Novel, proprietary target discovery platform

Galapagos’ target discovery platform provides a significant and substantial competitive advantage in its portfolio of novel mode of action medicines as it:

• closely mimics the in vivo situation through the use of primary human cell with relevant trigger and readout for a specific disease phenotype
• identifies the optimal point to intervene in a disease pathway by knocking down of a given protein in these assays
• enables us to rapidly analyze all of the drugable genome and select pharmaceutically tractable protein targets directly by their ability to regulate key disease biology

Galapagos’ product candidates in Phase 2 clinical development, filgotinib and GLPG1205, both act on targets whose role in the specific disease were discovered by Galapagos using its discovery platform and are proof of success of this approach. Filgotinib acts on JAK1 and could confirm potential for a best-in-class profile in rheumatoid arthritis and Crohn’s disease clinical trials. GLPG1205 acts as a GPR84 inhibitor which has shown activity in an inflammatory bowel disease animal model and is currently being tested in a Phase 2 ulcerative colitis trial.

The human genome is made up of tens of thousands of genes which code for the proteins that make up the human body. Nearly all chronic diseases and disorders are caused by a disruption in the normal function of certain proteins. The main goal of pharmaceutical companies is to design drugs that alter the activity of these proteins so that normal function returns and the cause of the disease is minimized or eliminated. One of the main obstacles in discovering new drugs is to understand exactly which of the body’s thousands of proteins play a key role in a particular disease. Once these proteins are discovered, they become targets for drug design. Finding these targets is one of the critical steps in the drug discovery process.

Galapagos’ approach to target discovery is unique as its discovery platform focuses on target identification using primary human cells, which provides a good system to study the effect that a protein might have on the disease in the human body. Moreover, Galapagos concentrates its efforts on so called “drugable” proteins and utilizing high throughput screening technology to screen these protein targets efficiently in human cells. This discovery approach may increase the chances of success in bringing new mode of action drugs to the market. Since 2009, Galapagos has generated 22 pre-clinical candidates using the discovery platform, of which 16 have novel modes of action. Of these, 10 have entered the clinic, of which seven have novel modes of action.

In order to study proteins in human cells, Galapagos takes advantage of the distinctive properties of adenoviruses. Adenovirus is the virus that causes the common cold and has the capability to infect almost every type of human cell. The adenoviruses Galapagos works with have been engineered to act as a shuttle vehicle, allowing the delivery of specific pieces of DNA into human cells. Additionally, these viruses have been made replication incompetent, meaning they do not replicate in the human cell they infect, and so do not interfere with the processes in the cell. Galapagos has engineered the viruses to carry small pieces of DNA, specific for individual human genes. When the virus enters the cell, this DNA piece leads to the production of a short sequence of RNA that is processed in the cell to become “short interfering RNA”, or siRNA, that specifically interferes with the mRNA of the protein it was designed for. By using these viruses, Galapagos can cause the cells to block, or “knock-down,” the production of a certain protein, mimicking what a small molecule drug does in the human body. Galapagos has built a collection with these adenoviruses, now in excess of 20,000 viruses, that addresses over 6,000 drugable genes.

Galapagos’ drug discovery research is based on the targets discovered using this technology. Once a target is validated, it is tested against large collections of chemical small molecules to identify chemical structures that interact with the target and block or activate protein production. These chemical structures are then optimized to obtain “drug-like” characteristics followed by testing of the drug candidate in the clinic.

In addition to its pipeline of molecules in the clinic, Galapagos has 25 different discovery programs which are advancing toward clinical development. In addition to additional targets and molecules in RA, IBD, and CF programs, Galapagos is exploring new modes of action in osteoarthritis, metabolic diseases, fibrosis and immune inflammation.