Psoriasis is a common, long-term immune-mediated disease characterised by the rapid build-up and inflammation of skin cells. While targeted treatments, including interleukin (IL) inhibitors, offer relief for many patients, certain rare variants of this disease have been largely overlooked, meaning limited treatment options. We spoke with Dr Julien Grogg, CEO of Signal26 Biotherapeutics, about how his company is seeking a treatment to address these gaps and leave no psoriasis patient behind.

What is psoriasis? Why is it so difficult to treat?

Psoriasis is a chronic immune-mediated disease affecting 2–3% of people in Western countries and at least 60 million people worldwide. Its symptoms are quite distinctive: red scaly patches of skin. Or, at least, that’s plaque psoriasis – the variant that everyone knows. But there’s also a pustular variant, which is underserved by the medical field. That’s partly because it’s so rare, and partly because all forms of psoriasis are difficult to treat.

Where does this difficulty lie? Well, the immune system is complicated! If we imagine it as a balancing act between tolerogenic molecules, which suppress immune responses, and immunogenic molecules, which trigger them, then immune-mediated diseases are the result of that balance being disrupted. Restoring the balance without creating unwanted side effects is a real challenge.

What treatments are currently available?

If you’ve ever been to a dermatologist, you’ll know that corticosteroid cream is the classic choice to treat skin conditions, because it has a wide range of actions. It is therefore often the first-line treatment for psoriasis. However, once a diagnosis is confirmed, there are more specific treatments that can be prescribed, such as anti-IL biotherapies. These may target IL-17, a typical inflammatory signal for psoriasis – immune cells release IL-17 proteins, which bind to receptors on keratinocytes and cause skin cells to multiply too quickly. There’s also IL-23, which binds to receptors on a type of T cell called Th17, which are what produce IL-17. Accordingly, we can treat the disease with IL-17 inhibitors or IL-23 inhibitors.

However, all current psoriasis treatments control the disease but don’t cure it. We need to try and understand the root cause of immune-mediated diseases if we are to find a sustainable long-term cure.

So, how big is the market?

At the moment, the psoriasis treatment market is dominated by anti-IL-23 treatments, and it’s a big market, worth roughly US$30bn. However, those treatments are geared towards plaque psoriasis. As I mentioned before, pustular psoriasis patients have very few options. When the same drugs were tested in the pustular form that affects the hands and feet, the results were modest or disappointing. To be honest, for that form, the treatment market in Europe and the US right now is as barren as a desert. That’s also because it’s an orphan disease, affecting roughly 0.01–0.1% of people, depending on the country. Still, the potential market is estimated at around US$500m. But the market is only as good as your product: when there are no approved drugs, the market is solely theoretical.

What might Signal26’s treatment offer patients?

The treatment we are developing aims to target palmoplantar pustular psoriasis (also called palmoplantar pustulosis), a localised form of the pustular variant. Patients affected by this disease have a greatly reduced quality of life. Imagine trying to walk or pick up objects when you have large, painful pustules on your hands and feet. We can’t simply ignore that. So, we’re working to inhibit another type of IL      that was more recently discovered to play a part in pustular psoriasis: IL-26.

IL-26 has three roles. It kills bacteria by damaging their membrane. It also stirs up inflammation by grabbing loose DNA from bacteria and damaged cells and passing it to immune cells, which respond by triggering inflammation. Finally, it prompts skin cells to send out alarm signals that draw in more neutrophils, white blood cells that fill the pustules, so the inflammation sustains itself.

Our antibody is a potential first-in-class treatment designed to block IL-26 from binding to extracellular DNA, thereby disrupting a key mechanism that drives and sustains inflammation. In laboratory tests on skin samples from patients, published by the Lausanne University Hospital (CHUV) team in 2024, blocking IL-26 with an antibody switched off key inflammatory signals, whereas blocking IL-17 did not.

Patients affected by pustular psoriasis show high levels of IL-26, while in healthy subjects the level is relatively low. Thus, we believe that inhibiting this pathway should not greatly affect the skin’s line of defence against bacteria. However, that is still to be demonstrated. Nobody has tried using this treatment in humans before.

Could your anti-IL-26 therapy tackle other immune-mediated diseases?

IL-26 also plays a part in inflammatory bowel disease – Crohn’s disease or ulcerative colitis. The gut is filled with bacteria, after all. So the answer is ‘possibly’ – it’s an open question whether Signal26’s anti-IL-26 therapy could one day be used to treat these sorts of diseases.

How did you find out about the potential of IL-26? What’s the story behind Signal26’s approach?

It all started with a team of researchers at the CHUV, led by Professor Michel Gilliet. In 2015, they published their initial findings on IL-26’s inflammatory properties in Nature Immunology. The team then began exploring whether blocking IL-26 could prevent inflammation. By 2021, this approach had received patent protection, and in 2024 Signal26 was set up to license the patent and take the project forward.

Our therapy is currently at the preclinical stage. Even though production processes are streamlined, it’s been tough because standard animal testing models aren’t readily available. Mice, the usual go-to model, don’t get psoriasis and don’t even have the gene for IL-26. One workaround is to genetically engineer mice to produce IL-26, but the psoriasis-like inflammation these mice develop is not the same as the human pustular disease.

Another solution for preclinical studies is to use human skin tissue from affected donors to produce what we call transcriptomic readouts. These show the drug’s impact on gene expression, which is useful, but that doesn’t give us a full picture, since a small piece of tissue doesn’t account for the complexity of an entire organism. Nevertheless, our studies show promising results and we look forward to conducting our first clinical trials next year.

Are there any remaining challenges before you launch the clinical trials?

One challenge here is regulatory. For authorities to approve new biologics for clinical trials, they need evidence that the drugs are safe enough to test in people, plus a sound scientific case that they could work. But it’s hard to build that case when you can only carry out testing on animals that don’t have the disease. Fortunately, the regulatory agencies are familiar with this challenge for new kinds of medicine and are open to early dialogue, so we can agree with them on what evidence is appropriate.

There are, of course, things that remain uncertain. But I don’t think we could call our work ‘pioneering’ if it didn’t involve some level of risk-taking. We’re lucky to have the backing of an investor who believes in our research as much as we do, and the move to human testing could give us the breakthrough we’ve been looking for.