First Tracks Biotherapeutics (TRAX) trial results, October 12, 2026 transcript

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 AMB033 from Covert 1 and Celiac Disease exceeded our expectations. After my introductory remarks, Dr. Paul Lazul, our CMO, will review the study results in detail. I'll 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 and inflammatory diseases are treated for patients in need. Today we are focused on AMB033, a potent and subcutaneously delivered CD122 antagonist that was discovered by our research team. This program has true pipeline and a product potential across GI, derm, and broader autoimmune diseases.

Our first indication in development is to treat celiac disease. Celiac is the largest autoimmune disease without an approved therapy. It is a serious, chronic, new-mediated disease affecting more than 2 million adults in the United States.

Currently, our Phase 1B 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 in 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, AMB-033 achieved every single one of these aims. As far as we are aware, AMB-033 is the first therapeutic to show statistically significant and clinically meaningful protective effects on both gluten-induced intestinal damage and symptoms and gluten challenge. Importantly, AMB-033 had a clean safety profile and was well tolerated. We believe this dataset is compelling, differentiated, and reinforces the potential advantage of blocking both IL-15 and IL-2 signaling.

With that, I'll 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. This regulated 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. AMB033 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. A and B033'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.

A and B033'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, A and B033's ability to block IL-2 signaling in the laminate appropriate 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 AMB033 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 AMB033 blocks these cells from causing downstream tissue damage in the lamina propria. As a result, AMB033'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 AMB033 in celiac.

In our 80 participant Phase Ia study and healthy volunteers, AMB033 was well tolerated with no safety signals observed across all doses. Following subcutaneous administration, AMB033 has a half-life of up to three weeks, which allowed us to initiate our Phase Ib 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 on celiac disease. The study has two separate cohorts. Cohort 1 enrolled patients with a baseline endoscopy VHCD ratio 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 A&B 033.

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 eucosal healing with ANB033. As a reminder, this global placebo-controlled study enrolled participants across the US, UK, Western Europe, Australia, and New Zealand. Let's look at cohort one in more detail. We evaluated 32 patients who are randomized approximately one-to-one with 17 on A&B 033 and 15 on placebo who completed dosing and the gluten challenge. Participants received three subcutaneous loading doses of A&B 033 or placebo at week zero, two, and four.

They then completed a 14-day gluten challenge consuming a total of six grams of gluten per day. This is equivalent to approximately two slices of bread. The primary analysis was conducted at week 6, and the study assessed safety and tolerability and evaluated key histologic measures, including change from baseline in the VHCD ratio, the change in IEL density, and the VC-IEL composite scale. We also captured the daily frequency and severity of symptoms.

We enrolled patients whose baseline characteristics were well-balanced between the AMB033 and placebo harms. The baseline VHCD ratio across both arms was 2.75, a typical population enrolled in gluten challenge studies.

With that, let's turn to the results. The VHCD 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 6 primary analysis ANB033 demonstrated a statistically significant VHCD histological benefit versus placebo The mean change from baseline was minus 0 for ANB033 versus minus 0 for placebo The magnitude of the mucosal injury as captured by the decline in the VHCD in the placebo arm was robust and indicative of the expected outcome from an effective 14 gluten challenge The remarkable 75% reduction in VHCD decline relative to placebo for A&B 033 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 A&B 033 arm, the mucosal histology was preserved. The 0.17 change in VHCD remained below the approximate 0.25 threshold considered clinically meaningful. Let's look at IAL density on the left, which exceeded expectations. AMV033 not only prevented an increase, but reduced intraepithelial lymphocytes, or IAL density, despite an intense gluten challenge. As a reminder, abnormally high IALs are a hallmark of celiac and cause tissue damage. At week 6, the mean change from baseline in IELs was a decrease of 1.2 with AMB033, 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 VC-IAL composite combines the VHCD and IAL into a single unified scale.

On VC-IAL, the AMB033 achieved a statistically significant placebo-adjusted delta of 3.33. This collectively represents preservation of villous architecture and a reduction in the immune cell response that drives tissue injury. And 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 experience a marked increase in their symptoms that is consistent with what you would expect during an intense gluten challenge, whereas treatment with A&B 033 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 AMB033 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 AMB033 versus placebo were not only meaningful, but also statistically significant from the first through the seventh day.

Finally, the benefit extended to moderate to severe symptoms, which were significantly lower with ANB033 than with placebo from the first through the twelfth day.

Now turning to safety. As you can see, there were no treatment-related serious adverse events and no adverse events leading to treatment discontinuation in ANB033-treated patients. There were numerically fewer moderate severity events in ANB033 relative to placebo. However, it's also notable what happened to placebo patients during the study. We saw a remarkable increased incidence of GI adverse events reported in the placebo patients. This was correlated with the gluten challenge and further corroborates the patient's self-reported symptom data as well as their increased utilization of concomitant medications. In totality, the favorable safety and tolerability profile observed for AMB033 to date is particularly encouraging for a therapy under development for chronic use in immune-mediated diseases. Dan, I'll pass it back to you now.

Thanks, Paul. AMB033 demonstrated statistically significant and clinically meaningful results versus placebo on both key outcomes, gluten-induced intestinal damage and symptoms. Equally impressive is AMB033's protection of the intense intestinal mucosa across every histological measure evaluated during an intense gluten challenge. In addition, the impact to patients was tangible. Those who received AMB033 experienced fewer GI adverse events and were substantially less likely to require medications to manage their symptoms. Given the modest size of this trial, the statistical significance achieved is even more notable. In particular, seeing consistency across symptoms scores and all histological measurements provides increased confidence in our data. To put these results into context, we've shown them alongside other CD122 antagonist denial 15 targeting programs. It is important to recognize that cross-trial comparisons are limited, and there have not been any head-to-head studies conducted.

But what we do have with AMB033 is a potent CD122 antagonist with extended PD that is administered subcutaneously. And the data from our trial speaks for itself. We believe there is value in the consistency of the results across histology and symptoms, reinforcing the potential advantage of AMB033 blocking both IL-15 and IL-2 signaling.

As I said earlier, celiac is the largest autoimmune disease without an approved therapeutic option available for patients. Biopsy confirmed prevalence rates suggest nearly 1% or more than 2 million adults in the United States have celiac, and as many as twice that number of patients are positive for serological markers. With diagnosis rates known to increase upon approval of the first therapy for a disease, we expect to see the rate in celiac disease increase to more than 50%, exceeding 1 million adults in the U. S. alone over the coming years. 25 to 40% of patients are considered to have non-responsive celiac disease, or NRCD, meaning they continue to experience symptoms and frequent significant mucosal damage despite adherence to a gluten-free diet.

Market research suggests that a safe and effective celiac drug can command specialty pricing and payers are likely to reimburse with limited utilization management. Taken together, if all U. S. adult NRC-D patients were treated, it implies a market opportunity greater than $20 billion, and this excludes the potential to treat a broader set of patients who, even with symptom control, have moderate to severe mucosal injury, which may lead to downstream clinical complications.

Our unique experience with patients in both cohort 1 and cohort 2 may inform multiple registrational paths forward. As mentioned at the top of the call, AMB 033 has true pipeline and product potential. Today's top line readout is planned to be presented at ICDS in Melbourne in Bindovecker. Codework 2 of AMB 033's Phase 1B trial in celiac, designed to assess mucosal healing through 12 weeks in patients with a broad range of pre-existing histological and symptom severity, is on track to complete enrollment imminently. with top-line data anticipated in the first quarter of 2027.

As a reminder, FDA has already granted AMB-033 with fast-track designation. We plan to continue to engage with the FDA and other regulatory agencies to align on the next phase of development for AMB-033 and celiac. We anticipate starting a late-stage trial in 2027. In addition to Celiac, our Phase 1B cohort for AMB033 and EOE is enrolling with top-line data anticipated in the third quarter of 2027.

And today, we also announced one of our two additional planned Phase 2 trials that we'll initiate in the first half of 2027 will be in vitiligo. Additional details on this trial design will be disclosed upon study initiation. Overall, we're incredibly excited about AMV033's broad potential across multiple immune-mediated diseases and the progress we're making to realize it. We will now turn the call over to the operator for your questions.

Hey thanks Anupam It Paul So to answer your second question no we don Have to wait for Cohort 2 and obviously we really excited about these data and going to the FDA will be an important step and obviously we going to have to have conversations with them about the path forward but certainly Cohort 2 is not a gating factor to the development path here Yeah I just add on to that You know we believe there may be multiple paths to registration and we have often talked about prevention and healing slightly differently I think to Paul's point, these are exactly the discussions we'll take with regulators. We shared a lot of information today.

We have a lot more information internally, and there's more information to come. I think it's an exciting time for patients. I think with this information, we'll be able to work with the FDA to discuss what the right primary or co-primary endpoints are going to be with either or both of those paths moving forward.

Thank you.

Yeah, thanks, Yihaz. It's Paul. I don't think we're changing how we're approaching cohort two here. So, you know, as we've always stated coming into this, you know, that trial, we're looking for a signal and trend there, and we'll continue to do that. I mean, certainly we're encouraged by the data today that exceeded our expectations, but if you recall that cohort two, that's not a gluten challenge study, and we're giving a similar loading dosing regimen and then looking for healing out at 12 weeks. So, you know, I think at this point in time, certainly CORD 1 data are encouraging, but we'll continue to look for that signal or trend in that study.

Thank you.

Yeah, thanks, it's Paul. On the first question, you know, certainly as we've discussed and showed in our mechanism of action slides, we certainly believe that there is an added benefit to being able to inhibit or impact IL-2 signaling, both from a perspective on the histology, but also importantly on the symptoms as well, and I think that's what we're likely seeing here reflecting in the data with a very strong, you know, signal we're seeing here on symptoms. And the study and showing both of those at the same time is, you know, really unique as we've said before. And the second question was on placebo. Yeah, so in cohort two, you know, certainly, you know, you are correct in studies.

There is a potential for patients to be a little bit more diligent about how they're behaving and doing in the gluten trial. But, you know, as we said in that trial, we're certainly looking for, you know, a delta there and a signal between the active So even if there is some relative improvement in the placebos, if they're behaving better in their gluten diet, we would anticipate to see, you know, much more activity and protective effect in the active arm.

Thank you.

Yes, I'll address the comment on the intensity of the challenge. I think, as we've been describing for many months, there are multiple ways to run a gluten challenge across the number of days, how much gluten you're given in any single day, the way the gluten is administered. And what we're emphasizing here is that even in a relatively short course trial over 14 days, what you could observe on the placebo arm in terms of the degradation of VHCD that we're seeing here in the 0.6 to 0.7 range, this was a very significant outcome or impact on the patients that were randomized to that placebo arm. So the intensity was there. I think the other attribute that, you know, again, quite frankly, I think exceeded expectations only because no other drug has seen this before in the space.

But the patients on placebo, half of them were taking medicines along the way to control the symptomatic impact. And that really says a lot, and that really bridges into, right, we saw statistical significance on the drug arm on a relative basis on histology, on VHCD, but we also showed that protective effect. So we know it was a hard-hitting challenge given how big of an impact VHCD had on placebo. And then on the symptoms, and Paul, you can add on to this, on the symptoms, what was quite, I think, amazing here is right out of the gate, right? And that's why we're emphasizing the statistical significance as early as that first day. There was a very meaningful prevention of symptoms or increase in symptoms on the active drug arm.

So it was immediate. And, you know, there was a question earlier on what could be a potential reason that we're seeing this. In the sense, the protective effects of, and I think maybe the power of really blocking both IL-2 and IL-15 signaling. We're emphasizing as well that the patients on the active arm did not see any increase in symptoms throughout the entire study. I think that's what's truly notable here. And so we know we have a hard-hitting challenge in only 14 days. We gave a very significant two slices of bread a day challenge on a daily basis. I think the results, as we've been mentioning, kind of speak for themselves on a relative basis, not just active versus placebo, but then across, you know, looking at the results from other trials with very different gluten challenges.

Do you want to add anything, Paul? I think you covered it, Dan. Good job.

Look, I think this is a small study, and some of the impact is in the p-value itself in a small study and seeing how highly significant these results are.

I'm glad you're hitting on this, Yadon. It's not just the spread versus placebo. We need to show the drug has a real clinical effect in trials in a placebo. But from a patient perspective the most important thing here is the you know again it on both types of outcomes here It the prevention of deterioration in the in this case very significant exposure to gluten in a way that not clinically meaningful That was an incredibly important outcome while still showing that placebo delta was statistically significant But again, you know, it's hard. It's still early days here for the broader field. But with a CD122 antagonist, we are able to show a very tangible symptomatic outcome here that was statistically significant, but again, also clinically meaningful.

The thing that pairs with the Delta versus placebo on symptoms is the fact that patients did not see an increase in symptoms when they were exposed to We're running the second cohort on healing. We're not going to be giving them this intense gluten hit, right? So it's going to be a very different type of trial running in cohort two. I think we have the potential there, although we have to see, right, because that hasn't been done before. But we have the potential there to see pretty significant healing or increase in VHCD in a very different type of trial design. And that's why we were saying earlier there could be multiple paths forward here in registration.

I think the reason we're able to say that with confidence is we have a mechanism of action, a potent drug, not just the C1-2 antagonist, but it's a potent molecule that could give us viability across multiple ways to treat a really large patient population here that have various issues on presentation, whether that's damage and they don't know they have the damage because they don't have acute symptoms every single day. On the flip side, they're very prone to or sensitive to exposures to gluten, and they might feel an impact out of the gate, but otherwise they had a healthy VHCD that just deteriorates over time. There's multiple ways to look at this. We're really excited about the results today, and we think this opens up at least one of those two paths forward.

You know, we did a large number of assessments and evaluations in a very thorough, comprehensive translational package, but, you know, these are top-line data. We don't have all that information. And at this point in time for ICDS, you know, we're committing to what we're presenting today, and that likely will be it. And, you know, we'll make determinations in the future as to what additional data we'll be presenting.

Yeah, Derek, I appreciate that question a lot. We don't have that information yet, although given the quality of the clinical results, I'm quite excited to ultimately have access to that information internally. I think we're ultimately going to have a lot of judgment call here, given the competitive intensity of what we share translationally.

Finally, we do think a lot of the devil is in the details on how you're going to design a very successful and de-risked registrational trial. And so some of what I think we've already learned by seeing the symptom data, which is why we kept, we actually described today, I think, a little more than we thought we were going to coming into these results from a public perspective. And there's a lot of, you know, amazing information we now have internally, and then the translational information is going to stack on top of it. But the thing that we're focused on most here is ensuring that not only we move quickly, but that we maintain a competitive intensity on a relative basis over, I think, the next critical 12, 18 months as we're all moving forward into late-stage or registrational trials.

Yeah, so I'm not going to comment on this relative to the competitor, but what I think is a major takeaway from this call and the data we're presenting with the 0.17 on active is it is clearly below a range that is considered clinically meaningful in terms of deterioration, i. e. , we did not see a meaningful deterioration on active in this study. And that is really important here in terms of the, we think, the commercial viability of these types of approaches moving forward in the field of treating celiac disease.

Yeah, I mean, Gavin, unfortunately, I think it's a little bit of a repeat what we've been saying here is, We have learned a lot in this study and really the intention of running a phase 1b. We gave a very hard-hitting amount of gluten very quickly over a 14-day period. We did not have dropouts in this trial, but we did observe placebo patients needing the equivalent of what was rescue medicine or conchalant medicine control symptoms. So this is exactly what we were hoping to see. I know yourself and others are going to be very focused on what do registrational trials look like. And like I keep saying, we have a lot of ideas for one or more paths moving forward.

We're going to take a very, I think, impressive data set forward to the FDA and have the right discussions to work with them on how do we think about the right endpoints on both histology, I'm going to turn it over to the FIRO and the FIRO to progress forward. And like I said, there could be one or more paths to doing this that we could pursue in parallel.

Yes, that's correct. We haven't disclosed the dose. Again, I think, you know, similarly, for competitive reasons, we're going to keep that undercover for right now. But I'll emphasize, we do think the dose that we are using in this trial, which in this case we really think of as a loading dose, was already, one, subcutaneously administered, and two, as we've been forecasting, I think we can lean into this further, I don't think we're going to be testing higher doses. I do think we're going to have the opportunity to test lower doses with extended dosing intervals in future trials.

Yeah, we'll have more to say or think about this over time as we have access and have reviewed the translational data. I think that is the honest answer. But from the clinical results, again, this wasn't the largest study. But the p-value that we observed in a study like this and the protective effect of the drug, it really is almost impossible to have better results than this.

Just when you look at it, it was protective on histology, on every outcome measure, and we saw no impact or increase of symptoms for patients that actually received the drug. You just can't do better than that. And so, I think I'll leave it at that. It's a great way to end today's discussion.