Updated: Jul 14, 2021
RNA is the target that forms the basis of Ionis's Pharmaceuticals (FRA: ISI) and (NASDAQ: IONS) novel drug discovery platform, The company's antisense therapies are attemting to disrupt diseases and change the course of the rarest of conditions that impact millions of people.
Antisense: changing the course of disease
To fully understand how Ionis is using antisense technology to revolutionize drug discovery, it is important to first look at how traditional medicines work in the body.
The human body is made up of billions of cells, each containing the unique genetic information, or DNA, that defines a person. Contained within DNA are instructions for making all the proteins in the human body.
Proteins are crucial building blocks for the structure and function of all organs and systems within the human body. Sometimes, however, over or under production of a protein, or production of a mutated protein, are common causes of many human diseases. For more than 100 years, most traditional medicines like small molecule inhibitors or, more recently, antibody-based therapies have worked to target these proteins once they are produced and doing damage in the body.
Antisense therapies change the process of producing a protein before it even begins. To build a protein, a cell must make a copy of the DNA, which contains specific instructions for how to make that particular protein. This copy, called messenger RNA (mRNA), carries the instructions to the part of the cell where proteins are made.
Antisense therapies are designed to seek out, bind to and destroy a mRNA in a highly specific manner, so that the amount of disease-causing protein is dramatically decreased. Antisense therapies can also treat diseases caused by too little protein by increasing the production of the protein, thereby restoring the protein to normal levels.
The story behind Ionis - passion and purpose
Stanley Crooke founded Ionis Pharmaceutical with the notion there was a possibility to control protein function by stringing together the right set of nucleic acids. At its core Antisense drugs contain part of the non-coding strand of messenger RNA (mRNA), a key molecule involved in the translation of DNA into protein. Antisense drugs hybridize with and inactivate mRNA. This stops a particular gene from producing the protein for which it holds the recipe.
The concept was exciting - short strands of oligonucleotides that could turn up or off the production of specific protein.
In the early years of Antisense drugs there were significant difficulties with
making modified oligonucleotides that could act on a protein target without degrading or hitting myriad other targets,
Spinraza changed everything for Ionis and Antisense companies globally.
- the drug was specifially developed gto treat spinal muscular atrophy (SMA). To be successful the drug would be treating infants and assisting to manage the disease. To do so he drug had to safely reach patients brains and spinal cords through an injection into the spinal canal. In late 2016, the FDA approved Spinraza, making it the first-ever treatment for SMA.
Although Spinraza will likely soon face competition from a gene therapy and a small-molecule drug, Ionis’s pipeline is producing other treatments that could keep the firm growing. One is Tegsedi, a rare-disease treatment approved last fall and marketed by an Ionis affiliate, Akcea Therapeutics. And many investors are excited by several other advanced molecules, including a cardiovascular treatment that blocks the production of Apo(a), a protein involved in lipid metabolism.
Optimizing antisense technology
Optimising Antisense therapies has been a focus of Ionis's efforts as advances in medicinal chemistry have occured. Ionis states their antisense drugs are stable, able to penetrate certain tissues and cells, can target hit certain cells, have significant binding strength and have limited side effects. One new Ionis product is Ligand-Conjugated Antisense (LICA) Technology.
LICA, or Ligand Conjugated Antisense, is a chemical technology the company developed that involves the attachment of a molecule called a ligand that binds with receptors on the surfaces of cells in a highly specific manner.
Ionis licences its technology to global partners such as Antisense Therapeutics (ASX: ANP) and (FRA: AWY) which increases potential for future royalty streams and de-risks the company for investors.
The latest company annual report can be downloaded here
An Australian company, Antisense Therapeutics Limited (ASX: ANP) and (FRA: AWY) is also licencing Ionis Products for unmet needs for rare genetic conditions such as Duchenne Muscular Dystrophy (DMD) with an estimated addressable market of EUR 3.5 billion.
The company's English and German langauge presentations can be downloaded here