Conference Transcript - ATYR 2026-03-11

Tom Smith, Analyst — Leerink Partners

Great. Good morning, everyone. Thanks for joining us here at day three of the Leering Partners Global Health Care Conference. My name is Tom Smith. I'm one of the senior biotech analysts here at Leering. And it's my pleasure to introduce our next presenting company, Atire Pharma, and happy to be joined on stage here by CEO Sanjay Shukla. Sanjay, thanks so much for joining us. And I know you have a presentation here. Why don't you take it away?

Sanjay Shukla, CEO

great thanks Tom good morning everyone Sanjay Shukla from ATAR Pharma and we're gonna talk today about how we're translating tRNA synthetase biology into new therapies for inflammation and fibrosis here are some of our forward looking statements so at ATAR we are translating a new area of biology around our platform of tRNA synthetases and these are enzymes that exist within all of our bodies and for many years we knew them to do really one function and that is to help conjugate a reaction between a specific amino acid and a tRNA so these were shepherds that brought this reaction catalyzed it together what we've discovered is these tRNA synthetases break apart into fragments and those fragments do something very different they have an interplay with the immune system and that's where we see this as a potential new class of medicines our focus is inflammation and fibrosis where we believe there's an untapped potential to leverage some of this evolutionary intelligence within all of our bodies and this is a very very differentiated approach which presents multiple opportunities to address different diseases Efsofitomod is our lead therapy that has just completed a Phase III trial, and I'll go through some of those results, which is scheduled for a U.S. FDA Type C meeting upcoming here in mid-April. In addition, we expect to complete enrollment in a Phase II EfsoConnect trial focusing on scleroderma-related ILD. That will complete enrollment in the first half of this year, and we'll expect to have data about six or seven months after that. We just reported a cash of just over $80 million as of year-end, so we're really in good shape here to complete some of this work but also have this important FDA meeting that's upcoming. Here's our pipeline. I'm going to talk more today about the results, but before that I'll go through some of the background here. Epsofetamod dominates the top of the pipeline, But I'd also highlight O101, which is a separate tRNA synthetase fragment that has done some really interesting things in modulating myofibroblasts, and we think this could be really useful in fibrosis. I'm anticipating that I'll be in the clinic next year, a true antifibrotic, I describe it, as opposed to the fibrostatic drugs that have been available really for the last several decades. So efsofitamon, let's get into that. Interstitial lung disease is really the target here for efsofitamide and these are a group of diseases, chronic inflammatory diseases that cause lung fibrosis. And while patients are dealing with interstitial lung disease and this inflammation, that inflammation creates a cascade of worsening lung function, fibrosis, and extremely poor quality of life. Many of these forms of fibrotic lung disease have survival rates that are worse than many common cancers and right now unfortunately most of the therapies being used are either toxic not the disease modifying or both so esofitomide presents a really interesting novel mechanism of action that addresses this significant unmet need we're advancing of so fit a mod as what we believe is the standard of care for interstitial lung disease. And we are focusing on the inflammatory side of the fence. ILDs can have a large swath of conditions that some present with an inflammatory phenotype, others can be quite fibrotic. Our focus is really to look at the inflammatory side of the fence first, looking at sarcoidosis and scleroderma-related ILDs. IPF is the most extreme form of interstitial lung disease, a very fibrotic form. This is an area where there are two drugs that generate multiple multiple billions of dollars of revenue but unfortunately those drugs have toxicity and are not disease-modifying so we view this as a very large market up to five billion dollars our goal is to first develop therapies on the inflammatory side and then potentially look to expand into fibrosis some key elements and highlights of esofitamide it targets the innate immunity at the site of inflammation it's designed to down regulate many of those pro-inflammatory and pro-fibrotic signals, primarily through its interaction with myeloid cells, macrophages in particular. It's addressing a really complex immune biology by working upstream through a receptor called neuropilin-2. We find it to be very restorative of immune balance, but it doesn't tip you over into any overt signs of immunosuppression. This is really important because many immunomodulators can be quite heavy-handed with patients. Epsofitamide is a rather elegant immunomodulator that offers the benefits of tweaking and retuning the immune system without having some of that toxicity. A little bit more into the details here. We published this in a landmark paper, made the cover of Science Translational Medicine. Very rare for a biotech to have gained that notoriety. The mechanism here, as I said, is through macrophages. Inflammation in many of these conditions is triggered by a number of agents that can be coming from the environment. They can be toxic inhalation. Sometimes it can be an autoimmune disease like scleroderma. Sometimes the unknown etiology, as in sarcoidosis, it causes sometimes a trigger, and that trigger then creates a cascade of macrophage-driven inflammation. Now, sofitomot binds the macrophage by this receptor called norepillin 2, which is expressed on the surface of this immune cell. And by binding, it retunes and nudges this macrophage into a less inflammatory phenotype. And there you see a number of markers that we've observed can be downregulated. turns a hot red inflamed lung into a more calm blue lung there as you see here in this cartoon quickly on pulmonary sarcoidosis this is a rather large orphan disease some some believe we're looking at 300 400,000 patients in the US but what we know is it's just about 200,000 patients this is a chronic inflammatory lung disease. It's characterized by clumps of immune cells within our lungs called granulomas. It's those granulomas that provide a target, a nidus of inflammation. Most patients are presenting with sarcoidosis in the lungs, pulmonary. You see about 200,000 patients in the US, nearly as many in Europe. Diagnosis is done by looking at this granuloma, ensuring it is not TB, a non caseating granuloma is what the pathologists call it prognosis you see most patients progress on to treatment most are using steroids but I'm going to come back to that because our data is changing practice patterns as we speak unfortunately 20% of these patients are developing lung fibrosis these patients are suffering from both the high disease burden but also the treatment burden and again, we are changing because of our EFSOFIT data treatment practice as we speak. Limited alternatives, many off-label rheumatological drugs are used, but all of these drugs cause an eventual robbing of quality of life for these patients, a decline in their socioeconomic status, and again, 20% of these patients are becoming fibrotic. The target population here, you see a large swath of these patients are in that moderate to progressive range, half the patients, and again, this was before our FSOFIT data, 75% of the patients were being treated with steroids or steroids plus immunomodulator. That's really not acceptable at this point in time. Steroids are a legacy treatment, and we've proven some of that with our FSOFIT data. It's positioned here to be a frontline steroid sparing agent. I think We've already done that, and it is reducing and eliminating the need for steroids. Here are some of the benchmarks. A number of drugs here in rare disease, other inflammatory diseases, and also those that slow lung function. We're right in the mix here with a number of these well-known approved therapies for other conditions. Efsofitamide is now the lead candidate, and I think continues to be the lead candidate potentially for sarcoidosis. So let's get into our top-line data that was presented in Amsterdam in September. So as a reminder, this was a global phase-free trial, about 90 centers, nine countries around the world, where we tested five milligrams per kilogram of esophetamide compared to three milligrams per kilogram, and placebo. The goal was to enroll about 88 patients per arm. We enrolled 268 patients in US, Europe, Japan, and Brazil. This was a trial where we wanted to have stably managed SARC patients come in anywhere between seven and a half to 25. And we were the first trial to basically try a very rigorous every two weeks steroid taper protocol based on the patient's global assessment, the PGA, largely anchoring that. The goal here was to really test a hypothesis that look, can you get these patients off steroids? Can you do so more with efsofitamon? What experts told me based on 40 or 50 years experience is that the expectation here's the placebo would have a really tough time getting off steroids in this rigorous manner. Maybe you might see 10, 20% max of these patients be able to tolerate no steroids for a year. Let's see what we saw. Here's a study discontinuation. I think the take home here is very low numbers from a discontinuation standpoint. We wanted to be in those more or less single digit numbers And there you see epsofitamide, also the high dose, no real signal there, that's good. And a large swath of these patients completing this study, so it allowed us to maintain our statistical power. Baseline characteristics, largely balanced. You know, there could be some numerical differences here, but the takeaways here are age, sex, race, it's what we expected. Sarcadosis can disproportionately affect Those in the black population, especially black women, these numbers having about 15, 20% is what we expected. In the US, you see this more like 30%, which is an outstanding number. There were some questions whether or not sarcoidosis is a type of study that can enroll in certain populations. I think we dispelled that. It really speaks to the need of therapy here. Duration of disease, you're looking at seven, eight, nine years, so these are chronic patients. Most of these patients have some, it's pulmonary sarcoidosis, but some can have, a third of these patients have some extra pulmonary symptoms, sometimes the skin, sometimes the heart, sometimes the nervous system. These were patients that were sick by the KSQ lung, and they also, as you see, had about 10 milligrams average steroid dose coming into the trial. The primary endpoint, we were looking at steroid reduction. So the expectation here was the drug would be able to perhaps get people 50, 60, maybe 70% in a best case scenario off their steroids. We saw that with epsofetamide, almost 80% reductions. What was unexpected is the relative matching in placebo. We expected to see placebo decline maybe three, four milligrams. To see these curves overlap is disappointing, but we're learning quite a bit from this, and as I said, treatment practice is changing as we speak. Now, esofitamide had a fairly strong trend here in steroid withdrawal, but again, we just missed the p-value by a couple patients. Again, largely driven by this 40% in the placebo. Our modeling had, we assumed, as I said, the experts maybe 20% max. We modeled to just, we thought to be safe, 30, 35%. This was a number that I think everyone in the audience in Amsterdam, among the pulmonologists, really were surprised. And what one pulmonologist told me is, she went back to North Carolina from ERS and immediately started to take about 40% of her patients off steroids, patients that sometimes had been managed for 10 years in her clinic. This, again, is I think a transformative result for the field. Unfortunately, we're not showing efficacy here for epsilfitomod purely from the standpoint of statistical significance. But again, very strong trends. And I'll point you to the Kaplan-Meier curve. There you can clearly see a very durable separation that's maintained when you go out to 180, 210, 240 days, 270 days. So you're talking about a really, really long time where patients are seeing a durable response. Again, if you had told me that the drug would get people 70, 75% off their steroids and more than 50% would be at zero, that would have been our best case scenario for efsofitamide. It's really what happened with steroids in the placebo arm that we are now really unpacking. When you look at quality of life, this is really where the drug activity starts to emerge and breaks away from placebo. So the King's Arcoidosis Questionnaire, the KSQ lung, is the primary quality of life instrument we looked at. And this is an amalgam of cough and shortness of breath questions that experts use to determine severity and symptoms of disease. And here what you saw is a significant result when you look at the dark green dots and bars with the competence intervals. this is plotting against a flat placebo line there. What you see is right after, say about week eight, immediately you start to see patients feeling better. And that's maintained across every time point. So we're not picking a certain time point where we see STAT-SIG. When you look at all across the study, it's a very durable, potent response where basically patients are feeling great. And we heard this all along from experts that patients are feeling great, their lung symptoms improve immediately, and now we can see that's largely attributable to efsofitomod, in particular the high dose of efsofitomod. When you look at other pre-specified quality of life measures, looking outside the lung, at the FAS, which is the fatigue assessment score, as well as the King's sarcoidosis general health, which is more systemic aches and pains, and some of the rheumatologic symptoms that some of these patients have, you see the same consistent finding. That benefit observed for efsofitamide is consistent, it's durable, it shows clear drug activity that when you administer, especially our high dose of efsofitamide, patients' lung symptoms, they feel better, their overall health, their fatigue. One of the experts in Amsterdam pointed out this is the only therapy for sarcoidosis that's ever shown such a consistent quality of life benefit over any available therapy that's currently being used. steroids, methotrexate, infliximab. These are drugs that patients don't feel good. We are clearly showing that patients are seeing significant benefit from epsilfitamide over and over and over again with these quality of life measures. When you dig in even a little bit deeper and look at composites, even higher bars here, where we had a number of these composites in our pre-specified analysis, looking at patients who are not only able to get off steroids but feel better. that's really what's important for these patients can you get me off steroids and will I feel better and will I feel substantially better again you see efsofitamide here in the steroid free and improved KSQ so this is folks that have more than eight points of improvement in their King sarcoidosis you see a highly statistical significant result and a dose response also when you look at three milligrams in five looking on the right there I'll point you to the bottom almost two and a half times you're more than two and a half times more likely to be steroid free and significantly improve with your lung symptoms when you're on Epsilfitamon 5 milligrams that's what that box and whisker plot shows there at the bottom and clearly that is statistically significant because it doesn't overlap this is something that many of the experts have pointed out they continue to point out many of them would like to see the drug approved immediately based on that signal because this is exactly what they've been looking for, really, over the last 50 years in a therapy for sarcoidosis. Forced vital capacity, this is an important functional measure. We wanted to be able to look at this. In a steroid, aggressive steroid taper trial, we would have expected FVC to decline. It's well known in the literature that if you administer prednisone, patients get a boost in FEC as you remove it there's a slow decline the key here was do we see massive declines we do not we we manage these patients really really well and experts have pointed out that look when you look at five milligrams it is better than three and and placebo did about what we expected to see about a two to three percent decline so fit a mod it wasn't designed and powered to look at this because again we wanted to make sure we didn't worsen but I also think there's some elements here where we start to see some separation as well, where there's just some nominal declines with FVC when you look at this population. I'll also point out that this is a very homogeneous population. Sargonosis patients can present with upper airway disease, lower airway disease, mixed, diffusion limited. There's a number of phenotypes we see in here. FVC is probably the most sensitive for a restrictive population, so stay tuned. This is some of the discussions we're having with the agency that perhaps a restricted population may benefit even more with efsofitamon a little bit more on the safety well tolerated here we do not see a dose response here we don't want to see that when you think about safety I'll point out here a low number of SAEs AEs leading to discontinuation this is a disease where patients are quite sick so to see this over the course of a year with almost single-digit numbers here for FSO5 milligrams is really positive we consider this a very safe and well tolerated drug when you look at anti-drug antibodies since this is administered once a month through an IV infusion something to pay attention to we don't really see any treatment boosted elements here and you can even see sometimes even before even in the placebo you see some ADA is developed It tells you a little bit about some of the maybe inconsistency even with the assay there. But, again, nothing really concerning at this step. So key takeaways here. We did not meet the primary endpoint. We think we have effectively sunsetted steroids as an endpoint at this point. We did something that was really highly unexpected by showing this amount of decline in those number of patients who can get off. When this data, and it is being written in a medical manuscript, comes out, it's going to serve as the basis of a change in the treatment guidelines. I would expect ATS and ERS guidelines are going to change because of the EFSOFIT data. You are seeing the whole world now getting folks off steroids and even maybe sometimes at a minimum lowering them closer to the levels we saw in our trial. We are changing treatment practice. Nonetheless, the improvement in quality of life and some of those consistent trends have us very intrigued, and this is why we're going to be sitting down with the FDA to review the results, determine the path forward. And in the event that the FDA asks us to run another trial, we feel very confident at this point that we have a protocol that they'll really like. Experts have spent a lot of time with us over the last three or four months, and we feel as though we have a really excellent briefing book that we've presented to the agency. I'll end here with just a two minutes on the scleroderma trial another very difficult disease to treat much more fibrotic can also have really debilitating skin symptoms from the systemic sclerosis again an orphan disease where there's a large amount of morbidity and mortality patients become quite fibrotic it's more fibrotic disease than sarcoidosis so we're testing the drug now in a different patient cohort but again here is a therapy that could be positioned as a second line most of these patients are on MMF for their systemic sclerosis but once the drug once a disease impacts the lungs patients can really become 30% of them become fibrotic rather quickly so it's a really bad manifestation of systemic sclerosis when you have ILD our trial looks at again a high dose low dose these are we're testing here a fixed dose just to look at what 450 versus a weight based might look like but 450 270 this approximates five milligrams and three milligrams it's a six-month trial we're focusing on FVC here because this is a very restrictive disease but I think the key thing here is we're also looking at skin symptoms within three months and we have reported an interim finding which is rather quite exciting that three out for patients who have skin manifestations, diffuse skin disease, have already responded in three months to epsofitamide based on some early interim unblinding. If that trend continues, I'll remind everyone, no drug has ever improved skin symptoms for scleroderma. So we're very excited to see this result, as I said, towards the end of the year here, with enrollment expected to finish here in the first half of 2026. So just to wrap up here, efsofitamide talked a lot about it. Large market opportunity. The key is gonna be this FDA meeting upcoming here mid-April. We expect to come out of that with a clear signal around, is this program viable with sarcoidosis? We feel as though it is. And what would be the next steps? Preparing ourselves that we could potentially be asked to run another trial. Feel really good about some of the learnings from the previous trial. I would anticipate we would focus a lot more on quality of life and perhaps also looking at function, pulmonary function in the next trial. This is a trial that has changed treatment practice around the world, so patients now are being actively managed out of their steroid regimens because of EFSO-FIT. We'll also highlight that we have a burgeoning pipeline looking at other inflammation and fibrosis really feel like we're in a strong financial position at the moment as well. So I'll stop there and take any questions from you, Tom.

Tom Smith, Analyst — Leerink Partners

That's great. Thank you, Sanjay, for the presentation. Maybe just coming back to the Type-C meeting, may you just walk us through your base case, I guess, going into that meeting? Do you think there may be a path forward on the basis of some of the secondary analyses, some of which look, frankly, quite striking. And you alluded to a lot of the KOL feedback around things like steroid-free plus quality of life improvement. Or is the base case here you expect you would have to run another study?

Sanjay Shukla, CEO

I think the way we look at it, we want to be prepared in this discussion to do more than just say, hey, is the program viable or not? I think it is. I think we clearly have demonstrated in many of our pre-specified analyses says the drug has activity. The drug is certainly helping patients wean off steroids but also feel quite better while preserving their lung function. So, you know, I think there's always that chance that you have to look at that and say, well, could things go sideways? But we feel very confident that the program is going to have a green light. And the question then becomes, what does that green light look like? Is this something that immediately you can file off of our data package? I find that that will be very challenging. I think you have to own it and say you didn't have the primary endpoint. This is a primary endpoint that, again, I think now will never be used again because we effectively blew it out. And you see what happened with placebo. So there aren't going to be that many patients now managed on steroids. Nonetheless, methotrexate alone is not going to do the trick for these patients. So epsofitamide, based on the experts, they feel as though it can play a role, maybe not a frontline role, but it could be used in maybe more of a severe population. That's where we want to be prepared with a base case of here's another protocol, let's get some feedback on it and treat this discussion more than just a typical type C, really get a protocol assessment, if you will, at the same time.

Tom Smith, Analyst — Leerink Partners

That makes sense. And maybe just the way you're thinking about communicating results, type C meeting in April, possible we could get feedback coming out of that meeting do we need to wait for the meeting minutes like how you think about communicating to the street

Sanjay Shukla, CEO

I think given the current shall I say this the current climate if you will environment at the FDA probably best for us to have a meeting and then wait for some official correspondence I think that's smarter I think most biotech companies are doing this so you typically would get a response you know about four weeks later you know things are not typical right now with the agency but we're planning to then communicate to the street once we have some definitive i'd like to see things written down and then if we are in fact asked to run another trial we'd be able to communicate exactly what that trial looks like the the size of the trial the power of the trial i mean these are all things that we've already prepared and the other key thing is what would the endpoints be this time around moving forward you know I think of this as a very late phase second phase three let's also lock down when you look at quality of life that could serve as a primary endpoint when you look at polling function tests okay if that's a direction we want to go I feel good about that too but then let's also hone in on which patients are we talking about obstructive patients you have to look at FEV1. Restricted patients you have to look at FEC. Diffusion limited you have to look at DLCO. So we have the largest natural history database in sarcoidosis ever so there's a lot of jump points from our data that we can go and look at. I haven't presented anything today post hoc so that's another thing that we're gonna we're gonna discuss with the agency. Yeah that makes sense.

Tom Smith, Analyst — Leerink Partners

Maybe just operate because you ran this large pivotal study some other operational learnings in terms of recruiting the patients you obviously have the scale and the relationships with the with the clinicians may just talk about how that would help you in a subsequent phase three well I think

Sanjay Shukla, CEO

we've already demonstrated we can enroll activate sites move forward I would say there's a good 15 or 20 in the US right now that want to get started on the next trial they want access to the therapy immediately and maybe understanding you have to run another trial. So the efficiencies there are set. We're the only company to ever have run a phase three trial. So we know what we're doing. And the execution, when you think about a well-controlled, adequate, single trial, we've already demonstrated we can do that. Big Pharma has never done this. ATAR has. So I feel very confident in our abilities to operationalize once again. Yep. That makes sense to me. All right, Sanjay. Well, unfortunately, we're up

Tom Smith, Analyst — Leerink Partners

against time, but important feedback coming, and we'll stay tuned.

Sanjay Shukla, CEO

Great. Thank you.