For the estimated one in 100 people worldwide living with celiac disease, the burden of disease extends far beyond their plate.
Living with celiac disease demands constant vigilance.
Decades after celiac disease was recognized as a serious autoimmune disease, patients still have no approved therapy beyond a lifelong gluten-free diet, a standard of care that places all of the burden on those living with the disease and their families.
Unfortunately, even the most disciplined adherence to a gluten-free diet cannot fully protect against the uncertainty of accidental gluten exposure, which leads to disruptive symptoms and intestinal injury in many patients.
That imbalance has shifted the conversation about celiac disease. Instead of viewing the disease simply as a condition managed through dietary restriction, the medical field now sees it as a distinct therapeutic category defined by a clear unmet clinical need for deeper biological insights with growing patient demand for innovative treatments.
First Tracks Biotherapeutics is one of several companies working to help define that next chapter by directly targeting inflammatory pathways central to persistent disease activity and pursuing a differentiated path toward disease modification.
The Limits of Diet Alone
Celiac disease is a systemic autoimmune condition with a clear therapeutic need.
“Gluten is difficult to avoid because it’s in 80% of our foodstuffs. Patients also must worry about cross-contact when eating out,” said Marilyn Geller, CEO of the Celiac Disease Foundation. “Too often, patients are told to go gluten-free but do not get professional support because dietitian care is typically not covered by insurance.”
While some patients improve significantly on a gluten-free diet, many continue to experience chronic nausea, abdominal pain and bloating indicative of ongoing intestinal injury. For those patients, diet alone may not adequately address the inflammatory processes driving symptoms, reinforcing the need for therapies that can both protect and heal the intestine.
A Mechanism-Driven Approach
Earlier drug development efforts in the field focused on neutralizing gluten before it could trigger disease. But researchers now know that celiac is an immune-mediated disease shaped by broader inflammatory signaling, including CD122-mediated pathways which involve interleukin 15 (IL-15) and IL-2, cytokines that promote pathogenic immune-cell activity.1,2,3
At First Tracks Bio, our investigational antibody, ANB033, is designed to target CD122, the shared beta subunit of the IL-15 and IL-2 receptors. ANB033 is currently being studied in both celiac disease and eosinophilic esophagitis (EoE).
ANB033’s mechanism is well suited to celiac biology, where both cytokines help drive the proliferation and survival of immune-cell subsets implicated in mucosal injury. These include CD8+ and CD4+ T cells, as well as natural killer (NK) cells, all of which are implicated in inflammatory disease.
By modulating this pathway, ANB033 has the potential to reduce inflammation and help maintain remission.
This approach is differentiated from programs that focused on narrower, single cytokine inhibition. To date, preclinical data suggest ANB033 may help prevent gluten-driven mucosal injury in the digestive tract.
Rethinking Trial Design
We are currently enrolling patients globally in a Phase 1b study with an innovative, two-cohort design intended to generate clinically relevant early evidence.
- Cohort 1 enrolls celiac disease patients with mild mucosal tissue disruption who undergo a two-week, six-gram gluten challenge to test whether ANB033 can prevent mucosal damage;
- Cohort 2 includes celiac disease patients with more severe mucosal injury to assess whether ANB033 can promote healing without an added gluten challenge.
By including patients with established injury in an early-phase trial, we are innovating traditional celiac trials and taking advantage of real-world needs, broadening the relevance of the study.
What Comes Next
With data expected in the fourth quarter of 2026, we are prioritizing histology alongside patient-reported outcomes using the Celiac Disease Symptom Diary, one of only two instruments developed in line with U.S. Food and Drug Administration (FDA) guidance, to capture changes in symptoms such as abdominal pain and nausea.
Ultimately, the broader aim is to give gastroenterologists and patients a therapeutic option for a disease that has long been managed without one.
“Historically, physicians have had limited tools beyond referring patients back to dietary counseling,” Murray said. “An effective therapy would make celiac a disease gastroenterologists can actively treat and monitor.”
The future of drug development will not be defined by statistical significance alone, but by whether new therapies also improve the daily burden of living with celiac disease.
“The first therapy to cross the line could change the field,” Geller concluded. “It would help establish celiac as a serious medical condition with options beyond a restrictive diet and open the door for what comes next.”
Dr. Paul Lizzul is chief medical officer at First Tracks Biotherapeutics, a clinical‑stage biotechnology company advancing antibody therapeutics that modulate immune pathways implicated in autoimmune and inflammatory diseases.
Marilyn Geller serves as an advisor to First Tracks Bio.
Footnotes
- Abadie V, Jabri B. IL-15: a central regulator of celiac disease immunopathology. Immunol Rev. 2014;260(1):221-234. https://doi.org/10.1111/imr.12191.
- Yokoyama S, Watanabe N, Sato N, et al. Antibody-mediated blockade of IL-15 reverses the autoimmune intestinal damage in transgenic mice that overexpress IL-15 in enterocytes. Proc Natl Acad Sci U S A. 2009;106(37):15849-15854. https://doi/full/10.1073/pnas.0908834106.
- Anthony S, Schluns KS. Emerging roles for IL-15 in the activation and function of T-cells during immune stimulation. Research and Reports in Biology. 2015;6:25-37. https://doi.org/10.2147/RRB.S57685.
