Discoveries made in the biomedical field within the last several years are transformative and will probably lead to major industry disruptions in the near future, attracting new investors and defining the R&D focus of the upcoming decade. This review describes notable innovative areas of the industry, highlights new market players, and shows major R&D breakthroughs.
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mRNA vaccines and RNA therapies
2020 and the beginning of 2021 showed the world the importance of flexibility in the healthcare sector – COVID-19 pandemics has brought everyone together in a common fight against the virus and boosted the development of biotechnologies, innovative therapies, and drug discovery methods.
Messenger RNA (mRNA) vaccines against Coronavirus disease from Pfizer and Moderna illustrated how powerful RNA-based treatments can be. RNAs are a class of molecules that modulate cellular processes without incorporation into DNA. They act by directly producing antigens inside our cells and triggering necessary immune reactions for us to have the cell memory about the virus in the future.
A completely different innovative approach to rule protein expression is developed by Urania Therapeutics. Urania focuses on RNA in ribosomes to treat monogenic orphan diseases. 10-15% of rare genetic diseases are caused by the loss of a full-length protein during translation. Nonsense mutations in genes lead to the formation of stop codons on mRNA that terminates the process of protein expression before it finishes. Urania works on “readthrough” compounds that help ribosomes to overcome early stop codons and produce a protein of target. Urania is a relevantly new company and in 2019-2020 it raised $6.2 million in Seed funding rounds.
A different method of treatment is to regulate and modify our own RNA molecules, changing protein expression patterns or sometimes even turning off the production of the protein in a body (so-called RNA interference). Massachusetts-based company Arrakis Therapeutics has recently signed a deal with big pharma drugmaker Roche to use Arrakis small molecule RNA-targeted drug discovery platform. Arrakis will receive up to $200 million in this partnership. A more recent collaboration with Amgen is focused on targeted RNA degradation.
AstraZeneca entered a collaboration with Gatehouse Bio to use its ‘sRNAlytics platform’. The platform uses a library of 1.4 million RNA features and exploits machine learning algorithms to determine RNA targets and discover next-generation therapeutics. The collaboration aims to identify new targets for respiratory and cardiovascular diseases.
Epigenetics is a well-known branch of modern genetics and almost every Life Sciences specialist is familiar with this term, however, epitranscriptomics is not that popular. The idea behind epitranscriptomics is analogous, it describes various RNA modifications, for example – methylation. From the therapeutic point of view, factors responsible for RNA modifications are interesting therapeutic targets as they modulate protein expression.
Accent Therapeutics found potential in inhibiting RNA-modifying proteins (RMPs) with inhibitory small molecule drugs (SMDs) to treat various cancer types. Improper functioning of RMPs causes a long list of malignancies, starting from leukemia and finishing with brain tumors, and Accent develops therapies based on this finding. In 2018 Accent received $40 million in Round A from three investors and two years later it raised $63 million more in Round B with strong growth prospects.
Scientific discoveries of Professors Tony Kouzarides and Eric Miska from Cambridge are in the heart of operations of another epitranscriptomics company – Storm Therapeutics. Storm is developing a drug discovery platform focused on RNA-modifying enzymes, especially RNA methyltransferases. In April 2021 Storm announced data about its first-in-class inhibitors of METTL3 that are effective against Acute Myeloid Leukaemia (AML) and solid tumors. The company raised a total of around $40 million in 5 rounds.
Targeting RNA with small molecules
Except for modifying the work of RNA regulators, a different approach of targeting it is a direct influence with small molecules. RNA is notoriously famous for its rigidity towards small-molecule inhibition, however, scientists managed to identify opportunities to change the status quo. Analyzing RNA sequence, it is possible to detect binding pockets and predict the nature of interaction there. To date, bioactive molecules can promote small molecule targeted degradation of RNA targets (ribonuclease-targeted chimeras, RIBOTACs) and even direct cleavage of RNA, locally controlling human transcriptome work.
Expansion Therapeutics originates from San Diego and was founded in 2016. The company raised over $135 million and is focused on targets to fight RNA-mediated diseases via small molecule medicines. A big deal in the world of small molecule RNA targeting is the abovementioned Arrakis Therapeutics, a company named a “life science disruptor” by Xconomy and is confidently moving forward. Its pipeline of drug candidates aims to treat neurological disorders, rare diseases, and cancers.
Deep learning and big data in drug discovery
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