8:00 am Registration & Virtual Coffee
8:50 am Chairs Opening Remarks
Optimizing Medicinal Chemistry to Streamline Proof-of-Concept & Enhance Robust Translation
9:00 am Rational Design of Bioactive Small Molecules Targeting RNA
Synopsis
• Exploring the utility of different compounds as both advancers of lead medicines and as chemical probes to advance understanding of previously unknown RNA biology
• Highlighting how the sequence-based small molecule rational design tool, dubbed Inforna, allows for targeted degradation of RNAs in cells and animals
• Understanding how these advances imply a necessary reassessment for
the future for SMIRNAs to deliver precision medicines
9:20 am Examining Methodologies, Chemical Biology & Structural Dynamics to Target mRNA with Small Molecules
Synopsis
• Examining the facts for mRNA targeting
• Understanding RNA structure and dynamics
• Outline and discuss the importance of small molecules focus
9:40 am Translation Control Therapeutics: Discovery of Selective mRNA Translation Modulators
Synopsis
• Discovery of small molecule drugs that selectively control mRNA translation in a novel target space
• Highlighting importance and utility of tissue selective drugs
• Navigating strong In Vivo data
10:00 am Live Panel Q&A – Ask the Speakers your Burning Questions
10:30 am Virtual Speed Networking & Morning Break
Unlocking the Facts: RNA Biological Mechanisms & How to Utilize for Viable Therapeutic Intervention
11:30 am Inducing Reversal of Disease Phenotypes Using RNA-Targeting Proteins – Ensure Optimal & Successful Translation into the Clinic
Synopsis
• RNA-Targeted proteins to modify RNA-mediated diseases
• Learning how to harness neurodegenerative models from IPSC cells model RNA defects
• Leveraging transcriptome-wide measurements confirm reversal of disease
11:50 am RNA-Binding Proteins, RNA Processing & Gene Expression
Synopsis
• A new biophysical model can extract quantitative descriptions of protein-RNA binding from in vitro measurements
• Harnessing such models can enhance predictability of In Vivo binding and function, detect cooperative binding and the RNA accessibility footprint of an RNA-binding protein
• Discuss how pre-mRNA processing can impact transcription as well as other steps in gene expression
12:10 pm Spinach Splice Sensor: A Cell-based Drug Discovery Platform for Splicing-related Diseases
Synopsis
• Explore using fluorescent aptamers for endogenous RNA splicing activity
• Demonstrate feasibility of sensor platform for splice-modulator drug
discovery
• Further applications for circular RNA and intronic RNA detection
12:20 pm Live Panel Q&A – Ask the Speakers your Burning Questions
12:45 pm Lunch & Virtual Networking
1:00 pm Session Details To Be Confirmed
1:45 pm Panel Discussion: From Theory to Reality: How to Target RNA Biology with Small Molecule Approaches
Synopsis
• Explore successful methods and mechanisms for the targeting of RNA through small molecule compounds
• How can we utilize industry achievements to aid progression into the clinic?
• Identifying, evaluating, and overcoming key challenges to unleash the full therapeutic potential of the field
• Investigating the benefits and disease applications of effective RNA targeting
2:45 pm Afternoon Break & Networking
Advancing Effective & Accurate Small Molecule Target Identification & Validation
3:15 pm The Landscape Beyond SMA: Expanding the Drug Discovery Toolbox for the Treatment of Genetic Disorders
Synopsis
• Exploring how the discovery and clinical success of risdiplam in treating SMA
• Reimagining how the use of small molecules to influence pre-mRNA splicing become a fertile ground for drug discovery
• Understanding can non-canonical 5’ splice sites to shift alternative splicing and cause exon skipping or induce inclusion of pseudo-exons
• State of the art platform technologies can aid discovery of novel splicing modifiers for therapeutically relevant splicing events
3:35 pm Revealing Fragment-Based Screening Approaches Using NMR Demonstrates the Druggability of Biologically Active RNA
Synopsis
• Discuss how NMR-based fragment screening demonstrates the druggability of biologically active RNAs
• Outlining how SMN2 splice modulators can enhance pre-mRNA association and rescue SMA mice
• Evaluating the utility of fragment-screening library-NMR-based quality control
3:55 pm Chemical Libraries for Exploring & Developing RNA Targeted Chemical Probes
Synopsis
Obtaining and utilizing chemical libraries is the fundamental starting point for subsequent successful small molecule RNA targeting. Optimal chemical libraries will facilitate and accelerate discovery of RNA targeted therapeutics.
• Evidence suggests a privileged chemical space exists for biologically active RNA-targeted small molecules, but more data is needed
• RNA-biased library curation may lead to higher quality hits
• Assays to validate these libraries must be carefully considered