Original Agenda
We are actively working with our speakers to confirm their availability for the virtual event. Initial response from our speakers has been very positive, and we are optimistic we will have the new programs ready to share here soon.

Cambridge Healthtech Institute’s 2nd Annual

RNA as a Drug Target

Expanding the Boundaries of Druggable Targets

September 16 - 17, 2020

In the past year, the idea of targeting RNA directly with either a small molecule-like drug or with oligonucleotides has gone from an interesting idea to a viable business plan. It is expected that the FDA plans to make a decision on the first oral small molecule targeting splicing. Join us at the 2nd Annual RNA as a Drug Target conference, part of Discovery on Target, as we discuss not only the identification of specific and potent novel binders of RNA, but also the unique challenges that come with a novel drug target class.

Tuesday, September 15

1:00 pm Pre-Conference Short Course Registration (Premium Package or separate registration required)
2:00 Short Courses 1-9 (see Short Courses page for details)
5:00 Close of Day

Wednesday, September 16

7:00 am Registration and Morning Coffee


8:00 Organizer's Welcome Remarks

Cambridge Healthtech Institute

8:05 Chairperson's Remarks

Paloma Giangrande, PhD, Director, Research, Rare Diseases, Moderna Therapeutics


Protein Replacement with mRNA for Inherited Metabolic Diseases

Paloma Giangrande, PhD, Director, Research, Rare Diseases, Moderna Therapeutics

Many rare inherited metabolic disorders are caused by deficiency of essential intracellular proteins (e.g. enzymes, transporters) responsible for maintaining proper homeostasis. Conventional protein replacement (e.g. enzyme replacement therapy or ERT) and gene therapy-based approaches are not an option for treating these disorders due to drug-delivery and efficacy/safety considerations. To develop new treatments for these diseases, we encapsulated nucleoside-modified, codon-optimized mRNAs, encoding these genes in lipid nanoparticles. Preclinical data demonstrating the efficacy and safety of our mRNA-LNP therapy for several rare metabolic disorders will be presented.

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

Utilizing small molecules to modulate splicing has emerged as a successful therapeutic approach to regulating protein expression. Here, three diseases where small-molecule splicing modulators can be utilized are described: spinal muscular atrophy; familial dysautonomia; and Huntington’s disease. For each of these indications, I will discuss the correlation between pharmacokinetics and pharmacodynamics, as well as the correlation between pharmacodynamics and efficacy.


Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy

Hasane Ratni, PhD, Scientist & Project Team Leader, Medicinal Chemistry, F. Hoffmann-La Roche AG

SMA is an inherited disease that leads to loss of motor function and ambulation, and a reduced life expectancy. We have been working to develop orally-administrated, systemically-distributed small molecules to increase levels of functional SMN protein. Herein, we describe the discovery risdiplam that focused on thorough pharmacology, DMPK and safety characterization and optimization. This compound is completing pivotal clinical trials and is a promising medicine for the treatment of patients in all ages and stages of SMA.

9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

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

John Schneekloth Jr. (Jay), PhD, Senior 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.


RNA Modulation of Translation of mRNAs for Novel Therapy in Neurodegenerative Disease

Jack Rogers, PhD, Director, Neurochemistry Laboratory, Associate Professor, Psychiatry-Neuroscience, Harvard Medical School and Massachusetts General Hospital

Our Neurochemistry Laboratory is advancing the therapeutic development of selective and potent alpha-synuclein (asyn), amyloid precursor protein (APP) and Prion protein (PrP) translation modulators. We discuss here the efficacy of key small molecules that alter translation rates of these disease associated proteins by the use of advantageous 5’UTR-directed repressor /reporters of the transcripts for their mRNAs (SNCA-mRNA, APP mRNA, PrP mRNA).  Our goal is to develop RNA directed molecules as neurotrophins for future treatments of Parkinson’s disease, as well as, neurodegenerative diseases that impair memory and cognition.


Translation Control Therapeutics: Discovery of Selective mRNA Translation Modulators

Yochi Slonim, Co-Founder & CEO, Anima Biotech, Inc.

Anima Biotech is advancing Translation Control Therapeutics, the first platform for the discovery of small molecule drugs that selectively control mRNA translation. Using patented technology that causes ribosomes to emit light pulses as they assemble proteins, we screen for drug candidates that decrease or increase translation with selectivity towards mRNAs, tissues, cells or pathways. We advance an internal pipeline of programs across therapeutic areas and in strategic collaboration with Lilly.

11:55 Sponsored Presentation (Opportunity Available)
12:25 pm Session Break
12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:05 Refreshment Break in the Exhibit Hall with Poster Viewing


1:50 Chairperson's Remarks

Natalie Dales, PhD, Director, Global Discovery Chemistry, Novartis Institute for Biomedical Research


Drugging RNA

Natalie Dales, PhD, Director, Global Discovery Chemistry, Novartis Institute for Biomedical Research

TANGO (Targeted Augmentation of Nuclear Gene Output) for the Treatment of Genetic Diseases

Isabel Aznarez, PhD, Co-Founder, Vice President & Head, Biology, Stoke Therapeutics

TANGO uses antisense oligonucleotides (ASOs) to prevent naturally occurring, non-productive splicing, and increase productive mRNA and fully functional protein. We identified non-productive events in > 50% protein-coding genes. ASOs targeting these events lead to increased mRNA and protein in a dose-dependent manner. TANGO-ASO treatment of Dravet syndrome mice lead to protein restoration to near normal levels, significant reversal of the survival phenotype, decreased seizure frequency and increased numbers of seizure-free mice. 

2:55 Sponsored Presentation (Opportunity Available)
3:25 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

Antibody Targeting of Oncogenic mRNAs

Daniel Fernandes, PhD, DSc, CSO, CharlestonPharma, LLC

Recently, keen interest has been expressed at scientific symposia and in the scientific literature regarding RNA as a potential drug target in various diseases. Most of the efforts in targeting mRNA have focused on small drug molecules, since larger molecules often have difficulty in penetrating tumor cells. CharlestonPharma has developed a panel of human IgG1antibodies that bind to the nucleonin transporter on tumor cells in order to gain intracellular access. Once inside the tumor cell, the antibodies interfere with the stabilization of certain oncogenic mRNAs by nucleolin.


Advances in Antibody Oligonucleotide Conjugates (AOCs)

Arthur A. Levin, PhD, Executive Vice President, R&D, Avidity Biosciences LLC
5:05 Transition to Breakout Discussion Groups
5:15 Interactive Breakout Discussion Groups
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.
6:15 Welcome Reception in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)
7:15 Close of Day

Thursday, September 17

7:30 am Registration and Morning Coffee


8:00 Chairperson's Remarks

Jennifer C. Petter, PhD, Founder & CSO, Arrakis Therapeutics

Jennifer C. Petter, PhD, Founder & CSO, Arrakis Therapeutics

RNA is upstream of all biology and presents a vast array of therapeutically attractive targets. Most therapeutic agents that bind directly to RNA are either antibiotics blocking bacterial ribosome function or oligonucleotides with their attendant pharmaceutical limitations. We have identified druggable RNA sub-structures in mRNA and orally available small molecules that bind to those structures selectively and thereby modulate mRNA function. I will describe recent results that support this larger mission.


Development of a Novel miRNA-Based Platform Technology for Cancer

Jingfang Ju, PhD, Professor, Program Director of Oncogenic Drivers and Mechanisms of Carcinogenesis, Stony Brook University

Treatment of pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge. We discovered that miR-15a suppresses Wee1, Chk1, Yap-1, and BMI-1, causing cell cycle arrest and inhibiting cell proliferation. We developed a miRNA-based platform by replacing uracil (U) in the guide strand with 5-fluorouracil (5-FU). In vivo we showed the therapeutic power of 5-FU-miR-15a alone or in combination with gemcitabine with near complete elimination of PDAC lung metastatic tumor growth.

9:05 Sponsored Presentation (Opportunity Available)
9:35 Coffee Break in the Exhibit Hall with Poster Viewing

Using Enzymatic Site-Directed Modification to Enable Analysis of RNA-Protein Interactions and Enrichment of Cellular RNA

Neal Devaraj, PhD, Professor, Departments of Chemistry, Biochemistry and Bioengineering, University of California, San Diego

Leveraging the ability to site-specifically and covalently label an RNA of interest using an RNA-modifying enzyme and unnatural nucleobase substrate, we demonstrate the identification of RNA-protein interactions and the selective enrichment of cellular RNA in mammalian systems. The flexibility and breadth of this approach suggests that this system could be routinely applied to the functional characterization of RNA, greatly expanding the toolbox available for studying mammalian RNA biology.


Chemoproteomic Approaches to Profile RNA Binding and Modifying Proteins

Ralph Kleiner, PhD, Assistant Professor, Department of Chemistry, Princeton University

The properties of eukaryotic messenger RNA can be modulated by dynamic chemical modifications that occur post-transcriptionally (known as the “epitranscriptome”). We are developing chemical proteomic strategies based upon metabolic RNA labeling with artificial nucleosides and synthetic oligonucleotide probes to discover and characterize RNA modification writers, erasers, and readers, and understand their biological roles. This should provide powerful and general strategies for interrogating fundamental RNA regulatory mechanisms and lead to new insights for targeting epitranscriptomic protein factors for therapeutic benefit.

11:20 Enjoy Lunch on Your Own
11:20 Conference Registration for Part B Programs


12:20 pm Event Chairperson's Opening Remarks
An-Dinh Nguyen, Team Lead, Discovery on Target 2020, Cambridge Healthtech Institute
12:30 Plenary Keynote Introduction (Sponsorship Opportunity Available)

Tackling Undruggable Oncoproteins: Lessons from the VHL Tumor Suppressor Protein

William G. Kaelin, Jr., MD, Professor and Investigator, Howard Hughes Medical Institute, Oncology, Dana-Farber Cancer Institute

VHL tumor suppressor protein (pVHL) inactivation is common in kidney cancer and upregulates the HIF2 transcription factor. PT2977/MK-6482 is an allosteric HIF2 inhibitor now in Phase 3 testing. Thalidomide-like drugs (IMiDs) bind to cereblon which, like pVHL, is the substrate-binding unit of a ubiquitin ligase. IMiDs redirect cereblon to destroy the myeloma oncoproteins, IKZF1 and IKZF3. We have developed new assays for identifying drugs that can destabilize oncoproteins of interest.


De-Risking Early Drug Discovery

Panel Moderator:
Nadeem Sarwar, PhD, Founder & President, Eisai Center for Genetics Guided Dementia Discovery, Eisai, Inc.
  • Data Sciences
  • ​Novel Chemical Modalities
  • Investment and Partnering Models
  • COVID-19 Progress as Examples of Successful Partnerships
Anthony A. Philippakis, PhD, Chief Data Officer, Data Sciences & Data Engineering, Broad Institute; Venture Partner, GV
Andrew Plump, MD, PhD, President, Research & Development, Takeda Pharmaceuticals, Inc.
2:00 Close of Plenary Keynote Program
2:00 Dessert Break in the Exhibit Hall with Poster Viewing
2:45 Close of RNA as a Drug Target Conference

Choose 2 Short Courses and 2 Conferences/Training Seminars
Sept. 15 Short Course: SC9: Understanding and Modulating the RNA Machinery
Sept. 16-17 Conference: RNA as a Drug Target
Sept. 17 Dinner Short Course: SC11: Insights into PROTACs and Targeted Protein Degradation
Sept. 17-18 Conference: Lead Generation Strategies