety performance and real-world usability of implantable intrathecal delivery platforms
- Exploring the future role of integrated drug-device solutions in scaling antisense oligonucleotide and advanced therapy delivery across CNS indications
Track 2: Biology & Implementation
Designed for:
Neuroscience, biology, pharmacology, DMPK, PKPD and translational development teams seeking to evaluate, implement and de-risk CNS delivery approaches within therapeutic programs.
Explore biodistribution, target engagement, in vitro and in vivo models, dose translation, safety assessment and disease-specific case studies to understand how delivery technologies perform in real-world development settings.
Case Studies of Testing Delivery Systems Within Disease Context
11:00 am Enabling Targeted Oligonucleotide Delivery to CNS for the Treatment of Neurological Pathologies
- We have developed a TfR1 mediated delivery platform capable of transporting therapeutic oligonucleotides to both muscle and the CNS
- This delivery platform has translated into clinically meaningful functional improvements in neuromuscular diseases, including DMD and DM1
- In the CNS, our approach achieves broad and homogeneous brain distribution of oligonucleotide payloads, reaching deep brain regions that are inaccessible via intrathecal administration
11:30 am Challenges & Opportunities in Treatment of CNS Tumors
- CNS tumors, including newly diagnosed glioblastoma (GBM) and brain metastases, represent a significant commercial opportunity in an area of urgent unmet medical need. The incidence of brain metastases is increasing, in part because advances in treatment for cancers such as colorectal, pancreatic, breast, and lung cancer are extending patient survival and allowing more time for disease to spread to the brain
- Many promising anticancer molecules are under development, but achieving effective concentration without causing toxicity remains a daunting challenge because of the blood brain barrier
- We compare several strategies for drug delivery to the brain for the treatment of CNS tumors, delineate their respective advantages and limitations, and assess the outstanding challenges that remain to be addressed, including technical, adoption-related, and supply chain-related barriers
12:00 pm Lunch & Networking
Track 1: Technology & Platform Development
Advances in Device-Mediated Delivery Bypassing the BBB
1:00 pm Targeted Blood Brain Barrier Opening Using Focused Ultrasound to Enable Spatially Precise CNS Drug Delivery Without Molecular Re-Engineering
- Demonstrating transient and region-specific BBB opening using microbubble-mediated focused ultrasound with reproducible safety across 300+ patients
- Enabling localized delivery of biologics, oligonucleotides and gene therapies with preserved molecular integrity and enhanced target engagement
- Quantifying biodistribution shifts and pharmacodynamic effects following ultrasound-mediated BBB modulation in oncology and neurodegeneration
- Positioning focused ultrasound within the broader CNS delivery toolkit alongside intrathecal dosing and receptor-mediated transport approaches
1:30 pm Effect of Extended Intracerebroventricular (ICV) Delivery on the Biodistribution of a Viral Vector in the CNS Of NHPs
- Achieving therapeutic levels in subcortical areas for the treatment of motor disorders is a daunting challenge in gene therapy
- This study compares bolus versus extended intracerebroventricular (ICV) administration schedules for delivering AAV vectors in cynomolgus macaques. Using a stereotactically implanted infusion system, animals received the same total vector dose either as two quick infusions or as eight smaller infusions over four hours
- The extended schedule led to greater gene expression in several brain regions, as well as peripheral tissues, suggesting that prolonged ICV infusion can enhance the distribution and expression of AAV-delivered genes in the CNS
- These findings support further exploration of extended infusion protocols to improve AAV gene therapy
Track 2: Biology & Implementation
De-Risking CNS Delivery Through Better Dose Prediction & Toxicological Understanding
1:00 pm Dose Scaling from NHP to Human: PKPD Modelling & Safety Margin Determination
- Build physiologically-based pharmacokinetic models that account for CSF volume, turnover rates, and brain tissue penetration to improve dose predictions
- Translate doses from non-human primates to humans using exposure-based rather than simple body weight scaling to improve safety margins
- Integrate target engagement biomarkers and pharmacodynamic endpoints into models that predict efficacious human doses
1:30 pm Understanding Toxicological Liabilities of Intrathecal Oligos to Enable Safer CNS Delivery
- Characterization of common CNS and off-target toxicological liabilities associated with intrathecal oligonucleotide delivery across preclinical models
- Application of in vitro assay systems to predict and mechanistically understand CNS toxicity and support translational risk assessment
- Strategies to differentiate sequence-specific versus platform-related toxicology signals when evaluating oligonucleotide candidates
- Integration of toxicology data into candidate selection frameworks to improve safety margins and de-risk direct CNS delivery approaches
2:00 pm Afternoon Break & Refreshments
Capital Allocation & Investment Trends in BBB Shuttles & Delivery Technologies
2:30 pm Panel Discussion: Direct vs Systemic Delivery: Driving Pharma Buy-In, Bottlenecks & Patient Perception
- Compare direct CNS delivery and systemic administration in terms of tissue exposure and selectivity, and their impact on target-site concentration, dose, and efficacy–toxicity balance
- Assess the limitations of systemic approaches that rely on plasma pharmacokinetics as a surrogate for efficacy versus direct delivery strategies that prioritise disease-site exposure
- Evaluate adoption barriers and translational challenges for direct delivery relative to systemic modalities, including device integration and demonstration of tissue-level pharmacological advantage
- Explore how patient, clinician, and commercial perspectives shape trade-offs between invasiveness and the potential for improved efficacy and reduced toxicity through targeted delivery