Explore the Agenda
7:30 am Check-In, Coffee & Light Breakfast
8:55 am Chair’s Opening Remarks
Expanding the Impact of Oligonucleotide Therapeutics Across Neurological Disorders
9:00 am Expanding Oligonucleotide Therapeutics into Pain: Platform-Enabled Targeting of NaV1.7
- Leveraging antisense oligonucleotides (ASOs) to modulate NaV1.7 expression as a novel non-opioid therapeutic strategy for chronic pain
- Positioning pain as an emerging and underexplored indication for oligonucleotide therapeutics beyond rare genetic and neurodegenerative diseases
- Applying AI and machine learning–enabled approaches to optimize ASO sequence and chemistry selection, improving target engagement and therapeutic index in preclinical development
9:30 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
10:00 am Morning Break & Refreshments
Engineering CNS Delivery Strategies That Balance Performance, Safety and Scalability
10:45 am Roundtable Discussion: Conjugation vs Intrinsic Chemistry – Is Targeted CNS Delivery Worth the Structural Complexity?
- Evaluating whether receptor-mediated conjugation strategies provide a translational advantage over intrinsic chemistry optimization, given the absence of a validated receptor–ligand specific to CNS
- Examining the structural and operational complexity introduced by antibody–oligonucleotide constructs and the requirement for highly efficient delivery at low systemic doses to avoid toxicity risk
- Debating whether emerging alternatives or intrinsic chemistry tuning remains the more scalable and practical strategy for CNS programs
11:30 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
12:00 pm Lunch & Networking
Applying Predictive PK/PD Models to Improve ASO Design & CNS Therapeutic Performance
1:30 pm Applications of Pharmacokinetics and Pharmacodynamics Principles for Optimizing the Design of Brain-Targeting Oligonucleotides
- Design of Brain-Targeting Oligonucleotides
- Intrathecal dosing enables effective CNS delivery of oligonucleotides, but limited brain biodistribution remains a key challenge, restricting their therapeutic potential
- PK/PD modeling and simulation provide a quantitative framework to integrate multiple oligonucleotide-related variables and predict target knockdown across the brain
- Model-guided optimization of oligonucleotide parameters such as the potency and tissue half-life provides an objective approach to lead optimization, to enhance their therapeutic application
2:00 pm 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
2:30 pm Afternoon Break & Refreshments
Advancing TDP-43 Therapies Through Data-Driven Dose Optimization & Clinical Translation
3:00 pm 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
3:30 pm Integrating Human-Relevant Preclinical Models to De-Risk ASO Potency, PKPD Translation & Clinical Dose Selection in TDP-43–Driven Neurodegeneration
- Leveraging patient iPSC-derived neurons that recapitulate TDP-43 pathology to screen and rank splice-correcting ASO candidates by potency, efficacy, and safety-enabling identification of leads with clinically relevant characteristics
- Utilizing a humanized mouse model to establish in vivo proof-of-concept and generate PKPD relationships that bridge human cell-based potency to CNS tissue exposure and target engagement
- Presenting NHP PKPD and tolerability data to support translational dose selection and inform therapeutic index ahead of clinical entry
- Outlining a clinical development strategy informed by integrated preclinical evidence across human cellular, humanized rodent, and NHP platforms to enable efficient first-in-human study design