Day One

• Reassessing the limitations of TfR1-mediated delivery, including broad peripheral expression, systemic sink effects, tolerability concerns, and limited cell-type specificity and discussing whether alternative receptor targets such as CD98, IGF1R and peptide ligands can deliver improved CNS selectivity
• Comparing emerging delivery modalities including antibody shuttles, peptide-mediated carriers, lipid nanoparticles (LNPs), viral vectors and other non-viral platforms, evaluating their ability to improve biodistribution, intracellular uptake, manufacturability and clinical translation
• Exploring both physical and non-physical approaches to overcoming the blood-brain barrier, including focused ultrasound, microbubble-assisted BBB opening and antibody-mediated modulation, while balancing enhanced CNS penetration with safety, reversibility and translational feasibility
• Debating which delivery strategies are most likely to enable systemic, repeatable and disease-specific oligonucleotide delivery for the next generation of CNS therapeutics

• Evaluating whether IT delivery can achieve significant exposure in deep brain structures implicated in Huntington’s and Parkinson’s disease
• Examining emerging chemistry-driven distribution strategies such as C16-siRNA conjugates and modified ASOs, and interrogating non-human primate data to understand current depth and dose limitations
• Comparing IT optimization strategies against systemic BBB shuttle approaches to determine which modality is better suited for specific diseases requiring deep brain penetration

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 CNS oligo drug development space. Designed to maximize your introduction to numerous new individuals and serve as a catalyst for ongoing discussions during the summit. 

• Explore how aptamer-based therapeutics can move beyond traditional delivery roles to directly modulate disease biology, unlocking new opportunities for targeting previously undruggable pathways in Parkinson’s disease
• Discover how early-stage discovery and in vitro validation of aptamers are shaping the next generation of CNS-targeting therapies and demonstrating functional activity
• Enable innovative therapeutic development by evaluating intrinsic oligonucleotide chemistry versus conjugation strategies, highlighting how modality design choices can influence CNS penetration, target engagement, and overall clinical potential

• Discussing a novel “Trojan horse” technology that enables the direct delivery of oligos to the brain via intravenous or subcutaneous administration
• Therapeutic efficacy in Huntington’s disease demonstrated at a dose significantly lower than the standard intrathecal ASO dose (less than 1,000 the dose used intrathecally) Over 95% halting of disease progression in chronic preclinical studies
• In a collaboration with a large pharmaceutical company, a single IV dose of an ASO complexed to our Trojan horse was able to achieve equivalent protein reduction as an ICV dose. Confirmed safety and consistent brain delivery in repeat-dose non-human primate studies
• This non-invasive delivery approach offers a significant clinical advantage over invasive modalities or other BBB shuttles and could be a powerful enabler for any siRNA/ASO or peptide/protein programs targeting CNS indications