"Hot" Research Areas in Drug Discovery - 2019

1.Targeting ribonucleic acid (RNA)

The majority of existing marketed drugs out there are designed to somehow modulate proteins in the body, thereby disrupting a disease progression. However, going one step back and trying to disrupt a pathological process earlier --  right before a protein is actually made in the body -- seems a powerful concept. This can be achieved by influencing ribonucleic acid (RNA), a central actor molecule in the process of gene expression -- the one leading to formation of proteins as instructed by human genome.

Epitranscriptomics

One rapidly growing strategy to deal with RNA involves targeting natural enzymes and proteins that are responsible for its chemical modifications (for example, methylation or de-methylation). The interest to this idea was ignited by a Rupert Fray’s study in May 2008 showing the essential role of RNA methyl-adding enzymes in plant development. In just several years it has become a whole new area of science, called “epitranscriptomics” (a term coined in 2012 by Samie Jaffrey), and the key players here include three biotech startups: Accent Therapeutics, launched with $40 million in May 2018, Gotham Therapeutics, launched with $54 million in October 2018, and Storm Therapeutics being in the process of raising approximately $65 million for its second round of cash from investors. All three startups are focusing on developing novel small molecules to inhibit RNA-modifying enzymes. There is a wonderful review about epitranscriptomics and its short history in C&EN.

Targeting RNA with small molecules

Beyond epitranscriptomics, there is also a “golden rush” for small molecules targeting RNA directly. Not only a number of startups, like Expansion Therapeutics ($55.3 million Series A investment) and Arrakis Therapeutics ($38M series A investment) have emerged out of know-hows of top academics, but also a number of big pharma players are now developing programs in RNA space: Biogen, Boehringer Ingelheim, Merck & Co, Novartis, and Pfizer.