8:00 am Registration & Morning Networking Coffee

8:50 am Chair’s Opening Remarks

  • Matt Woll VP – Head of Chemistry, PTC Therapeutics

Developing Novel Approaches to Target RNA with Small Molecules

9:00 am KEYNOTE ADDRESS: Navigating the Current & Future Landscape of Innovative Approaches to Target RNA with Small Molecules


  • The past, present, and future of structure-based methods to accelerate RNA small molecule drug discovery
  • Novel structure-based approaches enable broad explorations of chemical space and can also guide hit optimization
  • Dynamic ensembles of RNAs are needed to increase the accuracy of predictions and to implement structure-specific mechanisms to inhibit RNAs.

9:30 am Novel Approaches to Reprogram RNA Processing with Small Molecules

  • Peter Smith Co-Founder, President & CEO, Remix Therapeutics


  • Recognizing data science techniques for RNA processing variation analysis in genomic data
  • Using small molecules as research tools in RNA processing
  • Exploiting therapeutic intervention possibilities

10:00 am RNA Genomics Technologies: Accelerating RNA Therapeutics Development


  • Novel RNA genomics technologies go beyond traditional RNA-Seq and illuminate structural and regulatory features of RNA, as well as the RNA interactome
  • RNA structure probing for IVT-mRNA as well as whole transcriptome
  • Simplified assays for ribosome occupancy

10:30 am Morning Break & Speed Networking

11:30 am Identification & Characterization of Small Molecule RNA binders with Affinity Selection Mass Spectrometry (ASMS)


  • PureHoney Tech has optimized a process for high throughput screening of large chemical libraries to identify small molecule binders of RNA targets using ASMS. As many as 100K test compounds can be screened in a little over a day from which hit lists can be generated. The only limitation on target size is solubility allowing for oligos as small as 20 bases and as large as thousands of bases to be screened
  • The binding affinity of hits can be determined by running dose-response experiments to generate binding curves. Alternately the binding affinity of up to 10 test compounds can be rapidly rank ordered by running the test compounds in pools against different concentrations of the RNA target
  • ASMS has been successfully used as a tool in multiple SAR and medicinal chemistry supporting drug development programs

11:50 am Biopharma & Investment Partnerships Panel — Exploring the Future of RNA Investment & Collaborations Space for Small Molecules


The biopharmaceutical sector is considering small molecule medications as a vital component. This community thrives on strategic alliances, which allow for cross-functional sharing of knowledge, skills, and experience across different disciplines to truly advance RNA-targeted small molecule drugs to patients. This session is the ideal opportunity to get face-to-face time with many of the brightest minds working in the RNA small molecule field and establish meaningful business relationships to pursue for the rest of the conference.

  • Exploring the complexities, risk, and decision-making strategies for developing, acquiring, and advancing innovative approaches
  • Where are the gaps using RNA-targeting small molecule approaches that the biotechnology sector can fill?
  • Developing successful expertise in house vs asset acquisition partnering strategies

12:30 pm Networking Lunch Break

Unleashing RNA Structure-Based Design to Enhance Compound Selection

1:30 pm Expanding the Chemical Space of a Hit Molecule Obtained by Fragment Screening

  • Barak Akabayov Principal Investigator, Ben-Gurion University of the Negev


  • The development of antibiotics through rational design by pinpointing fragment molecules that bind an RNA hairpin within the ribosomal PTC and then ‘grew’ the fragment molecules computationally into drug-sized molecules with improved inhibition
  • The use of state-of-the-art data-driven algorithms to effectively grow the fragments into drug-sized molecules
  • The study yielded four molecules that effectively inhibited ribosomal activity through specific binding to the PTC

2:00 pm Expanding the DNA-Encoded Library Toolbox: Identifying Small Molecules that Target RNA


  • RNA targets interact with DEL DNA tags in a sequence dependent manner
  • DNA:RNA interactions induce false negative signals by consuming the majority of sequencing throughput while also promotes false positive features
  • RNA patches can efficiently block the level of DNA:RNA interaction by pre-occupying the binding site on the DNA tags
  • DNA binding motifs and false positives can be predicted by customized algorithms for RNA targets
  • Binders were identified for multiple RNA targets, including FMN Riboswitch and a novel RNA motif predicted from our in-house informatics pipeline

2:30 pm Panel Discussion – Unravelling Methods to Delineate the Structure-Function Relationship


  • How do we come up with methods to explore the target structure-function relationships?
  • Can we effectively determine the mode of action of small molecules that bind to RNA and improve target engagement?
  • How do you find the right binding pocket for there to be a functional effect and drive pharmacology to reach the therapeutic index?

3:00 pm Afternoon Networking Break & Poster Session

Deciphering the Structure – Function Relationship of RNA Targets

3:30 pm Modulating the Conformation & Function of Disease-Relevant RNA with Small Molecules


  • Bioactive small molecules targeting RNA occupy a specific chemical space that can be further explored by synthesis of scaffold-based libraries
  • Small molecule binding and degradation of the MALAT1 triple helix can be predicted via machine learning
  • Amiloride derivatives targeting viral RNA reduce translation and replication of enteroviruses and coronaviruses

4:00 pm How to Define Disease-Specific RNA Structure-Function Relationships


  • Using human genetic data for RNA-targeting drug discovery
  • Functional genomics aided RNA target discovery
  • Computational tools and screening approache

4:30 pm Small Molecule-RNA Interactions that Control Expression of Bacterial mRNAs

  • Robert Batey Professor & Associate Chair, University of Colorado Boulder


  • A spectrum of small molecule metabolites directly binds mRNA to control gene expression
  • mRNAs use a variety of structural motifs to bind small molecules with high affinity and specificity
  • Chemical analogs of natural metabolites bind these RNAs in unexpected way

5:00 pm Chair’s Closing Remarks