As John Puisis was building a biotech company based on immune tolerance research from Northwestern University, venture capitalists asked him, “Why not just be a celiac disease company, a Type 1 diabetes company or a multiple sclerosis company?”
The answer was simple: He didn’t want to build a one-trick pony and then hand it off. The technology, the result of 30 years of research in the lab of Northwestern microbiology and immunology professor Stephen Miller, Ph.D., could be useful in all of those diseases, Puisis, CEO of Cour Pharmaceuticals, told FierceBiotech.
“We understood the benefits of focus, but we didn’t just want to become a one-disease company and then sell it, or flip it,” he said.
Now, with positive phase 2 data and a licensing deal with Takeda worth up to $420 million, Chicago-based Cour has a partner to help get its celiac disease treatment to patients. Celiac is a genetically linked disease in which eating gluten, the protein found in certain grains, leads the immune system to damage the gut. Symptoms may vary, and there there is only one treatment: a gluten-free diet. Problem is, these diets can be hard to stick to, and, for some people, they don’t work.
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Cour’s treatment is a nanoparticle loaded with gliadin—a component of gluten—to reprogram the immune system so it doesn’t attack the intestines when a person with celiac disease is exposed to gluten.
The company unveiled data from a small phase 2a study at the annual meeting of the United European Gastroenterology organization showing that its treatment, CNP-101, cut levels of inflammation-promoting cytokines.
The study tested the treatment against placebo in 34 adults with proven celiac disease. The patients received either CNP-101 or placebo by intravenous infusion on days one and eight of the study and then underwent a gluten challenge a week after their second dose. Read: They ate 12 grams of gluten each day for three days and then 6 grams of gluten each day for 11 days after that. Of the 34 patients, 28 finished the trial and six quit due to gluten-related symptoms.
The trial hit its primary endpoint, the change from baseline in the pro-inflammatory cytokine interferon-gamma. And not only did the treatment knock down the “primary immunological culprit" behind celiac disease, but it also protected intestinal tissue “against an inflammatory onset,” Puisis said.
Patients treated with CNP-101 developed fewer interferon-gamma spot forming units, a direct measure of gluten-specific systemic T cell activation in celiac disease, than those on placebo: 2.1 versus 17.57. And the treated patients had less damage to the mucous membrane of their small intestine than did placebo patients.
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The results were so encouraging that Takeda pulled the trigger on a global license for the program, which now goes by the dual moniker CNP-101/TAK-101. The partners did not disclose how much Takeda paid upfront but did say the Japanese drugmaker promised up to $420 million in milestones and royalties. Takeda will move the program into a dose-ranging study.
“As Takeda assumes responsibility for the celiac disease program, Cour will focus on advancing our pipeline of therapies for a variety of other immune disorders ranging from multiple sclerosis to peanut allergy,” Puisis said in a statement.
The technology, which aims at the innate immune system, could retrain the immune system not to attack certain tissues, such as the myelin sheath of nerves in multiple sclerosis.
“Stephen Miller … devoted 30 years to understanding this idea of antigen-specific immune tolerance, where the immune system will accept a foreign antigen or itself and won’t activate. Meaning, it won’t attack a tissue that should not be attacked,” Puisis said.
“He saw these monocytes—which are kind of the guardians of the immune system—very far up the stream in the immune cascade. They uptake cellular debris and pathogens and they bring them into the spleen and liver to die. What Steve learned was, if you could load an antigen, or a protein, or a peptide with a carrier—so, a nanoparticle—you can get the monocyte to interact with the nanoparticle and bring it to the spleen."
Once in the spleen, the antigen or peptide is released, where they start to reprogram the immune system, stopping it from attacking the body's own tissues or mounting a response to an allergen, such as peanuts.