8:00 am Networking & Virtual Coffee

Navigating the Landscape of RNA Structure & Function – Advance the Potential of RNA Targeted Therapeutics

9:00 am Targeting the Tertiary Structures of Pathogenic RNA Molecules

  • Anna Marie Pyle Sterling Professor , Yale University & HHMI Investigator


• Understanding folded tertiary structures within RNA in order to target with high specificity
• Benchmarking the difference in RNA metabolism and RNA structure between pathogens and humans
• Targeting the RNA tertiary structures unique to microbial pathogens is a powerful new therapeutic strategy for well-tolerated drugs

9:30 am Spliceosome Modulation – Harnessing the Spliceosome to Target pre-mRNA Splice Factors


• Outlining spliceosome mutations in cancer
• Rethinking effects of indirect targeting of RNA via spliceosome for delivery of a potential therapeutic target
• Assessing the methodologies and technologies to effectively drug the spliceosome
• Future applications and perspectives of targeting the spliceosome

10:00 am Structure of the full SARS-CoV-2 RNA genome in infected cells

  • Silvi Rouskin Principal Investigator & Whitehead Fellow , Whitehead Institute for Biomedical Research


• Uncovering drastically different structures forming in cells than prevailing models based on Nuclear Magnetic Resonance (NMR)
• Detecting multiple, distinct conformations formed from the same underlying sequence
• RNA structure at local regions is influenced by the sequence context of the entire molecule (30kb for SARS-CoV-2)

10:30 am Benchmarking the Structural Insights into RNA Function to Successfully Drug the Undruggable


• RNA biology is core to gene expression and can drive human disease
• Structural understanding of RNA function can lead to novel insights into RNA biology
• Targeting RNA biology with small molecules opens novel opportunities to drug the undruggable

11:00 am Virtual Speed Networking & Morning Break

Leveraging Mechanistic & Computational Biology to Enhance the Therapeutic Potential of RNA Targets

12:00 pm First-in-Class Inhibitors of the RNA: Targeting Cancer with m6A Methyltransferase METTL3


• Introduction to RNA modifications, the role of METTL3 and the m6A modification on selected mRNA species
• Overview of our drug discovery efforts to identify potent and selective inhibitors of METTL3
• Characterisation of potent, selective, bioavailable inhibitors of METTL3 in biochemical, biophysical, and cellular assays
• Exploration of utility of METTL3 inhibitors in haematological and solid tumor cell lines
• Demonstration of in vivo activity of METTL3 inhibitors in hematological and solid tumor models

12:30 pm Leveraging Insights from Antisense Oligonucleotide Drugs to Enhance Efficacy of Small Molecule Therapies


• Consideration and exploration of oligonucleotide and anti-sense
molecule approaches
• Harnessing successes from large molecule strategies to implement in
small molecule design and progression
• Understanding important preclinical ASO data in large molecule
approaches to take back to the clinic
• How can the small molecule community compliment and build on proofof-
concept data?

1:00 pm Lunch & Virtual Networking

What is Next for RNA-Targeted Therapeutics? Streamlining RNA Therapies into Clinic


This practical and highly interactive breakout roundtable session will join attendees to crowd-source solutions and share opinions around preassigned topic areas. A valuable chance for attendees to unite around hot topics, debate key milestones for RNA progression and overcome the bottlenecks for the RNA community. No more sitting quietly, this is a dedicated opportunity for you to voice your experiences, expertise and opinions.

Through the Investor Looking Glass: Exploring RNA Targeted Drug Development Progressions & Potentials

• An investor’s perspective on the opportunities and challenges of RNA targeted drug development
• Navigating the existing landscape of RNA targeted therapies
• Understand the current state & potential paths forward for RNA targeted therapies

Nikola Trbovic, Principal & Executive, Director Pfizer Ventures

How to Harness Epitransciptome Regulation to Revolutionize RNA Targeted Therapies

• Discuss how RNA-modifying protein biology can lead to huge drug discovery possibilities
• Understand the benefits o harnessing post-transcriptional chemical modifications of RNA
• Why targeting cancer-linked RNAmodifying
proteins (RMPs) with precision therapies will benefit patients in need

Robert Copeland, President & Chief Scientific Officer, Accent Therapeutics

Technical Considerations for RNA Structural Analysis & Screens

• Experimental and computational methods for determining RNA structure with an emphasis on chemical probing
• How reagent-grade RNA constructs can be procured or created with minimal overhead
• An overview of techniques for assessing off-target engagement

Gabe Sholder, Senior Scientist, AbbVie

3:00 pm Key Steps for Progression from Discovery to Translation: Discovery of Risdiplam – An RNA Splicing Modifier Medicine for SMA


• Outlining a framework for RNA targeted therapy guided design for splicing modifier, Risdiplam
• Evaluating RNA drugging with small molecule compounds
• Essential steps to outline how to achieve effective selectivity and safety

3:30 pm Targeting RNA-Modifying Proteins for Precision Cancer Therapeutics

  • Robert Copeland President & Chief Scientific Officer , Accent Therapeutics


• RNA modifications control many aspects of RNA biology, including translation
• Dysregulation of gene transcription and translation control mechanisms is common in cancer
• Accent is targeting selective RNA modifying proteins for specific cancer indications

4:00 pm Targeting mRNA Modifications to Control mRNA Stability & Translation in Disease

  • Samie Jaffrey Pharmacology Greenberg-Starr Professor , Weill Cornell Medicine


• Examining epitranscriptomic readers, writers, and erasers as therapeutic targets
• Molecular mechanisms of RNA modifications on mRNA translation and stability
• Understanding the scope of the nucleotide modifications that comprise the mRNA epitranscriptome

4:30 pm Chair’s Closing Remarks & End of 3rd RNA-Targeted Drug Discovery Summit