Our Science
Protein targets have been a productive source for drug discovery and development. However, only a small fraction of disease-causing proteins has ever been successfully drugged, and many are considered “undruggable” by conventional approaches.
Ribometrix has risen to this biological challenge by targeting mRNAs, interfering with their translation, and leading to reduction of the target protein. This approach has been highly validated by oligonucleotide therapeutics, although wider adoption has been hampered by significant delivery challenges.
Small molecules have inherent advantages with oral bioavailability, wide distribution to tissues and high cellular penetration.
Our platform enables us to modulate RNA biology for therapeutic effect with two independent yet related strategies to develop small molecule therapeutics: We use direct targeting of complex RNA structures and disruption of RNA/RNA-binding protein interactions to create a comprehensive pipeline of small-molecule therapeutics.
Direct RNA Targeting
Until recently, it was impossible to systematically target RNAs with small molecules because there were no reliable methods to consistently identify the three-dimensional structures of most RNAs, and no robust assays to screen and optimize RNA-targeting small molecules. Ribometrix has built an industry-leading technology platform that leverages proprietary capabilities to identify and drug complex RNA structures in therapeutically compelling RNAs.
Our platform has revealed that many of these RNAs adopt unique three-dimensional structures. We screen large chemical libraries to identify small molecules that bind specifically and potently to these RNA structures. Our team is continuously evolving our platform with additional state-of-the-art capabilities to progress ligands that specifically target these structures into therapeutics.
RNA-RBP interactions
RNA exists in a complex intracellular environment where it encounters numerous macromolecules that direct its function and activity. One class of these macromolecules, RNA binding proteins (RBPs), constantly interacts with RNA to dictate and modify RNA function.
RBPs represent a large universe of potential drug targets and many RNA-RBP interactions are mediated by complex RNA structures. Our platform is uniquely positioned to efficiently identify and directly target RNA-RBP interactions to impart specific therapeutic effects. To achieve that, we target individual RNA-RBP interactions and RBPs that modulate distinct disease-associated pathways.
RNA Degraders
RNA degraders represent a convergence of direct RNA targeting and RNA-RBP interactions. When we combine an RNA-binding small molecule with a nuclease-recruiting molecule, the resulting “bi-functional” molecule can specifically target an RNA for degradation, ensuring that the mRNA-encoded protein is not produced.
Analogous to PROTACS and protein degradation, RNA degraders represent a potent mechanism to downregulate protein expression at the RNA level.
Platform Technology Capabilities
To discover and develop RNA- and RBP-targeting small molecule therapeutics, Ribometrix has built an industry-leading drug discovery platform that employs proprietary RNA structure determination, RNA-RBP interaction mapping, biophysical, biochemical, and functional assays, structural biology, and proprietary AI/ML capabilities.
