Pre-Conference Discussion Day
Monday, June 13 2022
Seminar: A-Z Oligonucleotide Bootcamp: Upgrade Your Oligonucleotide Design & Development to Unleash the Full Potential of Oligonucleotide Therapeutics Within the CNS
9:00 am
Breakfast & Registration
Manipulating Oligonucleotide Chemistry to Maximize Therapeutic Potency & Precision
10:00 am Deep Diving into Modifying Chemistry of siRNAs for Optimized Extra- Hepatic Delivery
Synopsis
- Revealing key oligonucleotide modifications you can make to optimize RNAi activity
- Illustrating how chemical modifications can mitigate off-target effects
- Exploring tips and tricks to employ chemical modifications to upgrade your delivery
10:30 am Investigating Data Driven Approaches to Oligonucleotide Molecule Design
Synopsis
- Learning how to utilize AI to inform molecule design
- Characterizing off-target effects
- Exploring how to incorporate knowledge graphs to support ASO design
11:00 am Discovering Basic Chemical Modifications Required for Deeper Penetration & Better Distribution for Different Oligonucleotide Modalities
Synopsis
- Exploring the current landscape of modified monomers and ligands target CNS and different organs
- Explore the barriers that influence oligonucleotide access to tissue sites,
- To understand the deeper penetration and biodistribution of ASO and siRNAs
11:30 am
Morning Break & Networking
12:00 pm Revealing Structurally Constrained Internucleotide (E)-Vinyl Phosphonate Backbone Impacts siRNA Potency & Allele Specificity
Synopsis
- Adding structure-constraining of sugars, such as 2′-fluoro and LNA, has been shown to enhance oligonucleotide stability and affinity to target mRNA
- Exploring the synthesis and impact of a structurally-constrained inter-nucleotide (E)-vinylphosphonate backbone (iE-VP) where we show iE-VP can modulate metabolic stability, enzyme interactions and siRNA activity
- Demonstrating how iE-VP induces significant mismatch-discriminating properties without compromising on-target silencing
- Explaining how our study covers a broad range of interests and paves the path towards fully allele-specific siRNAs for CNS disorders such as Huntington’s disease
Scaling Up & Scaling Out: Discovering How to Maximize Efficiency of Oligonucleotide Manufacturing
12:30 pm Investigating New Horizons for Oligonucleotide Drug Substance Manufacturing for CNS Products
Synopsis
- Revealing our strategy for drug substance manufacturing for CNS products
- Exploring emerging technologies we’re developing for drug manufacture and understanding how these can be applied to the CNS
- Deep diving into convergent synthesis
1:00 pm Lunch Break & Networking
2:00 pm Scrutinizing & Analytical Challenges of Oligonucleotide Delivery Systems & their Translation to the Clinic
Synopsis
- Understand key points in formulation design and definition of critical quality attributes
- Analytical methods associated with characterization, stability, and assessment of reproducibility and scalability
- Evaluation and selection of appropriate delivery systems
2:30 pm Learning How to Work With CMOs & CROs for Effective Oligonucleotide Manufacturing in Line With Regulatory Expectations
Synopsis
- Executing efficient GMP oligo manufacturing at your CMO
- Learning how to manage impurities in your oligo drug substance
- CMC for oligos 101: Incorporating information from regulators to optimize oligo development
3:00 pm Design, Screening & Optimization of Oligonucleotide Therapeutics with Optimal Profiles Across Large-Scale Data Sets of Individual Neurons for Targeting CNS Diseases
Synopsis
- Exploring antisense oligonucleotide (ASO) design, screening and optimization
- for CNS applications, with a focus on assessment of ASOs at the cellular level in diverse neuronal types
- Outlining the development of deep-learning techniques with large scale data sets to characterize desired phenotype rescue and undesired toxicities associated with candidate ASO therapeutics
- Revealing findings in the context of CNS disorders such as genetic epilepsies and chronic pain conditions