RNA molecules are crucial for delivering cellular information and genetic regulation, but until recently, the drug discovery world has emphasized protein drug targets. Our lack of knowledge in RNA biology prevented us from exploring possibilities of RNA drug targets, but with recent advances in technologies such as sequencing, new therapeutic strategies are being explored. Join us at the Inaugural RNA as a Drug Target conference, part of Discovery on Target, as we discuss RNA as a novel target site for therapeutics.

Final Agenda

Wednesday, September 18

11:20 am Conference Registration Open

Click here for full abstracts.

12:20 pm Event Chairperson’s Opening Remarks

An-Dinh Nguyen, Team Lead, Discovery on Target 2019, Cambridge Healthtech Institute


12:30 Plenary Keynote Introduction

12:40 Base Editing: Chemistry on a Target Nucleotide in the Genome of Living Cells

David R. Liu, PhD, Howard Hughes Medical Institute Investigator, Professor of Chemistry & Chemical Biology, Harvard University



1:20 PROTACs: Past, Present, and Future

Craig M. Crews, PhD, Professor, Chemistry; Pharmacology; Molecular, Cellular & Developmental Biology; Yale University



2:00 Close of Plenary Keynote Program

2:00 Dessert Break in the Exhibit Hall with Poster Viewing

Small Molecules to Target RNA

2:45 Organizer's Welcome Remarks

2:50 Chairperson’s Opening Remarks

Meizhong Jin, PhD, Senior Director, Chemistry, Arrakis Therapeutics

2:55 FEATURED PRESENTATION: Non-Coding RNA as a Small Molecule Drug Target

Elliott Nickbarg, PhD, Principal Scientist, Pharmacology Department, Merck & Co, Inc.

To understand RNA-small molecule druggability, we have validated an affinity-selection mass spectrometry screening system for detection of RNA-small molecule interactions. This system was used to screen a variety of RNA targets against diverse small molecule collections, functionally annotated compounds, and collections enriched in RNA-binding properties. The system generated a large dataset of small molecule-ncRNA interactions. Here, we outline our approach and results, and discuss implications for new drug discovery efforts.

3:25 Directly Targeting RNA with Small Molecules

Meizhong Jin, PhD, Senior Director, Chemistry, Arrakis Therapeutics

RNA plays critical roles in gene expression and regulation and, as such, RNA molecules are implicated human disease, often via the undruggable proteins expressed by those RNAs. RNA as a therapeutic target has been validated clinically by oligonucleotide drugs although with limitations. Recent advances in RNA structure and biology point to the exciting potential of directly targeting RNA with drug-like small molecules, offering potential advantages over oligonucleotides.

3:55 Sponsored Presentation (Opportunity Available)

4:25 Refreshment Break in the Exhibit Hall with Poster Viewing

5:00 Precise and Potently Bioactive Small Molecules Interacting with RNA (SMiRNAs)

Suzanne Rzuczek, PhD, Associate Scientific Director, Expansion Therapeutics

The expanding role of RNA in disease has led to exploring RNA as a drug target; however, the ability to selectively target RNA remains challenging. We have assembled technologies and tools to facilitate the identification of specific and potent novel small molecule binders of RNA. We will highlight this generally applicable technology to the design and study of potently bioactive and selective SMiRNAs targeting CUG repeats in Myotonic Dystrophy Type 1 (DM1).

5:30 Targeting Structurally and Functionally Diverse RNAs with Drug-Like Small Molecules

John S. Schneekloth Jr. (Jay), PhD, Principal Investigator, Chemical Biology Laboratory; Head, Chemical Genetics Section, Center for Cancer Research, National Cancer Institute, NIH

The past twenty years have seen an explosion of interest in the structure and function of RNA and DNA. While some 80% of the human genome is transcribed into RNA, just ~3% of those transcripts code for protein sequences. Here we discuss our group’s efforts to target RNA and DNA with drug-like small molecules using a Small Molecule Microarray (SMM) screening platform and the molecular basis for these interactions.

6:00 Targeting Pre-mRNA Splicing with Small Molecules

Marla Weetall, PhD, Vice President, Pharmacology, PTC Therapeutics

Pre-mRNA splicing is emerging as a key control point in the expression of disease-modifying genes. Muta-tions causing alterations in splicing may result in diseases. Small molecules that affect pre-mRNA splicing have been identified and are being clinically developed. At PTC, we have developed a general approach to discover and develop drugs targeting splicing. Here we describe the application of this approach to spinal muscular atrophy, familial dysautonomia, and Huntington’s disease.

6:30 Dinner Short Course Registration
Click here for details on short courses offered.

9:30 Close of Day

Thursday, September 19

7:00 am Registration Open

7:30 Interactive Breakfast Breakout Discussion Groups

Grab a cup of coffee and join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic. Visit the conference website for discussion topics and moderators.

8:30 Transition to Sessions

RNA-Protein Complexes

8:40 Chairperson’s Remarks

Razvan Nutiu, PhD, Investigator, Chemical Biology & Therapeutics, Novartis

8:45 RNA Splicing Modulation… Application to CD33

Tom Chappie, Associate Research Fellow, Pfizer

GWAS studies on large populations of patients with late-onset Alzheimer’s Disease have identified a SNP in the innate immune-response receptor CD33 (Siglec 3) that is protective for Alzheimer’s disease. This protective SNP is hypothesized to induce an exon skipping event in the translation of CD33 protein. A phenomimetic strategy for hit identification of small molecule splicing modulators will be described.

9:15 Translation Control Therapeutics

Kevin Pong, PhD, Vice President, Business Development, Anima Biotech, Inc.

Anima Biotech is advancing Translation Control Therapeutics, the first platform for the discovery of small molecule drugs that specifically control mRNA translation as a new strategy against many diseases. With novel biology that monitors the translation of proteins and proprietary cloud-based analysis software, we identify drug candidates that modulate a target protein’s production. We develop a pipeline across therapeutic areas and partner with Pharma for their targets including our +$1B collaboration with Lilly. Our approach was further validated with 5 granted patents, 14 peer reviewed publications and 17 scientific collaborations.

9:45 Modulating the Epitranscriptomic RNA Modifications for Cancer Therapy

Pawel Sledz, PhD, Senior Scientist, Department of Biochemistry, University of Zurich

The modifications of transcriptomic RNA (also called epitranscriptomic modifications) have recently emerged as mechanism of regulation of gene expression, and due to implication in a number of diseases have attracted attention of the drug discovery community. We have pioneered early discovery in epitranscriptomic target space focusing on modulating the protein-RNA interactions (PRIs) and RNA-modifying proteins (RMPs), and delivered lead candidates in two programs. In my talk I will discuss the challenges and opportunities in this target space, as well as provide update on our portfolio: lead generation efforts, preclinical studies, and drug-discovery platform.

10:15 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced


10:55 Enabling Modulation of RNA Biology in Human Disease with Small Molecules

Razvan Nutiu, PhD, Investigator, Chemical Biology & Therapeutics, Novartis

RNA biology is relevant to human disease and drug discovery. To enable drug discovery in the RNA space, several key challenges have to be addressed: what are the most relevant RNA biology phenotypes that affect human disease? What are the molecular interactions that control these phenotypes? What is the chemistry capable of modulating relevant RNA structures and/or RNA/protein complexes? The presentation aims to discuss some of these challenges and to propose an integrated approach to RNA targeted drug discovery using small molecules.

11:25 Structure-Based Discovery of New Functions in Large RNAs

Kevin Weeks, PhD, Kenan Distinguished Professor of Chemistry, University of North Carolina

The functions of many RNA molecules – including mRNAs, long non-coding RNAs, and the genomes of RNA viruses – require that an RNA fold back on itself to create intricately and complexly folded structures. This talk will focus on recent progress in our lab with high-resolution RNA structure probing over large scales such that both secondary and tertiary structure elements can be identified and such that these structural data can be used to identify RNA elements likely to have direct and important roles in cellular function and gene regulation.

11:55 Sponsored Presentation (Opportunity Available)

12:25 pm Session Break

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing

Oligonucleotides and Other Novel Methods to Target RNA

2:05 Chairperson’s Remarks

Arthur A. Levin, PhD, Executive Vice President, R&D, Avidity Biosciences

2:10 Oligonucleotide Therapeutics Now on Target: Advances in Antibody Oligonucleotide Conjugates (AOCs)

Arthur A. Levin, PhD, Executive Vice President, R&D, Avidity Biosciences

The ability to utilize genomic information to design oligonucleotide therapeutics is the goal of the industry. Their broader potential as therapeutics has remained untapped because delivery to cells is limited. We are utilizing monoclonal antibodies against internalized cell surface proteins as a delivery mechanism for oligonucleotide therapeutics. We have developed a technology that allows us to successfully delivery oligo payloads to multiple cell types.

2:40 FANA ASO Therapy to Silence Foxp3, Impair Treg Function and Promote Anti-Tumor Immunity

Wayne Hancock, PhD, Professor of Pathology and Laboratory Medicine, University of Pennsylvania; Chief of the Division of Transplant Immunology, Children’s Hospital of Philadelphia (CHOP)

Since Foxp3+ Treg cells limit host anti-tumor immunity, we tested the efficacy of FANA antisense-oligonucleotides that spontaneously enter cells. Unlike scrambled controls, Foxp3-specific FANAs decreased Foxp3 mRNA and protein expression and impaired Treg function in vitro. Comparable effects occurred in vivo. Mice receiving Foxp3 FANA had impaired tumor growth, with 50% clearing tumors and markedly reduced Foxp3+ Treg infiltration. Hence, FANA oligos modulate Foxp3 expression and Treg function, providing a major new approach to cancer immunotherapy.

3:10 Identification of Development Candidate eFT226, a First in Class Inhibitor of eIF4A RNA Helicase

Justin Ernst, PhD, Director of Medicinal Chemistry, Effector Therapeutics

Dysregulated translation of specific mRNAs is an important driver of uncontrolled growth, immune evasion and metastasis in many types of cancer. eIF4A (eukaryotic initiation factor 4A), an ATP-dependent DEAD-box RNA helicase and a key component of the eIF4F complex, plays a crucial role in translational regulation of several oncogenes, rendering it a promising therapeutic target for the treatment of cancer. Flavagline natural products have been shown to inhibit eIF4A by RNA-sequence specific formation of a stabilized eIF4A/RNA/flavagline ternary complex; however, these compounds generally suboptimal drug-like properties. This presentation describes the design of and physicochemical property optimization in novel flavagline cores to support intravenous delivery, culminating in clinical candidate eIF4A inhibitor eFT226.

3:40 PATrOL-Enabled Therapies Targeting Mutant RNA Primary and Secondary Structures

Dietrich A. Stephan, PhD, Founder and CEO, NeuBase Therapeutics

NeuBase is developing next-generation gene silencing therapies with a flexible, highly specific synthetic antisense technology. The proprietary peptide-nucleic acid (PNA) antisense oligonucleotide (PATrOL™) platform allows for the rapid development of targeted drugs, increasing the treatment opportunities for the hundreds of millions of people affected by rare genetic diseases, including those that are impossible to treat using traditional antisense approaches. Using PATrOL technology, NeuBase aims to first tackle rare, genetic neurological disorders.

4:10 Close of Conference