Small molecule drugs are very popular in pharmacology. What makes them different from large-molecule drugs is their weight. They are so small that they can easily cross the cell-membrane and interact with intracellular molecules like proteins to achieve their therapeutic aims . Everyday example of small molecule drug is for instance aspirin – a common drug taken for relieving minor aches, pains or fevers.
Key pharmaceutical players have been investing their time and resources in small-molecule drug discovery and development like AstraZeneca. However, did you know that Poland has its own strong player in this market? It is Molecure, a pharmaceutical company based in Warsaw.
The science behind Molecure
Molecure is a pharmaceutical clinical-stage company which means that at least one of its drug candidates is being tested in clinical trials. What makes Molecure stand out against the competition is its unique RNA platform that allows them to develop first-in-class small molecule drugs that directly modulate unexplored protein targets and the function of mRNA to treat multiple incurable diseases .
In the human proteome (the entire complement of proteins that can be expressed in an organism) there are estimated 20,000 proteins of which only 15% can serve as drug targets . It is such because only a fraction of all human proteins involved in various disease conditions can bind to small molecules. As a result, the human transcriptome (a sum of all messenger RNAs expressed from the genes in an organism) is still largely underexploited as a new source of therapeutic targets. It does not play an important role in pharmaceutical drug discovery . This is when Molecure enters the equation with their bioinformatics RNA platform positioned to outperform standard methods in small molecule discovery processes.
Their platform involves a couple of crucial steps enabling the discovery of hit compounds and demonstration of the druggability of mRNA targets. Firstly, via exclusive algorithms, scientists identify unique, stable and functional motifs (a dominant or recurring sequence) within mRNA of clinically relevant genes associated with various diseases. Those predicted motifs are then confirmed at a single nucleotide resolution. Afterwards, thanks to AI and NMR testing (that enables verification of chemical synthesis and compound characterisation), scientists focus on the mRNA motifs with sufficient structural sophistication which makes it likely that small molecules may bind to mRNA with strong affinity and specificity. This is when potential binding sites are being mapped out as well. Now, it is time to design a small molecule fit for purpose. Using a combination of virtual modelling and traditional chemistry, screening and refining of hit (any compound that has a binding activity to a biological target) and lead (a compound with pharmacological activity but still needs to be optimised for therapeutic effect and safety profile) compounds take place. These compounds are further assessed based on their potency in vitro and in vivo. To understand it better, below there is a video created by Molecure explaining their RNA platform in great detail: https://youtu.be/-yux6pd64WU
Molecure currently has 2 programs in clinical development and another 6 under the belt. OATD-01, the first Molecure program in clinical phases, is a chitinase inhibitor – a potential drug to treat sarcoidosis and other ILDs . Sarcoidosis is an inflammatory disease involving the overreaction of the immune system and the formation of clusters of inflamed tissue in various organs in the body known as granulomas . The cause of sarcoidosis is unknown, although it is thought that both genetic and environmental components play an important role in the disease progression . At the moment, there is no cure for sarcoidosis and existing treatments (e.g. corticosteroids) only modify the formation of granulomas and come with a lot of side effects .
Another Molecure drug program in clinical development is called OATD-02 and it is an arginase 1 (ARG1) and arginase 2 (ARG2) inhibitor which are validated targets found on a variety of tumor types . Increased activity of both ARG1 and ARG2 correlates with more advanced disease and worse clinical prognosis. OATD-02 has been selected as a clinical candidate for the potential treatment of a variety of solid tumors in combination with other anti-cancer drugs because it restores effective tumour responses by increasing levels of arginine.
Other programs that Molecure focuses on include for instance deubiquitinase inhibitors which may be used to treat numerous solid tumors or the YKL-40 Program – a molecule whose high levels are associated with poor prognosis, progression and the severity of various inflammatory disorders and types of cancer .
Collaborations and plans
Molecure actively collaborate with the world’s leading research institutions such as Galapagos on their OATD-01 project and the University of Michigan with which Molecure entered into an option-to-license agreement to develop novel small molecule inhibitors for the treatment of fibrotic diseases . Molecure’s activities and its long-range plans will undoubtedly have a positive impact on the Polish small-molecule drug market and biomedical sector.
Molecure continues to develop and grow rapidly, making effective treatments for cancer and inflammatory diseases more available in the future – so keep a close eye on its activities!
- AstraZeneca. A big future for small molecules: targeting the undruggable [Internet]. 2023. (www.astrazeneca.com). Available from: https://www.astrazeneca.com/r-d/next-generation-therapeutics/small-molecule.html
- Molecure. About Molecure S.A. [Internet]. (www.molecure.com). Available from: https://molecure.com/about/
- Molecure. Pipeline Overview [Internet]. (www.molecure.com). Available from: https://molecure.com/pipeline/
- Association AL. Learn About Sarcoidosis [Internet]. 2023. (www.lung.org). Available from: https://www.lung.org/lung-health-diseases/lung-disease-lookup/sarcoidosis/learn-about-sarcoidosis