First Tracks’ ANB033 Clears Key Phase Ib Celiac Disease Study Goals

Key Points

• ANB033 met all stated goals in the first 32-patient Phase Ib celiac disease cohort, significantly reducing gluten-challenge-related intestinal damage versus placebo, including a 75% reduction in the decline of the Vh:Cd ratio.
• Treated patients reported no increase in key symptoms such as abdominal pain, bloating, nausea, diarrhea, and fatigue, while placebo patients experienced worsening symptoms. No treatment-related serious adverse events or discontinuations were reported in the ANB033 group.
• First Tracks plans to complete a second Phase Ib cohort focused on 12-week mucosal healing, with data expected in the first quarter of 2027, and anticipates starting a late-stage celiac trial in 2027 following regulatory discussions.

First Tracks Biotherapeutics NASDAQ: TRAX reported top-line results from the first cohort of its Phase Ib study of ANB033 in celiac disease, saying the investigational CD122 antagonist met histologic and symptom-related objectives during a placebo-controlled gluten challenge.

The cohort enrolled 32 patients with celiac disease, including 17 who received ANB033 and 15 who received placebo. Participants received subcutaneous loading doses at weeks zero, two and four, followed by a 14-day gluten challenge consisting of 6 grams of gluten daily, which the company said was equivalent to about two slices of bread. The primary analysis occurred at week six.

Dan Faga, First Tracks’ president and CEO, said the results exceeded the company’s expectations. “ANB033 achieved every single one” of the study’s aims, including prevention of clinically meaningful histologic damage and increased symptoms relative to placebo, he said.

Histologic Measures Showed Placebo-Adjusted Benefit

The study’s primary histologic measure was the change in villus height-to-crypt depth, or Vh:Cd, ratio, an indicator of intestinal structure and damage. The mean change from baseline at week six was negative 0.17 for patients receiving ANB033, compared with negative 0.66 for placebo.

According to First Tracks, the resulting placebo-adjusted difference of 0.49 represented a 75% reduction in the decline of the Vh:Cd ratio and was statistically significant, with a p-value of 0.009. The company said the decline in the ANB033 arm remained below an approximate 0.25 threshold considered clinically meaningful.

ANB033 also reduced intraepithelial lymphocyte, or IEL, density during the gluten challenge. Mean IEL density decreased by 1.2 from baseline in the treatment group, while it increased by 18.8 in the placebo group, producing a placebo-adjusted difference of 20 and a p-value of less than 0.001.

The company also reported a statistically significant placebo-adjusted difference of 3.33 on the VCIEL composite scale, which combines Vh:Cd and IEL measures.

Company Reports Symptom Protection and Favorable Tolerability

Participants completed the Celiac Disease Symptom Diary, which evaluates abdominal pain, bloating, nausea, diarrhea and tiredness. First Tracks said placebo recipients experienced a marked increase in symptoms during the challenge, while ANB033-treated patients did not experience an increase in those symptoms throughout the challenge period.

The company said symptom-score differences between the treatment and placebo groups were statistically significant from the first through seventh day of the gluten challenge. Moderate-to-severe symptoms were significantly lower with ANB033 from day one through day 12, according to the company.

Use of permitted medications for gastrointestinal symptoms also differed between groups. First Tracks reported that 47% of placebo patients used concomitant medications, compared with 6% of ANB033-treated patients.

Paul Lizzul, the company’s chief medical officer, said there were no treatment-related serious adverse events and no adverse events resulting in treatment discontinuation among ANB033-treated participants. He also said the treatment arm had numerically fewer moderate-severity adverse events than the placebo arm.

Dual IL-15 and IL-2 Mechanism

ANB033 is an investigational, subcutaneously administered antagonist of CD122, a receptor component involved in signaling by both IL-15 and IL-2. First Tracks said dysregulated activity of those cytokines contributes to immune-cell survival and proliferation in celiac disease and other inflammatory conditions.

Lizzul said ANB033’s ability to block both IL-15-driven inflammation and IL-2-mediated T-cell proliferation differentiates it from therapies that only target IL-15. He said the company believes the dual mechanism may have contributed to the observed symptom findings as well as the histologic results.

Faga cautioned that cross-trial comparisons with other programs are limited and that no head-to-head studies have been conducted.

Next Steps Include Cohort Two and Regulatory Discussions

The Phase Ib trial includes a second celiac cohort designed to assess mucosal healing over 12 weeks in patients with a broader range of baseline histologic damage and symptom severity. Unlike cohort one, cohort two does not include a gluten challenge.

First Tracks said cohort two is nearing enrollment completion, with top-line data anticipated in the first quarter of 2027. The company plans to present the cohort one results at ICDS in Melbourne in mid-November.

During the call, Lizzul said the company does not need to wait for cohort two data before engaging with the U.S. Food and Drug Administration on the development path for ANB033. The FDA has granted Fast Track designation to the program, and First Tracks anticipates beginning a late-stage celiac trial in 2027.

The company is also enrolling a Phase Ib cohort in eosinophilic esophagitis, with top-line data expected in the third quarter of 2027. In addition, First Tracks said one of two planned Phase II trials scheduled to begin in the first half of 2027 will evaluate ANB033 in vitiligo.

About First Tracks Biotherapeutics (NASDAQ:TRAX)

First Tracks Biotherapeutics is a clinical stage biotechnology company advancing antibody therapies which modulate immune pathways implicated in autoimmune and inflammatory diseases. Its pipeline includes ANB033 and ANB101. First Tracks Biotherapeutics is based in SAN DIEGO.

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