Idorsia More knowledge – Powered by science

More knowledge –
Powered by science

It all starts with an idea

It all starts with an idea Idorsia

At Idorsia, our drug discovery approach focuses on families of proteins, which are characterized by the way they work. We call this the “platform approach”.

We strive to identify innovative programs on proteins which have not been targeted up to now, to discover drugs with novel mechanisms of action.

The drug discovery process starts with an idea from our scientists. We scour the literature to see what others have not yet discovered, to generate ideas and then translate them into a concept which can lead to new treatments for patients.

Our work in the lab begins with the target. This may be a particular protein which, when its activity is modulated, can normalize a biological process in the body – with a beneficial effect for patients. To see whether we can affect the protein’s activity, we first need to be able to measure it.

We produce, or “express”, the target in large quantities and measure its natural activity in assays. The assay needs to be sensitive, accurate and highly reliable. Plus, in order to perform hundreds of thousands of measurements, it needs to be automated, using robotic equipment.

“We need creativity to be innovative, so we need a brilliant idea and a deep understanding of the disease, to translate it into a molecular mechanism, and to try to find a drug to treat that disease.”

A world of molecular possibilities

A world of molecular possibilities Idorsia

“For me, invention is making something out of a daring idea. And I really have the feeling that’s what we are trying to do at Idorsia.”

But there are two sides to the discovery process – a target and a compound.

Compounds are substances which, we hope, will modify the activity of a target involved in a pathological process and can then be developed into a drug for patients.

At Idorsia, we maintain a library consisting of hundreds of thousands of different compounds. To begin our hunt for drugs, we test the entire library of compounds on the target, in the hope that one of them will modify the activity of the protein. This process is called high throughput screening; if it’s a simple assay, we can test the whole library within a matter of weeks. At this stage, the goal is to identify compounds which exhibit some activity.

The project team then analyzes these compounds to decide which of them is the most promising starting point for optimization using the art of medicinal chemistry.

Obviously, huge amounts of data are generated, and powerful IT tools are required to extract the knowledge we need. To really understand the data, we visualize them and study the relationship between chemical structures and biological properties.

Target and compound fit together like a lock and a key. The compound can be modified so that it fits better and, ideally, becomes more potent.

From molecule to medicine

From molecule to medicine Idorsia

Our formulation specialists take a compound which has been optimized by the chemists and ask how it can best be delivered to the patient.

Medicinal chemistry involves the use of chemistry’s tools to design molecules that are potential drugs. We manipulate the molecular structure and then send the compounds back to our biologists or pharmacologists for testing in an iterative process. With each cycle the compound is further optimized to finally become a drug.

At first, we seek to enhance the potency of its effects on the target protein, but as we advance we look at other activities which may cause side effects. The aim is to ensure that the compound’s overall properties allow it to become a drug.

For example, our electrophysiologists screen drugs for side effects by monitoring electrical activity in the heart or brain. Here, electrical communication depends on ion channels in the cell membrane; if a drug blocks some of these ion channels, it can have serious adverse effects.

Small-scale testing for initial assays requires only milligram quantities; for subsequent testing, however, much more material is needed. This is where our process research teams come into the picture. They are responsible for scaling up from milligram to gram quantities, and finally to the kilogram batch which is used for preclinical testing.

It’s no good having a potent compound which gets destroyed by the body before it has a chance to do its job. Our formulation specialists take a compound which has been optimized by the chemists and ask how it can best be delivered to the patient. One way to protect the compound, for example, is to package it in a capsule; alternatively, it may be better to develop an injectable form.

For Idorsia, the process which begins with drug discovery and preclinical development ends, we hope, with a novel molecule that will help patients in diseases which still have a high medical need.

“This is a group of extraordinary, highly dedicated people, and over the next few years we may see the fruits of all their work – which has the potential to change the lives of so many patients.”