ARGX-118 Case Study:
An Uncharted Approach to Airway Inflammation
ARGX-118 marked a big innovation in the therapeutic approach to severe asthma and persistent mucus plugs. It was designed as a highly differentiated antibody against Galectin-10, the protein of Charcot-Leyden crystals (CLCs). Before ARGX-118, these crystals hadn’t even been seen as a major contributor to inflammation.
ARGX-118 was engineered in partnership with Prof. Bart Lambrecht, M.D., Ph.D. from VIB.
He uncovered the immunology breakthrough that allergic airway inflammation is a crystallopathy caused by CLCs. Together, Prof. Lambrecht and our team engineered prototype therapeutic antibodies to dissolve these crystals.
ARGX-118 is the result of a co-creation to try to address airway inflammation in an unconventional way.
“It was much better than we anticipated. All of a sudden, the crystals that seemed unresolvable, resolved in front of our eyes.”
Prof. Bart Lambrecht,M.D., Ph.D.
VIB, Flemish Institute for Biotechnology Research area(s): Inflammation and immunity
Searching for an Answer
This is the story of Prof. Bart Lambrecht and how a seemingly crazy idea kickstarted a journey to develop a potential treatment for asthma and airway inflammation. It’s a story about a passion for science, and collaboration between academia and biotech.
The VIB Center for Inflammation Research in Ghent is mainly studying inflammatory diseases. Asthma is one of the diseases that is very close to Prof. Lambrecht’s heart. It is also a very common disease affecting about 8 to 10% of people.
Finding the Crystals
The Charcot-Leyden crystals played an important role in the discovery process. “We knew, that in this disease, proteins which are normally in a soluble state, can crystallize. And these protein crystals are known as Charcot-Leyden crystals.”
This had been known for 150 years, but nobody had focused on this aspect of the disease until the partnership between Prof. Lambrecht’s team at VIB and us.
“We have unraveled what these crystals are doing. We found that the crystals are made in the airway of severe asthmatics and that most of the people that you see in the clinic already have sticky mucus with Charcot-Leyden crystals in them.”
The Search for Antibodies
To accelerate the discovery process, Prof. Lambrecht sought out antibody engineering expertise: “We had some experience already with argenx, in developing antibodies. They have a very efficient platform to generate antibodies.”
Initially, the goal was just to neutralize the target protein, Galectin-10. But beyond expectations, the team demonstrated that the antibodies were also able to dissolve existing crystals by attacking the component protein.
Co-Creating With argenx
“As an academic-physician-scientist, your ultimate dream is to translate your findings into a product. Through our collaboration with argenx we had access to their key technologies. It enabled us to elucidate the crystal structure and we discovered how the antibody could dissolve the crystals. That created a whole class of antibodies we can work with. The speed by which this was achieved, surprised all of us.”
Finally, Prof. Lambrecht explains why trust between academia and biotech is so important and what a solid collaboration can achieve: “For these types of relationships between biotech and academia, we need a lot of trust. That both the inventor and the group of scientists who discovered the target, have a feeling of ownership. They have to be involved in the project, but it is not your own baby anymore. It is a kind of shared parenthood. And if you can find each other there, you build these long-term relationships that could potentially lead to inventions and to products.”
The Ultimate Goal
“My hope is that we will be able to turn ARGX-118 into something that will benefit patients with severe asthma.”
Proposed Mechanism of Action
ARGX-118 is designed to bind to an epitope of Galectin-10 that is critical for crystal packing. It thereby not only prevents Galectin-10 crystallization, but also rapidly solubilizes CLCs.
CLCs are frequently observed in the mucus of patients with eosinophilic respiratory diseases and promote type 2 immunity and mucus plugging. By nebulization of ARGX-118, argenx aims to improve the viscoelasticity of mucus.
Publications
Further explore ARGX-118 and the science behind it.
Partner With Us
argenx fosters genuine partnerships with academic institutions and experts, focusing on co-creation to accelerate discovery processes to bring solutions to patients who need them. Learn more about the IIP and collaboration the argenx way today.
For more information on partnering opportunities, please contact IIP@argenx.com.
Explore More
At argenx, every piece of the innovation story connects. See where it leads next.
Antibody Engineering
See how our platform technologies help optimize antibodies and amplify possibilities in immunology.
Co-Creation in Action
See what happens when our team takes promising leaps alongside leading scientists, physicians, and researchers.
Publications
Peer-reviewed publications that reflect our range of immunology innovation.
