Experimental Drug ANB033 Shields Celiac Patients From Gluten Damage in Early Trial

An experimental drug developed by San Diego-based First Tracks Biotherapeutics has shown it can protect people with celiac disease against intestinal damage and symptoms caused by gluten exposure, according to top-line results from a small early-stage clinical trial announced on Monday, October 12, and highlighted by Reuters on Wednesday.

The drug, ANB033, is an investigational antibody designed to block signaling through CD122, a receptor component shared by the immune messengers interleukin-15 (IL-15) and interleukin-2 (IL-2). In a 32-patient Phase 1b gluten-challenge study — the first cohort of the trial — ANB033 demonstrated statistically significant protection against gluten-induced intestinal damage compared with placebo, while also preventing a rise in symptoms throughout the entire gluten challenge, according to the company.

The findings are notable because celiac disease, an autoimmune condition triggered by gluten, has no approved drug treatment. The only therapy available today is a strict, lifelong gluten-free diet — and even patients who follow that diet carefully can suffer intestinal damage and debilitating symptoms from trace gluten exposure, a problem this study was designed to model directly.

What the trial tested

The randomized, placebo-controlled study enrolled 32 participants who had been diagnosed with celiac disease at least a year earlier and were following a gluten-free diet, but who still showed moderate damage to their intestines on biopsies at the start of the trial — the situation of a meaningful share of patients in real life, according to the researchers, since even careful adherence to a gluten-free diet does not always allow the gut to heal fully.

Seventeen participants received three subcutaneous injections of ANB033 — at the start of the trial and at weeks two and four — while 15 received a placebo, according to Markets Daily, which covered the announcement on Wednesday. After dosing, all participants underwent two weeks of daily gluten consumption at six grams per day, which the company said was roughly equivalent to eating two slices of bread daily — a deliberately intense challenge designed to test whether the drug could hold the line against a heavy, sustained gluten assault.

At the end of the study, a second round of biopsies was compared against the first. On the trial’s key histologic measures, the results favored ANB033 decisively. The change in the villus height-to-crypt depth ratio — a standard measure of the condition of the finger-like villi lining the small intestine, which flatten under gluten attack in celiac patients — averaged a decline of 0.17 in the ANB033 group versus 0.66 in the placebo group, a placebo-adjusted improvement of 0.49 that was statistically significant (p=0.009), according to trading-industry coverage of the company’s data. Intraepithelial lymphocyte density — a measure of immune cells infiltrating the gut lining — fell slightly in the ANB033 group while surging in the placebo group, a placebo-adjusted difference of 20.03 that was highly significant (p<0.001), according to cGxP.wire, a clinical-trial industry publication.

Crucially for patients, the drug’s effect showed up in how people felt, not just under the microscope. ANB033 prevented an increase in symptoms throughout the entire gluten challenge, and patients on the drug scored lower on the Celiac Disease Symptom Diary than those on placebo — a difference that reached statistical significance from the very first day of the challenge, according to the company. Only 6% of patients on ANB033 needed permitted medications to manage gastrointestinal symptoms, compared with 47% of those on placebo, Reuters reported.

The company also reported that ANB033 was well tolerated, with no safety signals observed to date, no serious adverse events, and no treatment discontinuations attributed to adverse events in the ANB033 group.

How the drug works

ANB033 targets a signaling pathway that sits at the center of celiac disease biology. When people with celiac disease eat gluten, the protein triggers an immune response in which IL-15 plays a central role, driving the immune cells that attack the lining of the small intestine and producing the villous atrophy and inflammation that define the disease. By antagonizing CD122, the shared receptor component for IL-15 and IL-2, ANB033 is designed to quiet that destructive signaling on immune cells.

“For people living with celiac disease, trace exposure to gluten can cause intestinal damage and debilitating symptoms despite general adherence to a gluten-free diet,” Daniel Faga, president and chief executive officer of First Tracks Biotherapeutics, said in the company’s announcement. “After treatment with ANB033, patients underwent a 14-day gluten challenge consuming the equivalent of two slices of bread a day. ANB033 achieved a statistically significant and clinically meaningful protective effect against gluten-induced intestinal damage and symptoms, while maintaining a favorable safety profile.”

The company said the results exceeded its own expectations — CEO Dan Faga told investors that ANB033 “achieved every single one” of the study’s aims, according to Markets Daily — and that it now plans to discuss the results with regulators and advance the drug into late-stage development in 2027. ANB033 already carries the U.S. Food and Drug Administration’s Fast Track designation, which is intended to speed the development and review of drugs for serious conditions with unmet medical needs.

The landscape it enters

The unmet need is substantial. Celiac disease affects roughly one in every 100 people worldwide, and while the strict gluten-free diet remains the cornerstone of management, the DelveInsight market analysis notes that about 5% of patients continue to suffer symptoms even with good adherence, and intestinal healing is often incomplete. There is no FDA-approved pharmacological therapy for celiac disease — a fact that has drawn more than 25 companies into the race, with over 30 therapies in development across clinical stages, according to DelveInsight.

ANB033 is part of a crowded but still unproven field. Other candidates in the pipeline include latiglutenase from Entero Therapeutics, Takeda’s TAK-101, TAK-062 (zamiglutenase) and TAK-227, KAN-101 from Anokion, ZED1227 from Zedira, and IMU-856 from Immunic, each taking a different mechanistic approach, according to DelveInsight’s pipeline tracking. The IL-15 axis itself has attracted heavyweight attention: Amgen’s ordesekimab (formerly PRV-015) is an anti-IL-15 antibody in mid-stage development, and Teva’s TEV-53408, another anti-IL-15 antibody, received FDA Fast Track designation in May 2025 and is in Phase 2a, according to pipeline reporting. ANB033’s differentiator is its mechanism — a CD122 antagonist delivered subcutaneously, blocking both IL-15 and IL-2 signaling — and its delivery format, which would be far more practical than the intravenous infusions some competitors require.

The context also includes recent disappointments that underline how hard this disease is to drug. The Reuters Health Rounds column that carried the ANB033 news sits alongside a broader record of celiac programs that have stumbled in late-stage testing, which is why investors and clinicians alike treat early gluten-challenge wins with cautious optimism rather than celebration.

Analysis: Why It Matters

The ANB033 results matter less for what they prove than for what they signal — and the distinction is worth keeping sharp.

First, the trial design itself deserves attention. Gluten-challenge studies are deliberately brutal: asking celiac patients to eat the equivalent of two slices of bread a day for two weeks after carefully avoiding gluten is the closest researchers can get to a stress test, and it is precisely the scenario the drug is meant to guard against. That ANB033 showed both histologic protection and symptom control under that kind of assault — with the symptom benefit significant from day one — is a stronger signal than a gentle, real-world “trace exposure” study would have been. If a drug holds up under a sledgehammer, it has a plausible chance against the everyday taps of cross-contamination.

Second, the mechanism is targeting the right biology at the right time. IL-15 has emerged as one of the most validated targets in celiac research, with two Big Pharma programs (Amgen’s ordesekimab, Teva’s TEV-53408) chasing the same cytokine. That convergence is both validating and competitive: it confirms the industry’s belief that IL-15 blockade is the most promising route to a drug for celiac disease, but it also means ANB033 will be judged against well-funded rivals as all of these programs mature. The subcutaneous route is a genuine practical advantage — a celiac drug that requires regular infusions at a clinic faces a much steeper adoption curve than one a patient can inject at home.

Third, the commercial and clinical stakes point in the same direction: this would not replace the gluten-free diet, at least not initially. The realistic near-term framing, and the one the data supports, is protection against the accidental exposures that make the diet so exhausting to maintain — the restaurant meal, the shared kitchen, the mislabeled product. For the roughly one-in-a-hundred people living with celiac disease, that distinction matters enormously: the diet’s burden is not just medical but social and psychological, and a “safety net” drug would change the lived experience of the disease even if the diet remained the foundation of care.

Fourth, caution is warranted on the numbers. Thirty-two patients is a small trial, and top-line announcements are, by definition, the company’s best presentation of its own data. The p-values are strong, but the field has seen early celiac wins fade in larger studies — which is exactly why the planned late-stage trial in 2027, and the regulatory discussions before it, are the real events to watch. The absence of safety signals is encouraging, but CD122 blockade touches fundamental immune signaling (both IL-15 and IL-2), and larger, longer studies will be the true test of the risk-benefit balance.

Finally, there is the timing. With multiple IL-15 programs converging, 2027 is shaping up to be a decisive year for celiac drug development. Whoever reaches late-stage testing with clean data first will set the terms — on endpoints, on labeling, on what “protection” means in practice — that everyone else must meet. ANB033’s Fast Track designation gives it a regulatory tailwind. The race is real, and for the first time in the history of celiac drug development, it has more than one credible runner.

What to Watch Next

1. Regulatory discussions: First Tracks says it will discuss the Phase 1b results with regulators. What the FDA asks for in a late-stage trial — which endpoints, how long, how large — will define the program’s timeline and cost.
2. Late-stage trial design in 2027: Whether the company moves to a real-world exposure study, another gluten challenge, or a combination will reveal how confident it is in the drug’s effect outside the artificial conditions of a challenge trial.
3. Competitor readouts: Amgen’s ordesekimab and Teva’s TEV-53408 are the closest IL-15 rivals. Their data will either validate the pathway further or raise questions ANB033 must answer.
4. Full data presentation: Top-line results are summaries. A peer-reviewed publication or medical-conference presentation with full histology, subgroup, and durability data will let independent experts judge the strength of the signal.
5. Safety in larger cohorts: No safety signals in 32 patients is a start, not a verdict. Longer treatment and larger numbers — especially given the drug’s action on core immune signaling — will be the critical watch item through late-stage testing.

Sources

• First Tracks Biotherapeutics press release (GlobeNewswire, Oct. 12, 2026)
• Reuters, “Experimental drug treats gluten-caused intestinal damage in celiac patients” (Oct. 14, 2026)
• cGxP.wire, “First Tracks Reports Positive ANB033 Phase 1b Celiac Data” (Oct. 12, 2026)
• Markets Daily, “First Tracks’ ANB033 Clears Key Phase Ib Celiac Disease Study Goals” (Oct. 14, 2026)