Explore the Agenda
8:00 am Check-In, Coffee & Light Breakfast
8:55 am Chair’s Opening Remarks
Upregulating Gene Expression with CNS Oligos: Translating SYNGAP1 Biology into the Clinic & Rethinking Regulatory Frameworks
9:00 am Advancing a Gene-Upregulating Oligo for SYNGAP1: From Preclinical Validation to Clinical Entry Preparation
- SYNGAP is a synaptic protein that when mutated results in haploinsufficiency characterized by developmental delays, behavioral issues, limited communication, and epilepsy
- CMP-002 is an antisense oligonucleotide that targets a noncoding regulatory RNA to increase SYNGAP1 transcription, which ameliorates multiple phenotypes in a mouse model and increases SYNGAP protein in monkeys when administered by intrathecal injection
- Preparation is underway to enable the assessment of CMP-002 in a global Phase 1/2 clinical study in SYNGAP1-related disorder patient
9:30 am Roundtable Discussion: Enabling Platform-Based Regulatory Strategy for CNS Oligonucleotides
- Reassessing the necessity of fully independent nonclinical toxicology packages for each candidate by examining shared chemistry, mechanism of action, and accumulated class safety data across oligonucleotide platforms
- Identifying the scientific commonalities that could justify a proportionate, risk-based regulatory approach, rather than repeating comprehensive packages where prior pharmacology and toxicology knowledge already exists
- Exploring practical strategies to align regulatory bodies around a platform framework, including early agency engagement, cross-program data integration, and clearer articulation of class-based evidence to enable streamlined, science-driven IND progression
10:00 am Morning Break & Refreshments
From Splice Correction to Clinical Strategy in ALS: STMN2 & SYF2 Targeting with Optimized ASO Dosing & Regulatory Alignment
11:00 am The Discovery & Early Development of QRL-201: A Splice Switching ASO Targeting STMN2 for the Treatment of ALS
- ALS is characterized by the mis-splicing of RNA resulting from TDP-43 LOF
- STMN2 pre-mRNA mis-splicing leads to loss of neuromuscular junctions and motor dysfunction
- The discovery and early development of QRL-201, a splice switching ASO that corrects the mis-splicing of STMN2, will be presented
11:30 am Optimizing Splice-Correcting ASO Dosing & Regulatory Strategies to Target TDP-43–Driven Neurodegenerative Diseases
- Discuss how a comprehensive, data-driven non-clinical development for ASOs can help optimize clinical dosing strategies, for a favorable safety profile, reducing toxicity risks and enabling a more efficient trial design
- Align non-clinical evidence with regional regulatory requirements to facilitate efficient clinical development and access to novel therapeutics for rare disease patients
- Utilize emerging clinical data and real-world insights to refine clinical trial designs and increase chance for early clinical proof-of-concept
5:05 am Chair’s Closing Remarks & End of Conference
12:00 pm Lunch & Networking
Programmable Cell-Selective RNAi & CNS Distribution Limits: Evaluating IT, Systemic & Chemistry-Driven Deep Brain Penetration
1:30 pm Tissue & Cell Selective Conditionally Activated siRNA Targeting APOE & C1q
- Outlining the design principles of switchable oligo platforms, including triple-stranded siRNA architectures that enable RNAi activity to be modulated or restricted based on cellular context
- Showcasing pipeline applications in neurodegenerative disease, including programs targeting APOE and C1q, to illustrate how cell-selective RNAi can be aligned with disease-relevant biology, and sparing target mediated AEs
2:00 pm Roundtable Discussion: Achieving Safe, Deep Brain Penetration – Can Intrathecal & Systematic Delivery Reach the Regions That Matter?
- 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
3:00 pm Afternoon Break & Refreshments
Aptamer-Based CNS Therapeutics & Alternative Delivery Systems: Evaluating Modality Design, Nanoparticles, Peptides & BBB Modulation
3:30 pm Advancing Aptamer-Based Therapeutics: Unlocking CNS Delivery & Expanding the Potential of Oligo Modalities
- 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
4:00 pm Safety-Led Oligonucleotide Development: Predictive CNS Toxicity Modelling & Aptamer-Enabled BBB Delivery
- Session details to be announced
4:30 pm Panel Discussion: Diversifying CNS Delivery of Oligos: Nanoparticles, AAV, Peptide Carriers, Physical & Non- Physical BBB Modulation
- Exploring LNP strategies for CNS delivery, discussing their capacity to encapsulate and protect oligonucleotides, enhance systemic stability, modulate biodistribution, and potentially enable controlled transport across or around the blood–brain barrier
- Advancing peptide-mediated delivery approaches that utilize small targeting or cell-penetrating peptides to facilitate BBB traversal and intracellular uptake, evaluating their modularity, scalability, and potential advantages over antibody-based shuttle platforms
- Evaluating physical BBB modulation techniques, including focused ultrasound and microbubble-assisted disruption, to transiently increase permeability and enable localized brain access, while critically assessing reversibility, safety margins, spatial precision, and translational feasibility