The value of the immunology space to the pharmaceutical industry is indisputable. There's a reason AbbVie's Humira sat atop the list of bestselling drugs for so many years and why many of the largest companies have a foothold in the therapeutic area — advances over the years have made "magic bullet" immune inhibitors a winning business prospect with a wide range of medical need.
And despite the crowded field of monoclonal antibodies designed to treat immunological diseases like arthritis, psoriasis, ulcerative colitis and Crohn's disease, Big Pharma is still clamoring to bring the next big iteration to market. Earlier this month, Merck & Co. announced a $10.8 billion acquisition of Prometheus Biosciences, which holds phase 2 data for its lead molecule in patients with Crohn's disease, reflecting the appeal of promising clinical candidates in immunology.
"In the next three to five years, we're going to see a lot of advances."
VP and IL-23 pathway area leader, Janssen
Often, success in the field breeds more success down the road. For example, as AbbVie faces more and more biosimilar competition to Humira, the company's two updated brands — Skyrizi and Rinvoq — have begun to take up the mantle.
J&J's pharmaceutical division Janssen has gone down a similar path, harnessing the interleukin-23 — or IL-23 — cytokine pathway with the blockbuster monoclonal antibodies Stelara and Tremfya. Overall, these and other immunology drugs work by blocking communication between immune cells and other cells, which is facilitated by proteins called cytokines, reducing the inflammation associated with these diseases.
Now, with Stelara facing a patent expiration this year, Janssen is readying its next-generation immunology prospects. Among the leaders of that effort is the "father" of this particular cytokine pathway who helped showcase its utility in the field — Daniel Cua, vice president and IL-23 pathway area leader at the company. Cua is also Janssen's distinguished fellow for the pathway he helped discover, touting its benefits for patients and other scientists.
"The future is all about getting these drugs to as many patients as possible," Cua said.
The rise of IL-23
Just getting the scientific establishment to recognize the IL-23 pathway as a viable immunology target was "an uphill battle," Cua said of the beginning of his career at a small biotech near Stanford University, where he began to explore the space. Up to that point, most of the research had been focused on IL-23's "older brother," called IL-12 — but Cua and his team discovered that the two pathways shared an active receptor subunit p40 and that IL-23 could be a more specific target for immune pathology.
"That's something that had never been demonstrated before, and I had the idea that when you target the p40 subunit, you can actually be affecting multiple cytokines," Cua said. "It was confusing at the time, so our work clarified that it is IL-23 that's driving most of the other immune inflammatory diseases."
Since that time, investment in IL-12 has fallen by the wayside as IL-23 has soared on the wings of efficacy and low toxicity.
Now, Cua and his team at Janssen are looking for the next immunology drugs that can offer even more potent effects to patients while offering the greater convenience of a pill rather than an injection.
The company is also looking at a combination of IL-23 with the class of drugs called anti-tumor necrosis factor, or anti-TNF — Janssen brought the first anti-TNF drug to the market in 1998, which became the blockbuster Remicade. The combination of the IL-23 inhibitor Tremfya and anti-TNF Simponi could bring about a new wave of benefit for patients with immune diseases like ulcerative colitis. Two phase 2 studies of the combination therapy in ulcerative colitis and Crohn's disease are among 25 clinical immunology programs at Janssen, including new uses for brands like Stelara and Tremfya, and a swath of novel compounds.
"In the next three to five years, we're going to see a lot of advances," Cua said.
The Prometheus promise
With immunology drugs reaching blockbuster status left and right, it's no wonder analysts place the therapeutic area near the top of M&A prospects in the biopharma realm, behind only oncology and gene therapies.
Merck's Prometheus acquisition puts the company in a unique position when it comes to immunology, according to Michael Levesque, a senior vice president and analyst at Moody's Investors Services.
"Merck does not have presence as a leader in this market, although it does have a long history," Levesque said, noting that the pharma giant collaborated with J&J on Remicade. Notably, Cua led the immunology discovery program at Merck before joining Janssen in 2019.
But Levesque pointed out that the expanding field of immunology still has room for more entries, even from the companies that haven't made that a major focus of the last several years.
"Because the market is growing, it's still appealing," Levesque said. "And there's a lot more to it than simply Merck saying, 'Hey, let's try to become an immunology leader' — it's the attributes of the drug as well.”
Prometheus's lead candidate is a monoclonal antibody called PRA023 and is in mid-stage trials for ulcerative colitis and Crohn's disease. And the immunology space offers growth even with the saturation of products on the market for the same major diseases, Levesque said.
"When you look across the industry at the other branded immunology products, they should mainly be growing, so we're not expecting that there will be a lot of restrictions on these drugs," Levesque said, pointing to other blockbusters like Taltz from Eli Lilly and Cosentyx from Novartis.
It all comes through with the pace of advancement in the field, he said.
"As new mechanisms and new targets are discovered, the products tend to improve over time, and that's what's driving the growth and the appeal for investment," Levesque said. "It's really the dynamic of the innovation across the space."
The power of the immune system
The field of immunology in pharma is also unique and far-reaching because the immune system plays a role in so many other areas like cancer, infectious diseases and genetic conditions.
"Because you're targeting a very important pathway, it could be a two-edged sword — as you prevent the disease, you also prevent the immune system from doing its job," Cua said, adding that this is the reason the specificity of an IL-23 drug's action allows for a safe response while reducing the immune system's symptomatic reaction.
And the next phase of immunology is likely to be led by further understanding of human genetics.
"We're now beginning to gain insights on certain patients with certain gene expression patterns (that) can predict whether they will respond," Cua said. "And this is just the beginning stages of it, that we're going to be able to look at the genetics and gene expression in patients to predict treatment strategy."