Conference Transcript - ATYR 2026-05-20

Operator

Good afternoon, and welcome to the Jeffries Global Healthcare Conference in New York. My name is Michael Scharfenberger with the Jeffries Investment Banking Team, and it is my great pleasure to introduce Sanjay Sukhla, CEO of A-Tier Pharma.

Sanjay Shukla, CEO

Thanks for the invite, Jeffries. Happy to be here. Today I'm going to talk to you a little bit about ATAR and how we're advancing our lead candidate. I want to focus the corporate presentation today really on epsilfitimod in pulmonary sarcoidosis. Some of our forward-looking statements. I want to start here, switch it up a little bit. This is from our corporate presentation, but I want to start with this data and this snippet of data from a pre-specified table that we ran from our last study. about six months ago we convened a group of experts in San Diego sarcoidosis experts from all over the U.S. as we started to think about charting a pathway forward and one of the things that the experts told me is FSOFIT was a paradigm shifting trial it taught them a lot about steroid utility we obviously showed that steroids in these patients can be managed on significantly less steroids. We also showed that the efsofitamod program is the only drug, frankly, to show quality of life benefit in the last 70 years for these patients. But one of the things that I was asked to present is, let's dig into some of the functional benefit. And though that trial was targeting something different, one of the questions I got asked was, can we look at force vital capacity in restrictive patients. So this was one of the first pieces of data that we showed that audience of experts, and there were, I'd say, three major comments that came out of this when we showed this very slide. Number one, that's a very, very large treatment effect, almost unexpectedly large. That was one of the comments from the expert. Another expert said this might be the strongest evidence of drug activity you've ever shown me. That was from one of our more skeptical PIs in the U.S. And the consensus in the room was this was clear rationale that the drug can have utility as improved therapy in the future. So I want to keep that in mind as we present today. This is one of the key pieces of information that I think it's important for everyone to have front of mind as I present. So ATAR's outlook here, we're really looking to focus on efsofitamide, but we're creating first-in-class therapies focusing on inflammation and fibrosis. Efsofitamide, as a reminder, is an immunomodulator, has a novel mechanism of action. and EFSO-FIT, which I'll talk to you a little bit about today, is the largest interventional pulmonary sarcoidosis trial ever. We've emerged from a recent meeting with the FDA with a clear pathway around what it would look like to get the drug approved. It will require another phase three program protocol that we have planned to submit to the FDA later this month. But this gives us a really clear directionality on how to get the drug approved. Epsifetamide for ILD represents a rather large market opportunity. We see it as up to $5 billion, and I think interstitial lung disease is underappreciated, but we are, I would say, one of the leading companies in the world focusing on a new therapy for interstitial lung disease. Also want to highlight, not in this presentation, but our 0101 program is being developed as a, I would say, a true anti-fibrotic. I expect that to be in the clinic next year. And ATAR has a really interesting platform focusing on tRNA synthetase biology. But again, today, I really want to focus on efsofitomide and sarcoidosis. Sarcoidosis, as a reminder, this is a disease that's characterized by clumps of granulomas that largely occur in the lung. We have elucidated that these granulomas express a receptor called neuropilin-2. This is the binding receptor for efsofitomide. So the mechanism was established long ago, and we published a landmark publication in Science Translational Medicine last year, highlighting some of our preclinical learnings and discovery to move into sarcoidosis. It's a disease that is an orphan disease, under 200,000 in the U.S. Most of these patients present more common in women, also a little bit more prevalent in the black population. It's a progressive fibrotic disease. You see about 20% of the patients move to become fibrosis, fibrotic. You see a large proportion of these patients also have debilitating functional deficits, and we're going to get into some of that with the data that we present. Large unmet need, severely debilitating disease, not just the disease, but the treatments that are out there, quite toxic, steroids, methotrexate, the off-label use of infliximab, luflinamide. We have to do better for these patients. We need an approved therapy. Efsafetamide is the closest and best opportunity in my mind to get there for these patients. And as I mentioned, large market opportunity, no approved therapies, a green space opportunity for a therapy that I think fits very, very well in treating these patients. A little bit more about that Science TM article I mentioned. This was a big deal for us. It encompassed about seven or eight years of preclinical and discovery work. I would encourage everyone here to take a look at that. That's actually from our own lab, this granuloma that's stained for neuropilin 2. I think this was really a landmark publication, as I mentioned, that well establishes how our drug works as a neuropilin 2 modulator and really downregulates myeloid cells, in particular activated macrophages in this condition. EFSOFIT, as a reminder, the largest interventional trial conducted in pulmonary SARC. We ran this trial in about nine countries, almost 90 centers. This was a trial that we were focusing on steroid reduction, and I think we successfully showed that, well, you can reduce steroids in really all the patients here, not just those treated with EFSOFITAMOD, but those also on placebo. This is part of the reason why we didn't hit our primary endpoint. But I think that was a paradigm shift, and it's something that the SARC world is coming to grips with. I expect ATS and ERS guidelines to be updated. And moving forward, I think patients around the world are going to be managed on steroids with their sarcoidosis 50%, 60%, 70% less. That's a good thing for those patients, but it is a key learning from this study. And that substantial steroid reduction that we observed really in all the groups, this was a really important learning. I always said for many years that the drug was either going to show that it can benefit and win on steroid reduction, or we were going to change the treatment guidelines, and it's clear we're changing the treatment guidelines. This was largely due, I would say, to that placebo 40% that were steroid-free. This was perhaps four times higher than experts expected. Nonetheless, efsofitamide beat placebo, really, in all of the measures we were thinking about with steroid reduction. But when we start to look at clinical activity in the PROs, that's where you really start to see the emergence of a signal. And the first thing is to really look at kink sarcoidosis lung. And this is a questionnaire looking at cough and shortness of breath symptoms. And here we showed a significant benefit for these patients based on the KSQ lung at week 48, you know, a large signal. But what impresses me is it's a durable signal. It's not jumping around. Really, after about week 8, we start to see benefit emerge, and patients started to feel better. When we combine that with patients who were steroid-free, who had substantial, really, fluoride benefit, KSQ lung greater than 8, you start to see an odds ratio that's also highly statistically correlating to the fact that the drug can get you off steroids and get you feeling really really good and we heard that over and over again in this trial that this is one of the only therapies that's doing this when you look at other measures of patient reported outcomes the king sarcoidosis general health and also the fatigue assessment score beyond just looking at the lung this is aches and pains some of the rheumatologic features of sarcoidosis are captured in the KSQGH. The fatigue assessment score, a lot of fatigue for these patients. They are inflamed systemically with a lot of myeloid activation. Again, consistent and durable findings here, significant findings of improvement, cough, shortness of breath, fatigue, general health. This was remarkably consistent. This gave us a real strong signal that we had drug activity. In the last trial, we weren't really looking for FVC superiority. We wanted to make sure that in all of these patients, we maintained FVC, and we expected some modest declines, which we saw. But much of this was driven by how aggressively we tapered steroids. When you remove steroids, FVC is quite sensitive. But you might remember that first slide I showed you, and that's important when you start to think about superiority. You have to focus on the right phenotype for the right endpoint. So on the whole, we maintain force water capacity for all patients. But if you really want to look at specific functional benefit, you have to start to unpack the phenotypes and say, okay, what's happening in, for example, those restrictive patients. The last thing I want to highlight here is the safety. I've mentioned a lot of therapies that these patients have to basically be managed with. esophetomage, a much safer alternative than steroids, methotrexate, or some of those off-label immunomodulators. What we saw in the last trial where AEs were mostly mild or moderate, we didn't see any concerning signals from an SAE perspective, and then the proportion of patients who had any kind of immunogenicity was also very, very small. So this is very important as we develop this therapy. We don't want to create any kind of new toxicity that the patients want to have to grapple with as we start to show some of this benefit. So the FDA meeting, this was a really important moment for us. We spent a lot of time getting a briefing book together. The objective really was to align on a pathway forward. And what came out of it was a clear understanding that we can develop the therapy, but it will require another phase three trial. Now, this phase three trial is going to be different. The last trial focused on steroid reduction, but ATAR has frankly blown that endpoint out of the water. And as I said, treatment guidelines are being changed. So one of the key questions we had is when you think about force vital capacity, when you think about KSQ lung, where should we focus and what should be the primary endpoint? And what came out of those discussions was a clear understanding that FEC should be the primary. KSQ is a good endpoint. It's a solid secondary endpoint, but is it fit for purpose yet to be a primary? Probably not. There's a couple things we still need to do with validating this endpoint, but I think it's a very solid secondary endpoint. But FEC is going to be the primary in the next trial. Now, a sidebar win for us was also looking at dosing. We had a notion from the last trial with all the POPPK data that we collected that we may have an ability to increase the exposure of the drug if we went to a Q3 dosing regimen. This was presented to the FDA ClinPharm Division, and they agreed with our approach. The idea here is we started to see trough levels slightly dip below the EC50 in the last trial, and by going to Q3, we think we can get about 30 percent more drug exposure for these patients. What that translates to is in a one-year trial, they'll now get 17 doses as opposed to 12. So this is a nice way for us to thread the needle about getting more exposure, but also not going to a higher dose where you might actually start to then dig into some of that safety margin and the benefit. So I don't want new safety effects by going to a higher dose, but getting more exposure gives the drug a better chance to show benefit on FEC in the next trial. So I think this is a material win for us as we think about the next trial. The company plans to file a protocol here, and we want to be ready to start this trial later this year. Now, I want to take a step back, now that we know FVC is the primary, and I want to get back to that first graph I showed you. FVC is an endpoint that's relevant for a restrictive patient population. What I mean by restrictive is these are patients that have trouble expanding their lungs. They can't get air out. They can't get air in or out, frankly, but their lungs are restricted. This is the relevant endpoint that you would look at in a restrictive population, as opposed to obstructive, which is upper airway, where you can't breathe out. This is similar to COPD and asthma. There, the relevant endpoint is FEV1. So as we started to think about sarcoidosis, and we wanted to focus on superiority of FEC, we have to look at a more homogeneous lung phenotype. So we started to break out these phenotypes, and these were all in pre-specified tables that we had, because many of the experts, frankly, wanted to know how these phenotypes are behaving with F-safetamod. So we enrolled, of course, mostly normal patients. But when you compare our data to some real-world data, you can see that maybe a little bit less on the restrictive number of patients, but we still had 44 patients that we could look at their FEC. Obstructive was our next highest group, and mixed and isolated diffusion, you know, round out the bottom two there. But I think the key element here to pay attention to is FEC has been used as a registrational endpoint, but if we're going to use that as a primary endpoint, we have to start to focus on a restrictive lung phenotype of sarcoidosis. That's why we started to really hone in on these 44 patients. So when you look at these 44 patients, remember, this is a large treatment effect. A treatment effect of 124 milliliters in this slopes analysis is highly beneficial from a clinical point of view. Most experts are looking for 80, 90, 100 milliliters of improvement here. What's unexpected here is we, remember, tapered these patients aggressively off steroids. So the expectation would have been that we would have declined in all of our FVC measurements. So the fact that we're able to maintain FVC while removing 7, 8, 10 milligrams of prednisone, this is actually rather remarkable according to one of the experts. They said this is a really large treatment effect that we can now model off of and build into our next trial. Most of the drug approvals that you see in a more of this progressive restrictive phenotype and other adjacent interstitial lung diseases tends to be 50, 60 milliliters. So we've got a really large signal here to hone in on in the next trial. This clinically meaningful benefit is something that also is not confounded by anything with the steroid dose, for example. You might say, well, were there any differences in steroid use? Was it helping one group or the other? Quite the contrary. The epsofitimod 5-milligram group here actually had greater steroid reduction, over 70% compared to about 58%. Steroid-free, we had more steroid-free patients in the epsofitimod group compared to placebo. And I think the last thing is also really interesting. We had quite a bit of relapse that occurred in the placebo. Now, that should have helped the placebo. Nonetheless, we still see a 124-milliliter difference. So steroids are not confounding this signal, and this treatment effect, I think, can be preserved, and we can really look at it in the next trial more closely. A couple other things from a baseline perspective. As expected, FVC should be lower, is about 70% in this population. The larger ITT population had about a 90%. So you can see this is a sicker, more debilitated group that we're going to be focusing on in the next trial. AE profile, also rather similar to what we saw in the larger population, albeit maybe a little bit less wheezing, but that's also expected. Upper airway disease produces a bit more wheezing. I'll also highlight that these patients were slightly more obese. That's also expected. Restricted patients tend to be a little bit more overweight to their normal or obstructive counterparts. PROs were another thing that we wanted to unpack, what's happening in these 44 patients. And again, we see that same consistency we saw in the larger population. Kink sarcoidosis lung, Kink sarcoidosis general health, and the FAS also showing substantial benefit when you compare these two populations. So we are showing that functionally we can benefit these patients, but we also are showing consistent, durable quality of life benefit for these restricted patients. It can be quite exciting to offer this to these patients because these patients are frankly more in need than maybe their counterparts who have normal lung function, and these patients unfortunately are on a slippery slope to become fibrotic. This is a real promising development for them. So our go-forward plan right now, the primary endpoint in EFSO-FIT is shifting in the new trial to FVC at week 48, we are incorporating these changes largely based on feedback from the agency. The study design will hone in on a restrictive lung phenotype because if you're looking at FVC, you've got to tighten up that population and create a more homogeneous footprint. One of the things that's going to be different is also the steroid use and other background immunomodulatory use, the immunomodulators have to remain stable. What's happening in the world is patients are being, because of FSOFIT, put on less and less steroids. So in this next trial, we expect there's not going to be a need to have a steroid taper. We expect most patients will be on between zero to five milligrams. This in fact might allow us to even show greater benefit in FEC because if you look back at our Phase II trial, where patients more or less were kept at 5, there we showed FEC improvement of also 100 milliliters or more compared to placebo. So this is, I think, a very important thing in the study design to look at. And as I mentioned, dosing, this is also a nice material benefit to the patients that we think we can get more out of the drug. We're looking at a trial of approximately 372 patients. We want to overpower here. I'm looking for a treatment effect of about 80 milliliters. We think that's a good sweet spot. We don't have to go all the way to 120. 80, in my mind and the expert's mind, is still clinically beneficial and meaningful. And again, it's well above that threshold that we've seen other drugs get approved somewhere in the neighborhood of, say, 45 to 50 milliliters. It also allows us, with this larger N, to hit a highly stat-sig number. I want to be able to hit a p-value of less than .01 if we can hit our modeling there. It also allows us that if we're a little bit less, 70, 60, we can still be STAT-SIG if we enroll a larger cohort of patients. As I mentioned, the primary will be looking at FEC at week 48. KSQ will be the key secondary. And there's no steroid taper, so there's no confounding element when you think about steroids and FEC. Some key inclusion and exclusion criteria here, again, this is largely similar to what you saw in the previous infliximab and galimumab trials, a respiratory honing in on a PFT signature of between 50 and 80 for FECPP. These patients tend to be a little bit more symptomatic with dyspnea and a lower KSQ score, and again, really making sure that they're on a stable dose. We want to keep steroids and background immunomodulators stable so it doesn't impact or actually coerce the FEC signal to look differently. I don't want the highly fibrotic patients. Frankly, if you have more than 20% fibrosis, you should be on an antifibrotic and you shouldn't be in the trial. So this study is really focusing on the right patient for this right endpoint that we've been guided towards in our development plan. I want to end here with some thoughts around the target population. It is a smaller footprint than we previously were looking at. We thought our therapy as more of a frontline agent might be appropriate for about 90,000 patients. When you look at the restrictive patients in the U.S., you're looking at just about 40,000 patients. But these are patients who, frankly, have more of an unmet need. They have burned through steroids and methotrexate. They're not yet eligible to receive nintentative or proffinidone, and they're stuck. That's what was the word that was described by one of our key opinion leaders. She said, these patients are stuck. I've got a lot of these patients who have really poor quality of life. They're forced to choose these off-label toxic therapies, and EFSO could be a very, very solid second-line therapy to address this population. Mixed, diffusion, limited. These are patients that could also be amenable to our therapy. But I think for our trial, I really want to focus on restrictive because I'm trying to reduce the variability in force vital capacity. I want to be able to win in that population and then potentially expand. One thing I would say is with these 60,000 patients in these two populations, pricing initial payer work we have done, showing functional benefit on top of the quality of life benefit. We also believe that some of the pricing estimates are being revised upwards. Typically, these patients are sicker, more in need of a therapy. I think some of the comps are changing, and we're going to be updating some of the pricing estimates. But previously, we thought this would be priced somewhere between $150,000 to $200,000. When we update some of these numbers, we think we're going to be much more on the higher end there. That's typically what occurs when you go into a sicker population. So it's still very much a large market opportunity. Real quick on the biology, again, it's targeting Neuropilin 2, resetting pro-inflammatory macrophages. A question I had earlier today from an investor was, is there something unique about the restrictive patients that the drugs biology is working better on? That's actually not true. There's nothing necessarily special. So if we look at obstructive patients, of which we had about 70 of them, there you have to look at FEV1. These patients can't breathe out really fast. There you also see the biology holding intact where there's a greater than 100 milliliter difference in those obstructive patients when you look at FEV1. So the point I'm trying to make here is mechanistically from an MOA and biology point of view, regardless of the phenotype, When you hone in on the functional endpoint you're supposed to look at, the drug is acting as a very potent anti-inflammatory. Upper airway patients, obstructive patients, they have alveolar macrophages that express a lot of neuropilin. Just like those with more diffuse interstitial lung disease in the granuloma, you see a lot of neuropilin. So from that standpoint, there's nothing around a particular phenotype that the drug works better or worse. it's just you have to look at the specific endpoint that you're looking for in that specific population. Interstitial lung diseases, as I said, umbrella term, about 200 disorders that are out there. I think esofitomide is one of the most exciting opportunities in ILD right now. Very large market opportunity. Unfortunately, these patients are being treated with outdated old therapies, off-label therapies, and I think our mechanism, as well as some of the insights that we've learned from the EFSO-FIT trial, is really going to help us move the field forward. Our pipeline, I'll end here by saying that we do have a SSC small proof-of-concept trial that we expect to finish enrollment here very soon, mid-year at this time. That's a trial that's a six-month trial, primarily looking at skin to see if we can and improve some of the inflammatory and fibrotic markers of the skin. And then, as I mentioned, the 0101 program, we'll get into the clinic next year. This is an estate from our in-house tRNA synthetase library, which the company was built off of. Strategic outlook, what to look for, it's this plan phase three design right now that we really are focused on. I expect to, as I said, get the protocol to the FDA within this month. There's a real need here in F-Safidamad. It will take us a little bit longer here to get this approved, but I feel like we have a real cogent plan here, building off of some of the rationale from our last study, our engagement with the experts, and also the ability to align things with worldwide regulators. That was really important for us to do since last fall. From a pipeline and cash perspective, we're in good shape right now. We have to figure out we want to advance this program in the most capital efficient manner. So that's something that we also are honing in on here as we look to get this trial started. Thank you, everyone.