By Rabia Khan and Aaron Lazarus
Despite the significant target space (70% of the human genome encoding RNA), there are relatively few companies targeting RNA with small molecules.
Over the past years, we learnt a lot by mapping the history of small molecules targeting RNA, and creating a map of companies that are building upon these tools.
We wanted to share our view of this ecosystem, which spans basic research into RNA structure probing, to more high throughput approaches and ultimately the first companies targeting RNA with small molecules.
The timeline is based upon the publication High-throughput determination of RNA structures by Strobel et. al. in 2018.
PTC has pioneered the notion that splicing can be modulated utilizing small molecules. Over the last 20 years, we have perfected our RNA splicing technology. Using this technology, we have successfully identified an oral small molecule for the treatment of spinal muscular atrophy, Evrysdi® (risdiplam). Evrysdi® was the first ever small molecule protein every approved to affect splicing which led to the production of a stable, functional SMN protein.
Base4 (formerly Nymirum)
Proprietary platform is built on unparalleled advancements in RNA structural biology that allows for the visualization of RNA dynamics at the atomic level with unprecedented sensitivity, enabling the targeting of potentially hidden druggable conformations.
Eloxx Pharmaceuticals is a clinical-stage biopharmaceutical company developing novel RNA-modulating drug candidates. They lead the development of eukaryotic ribosomal selective glycosides (ERSG) aimed at treating rare and ultra-rare premature stop codon diseases.
Anima’s mRNA Lightning platform combines high scale phenotypic screening that discovers mRNA biology modulators with MOAi technology that uses AI to elucidate their mechanisms of action
Founded by Kevin Weeks, and built upon the SHAPE-MaP and RING-Map methods, they elucidate 2D shape of RNA and use NMR and other methods to screen for small molecules
Founded on unique chemistry and the PearlSeq platform, Arrakis identifies highly selective, potent RNA-targeted small molecules (rSMs) capable of directly binding to RNA structures. They are one of the most well established company's in the ecosystem.
Founded by an ex-PTC team, SkyHawk uses their SkySTAR platform (SkyHawk small molecule therapeutics for alternative splicing in RNA) which integrates information from computational, kinetic and structural models of RNA. From our understanding, they focus on splicing and use phenotypic screening approaches.
Founded by Matt Disney, Expansion targets expansion repeat disorders.
Saverna has integrated fragment-based screening (FBS) by Nuclear Magnetic Resonance (NMR), to find small molecule RNA binders.
Rgenta' splatform designs small-molecule glues to modulate the interactions among the spliceosome, regulatory proteins, and RNAs.
Reborna has a number of programs in development, with the furtherest program past lead optimisation. They use RNA 3D structure to find small molecule binders.
Panorama is targeting splicing using a combination of computational and other methods.
Founded in Japan, the company uses computational methods to discover selective RNA-structure specific binders
Remix has a focus on splicing, combining data generation and in silico methods. The REMaster platform combines data analytics, novel high through-put screening technologies, and next-generation chemistry to identify and design molecules that can selectively degrade RNA, enhance expression, induce exon skipping, or rescue genetic lesions.
Ithax Pharmaceuticals is a new spin-off biotechnology company located in Seattle and focused on developing small drug-like molecules that target non-coding RNAs in cancer and other chronic diseases.
Revir is developing vitro and in cell screening assays to probe RNA regulatory regions and their function and discover small molecules modulating the functional impact, mainly using phenotypic screening
Building upon work from Standfold, Atomic AI uses AI to predict the three-dimensional structure of RNA and discover novel small molecule binders to RNA 3D structures
Ranar is founded by Gabriel Varani, the company targets RNA structures with small molecules to treat cancer and other serious human diseases.
A stealth biotechnology company, founded by an ex-Arrakis team, they developing small molecules targeting RNA. The company was likely incubated by Evotec and funded by Qiming, Droia Ventures, Platanus, and Taiho Ventures
Ribostrike Platform Stealth Company
Ribostrike is a deep learning framework that identifies small molecules against specific microRNAs.
A University of Portsmouth company discovering small molecules that target RNA.