RNA-Targeted Small Molecules 2019: a landscape analysis of companies, technologies, targets, investors and partners from an industry perspective

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Publisher: La Merie Publishing
Pages: 223
Format: PDF
Product Line: Full Report
Product Code: LMFR0030
Release Date: September of 2019

RNA-Targeted Small Molecules 2019: a landscape analysis of companies, technologies, targets, investors and partners from an industry perspective

This report provides you with a landscape description and analysis of discovery and development of small molecules against RNA as a drug target from an industry perspective as of September 2019.

The report brings you up-to-date with information about and analysis of

  • Approaches to target RNA with small molecules: splicing, translation, epitranscriptomics and direct RNA targeting;
  • Stakeholders in the field: technology and major pharmaceutical companies, investors and CROs;
  • Technologies of RNA biology and small molecule drug discovery in a repeatable and scalable way;
  • Preclinical and clinical experience with selected RNA-targeted small molecules;
  • Targets and indications selected for RNA-targeted small molecule drug discovery;
  • Financing situation of technology companies and key investors in the field
  • Partnering deals with financial terms;
  • Comparative assessment of technology companies.

Since 2017, nearly US$ 1 bln has been raised by start-up companies targeting RNA with small molecules in financing rounds and from partnering deals. This huge amount of money highlights the tremendous interest from investors and major pharmaceutical companies and the opportunities they recognize in these new approaches to target RNA with small molecules.

Nearly all small molecule-based drugs in clinical use target proteins. It is estimated that about 20,000 human proteins are expressed by the human genome and 10-15% are thought to be disease-related. However, many of them are considered as undruggable for various reasons, e.g. because they lack a distinctive motif for small molecule binding.

Originally thought to be merely a conduit for moving information encoded in the nuclear genome to the protein translational machinery in the cytoplasm via the canonical DNA-RNA-protein pathway, RNA is now increasingly known to have multiple roles, both coding and non-coding and to take myriad forms. Besides messenger RNAs (mRNAs) which encode proteins, and the ribosomal RNAs (rRNAs) involved in translating them, understanding continues to grow of the multitude of non-coding RNA (ncRNA) molecules, such as microRNA (miRNA), piwiRNA, long non-coding RNA (lncRNA), antisense RNA, short hairpin RNA and circular RNA. About 75% of the human genome is transcribed into RNA, yet only 1-2% encodes proteins

The recent advancement in the knowledge about diversity, structural and functional information related to RNAs has put them in the lime light as a drug target. RNA has an important role in the transcription regulation, regulation of the translation, catalysis, protein function, protein transport, peptide bond formation and RNA splicing. New findings have identified RNA as a potential target in multitude of diseases including bacterial/viral infections and cancer. Just like proteins, RNAs can form well-defined tertiary structures, such as double helices, hairpins, bulges, and pseudo-knots.

With the ability to target RNA, the potential pool of drug targets would dramatically expand

Strong proof-of-principle for RNA-targeted drugs has been provided by antisense oligonucleotides and synthetic RNAs that e.g. redirect the cellular RNA interference (RNAi) machinery. In addition to antisense and RNAi, which includes short interfering RNA (siRNA) and miRNA, other RNA therapeutics include mRNA, self-amplifying mRNA (samMRNA) and small activating RNA (saRNA).

However, nucleic acid-based therapeutic approaches involve large, often highly charged molecules with the associated delivery challenges, e.g. they do not pass the blood-brain barrier to to reach the brain or spinal cord, and have some toxicity issues (e.g. platelet count).

Another strategy to target RNA involves using small molecules as modulators of RNA. Small molecules are one of the most recent emerging RNA-focused therapeutics. They have several advantages over RNA molecules, including oral administration, easier entry into cells and better stability.

Several approaches are pursued to target RNA with small molecules:

mRNA Translation Regulation: Regulation of gene expression at the level of mRNA translation is a fundamental mechanism for moderating cellular events. The translation of single specific mRNAs, subsets, or even a majority of the mRNAs in a cell, is controlled almost exclusively through a multitude of interactions that occur between RNA-binding proteins and regulatory elements embedded throughout the mRNA.

RNA Splicing Modification; Post-transcriptional modification or co-transcriptional modification is a set of biological processes common to most eukaryotic cells by which an RNA primary transcript is chemically altered following transcription from a gene to produce a mature, functional RNA molecule that can then leave the nucleus and perform any of a variety of different functions in the cell. Three major steps significantly modify the chemical structure of the RNA molecule: the addition of a 5′ cap, the addition of a 3′ polyadenylated tail, and RNA splicing.

Direct RNA Targeting: RNA can form complex three-dimensional structures through canonical Watson-Crick base pairing and complex tertiary interactions that are mediated by non-canonical bonds. Such structures can be as intricate and stable as those formed by proteins and can recognize small-molecule ligands, other nucleic acids, or proteins with high affinity and specificity. Modern molecular techniques provide in-depth insides to the RNA structure and function. X-ray crystallography, nuclear magnetic resonance, and cryo-electron microscopy yielded a solid foundation for understanding the chemical and structural basis of RNA functions at atomic resolution. The development of RNA-centric deep-sequencing probing techniques opened up the possibility for the global assessment of RNA structures at a single nucleotide resolution, and in various biological contexts.

Indirect RNA Targeting – Epitranscriptomics: The epitranscriptome includes all the biochemical modifications of the RNA (= the transcriptome) within a cell. Epitranscriptomics involves all functionally relevant changes to the transcriptome that do not involve a change in the ribonucleotide sequence. Thus, RNAs are indirectly targeted via the proteins they interact with.

What will you find in the report?

  • Profiles of technology companies active in the field;
  • Description of Big Pharma’s role in the field (in-house R&D, partnering and investing);
  • Comprehensive description and analysis of emerging technologies with a directed, intentional approach to drug-RNA structure;
  • Preclinical and clinical profiles of RNA-targeted small molecules in all phases of development;
  • Technology selection and preferences of major pharma;
  • Key characteristics of technologies;
  • Target selection and competition of drug candidates;
  • Description and analysis of financing rounds (capital raised, investors);
  • Economic terms of collaboration and licensing deals;
  • Sources of financing.

Who will benefit from the report?

  • Venture capital, private equity and investment managers;
  • Managers of Big Pharma venture capital firms;
  • Financial analysts;
  • Business development and licensing (BDL) specialists;
  • CEO, COO and managing directors;
  • Corporate strategy analysts and managers;
  • Chief Technology Officer;
  • R&D Portfolio, Technology and Strategy Management;
  • Clinical and preclinical development specialists.

Table of Contents



1          Executive Summary


2          Introduction & Overview


3          mRNA Translation Regulation by Small Molecules


3.1       Overview

3.1.1    Companies

3.1.2    Technologies and Targets

3.1.3    Preclinical and Clinical Experience

3.1.4    Partnering and Financing

3.1.5    Comparative Assessment

3.2       Company Profiles

3.2.1    Anima Biotech

3.2.2    eFFECTOR Therapeutics

3.2.3    Eloxx Pharmaceuticals

3.3.      Selected Technology Profile

3.3.1    Translation Control Therapeutics Platform

3.4       Drug and Drug Candidate Profiles

3.4.1    BAY 1143269

3.4.2    eFT226

3.4.3    eIF4E Inhibitors

3.4.4    ELX-02

3.4.5    Tomivosertib

3.4.6    Translarna


4          RNA Splicing Modification by Small Molecules


4.1       Overview

4.1.1    Companies

4.1.2    Technologies and Targets

4.1.3    Preclinical and Clinical Experience

4.1.4    Partnering and Financing

4.1.5    Comparative Assessment

4.2       Company Profiles

4.2.1    H3 Biomedicine

4.2.2    Panorama Medicine

4.2.3    PTC Therapeutics

4.2.4    Skyhawk Therapeutics

4.3       Selected Technology Profile

4.3.1    RNA Splicing Platform

4.4       Drug Candidate Profiles

4.4.1    Branaplam

4.4.2    E7107

4.4.3    H3B-8800

4.4.4    PTC258

4.4.5    Risdiplam


5          Direct RNA Targeting by Small Molecules


5.1       Overview

5.1.1    Companies

5.1.2    Technologies

5.1.3    Targets and Indications

5.1.4    Partnering and Financing

5.1.5    Comparative Assessment

5.2       Companies

5.2.1    Arrakis Therapeutics

5.2.2    Expansion Therapeutics

5.2.3    Novation Pharmaceuticals

5.2.4    Nymirum

5.2.5    Ribometrix

5.2.6    Saverna Therapeutics

5.2.7    Target RNA


6          Indirect RNA-Targeted (Epitranscriptomic) Small Molecules


6.1       Overview

6.1.1    Companies

6.1.2    Technologies

6.1.3    Targets and Indications

6.1.4    Partnering and Financing

6.1.5    Comparative Assessment

6.2       Company Profiles

6.2.1    AC Immune

6.2.2    Accent Therapeutics

6.2.3    EPICS Therapeutics

6.2.4    Gotham Therapeutics

6.2.5    ImStar Therapeutics

6.2.6    STORM Therapeutics

6.2.7    Twentyeight-Seven Therapeutics


7          Major Pharmaceutical Companies as Stakeholders in RNA-Targeted Small Molecule R&D


7.1       Overview

7.2       Companies

7.2.1    Biogen

7.2.2    Boehringer Ingelheim

7.2.3    Bristol-Myers Squibb

7.2.4    Celgene

7.2.5    Eli Lilly

7.2.6    Merck

7.2.7    Novartis

7.2.8    Pfizer

7.2.9    Roche

7.2.10  Takeda Pharmaceutical Co

7.2.11  UCB


8          Outlook and Perspectives


9          References


10        Addendda


Addendum 1: Small Molecule mRNA Translation Regulators

Addendum 2: Small Molecule RNA Splicing Modifiers

Addendum 3: Direct RNA-Targeted Small Molecules

Addendum 4: Indirect RNA-Targeted Small Molecules (Epitranscriptomics)

Figures & Tables

Table 1           Overview of Small Molecule Translation Regulator Companies

Table 2           Key Features of Technologies to Discover Small Molecule mRNA Translation Regulators

Table 3           Targets of Small Molecule mRNA Translation Regulator R&D Programs

Table 4           Profiles for Selected Small Molecule mRNA Translation Regulators

Table 5           Financing of Small Molecule RNA Translation Regulator Companies by Investors and Collaboration Partners

Table 6           Comparative Assessment of Small Molecule mRNA Translation Regulator Companies

Table 7           Overview of Companies with Small Molecule RNA Splicing Modifiers

Table 8           Key Features of Technologies to Discover Small Molecule RNA Splicing Modifiers

Table 9           Targets/Indications of Small Molecule RNA Splicing Modifier R&D Programs

Table 10         Profiles for Selected Small Molecule mRNA Translation Regulators

Table 11         Financing of RNA Splicing Modifier Companies by Investors and Collaboration Partners

Table 12         Comparative Assessment of Small Molecule RNA Splicing Modifier Companies

Table 13         Skyhawk Therapeutics‘ Strategic Collaborations with Major Biopharmaceutical Companies for mRNA Splicing Modifiers Discovered by SkySTAR Technology

Table 14         Overview of Companies with Direct RNA-Targeted Small Molecules

Table 15         Key Features of Technologies to Discover Direct RNA-Targeted Small Molecules

Table 16         Targets/Indications of Direct RNA-Targeted Small Molecule R&D Programs

Table 17         Financing of Direct RNA-Targeted Small Molecule Companies by Investors and Collaboration Partners

Table 18         Comparative Assessment of Direct RNA-Targeted Small Molecule Companies

Table 19         Overview of Companies with Epitranscriptomic Small Molecule Modulators

Table 20         Key Features of Technologies to Discover Epitranscriptomic Small Molecule Modulators

Table 21         Targets/Indications of Epitranscriptomic Small Molecule Modulator R&D Programs

Table 22         Financing of Epitranscriptomic Small Molecule Modulators Companies by Investors and Collaboration Partners

Table 23         Comparative Assessment of Epitranscriptomic Small Molecule Modulator Companies

Table 24         Major Pharmaceutical Companies as Stakeholders in RNA-Targeted Small Molecule R&D

Table 25         Comparison of Four Approaches in RNA-Targeted Small Molecule R&D

AC Immune

Accent Therapeutics

Anima Biotech

Arrakis Pharmaceuticals


Boehringer Ingelheim

Bristol-Myers Squibb


eFFECTOR Therapeutics

Eli Lilly

Eloxx Pharmaceuticals

Epics Therapeutics

Expansion Therapeutics

Gotham Therapeutics

H3 Biomedicine

ImStar Therapeutics



Novation Pharmaceuticals


Panorama Medicine


PTC Therapeutics


Roche (Genentech)

Saverna Therapeutics

Skyhawk Therapeutics

STORM Therapeutics

Takeda Pharmaceutical Co


Twentyeight-Seven Therapeutics

UCB (The RNA Medicines Company)


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