New Treatments Being Studied for Celiac Disease: A Deep Dive into ZED1227 and TEV’408

Written by: Alyssa Ramuscak, September 18, 2026

A strict gluten-free diet remains the cornerstone to celiac disease management.(1–3) However, adherence to a gluten-free diet remains challenging due to expensive gluten-free foods, cross-contact, and unclear food labelling.(4–6) In addition, some people living with celiac disease continue to experience symptoms or intestinal damage, despite following a gluten-free diet.(7) As a result, 90% of celiac disease patients surveyed said they want a therapy to either replace or supplement the gluten-free diet.(8) This has led researchers to investigate medications that could complement the gluten-free diet by targeting different parts of the biological response to gluten in people with celiac disease.

What does “complement the gluten-free diet” actually mean?

The term complement is important; these medications are being developed to work alongside the gluten-free diet, not replace it. Researchers are investigating medications that target different stages in the body’s immune response to gluten, with the goal of providing an additional layer of protection against the effects of gluten exposure. Current mechanisms under investigation have included medications that could block the interaction between gluten and the immune system, reduce the inflammatory response triggered by gluten, or prevent or reduce intestinal damage. Two investigational treatments generating interest are ZED1227, which targets tissue transglutaminase 2 (TG2), and TEV’408, which targets interleukin-15 (IL-15).

ZED1227: What is it? What have we learned? Where is it at now?

ZED1227 is an oral drug that is designed to inhibit an enzyme called tissue transglutaminase 2 (TG2)

When a person with celiac disease eats gluten, the gluten is broken down during digestion, and TG2, found in the small intestine, changes some of the gluten proteins in a way that makes them easier for the immune system to recognize. In people with celiac disease, this recognition can trigger an immune response that leads to inflammation and damage to the small intestine.(9)

By inhibiting TG2, researchers hope ZED1227 will interfere with this process, reducing the immune response and helping protect the intestinal lining from gluten-induced damage.

Early clinical research on ZED1227 has provided promising findings. In a Phase 2 proof-of-concept study published in The New England Journal of Medicine in 2021, researchers evaluated ZED1227 in adults with well-controlled celiac disease who were following a gluten-free diet. (10) The study was conducted between 2018 and 2020 across 20 sites in seven European countries.

Participants were randomly assigned to receive one of three doses of ZED1227 (10mg, 50mg, or 100mg) or a placebo for six weeks. During this time, participants continued following a gluten-free diet but were also asked to consume a small, controlled amount of gluten each day, about 3g, to allow researchers to evaluate whether ZED1227 could protect the intestinal lining from gluten-induced damage.(10)

The results were encouraging. Compared with placebo, all three doses of ZED1227 reduced gluten-induced damage to the small intestine, as measured through biopsies. The effects were most pronounced with the 50mg and 100mg doses. The 100mg dose also showed potential preliminary improvements in some measures of celiac disease symptoms and quality of life.(10)

What comes next for ZED1227?

A larger Phase 2 study is currently underway in Europe to further evaluate the medication’s safety and effectiveness in people with celiac disease.(11,12)

An important distinction between this study and the 2021 proof-of concept trial is that participants from the 2021 study had well-controlled celiac disease and were deliberately given a moderate, controlled amount of gluten each day for six weeks. This allowed researchers to test whether ZED1227 could protect the intestine when participants were exposed to gluten under controlled conditions.

The newer study is designed to more closely reflect the experiences of people who continue to have celiac disease symptoms despite following a gluten-free diet. To be eligible, participants must have been following a gluten-free diet for 12 months while still experiencing symptoms and have evidence of intestinal damage. Rather than a moderate daily gluten challenge (3g/day), the study uses snack bars containing a small amount of gluten to be consumed three times a week (gluten amount is described as “much less than is found in a slice of bread”). With this study, researchers are primarily looking at whether ZED1227 improves gastrointestinal symptoms, while also examining intestinal damage, inflammation and other markers of celiac disease.(11,12)

The study began in 2024 and is ongoing, with participants receiving different doses of ZED1227 or placebo. The current European trial registry lists 70 sites across 11 European countries, with results expected after the study is completed in 2027.(11,12)

TEV’408: What is it? What have we learned? Where is it at now?

TEV’408 is an investigational monoclonal antibody developed by Teva Pharmaceutical Industries Ltd.(13) Monoclonal antibodies are lab-made proteins that are designed to recognize and bind to specific targets in the body.(14) In the case of TEV’408, the target is interleukin-15 (IL-15), a protein that helps regulate the immune system. TEV’408 is given as a subcutaneous injection, meaning it is injected under the skin.(13)

IL-15 is an inflammatory signaling protein (cytokine) that is overexpressed in the small intestine of people with celiac disease and can contribute to inflammation and damage in the small intestine following gluten exposure.(15) In other words, when a person with celiac disease eats gluten, IL-5 sets off the alarm bells to activate the immune system, which leads to inflammation and damage in the small intestine. By blocking these alarm bells, TEV’408 has the potential to help calm this immune response and reduce gluten-induced intestinal damage.(13)

On September 2nd, 2026, Teva Pharmaceutical Industries announced positive initial results from an ongoing Phase 2a clinical trial of TEV’408 in adults with celiac disease. The randomized, place-controlled trial study, included 50 adult who were following a gluten-free diet and had minimal intestinal damage at the start of the study. Participants received a single dose of TEV’408 or a placebo and, two weeks later, began a six-week daily gluten challenge. Researchers then assessed biopsy-based measures of intestinal damage and inflammation, along with patient-reported gastrointestinal symptoms.(13)

Compared with participants who received the placebo, those who received TEV’408 had statistically significant and clinically meaningful prevention of gluten-induced intestinal damage after the six-week gluten challenge. TEV’408 was also associated with less intestinal inflammation and lower gastrointestinal symptom scores compared with placebo. Overall, the treatment was found to be well tolerated, with no new safety issues observed to date.(13)

While these early findings are encouraging, it is important to remember that this was a relatively small Phase 2a study, and TEV’408 is still an investigational treatment. Teva concluded in their announcement that additional analyses of the Phase 2a study are underway, and that further data from the study will be presented at future scientific meetings.(13)

When will these treatments be available for people with celiac disease?

Developing a new treatment takes time. Before a drug can be approved, researchers first conduct pre-clinical studies to understand how it works and whether it appears safe.(16) If the results are promising, the treatment moves into clinical trials, where it is tested in people.

Clinical trials typically progress through four phases. Phase 1 focuses on safety and finding an appropriate dose. Phase 2 provides more information about safety and whether the treatment appears to work. Phase 3 involves larger groups of people to confirm the treatment’s benefits, monitor side effects, and compare it with existing treatments. If a treatment is approved, Phase 4 studies its longer-term safety and effectiveness once it is available to the public.(16)

Both ZED1227 and TEV’408 are currently in Phase 2 clinical trials. While early findings suggest that these treatments appear effective and safe, they still must undergo larger Phase 3 trials to ensure the treatment’s benefits outweigh any potential risks.

For now, the gluten-free diet remains the cornerstone of celiac disease management. These investigational treatments are being studied as potential additions to the gluten-free diet, not as replacements for it.

Bottom Line

The development of new treatments for celiac disease represents an exciting time in the research landscape. For decades, the gluten-free diet has been the only treatment available. While a strict gluten-free diet will remain essential, researchers are exploring whether medications could one day provide an additional layer of protection against the effects of gluten exposure.

ZED1227 and TEV’408 are two examples of how researchers are approaching celiac disease from different biological angles. While early findings are encouraging, there is still much to learn. As clinical trials continue, participation from people living with celiac disease will remain an important part of determining whether these treatments are effective and safe.

To learn more about how to get involved in Celiac Disease Research and Clinical Trials, see:

Celiac Canada’s Clinical Research and Trials for Celiac Disease: https://www.celiac.ca/get-involved/clinical-research-and-trials/

Government of Canada’s Clinical Trial Database: https://clinical-trials-search.canada.ca/en/home

Read more blogs!