Conference Day One

Wednesday July, 10

7:00 am Check-In & Coffee

7:55 am Chair’s Opening Remarks

BALANCING AFFINITY, EFFICACY & SPECIFICITY FOR OPTIMIZED & EFFICIENT DELIVERY OF OLIGONUCLEOTIDES TO THE BRAIN

8:00 am Using Site-Specific Transglutaminase-Based ASO Conjugation to Maintain Optimal Pharmacokinetics with Peripheral Administration

  • Kerstin Hofer Senior Scientist and Technical Project Leader, Roche

Synopsis

  • Using a stepwise process to identify optimal conjugation site, tags, reaction conditions and linker design to show high conjugate fidelity of peptide tags YRYRQ and RYESK
  • Mitigating increase hydrophobicity by ASO payload with appropriate choice of conjugations site at heavy chain position 297
  • Reviewing In vitro and in vivo pharmacokinetic behaviour of optimized brainshuttle-ASO conjugates based on a MAPT targeting oligonucleotide as a more widespread methodology for peripheral administration of ASO-baseddrugs for the CNS

8:30 am The FORCE™ Platform for Transferrin Receptor 1-Mediated Delivery of Oligonucleotides to Muscle and CNS

  • Nicholas Yoder Executive Director, Platform Development, Dyne Therapeutics

Synopsis

  • Dyne’s FORCE Platform was designed to deliver oligonucleotides to muscle cells via conjugation to a transferrin receptor 1 (TfR1)-targeting Fab, and is currently in clinical development for the treatment of myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD).
  • Consistent with TfR1-mediated uptake, we observe robust delivery of conjugated ASO to the brain of cynomolgus monkeys using FORCE, with broad uptake across different regions.
  • In a mouse model of DM1, FORCE delivers oligonucleotides to the brain, and reduces human toxic DMPK RNA expression and nuclear foci, indicating the potential to address the central nervous system manifestations of DM1. 

9:00 am A Landscape Review of Oligonucleotide Therapy Development for Neurological Disorders

Synopsis

  • The drug landscape, displaying critical data-driven therapeutic and clinical trial highlights, as well as current trends
  • A look at the developer landscape, allowing for understanding of the commercial market involving these drugs’ development
  • The outlook for the future of oligonucleotide therapies for the CNS from a preclinical and clinical perspective

9:30 am Speed Networking

Synopsis

This session presents a prime opportunity to introduce yourself to leading CNS drug developers specializing in oligonucleotides, fostering meaningful relationships with the brightest minds in the field.

10:00 am Morning Break & Networking

DECODING DISTRIBUTION: ASSESSING AND OPTIMIZING OLIGONUCLEOTIDES FOR EVEN BRAIN DISTRIBUTION

11:00 am CNS Delivery of RNA Therapeutics Using LAT1 Target Polymeric Nanoparticle

  • Branden Ryu CEO and Scientific Founder, Biorchestra Co. Ltd.

Synopsis

  • Biorchestra Drug Delivery System (BDDSTM) is a proprietary technology utilizing non-lipid polymer ion complex and LAT1 targeting ligand for BBB penetration
  • Preclinical assessment on ALS and Epilepsy of ASO therapeutics with BDDSTM technology
  • BDDSTM technology is compatible with multiple RNA species with various lengths (e.g., ASO, siRNA & mRNA) and shows a therapeutic potency in preclinical evaluation

11:30 am SCAD Platform for the Delivery of Duplex RNA to the CNS

Synopsis

  • SCAD (smart chemistry-aided delivery) is a simple yet effective platform for delivering duplex RNA including siRNA and saRNA to the CNS via intrathecal administration
  • SCAD delivered siRNA can achieve profound and durable target gene knockdown in rodents, nonhuman primates and human
  • SCAD platform has demonstrated a very favorable safety profile

12:00 pm Panel Discussion: Why is it so much Harder to Deliver Oligonucleotides to the Brain Compared to Other Organs?

Synopsis

  • 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

12:30 pm Lunch &Networking

INTEGRATING AI, ML & MULTIOMICS INTO BIOLOGICAL UNDERSTANDING FOR NEXT GENERATION OLIGONUCLEOTIDES TO DRUG THE ‘UNDRUGGABLE’

1:30 pm Engineering for Safety and Efficacy in Oligonucleotide-Based Medicines (OBMs)

Synopsis

  • Smart data versus big data: implementing novel design of experiment principles to generate comprehensive and highly informative in vivo pharmacological datasets, tailored to fuel a machine learning (ML) model to engineer safety, specificity, and efficacy
  • Precision engineering: employing both quantum computational chemistry and in vivo data to accurately modulate pharmacological effects with minimal chemical alterations and within genetic sequence constraints
  • Safety-first approach: utilizing large-scale transcriptomics and human ex vivo and in vitro assays, coupled with rodent in vivo assays, to optimize the safety of OBMs, while also reducing both development time and cost

2:00 pm Validating In Vivo Splicing of Target in the Hippocampus

  • Anne Valat Director of Research, Bolden Therapeutics

Synopsis

  • Identifying ASO candidates through in vitro screening to identify and validate targets to be used in vivo
  • Assessing efficient delivery and biodistribution at target brain region
  • Identifying the right model derived from iPSCs

2:30 pm Preclinical Development of AMX0114: An Antisense Oligonucleotide Inhibitor of Calpain-2

  • Evan Mizerak Lead of Preclinical Research, Amylyx Pharmaceuticals Corp.

Synopsis

  • Calpain-2 and axonal degeneration in neurodegenerative diseases
  • In silico design and screening of novel ASOs to inhibit calpain-2
  • Preclinical efficacy studies of AMX0114 in models of ALS

3:00 pm Afternoon Break & Networking

BRIDGING THE GAP FROM THE LAB TO THE CLINIC WITH TRANSLATABLE HIPSC & IN VIVO MODELS FOR SAFE & EFFICACIOUS OLIGONUCLEOTIDE DEVELOPMENT

4:00 pm Leveraging Humanized Preclinical Models for the Rapid Optimization of UNC13A ASOs on AcuraStem’s iNeuroRx® Technology Platform

  • Sam Alworth Co-Founder & Chief Executive Officer, AcuraStem Inc.

Synopsis

  • Exploring UNC13A biology in treating ALS & FTD
  • Utilizing accurate patient-derived hIPSC models of UNC13A pathology to optimize UNC13A ASOs
  • Utilizing humanized UNC13A mice to understand exposure and target engagement of UNC13A ASOs

4:30 pm Reducing the Burden of In Vivo Studies for IND & MAA Submission by Optimizing In Vitro Studies to Streamline Oligonucleotide Development to the Clinic for Ultra Rare Disease

Synopsis

  • Exploring the crucial minimum requirements for in vitro and in vivo studies needed for IND and MAA submission, where ultra rare disease patients might have limited treatment window
  • Using AI, chemistry and scaffold of the oligonucleotide to lower risk for candidate toxicity
  • Assessing dose-response, immune-response, immunogenicity and cell viability to get the most out of in vitro studies to reduce need for in vivo studies and satisfy regulatory requirements
  • Reviewing the value of longer-term studies to support chronic clinical dosing

5:00 pm Chair’s Closing Remarks

5:05 pm Scientific Poster Session

Synopsis

This session is a great opportunity to introduce yourself to experts across leading oligonucleotide biopharma working

on CNS pipelines. Enjoy face-to-face time and share your work with many of the brightest minds, displaying scientific

posters capturing the main advancements and challenges in oligonucleotide development for CNS to establish

meaningful business relationships

5:35 pm End of Conference Day One