Takeda acquires rights to new “Trojan horse” celiac antidote in US$420m deal

24 Oct 2019 --- Takeda Pharmaceutical Company has acquired an exclusive global license to develop and commercialize a celiac disease therapy developed by COUR Pharmaceutical Development Company. TAK-101 is a biodegradable nanoparticle containing gluten, which teaches the immune system that the antigen is safe. By hiding the allergen in a friendly shell, the nanoparticle acts like a Trojan horse to convince the immune system not to attack it. The acquisition follows promising trials by researchers at Northwestern Medicine, which also hinted that similar technology could be used for peanut allergies and multiple sclerosis (MS), as well as other conditions.

“TAK-101 is still in the early stages of development, and further assessments, including a dose-ranging study, will be required to explore the potential of TAK-101 in the treatment of celiac disease and to inform future registrational trials,” Luke Willats, Gastroenterology Communications at Takeda, tells NutritionInsight. “As further studies will be required to understand the optimal dose of TAK-101 and to determine the celiac disease patient population who may benefit from the treatment, we cannot speculate on development timelines or commercialization.”

Takeda intends to initiate a dose-ranging study to further explore the potential of TAK-101 in the treatment of patients with celiac disease on a gluten-free diet to inform future registrational trials. COUR is eligible to receive up to US$420 million in future payments, and royalties on sales of any commercialized products resulting from the license. The nanotechnology has also been granted Fast Track status from the US Food and Drug Administration (FDA). 

This acquisition fits in with Takeda’s pledge to explore areas of unmet medical need in gastroenterology, such as the area of celiac disease where there are limited treatment options outside of a gluten-free diet. Willats says that the license underscores the company’s commitment to celiac disease and the potential this investigational medicine may have in preventing gluten-induced immune activation in patients with celiac disease.

Researchers discovered that it is possible to induce immune tolerance to gluten in individuals with celiac disease.“Given the license by Takeda, COUR will focus on clinical programs in peanut allergy and MS in the near term, and broaden even further over time,” says John J. Puisis, President and CEO of COUR.

Backed by research
The scientists’ findings from the phase two clinical trial were presented on October 22 at the European Gastroenterology Week conference in Barcelona, Spain. They discovered that it is possible to induce immune tolerance to gluten in individuals with celiac disease. The nanoparticle technology could also potentially be used to treat diseases, including Type 1 diabetes and asthma. 

“This is the first demonstration the technology works in patients,” says Stephen Miller, the Judy Gugenheim Research Professor of Microbiology and Immunology and who has spent decades refining the technology. “We have also shown that we can encapsulate myelin into the nanoparticle to induce tolerance to that substance in multiple sclerosis models, or put a protein from pancreatic beta cells to induce tolerance to insulin in Type 1 diabetes models.”

The immune system is unconcerned when the allergen-loaded nanoparticle is injected into the bloodstream as it sees the particle as innocuous debris. The nanoparticle and its hidden cargo are consumed then by a macrophage, essentially a vacuum-cleaner cell that clears cellular debris and pathogens from the body.

“The vacuum-cleaner cell presents the allergen or antigen to the immune system in a way that says, ‘No worries, this belongs here,’” explains Miller. “The immune system then shuts down its attack on the allergen, and the immune system is reset to normal.”

In this trial, the nanoparticle was loaded with gliadin, the major component of dietary gluten, found in cereal grains such as wheat. A week after the treatment of 34 patients, they were fed gluten for 14 days. Without treatment, celiac patients eating gluten developed marked immune responses to gliadin and damage in their small intestine.

During the study, six patients discontinued due to gluten-related symptoms. The most frequent adverse events in patients receiving TAK-101 that exceeded the frequency seen in placebo-treated patients were nausea, headache, abdominal pain, and back pain. No patient had clinically significant changes in vital signs, routine clinical labs, or serum cytokines/chemokines, gliadin-specific T cell proliferation and cytokine secretion.

Overall, celiac patients treated with TAK-101 showed 90 percent less immune inflammation response than untreated patients. By stopping the inflammatory response, TAK-101 showed the capacity to protect the intestines from gluten-related injury.

A long-awaited breakthrough
While around 1 percent of the US population has celiac disease, doctors can only currently prescribe gluten avoidance. Miller points out that this is not always effective and carries a heavy social and economic toll for celiac patients. Autoimmune diseases generally can only be treated with immune suppressants that provide some relief but undermine the immune system and lead to toxic side-effects. TAK-101 does not suppress the immune system but reverses the course of disease.

“Celiac disease is unlike many other autoimmune disorders because the offending antigen is well known – gluten in the diet,” said Dr. Ciaran Kelly, Professor of Medicine at Harvard Medical School and director of the Celiac Center at Beth Israel Deaconess Medical Center. “This makes celiac disease a perfect condition to address using this exciting nanoparticle-induced immune tolerance approach.”

This breakthrough is the latest in a long line of innovations that could help people with celiac disease live an easier life. In Australia, the world's first vaccine for people who have celiac disease, Nexvax2 from ImmusanT, Inc, secured fast-track designation from the US FDA in January this year.

Also, a new gluten detection method can show which grain it comes from, making it simpler for food companies to correctly label products. Meanwhile, distinct markers in the blood of people with celiac disease can now be detected within a few hours of gluten being consumed, cutting the need for invasive testing. Also on the diagnosis front is FoodMarble, a start-up producing a portable breath test and app that can be used to track ease of digestion. 

Alongside such innovation, the market is also responding with a rise in gluten-free options. In fact, the gluten-free food market is estimated to grow to US$7.59 billion by 2020 in the US, primarily driven by the increasing numbers of people who choose to eat gluten-free products but do not have gluten-related medical conditions. These consumers report feeling better by consuming less gluten, pointing to the huge market potential of reduced gluten products, notes DuPont. 

By Katherine Durrell