8:00 am Morning Networking Coffee

8:50 am Chair’s Opening Remarks

Unraveling RNA Degradation to Expand the Druggable Genome

9:00 am Sequence-Based Design of Small Molecule RNA Degraders

  • Matthew Disney Professor & Chair; Department of Chemistry, The Scripps Research Institute

Synopsis

  • How to find small molecules that bind to RNA
  • How to assess target engagement in cells
  • How to convert to a degrader

9:30 am Targeting RNA Through Induced Proximity

  • Ryan Potts Executive Director & Head - Induced Proximity Platform, Amgen

Synopsis

  • Discuss the concept of induced proximity
  • How can induced proximity be utilized for targeting RNA
  • Evaluating RNA effectors for RNATACs

10:00 am Morning Networking Break

Evolving Platform Technologies to Optimize Biologically Relevant RNA-related Events

11:00 am Next Generation Splicing Modulators

  • Scott Barraza Discovery Chemistry Group Leader, PTC Therapeutics

Synopsis

  • The approval of Risdiplam for the treatment of SMA validated the approach of selectively modulating splicing with small molecules
  • PTC has developed a comprehensive discovery platform to identify novel splicing modulators for the treatment of diseases with unmet needs
  • Novel splicing modulators are being optimized for recently identified disease-relevant splicing events

11:30 am mRNA Lightning Platform – Discovery of Small Molecule mRNA Drugs & Their Mechanisms of Action

Synopsis

  • Target space opportunity: an overview of Anima’s mRNA biology modulators
  • mRNA Lightning platform combines mRNA Biology automated screening labs with cloud-based AI mRNA image analysis
  • Anima’s software integrates MOA visualizing and fingerprinting to calculate similarities to all previously seen MOAs in mRNA Biology

12:00 pm Lunch Networking Break

Afternoon Chair

Emerging Non-Coding RNA-Targeted Small Molecules to Overcome Therapeutics Hurdles

1:00 pm Developing Small Molecule Therapeutics Targeting lncRNAs

Synopsis

  • LncRNAs play an important role in human disease
  • LncRNAs exert their functions through interaction with proteins
  • NextRNA is developing small molecules inhibiting RNA-protein interaction

1:30 pm Unraveling Novel Small Molecules for Neuroprotective microRNA Activation in Alzheimer’s Disease

  • Anna Krichevsky Assistant Professor, Brigham and Women’s Hospital & Harvard Medical School

Synopsis

  • Diverse non-coding RNAs regulate all biological functions in a cell and expand the landscape of therapeutic targets in the CNS pathologies
  • miR-132 is the top neuroprotective miRNA associated with pathology in Alzheimer’s disease and other tauopathies
  • The first screen on human neurons identified small molecule activators of miR-132-mediated neuroprotection

2:00 pm Delineating Non-Coding RNA Therapeutics Avenues

Synopsis

  • Bioavailability and target interactions
  • Targetable sequence heterogeneity
  • Reverse translational consideration

2:30 pm Finding & Characterizing Small-Molecule Compounds Binding to Non-Coding RNA Targets Using Affinity-Selection MS

Synopsis

  • Affinity-selection MS screening can find binders to a wide variety of RNA targets
  • RNA-binding ligands can then be profiled to determine structural features that bias them to bind to RNA targets
  • Biophysical and cell-based techniques have been applied to characterize activities of novel binders to be bacterial and mammalian non-coding RNA targets

3:00 pm Afternoon Networking Break

Optimizing Selectivity & Specificity to Enable Potent Small Molecules Targeting RNA

3:30 pm Panel Discussion – Modelling Selectivity – Can we Develop a Model to Map Selectivity Binding?

  • Amanda Garner Associate Professor, University of Michigan
  • Barak Akabayov Principal Investigator, Ben-Gurion University of the Negev
  • Dave Mauger Director & Head of Data Science, Arrakis Therapeutics
  • Vijay Modur Head of R&D, Eloxx Pharmaceuticals

Synopsis

  • How to define selectivity and specificity?
  • How to improve efficient and potent cell, tissue, and disease selectivity?
  • Can we construct a suitable model for selectivity?
  • How to guarantee selective and specific binding of your RNA targeting small molecules?

4:00 pm Discovery of Novel Oncoribosome Selective Protein Translational Inhibitors via Synthetic Modified Macrolides

Synopsis

  • The TURBO-ZM platform represents an innovative leap in synthetic chemistry to generate Ribosomal Modulating Agents (RMAs) selective for the oncoribosome
  • RMAs spare normal cells while targeting a subset of cancers addicted to oncoribosome-driven protein translation
  • Proteomic analysis shows extreme susceptibility to protein translation inhibition of highly positively charged proteins that participate in translation initiation and ribogenesis

4:30 pm Chair’s Closing Remarks