Developing drugs

The adventurous journey of an immunological compound

In 2007, Dr Matthijs Moerland, who had recently joined CHDR, did a first-in-human study with an immunological drug candidate. After much wandering, the same compound returned to him more than 15 years later.

In recent years, the Immunology group led by Dr Matthijs Moerland has validated a set of challenge models to study compounds that affect the innate immune system. In a way, this interest in the innate immune response goes back to Moerland's early days at CHDR: 'One of the first compounds I researched was a MAP kinase inhibitor. These mitogen-activated protein kinases are an important link in the signalling pathway that starts at the toll-like receptors. They are a key element in the innate immune response, which is involved in many autoimmune diseases. In 2007, we did the first-in-human studies, single ascending dose, multiple ascending dose - the usual work. Based on our results, the client, the Dutch company Organon, wanted to study the compound further in rheumatoid arthritis patients. For years I didn't get around to writing up those results, but a few years ago I published a paper on our study.'

In the meantime, the promising compound had made an adventurous journey through the pharmaceutical industry. The original patent holder was acquired by another company, which in turn was acquired by a company that opted for other strategic priorities. The patent lay in a drawer for a while, was sold to a biotech company, and after several more acquisitions, it ended up with the biopharmaceutical company Poolbeg.

Coincidentally, Poolbeg approached CHDR to help them develop the compound by demonstrating its pharmacological effect in human subjects. Moerland: 'Initially, I had no clue. I read the file, and I told our contact at the company: "Yes, I can do something with that. I worked on a MAP kinase inhibitor years ago." And he exclaimed: "You must be the Moerland who was the first author of that paper!" So after more than 15 years, the compound returned to us. And relating to our theme of bridging the gap, we could now show how the compound modulates the immune response in healthy volunteers using the challenge models we have developed over the past years. In other words, we have bridged the gap between the results in the test tube and the human organism. Thanks to that proof of mechanism, the company has a nice dossier to show their investors how this compound can suppress inflammation both systemically and in peripheral tissue.'