Conference Transcript - TRAX 2026-06-03

Lucas Christensen, Analyst — Moderator, Jefferies Investment Banking

Good afternoon, and welcome to the Jefferies Global Healthcare Conference in New York. My name is Lucas Christensen with Jefferies Investment Banking, and it is my great pleasure to introduce Dan Figa, CEO of First Tracks Biotherapeutics. Thank you.

Dan Figa, CEO

Good afternoon, everyone. Thanks to Jefferies for having us here today. Again, my name is Dan Figa. I'm the CEO of First Tracks Bio. These are our forward-looking statements. so uh so our company is is young in terms of how long we've been around as a corporation but there's a deep legacy for almost two decades of where our science has originated we had spun out of a company called anaptis bio about a month and a half ago funded with 100 million dollars of cash from anaptis as well as some additional capital that raised at the time and we are developing antibodies to treat autoimmune diseases we're looking at novel targets our lead program in clinical development is amb033 it is a cd122 antagonist we also have two other programs in development a pd1 depleter called rosnolamab where we have had successful phase 2b data in arthritis as well as amb101 a bdc bdca2 modulator all three programs are in various stages amb0 through 3 we have two ongoing phase 1b trials one in celiac disease and one in eosinophilic esophagitis the celiac trial will read out data in q4 and the EUA trial by middle of 2027 2027 and we'll talk a lot more about that in some sequence slides as it relates to rosnolimab the pd1 depleter we are undergoing a strategic alternative review again we had positive data last year in a 424 patient arthritis trial we will not be moving that program forward ourselves into phase three in arthritis that has to do with the commercial implications the disease and the size we do believe that there is a market for this drug in second third line plus arthritis as well as potentially other indications in rheumatology and the BDCA2 modulator in B101 we are completing a phase 1a trial in healthy volunteers we've seen robust depletion of the target cell plasma cytoid dendritic cells as well as long profile PD complemented by a long half-life we will look to present that data medical conference at some point over the next six to 12 months and we are watching competitive data there as Biogen has two phase three trials reading out an SLE later this year and one in CLE and Q1 of 2027 based on the competitive results in our own profile we will then make decisions on how to further advance proof of concept studies in patients with this drug as I mentioned earlier we have 180 million dollars of cash at inception and that is a two-year runway that will drive through the principal focus a b033 the two phase 1b trials as well as an initiation of a third and fourth indication of phase 2 for a b0 through three that we anticipate in 2027 so focus the remainder of this discussion on AAMB033, our lead program. So CD122 is part of either a dimeric or trimeric receptor that is found on activated T cells. CD122, the component there, drives the signaling of IL-15 and IL-2 on those T cells, which would express an activated state, this dimeric or trimeric receptor. AMB-033 antagonizes CD122. We've designed this program to have a very specific epitope and is very high affinity, driving a potent outcome of the signal blocking. The result of blocking IL-2 and IL-15 would be the reduction of the proliferation of CD4s or CD8s, as well as reduction of the resultant secretion of various cytokines and chemokines. In diseases such as celiac disease and EOE, and I'll get more into the biology in future slides, there are specific cell types that express CD122 that are of the T cell phenotypes, cells like IELs, intra-epithelial lymphocytes, that densely express the dimeric receptor, including CD122, and other cells such as ILC2s that express the trimeric receptor, including CD122. So stepping back, there's a number of different disease areas within dermatology, GI, and others that we think are applicable for a target of CD-122. As I mentioned earlier, one of the mechanisms, IL-15 blocking, is in the IL-15 pathway. There are a couple of competitors that across the space that's what's going on right now, including ourselves we are in five different autoimmune diseases and there is an interesting data that will be presented over the next three to 12 months across diseases like vitiligo and atopic dermatitis that we are not yet exploring with our drug ourselves as well as proof of concept in the biology of celiac disease which is our near-term readout coming out later this year So we have run and completed a successful phase 1A trial with A and B 0 through 3. The results, I guess, no surprise at this point as we move forward. We showed a very safe, tolerable profile. The PK-PD was long-lasting. We observed with both IV and subcutaneous dosing up to three-week half-life, long-term PD effect receptor occupancy north of 30 days that's all off of single dosing at all doses we did not see a impact on peripheral total Tregs so I think more interesting are the PD results of the cell types of interest again in healthy volunteers in the periphery if you look in the top right corner of this slide in blue you're looking at a middle dose with iv administration single dose and in green you're looking at the initial starting dose subcutaneous administration the top right quadrant is looking at cd122 expressing nk cells nk cells express the dimeric receptor these cells are highly sensitive to IL-15 for survival so by blocking or antagonizing CD122 with a potent antagonist you're seeing a complete reduction of CD122 expressing in K cells in the periphery 97 98% off of the single dose if you look in the bottom right you'll get total on K cell impact what we're showing here is really the variability across patients that not all NK cells and healthy individuals are likely in disease as well express CD122 so while we're potent on what our target is you do sustain immune competency by not engaging with or impacting total NKC NK cell counts to full depletion on the top left we are showing the impact on CD122 expressing CD8 cells or Temera cells so again off of a single dose same setup here you're seeing three-quarter plus reduction of the CD8 CD122 expressing cells but no significant impact in CD8 cells overall so again, exactly what we'd want to be seeing here from this study off of one dose. To give an example of the PD effect, again, the same doses that we saw in the last slide. In green here, you can see that full reduction out over a month in the NK cell impact. And then you see a sustained duration over time that goes out multiple months off that initial dose. From a safety perspective, we are referencing Teva's data sets in the right-hand side of this page they have an IL-15 they have a long lasting IL-15 and you see data that exists from a longer duration phase 1a trial that goes out well over a year and no safety signals so I'll switch over to now our initial phase 1b indication in celiac disease from a commercial sense there are over 2 million patients in the United States alone that have their projected to have celiac disease today over a million of them are confirmed diagnosed confirmed via biopsy we could see the inflammatory damage and from there about a quarter million patients have mucosal injury while conforming to a gluten-free diet that's ultimately in our opinion the target patient population of interest the idea here is that we're looking to treat these patients who are are on gluten-free diets, have mucosal injury, clear out the information, and see a return to a sustained mucosal environment. And I'll get into some of those endpoints in a little bit. We think this is approximately a $5 billion market in the United States alone. Preliminary discussions with payers suggest that pricing here would look like other IBD diseases like ulcerative colitis or Crohn's disease. And I think it's important to note, and this really speaks to where this market can go over time and grow there are no approved therapies today on the market for celiac disease right now if you cannot sustain a healthy environment within your gut on a gluten-free diet there's no treatment for these patients right now so there's a huge white space opportunity for us moving forward if we're successful here post the phase 1b trial that we're currently enrolling so a little bit of the biology of the disease what you see here are two boxes on the page one in gold which is really targeting the il-2 signal blocking and then in in green targeting the il-15 blocking signaling component of our mechanism what happens when a patient ingests glugin is that's processed to glidin it's picked up as an antigen for those who have this disease by the APC is it's expressed and that activates CD4 T cells you see in within an hour a spike of IL-2 as well as an increase in inferior in gamma the inferior in gamma then downstream activates secretion of IL-15 for epithelial cells which which which signals and pulls through intra-epithelial lymphocytes. Those IELs then secrete chemokines such as granzyme B, which result in acute symptoms, such as nausea, diarrhea, bloating, pain, and that continues on in a cycle. And this happens from trace amounts of gluten. So again, if you're on a gluten-free diet, you can still be exposed, and patients are, in these trials that initiate this autoimmune mechanism for these patients. CD122 antagonists and specifically AMB033 target both pathways so by blocking IL-15 signaling on the IELs in the top right corner and again this is where we've seen proof of concept with other IL-15 blockers we should shut down and eliminate those IELs through starvation and that's reminiscent of what I showed in the phase 1a trial where we reduced the CD8 expressing tumor t-cells and in the gold box we're looking to suppress the activation cycle the cd4s in response to the gluten itself and decrease the interfering gamma and and stop the initiation now 15 secretion so by having a mechanism that targets both pathways we could shut down at source where gluten is presented as well as what's driving symptomatic and in impact and epithelial damage so we think we have a strong focus here on both pathways with our specific approach and then over the AL15s over time where I don't think they can show the same response of what we're highlighting here in the gold box we're in in pre-clinically a mouse experiment in sea like disease animal mouse model on the left hand side of the page is sham you're seeing the colon of the mouse there's no impact you have a healthy um healthy villi system uh in the middle so with um isotype on top of gluten which was then introduced you see the deterioration that's the white space in the middle and on the right uh not the case with gluten plus amb033 it's protective looks more like the sham what you're seeing there in the terms of deterioration in the middle are the villi and so what um the way you measure this in clinical trials and what we've done in this mouse experiment is on the ratio of villus height to crypt depth so represented on the right hand side of this page again sham on the left control on gluten in the middle and drug plus gluten on the right you're seeing a deterioration in the middle of the vhcd ratio as the villi have have reduced and you're seeing a sustained vhcd ratio on the right hand side of that graphic compared to the sham so interesting proof of biology from our own mouse experiment here you're looking at the uh then the the effect of the different cell types on pbmc's with patient derived blood for those who have celiac disease we are represented in the line in blue we have a very potent antagonist as I mentioned seen in terms of the lack of proliferation both on CD8s and CD4 T cells and we're comparing this to other other programs in the space whether that's Tiva's IL-15 in orange or Forte's CD122 in red you're seeing a differentiation in potency on the impact on the the TH cells T cells and then as well as the downstream cytokine or chemo connectivity i mean you see in the bottom right the interferon gamma same trend we have a more potent asset so the trial design uh what's ongoing right now in phase 1b we uniquely have two different cohorts of patients i think the consistency here across various trials is in cohort one we're looking at a gluten challenge these trials do look different across companies but the idea here is that you're taking patients who are well controlled on a gluten-free diet you're giving them gluten and you're looking to see patients who were on placebo deteriorate both on VHD as well as see symptoms and those patients on drug to be have a more protective effect on a relative basis we are dosing subcutaneously at baseline week 2 and week 4 you're then giving gluten for 14 days and at week 6 you're doing a biopsy measuring those endpoints that's a 30-patient trial, one-to-one randomization. The second cohort of patients we think is ultimately going to be more interesting in terms of informing Phase IIb design and the regulatory pathway. In this cohort, we're enrolling patients who have mucosal injury at baseline. So their VHCD in this cohort, by definition, will be less than or equal to 2. Now we've initially set this trial up these patients we dose one-to-one randomized with drug or placebo at baseline week two and week four and then we'll wait eight weeks and at week 12 we'll do a biopsy and we're looking for there is to see a numerical trend towards improvement at week 12 relative to the patients that are on placebo these patients are are controlled in a sense that they don't have severe symptoms at baseline so we're not explicitly looking for material change on symptomatic scores given the baselines are already starting in a well-controlled spot but on VHCD we should see a numerical benefit whereas in that first cohort we are looking for statistical significance and we're powered for a change in VHCD reduction this trial is set to read out across both cohorts in

Dan Figa, CEO

the fourth quarter of this year so moving on to eoe or eosinophilic esophagitis this is also a very

Dan Figa, CEO

large commercial market 340 000 patients diagnosed with eoe in the united states alone this is increasing at a pretty rapid pace eight percent CAGR year over year instigated a bit by having the first approved biologic depiction on the market now for a few years based on claims data to estimate that the picks and sold approximately $2 billion in the US alone last year in this disease and to minister on a weekly basis subcutaneous that said up to approximately 30% of patients don't respond to Dupixen and another meaningful percent of patients aren't full responders even if they have a directional benefit on that drug so there's a big opportunity here to bring a second drug to market into this disease it's about half the patients or so respond to initial lines of therapy PPIs or other steroid regimens before they move on to the biologic and biologic eligible population. We do have a phase 1b trial that was recently initiated. It is a 12-week study. We are dosing subcutaneously every other week for that period of time and we are powered to see both reduction in eosinophils as well as the PRO DSQ both of those at least in the Dupixent trials for approval were the co-primer endpoint so we are powered to see a change in in both of those in this trial and as a 50 patient trial one-to-one randomization versus placebo here similar to celiac disease there's two paths of immunology driving autoimmune disease we are defining these for simplicity as a dupy sensitive path ie targeting th2 cells as well as i'll see twos this is where dupy hits as I mentioned earlier both of these cell types express the trimeric receptor including c122 and I'll show you some data from animal studies in a little bit that shows a direct on target hit on these cell types in terms of the reduction of proliferation and resultant cytokine activity then in the right hand side patients who were not effectively treated with dupy are correlated with a increase in expression IL-15 and then similar to celiac disease by blocking c122 on the CD8 cells that are reacting to IL-15 we should see a significant reduction there is proof of concept in this disease with another IL-15 inhibitor in a very small study but for phase 1b that by just targeting IL-15 alone, they saw a reduction in eosinophils and a numerical trend of benefit on patient symptoms. This is important because CD122 is not expressed on eosinophils. We know that by targeting IL-15 or CD122, we are upstream in this disease by impacting inflammation directly from these upstream pathways and minimally from the perfect concept of IL-15s, you're then reducing the influx of eosinophils downstream. So we do believe there's good patient data that exists already out there as a proof of concept to what we're showing, and we already know depicts it works, and they're acting only in the green on the left-hand side. Here's a little bit of data to support what I'm just saying. We did run an aspergillus-induced eosinophilia mouse model. You're looking on this slide, both at the eosinophils in the esophagus as well as the lung and you're seeing in blue AB 033 which is more or less a full prevention of ESNFL recruitment relative to other mechanisms and then you know relative to to black isotype control you're also looking here we're able to measure there was an enough ILC twos to measure differences in the lung aspergillus again this is a lung-induced eosinophilia and so you are able to see the ILC2 recruitment in the lung, and we completely floored that in terms of the prevention of ILC2 increase with AMB033. And then lastly, from the same study, we're looking at the result in chemokines and cytokine activity. IL-5, IL-13, these are cytokines that are responsible. They're secreted from the CD8s. They're responsible for pulling in the eosinophils into the inflammatory environment. You're seeing a similar reduction there as well with AMB033 versus other comparators so in summary really excited about where we're going here with AMB033 two ongoing trials and see how can you we both on track to read out celiac later this year EOE next summer we are publicly committed to expanding to additional diseases there's a lot of clinical activity ongoing the space with other alpha teams that see doing to use again across five different diseases with the four players and we do believe that this is a pipeline and a product type asset really excited about the future we're going here both in these GI diseases and we're able to expand to and we do have two other clinical development stage programs in the portfolio into 2027 we do believe that there's increasingly path forward with both of those as well so we have four minutes left if there's any questions happy to take them thank