First Tracks Biotherapeutics, Inc. Ordinary Shares Study result

Please go ahead, sir. Thank you for joining us this morning. 2026 has been a very exciting initial year out of the gate for First Tracks.

Our top-line data for ANB033 from cohort one in celiac disease exceeded our expectations. After my introductory remarks, Dr. Paul Lizzul, our CMO, will review the study results in detail. I will then discuss next steps before we open the call to Q&A. This presentation contains forward-looking statements. First Tracks is focused on developing differentiated therapies that fundamentally change how autoimmune inflammatory diseases are treated for patients in need. Today, we are focused on ANB033, a potent and subcutaneously delivered CD122 antagonist that was discovered by our research team. This program has true pipeline and product potential across GI, derm, and broader autoimmune diseases. Our first indication development is to treat celiac disease. Celiac is the largest autoimmune disease without an improved therapy.

It is a serious chronic immune-mediated disease affecting more than 2 million adults in the U.S. Currently, our phase I-B trial is underway across two separate cohorts in celiac disease, as well as another GI-related disorder called eosinophilic esophagitis, or EoE. Today, we are focused on reading out top-line results for the first cohort from celiac, which was a gluten challenge. The basic goal of any placebo-controlled gluten challenge is to show the active drug arm prevents histological damage and the emergence of symptoms relative to placebo. However, the most positive outcome would be for patients in the drug arm to also see a protective effect on both measures. This means both any incremental histological damage would remain below the threshold considered clinically meaningful, as well as prevent an increase in symptoms. At a high level, ANB033 achieved every single one of these aims.

As far as we are aware, ANB033 is the first therapeutic to show statistically significant and clinically meaningful protective effects on both gluten-induced intestinal damage and symptoms in a gluten challenge. Importantly, ANB033 had a clean safety profile and was well-tolerated. We believe this data set is compelling, differentiated, and reinforces the potential advantage of blocking both IL-15 and IL-2 signaling. With that, I will turn it over to Paul to review the results in more detail.

Thanks, Dan. Let me begin with a brief review of how ANB033 works. CD122 is the beta subunit of a receptor complex required for signaling of both IL-15 and IL-2 cytokines. Dysregulated signaling by these cytokines through CD122 is integral to the survival and proliferation of pathogenic CD8 positive T cells, CD4 positive T cells, and NK cells, which are central to the initiation and maintenance of inflammation in celiac and many other immune-mediated diseases. ANB033 is an investigational high-affinity CD122 antagonist that blocks signaling of both cytokines through the receptor complex. As a result, it aims to inhibit the pro-inflammatory activities of the downstream signaling pathways, thereby reducing inflammation and its downstream effects. ANB033's dual mechanism of action to simultaneously reduce both IL-15-driven inflammation and IL-2-mediated T cell proliferation in adaptive immune responses differentiates it from therapies that only target IL-15.

ANB033's dual pathway inhibition is particularly relevant in celiac, a disease marked by excessive production of both IL-2 and IL-15. As this illustration shows, gluten is presented to gluten-responsive CD4 T cells, triggering a cascade of immune activation beginning with Th1 cells. As shown in the gold box, ANB033's ability to block IL-2 signaling in the lamina propria of the gut reduces the upstream CD4 T cell response, T cell proliferation, and importantly, interferon amplification of IL-15 expression. Apart from the impact on inflammation, IL-2 is also correlated with the GI symptoms associated with gluten ingestion, supporting the potential for ANB033 to show differentiated improvement in symptoms compared to IL-15 inhibitors. The olive box highlights the downstream role of IL-15, which plays a direct role in inducing IEL proliferation, leading to epithelial barrier destruction.

CD122 positive IELs are highly sensitive to IL-15, and ANB033 blocks these cells from causing downstream tissue damage in the lamina propria. As a result, ANB033's dual inhibition of these cytokines addresses both the upstream immune response to gluten and the downstream inflammatory response that collectively cause intestinal damage and symptoms. Let's turn to the clinical foundation for ANB033 in celiac. In our 80-participant phase 1a study in healthy volunteers, ANB033 was well-tolerated with no safety signals observed across all doses. Following subcutaneous administration, ANB033 has a half-life of up to 3 weeks, which allowed us to initiate our phase 1b trial with a convenient treatment profile, and in the future, explore extended dosing regimens. The dose shown here in green was the lowest subcutaneous dose tested.

After a single administration, we saw deep target engagement with CD122 positive CD8 T-cells decreasing by 74% and CD122 positive NK cells decreasing by 98%, versus essentially no change with placebo. A dose response was observed on relevant PD biomarkers, and we modeled the phase 1b dose in our celiac trial to achieve greater than IC90 on CD8 T-cell subsets in the target GI tissue. Now, let's turn to the phase 1b trial in celiac disease. The study has 2 separate cohorts. Cohort 1 enrolled patients with a baseline endoscopy Vh:Cd ratio of greater than 2, which is indicative of more modest mucosal damage. After a dose loading period, these patients then underwent an intense gluten challenge to demonstrate prevention of further mucosal damage on ANB033. A second endoscopy was performed at the week 6 primary analysis.

The second cohort is enrolling patients with a broad range of baseline histologic damage and symptom severity, and we will evaluate them over 12 weeks. These patients with more severe damage at baseline did not receive a gluten challenge. This cohort is assessing the ability to demonstrate a benefit in mucosal healing with ANB033. As a reminder, this global placebo-controlled study enrolled participants across the U.S., U.K., Western Europe, Australia, and New Zealand. Let's look at cohort one in more detail. We evaluated 32 patients who were randomized approximately one to one, with 17 on ANB033 and 15 on placebo, who completed dosing and the gluten challenge. Participants received three subcutaneous loading doses of ANB033 or placebo at week zero, two, and four. They then completed a 14-day gluten challenge, consuming a total of 6 grams of gluten per day. This was equivalent to approximately two slices of bread.

The primary analysis was conducted at week six, and the study assessed safety and tolerability and evaluated key histologic measures, including change from baseline in the Vh:Cd ratio, the change in IEL density, and the VCIEL composite scale. We also captured the daily frequency and severity of symptoms. We enrolled patients whose baseline characteristics were well-balanced between the ANB033 and placebo arms. The baseline Vh:Cd ratio across both arms was 2.75, a typical population enrolled in gluten challenge studies. With that, let's turn to the results. The Vh:Cd ratio is an objective and clinically important histological measure of intestinal structure and damage. Biopsies were taken from the duodenum in the worst affected endoscopic area and evaluated by a centralized expert pathologist. At the week six primary analysis, ANB033 demonstrated a statistically significant Vh:Cd histological benefit versus placebo. The mean change from baseline was -0.17 for ANB033 versus -0.66 for placebo.

The magnitude of the mucosal injury, as captured by the decline in the Vh:Cd in the placebo arm, was robust and indicative of the expected outcome from an effective 14-day gluten challenge. The remarkable 75% reduction in Vh:Cd decline relative to placebo for ANB033 resulted in a clinically meaningful placebo-adjusted delta of 0.49 that was statistically significant with a P value of 0.009. Importantly, in the ANB033 arm, the mucosal histology was preserved. The 0.17 change in Vh:Cd remained below the approximate 0.25 threshold considered clinically meaningful. Let's look at IEL density on the left, which exceeded expectations. ANB033 not only prevented an increase but reduced intraepithelial lymphocytes, or IEL density, despite an intense gluten challenge. As a reminder, abnormally high IELs are a hallmark of celiac and cause tissue damage.

At week six, the mean change from baseline in IELs was a decrease of 1.2 with ANB033, whereas it was increased by 18.8 with placebo for an overall placebo-adjusted delta of 20. This result was statistically significant with a P value of less than 0.001. The VCIEL composite combines the Vh:Cd and IEL into a single unified scale. On VCIEL, the ANB033 achieved a statistically significant placebo-adjusted delta of 3.33. This collectively represents preservation of villous architecture and a reduction in immune cell response that drives tissue injury. The histologic findings are only part of the story. Just as important are how patients feel and function. Participants completed the Celiac Disease Symptom Diary, or the CDSD, which is a validated patient-reported outcome measure that assesses the frequency and severity of five key celiac disease symptoms, which are abdominal pain, bloating, nausea, diarrhea, and tiredness.

The placebo patients experienced a marked increase in their symptoms that is consistent with what you would expect during an intense gluten challenge. Treatment with ANB033 prevented an increase in those same symptoms throughout the entire challenge. Stepping back in a very practical way, it is also recognized that when celiac patients have exposures to gluten, they will often resort to taking medications to try to help manage their symptom burden. This is exactly what we saw in the placebo group, with 47% of patients reporting they took permitted medications to manage their GI symptoms, whereas only 6% of ANB033 patients took a concomitant medication while on treatment. It was remarkable that despite so many placebo patients taking these types of medications, the change in symptom scores on ANB033 versus placebo were not only meaningful but also statistically significant from the first through the seventh day.