8:00 am Coffee & Networking

8:25 am Chair’s Opening Remarks

  • Jane Withka Director & Collaboration Lead, Pfizer Worldwide R&D

Optimizing Discovery & Design Strategies to Target RNA: Overcoming Binding, Selectivity & Drug-Like Challenges

8:30 am Imaging and Assaying Selective Binding of Small Molecules Binding to RNA

  • Samie R. Jaffrey Co-Founder of Gotham Therapeutics; Professor of Pharmacology, Weill Cornell Medicine


• Small molecule target engagement on RNA can be imaged in real-time
• Disease-relevant RNA sequences can be converted into fluorescent sensors for detecting small molecule binding

9:00 am Small Drug-Like Molecules Target Non-Coding RNA with nM Affinity


• A delve into the discovery of drug-like (Lipinski) molecules that bind to non-coding RNAs with low nanomolar affinity
• Structure-based design methods can be used to rapidly improve their affinity and specificity
• These molecules demonstrate specific activity in biochemical and cellular assays

9:30 am Targeting Structurally and Functionally Diverse Nucleic Acids with Drug-Like Small Molecules


• Our laboratory uses a Small Molecule Microarray (SMM) screening approach to profile and identify the RNA-binding properties of small molecules
• Drug-like small molecules are capable of both selectively binding and modulating the function of regulatory RNAs in the cell
• High resolution structural analysis by NMR and X-Ray crystallography is key to establishing a basis for both mechanism of action and molecular recognition

10:00 am Delivery of mRNAs to Promote Epigenetic Resetting of Cellular Age: A New & Safe Paradigm in Overcoming Aging & Aging-Associated Diseases


• Transient reprogramming based on non-integrative mRNA technologies reverses hallmarks of physiological aging of multiple human cell types and restores youthful regenerative response to aged, human muscle stem cells, in each case without abolishing cellular identity
• Turn Biotechnologies method of transient cell reprogramming paves the way to a novel, potentially translatable strategy for ex vivo cell rejuvenation treatment
• This approach holds promise for in vivo tissue rejuvenation therapies to reverse the physiological manifestations of aging and the risk for the development of agerelated diseases

10:30 am Morning Refreshments & Networking

Accelerating Robust Translation of Direct & Bioactive RNA Targeted Small Molecules

11:00 am Translation Control Therapeutics: Discovery of Small Molecule Drugs that Specifically Control mRNA Translation into Proteins


• The novel target space of mRNA translation regulation
• Discovery of small molecule drugs that selectively control mRNA translation
• Anima Biotech: bi-directional and tissue selective translation controlling drugs

11:30 am Drugging RNA with Small Molecules


• Our mission is to render all structured RNA druggable with orally available small molecules
• Structure ID, functional biology, and screening are all on that critical path
• New chemical biology establishes the connection of RNA binding with pharmacology

12:00 pm Identification of Small Molecules that Promote Exon 10 Skipping in MAPT Pre-mRNA


• Direct targeting of RNA with small molecules have the potential to expand target space
• This presentation will describe a collaboration with Prof. Matt Disney at Scripps, Florida: Using the Inforna lead-generation platform followed by virtual screening and hit expansions, small molecule leads have been identified that demonstrate dose-dependent skipping of exon 10 in MAPT pre-mRNA in cell-based assays
• Efforts to understand target-engagement and binding mode will also be highlighted

12:30 pm Networking Lunch

1:30 pm Modulation of RNA Biology with Small Molecules


• Gene expression is a complex process that involves multiple mRNA regulation events, such as transcription, splicing, miRNA regulation and translation
• mRNA processing is controlled through interactions between RNA structures and RNA binding proteins
• We aim to identify RNA / protein interactions critical to disease and to modulate them with small molecules

2:00 pm Panel Discussion: Targeting RNA with Small Molecules to Capture the Therapeutic Opportunities


• How to establish strategies & standards to provide clear guidance on how to intentionally target RNA with small molecules?
• How mRNA and its regulatory mechanisms can enable new strategies against previously undruggable targets? View of the right approach in this vast, novel target space.
• Partnering with pharma: Strategies for emerging platform companies in the RNA field for effective partnering

2:45 pm Interactive Round Table Discussions


Our breakout roundtables will allow you to have more intimate and open discussions on some of the hottest topics and key areas of debate. Drive your own learning, crowd-source ideas and get inspired. Immerse yourself in the following discussions:

• What are the clinical indications where small molecule RNAtherapeutics can be applied?
• Partnering What translational challenges do we foresee before the firstRNA targeted small molecule goes into clinical development?
• How to effectively probe RNA methylation biology with small molecules to get potent and selective chemical matters?

3:30 pm Chair’s Closing Remarks & Close of the 2nd RNA- Targeted Drug Discovery Summit 2019