Peter Ulrichts joined argenx, an immunology innovation company, in 2010 fresh out of a postdoc in immunology at Ghent University. Since then, he has shaped the company’s scientific innovation engine with a willingness to challenge ideas. Scientific American Custom Media recently spoke with Ulrichts about the company’s quest to develop therapies for people with diseases that lack innovative medicines.
[An edited transcript of the interview follows.]
argenx’s antibody-discovery approach starts with outbred llamas. Why? And what makes llamas effective for antibody engineering?
It works like this: Our llamas live happily outdoors in the South of France, where they encounter normal pathogens and develop fully functional immune systems. We give them small, safe doses of disease-related human proteins against which they will produce antibodies, a process very similar to vaccination in humans. A few weeks later we collect some blood containing their antibody-producing cells. Just a few llamas can generate as many antibody candidates as hundreds or even thousands of laboratory mice. This diversity is one big advantage of using llamas, as more choice gives you more options. Another feature of llamas making them the ideal partner in our antibody-discovery journey is that llama antibodies are very humanlike, so you don’t need a lot of engineering to make them suitable for human use. Starting from the cells of the llamas, we then further optimize their antibodies in the lab and select the best one for the intended purpose.
What stands out about argenx’s approach to antibody engineering, and why is it crucial for developing targeted therapies for autoimmune diseases?
Our premise is that while we know how to engineer antibodies, academic experts know more about the underlying biology. Through our Immunology Innovation Program, IIP, we combine these strengths: We keep our experts close and work together from an initial concept to antibody design, clinical development and beyond. Our partnerships are built on transparency and long-term commitment to shared success, and we are always interested in exploring collaborations.
You led the preclinical development of argenx’s first FcRn antagonist, efgartigimod, collaborating with Sally Ward, an immunologist at the University of Southampton in England. It went on to gain regulatory approvals and is being studied for other autoimmune diseases. How does this breakthrough exemplify the argenx Immunology Innovation Program?
That’s right. Dr. Ward spent years studying a protein called FcRn that ensures longer serum persistence of immunoglobulin G, IgG, one of the most abundant proteins in the bloodstream. She had the idea that blocking FcRn could lower levels of IgG autoantibodies, which could be a therapeutic approach in more than 100 different diseases. What started as a discussion about her research led to an ongoing collaboration with argenx and approval of the first FcRn-directed autoimmune treatments. We were convinced of the need to partner like this again and again. Every drug in our pipeline has originated with a collaboration. We believe that the future of healthcare innovation will be shaped by organizations that build ecosystems and networks, and the IIP is part of how we do that.
How do you see autoimmune disease treatment evolving over the next decade? How will that change the lives of patients?
Patients have traditionally been treated with broad-range immunosuppressants like corticosteroids that have significant side effects, especially higher risks of infection. Now we’re moving steadily towards engineered antibodies and other modalities that interfere specifically with the pathogenic driver of the disease. It’s like treating autoimmune disease with a scalpel instead of a bazooka. I think we’re going to see a lot more innovation in the next five to 10 years that allows for even more progress.
What is the ultimate ambition behind argenx’s approach to treating autoimmune diseases?
Our ambition is to develop cures, or at the very least to bring patients into a symptom-free state, without the toxicity that comes from chronic immunosuppression. The ultimate reward is seeing co-created innovation translate into treatments that help patients.
Learn more about how argenx engineers therapeutic antibodies.