Galapagos NV‘s potential new therapy for inflammatory bowel disease (IBD) — which stimulates anti-inflammatory signals while inhibiting pro-inflammatory ones — will move into Phase 1 clinical testing, the company announced.
The trial (NCT04106297), now recruiting participants in Belgium, will test the safety and tolerability of a second-generation molecule called GLPG3970. The molecule has successfully shown preclinical activity against a variety of inflammatory-based conditions, including psoriasis, rheumatoid arthritis, and IBD.
IBD is a general term used to describe several chronic inflammatory disorders of the digestive tract. There are two main types of IBD: Crohn’s disease, characterized by inflammation of the digestive tract lining, and ulcerative colitis (UC), which causes ulcers (long-lasting inflammation) in the large intestine, known as the colon, and rectum.
Anti-inflammatory medications such as corticosteroids usually are prescribed to treat IBD flare-ups. However, steroids can have unpleasant side effects, especially with long-term use.
Galapagos has identified a family of drug targets — proteins that play a role in the disease process — it has given the code name Toledo. Molecules that inhibit this target family produce a dual effect. They stimulate anti-inflammatory signal proteins, called cytokines, while at the same time inhibiting pro-inflammatory proteins.
Early in 2019, the company announced the launch of its Phase 1 safety trial (NCT03800472) of another first-generation, Toledo-targeted, anti-inflammatory molecule, called GLPG3312. Results of that trial are expected in early 2020.
In three preclinical IBD models, GLPG3312 demonstrated effectiveness against different inflammatory mechanisms. This is the first time one single molecule was effective against all three models, the company said.
Based on those results, a Phase 2 trial to test the effectiveness of GLPG3312 in UC patients is now scheduled to start in 2020.
The new molecule (compound), GLPG3970, is more selective. This new trial — a double-blind, placebo-controlled study — will assess the safety and tolerability of GLPG3970 in 52 healthy male volunteers. They will test both single doses and multiple increasing doses to identify potential adverse events associated with the new therapy. Information on enrollment is available here.
Additionally, the pharmacokinetics and pharmacodynamics — how the body processes the drug — of an oral GLPG3970 solution will be compared with a solid (tablet) formulation in response to a high-fat, high-calorie diet.
The results of this trial are expected to be released in late 2020.
“With the start of this trial, we are on track to potentially launch multiple proof of concept studies in parallel in 2020, in a range of inflammatory diseases. Thanks to its unique mechanism of action, the Toledo program has the potential to become a new paradigm in the treatment of inflammatory diseases,” he said.