Welcome to our Piper Sandler Healthcare Conference. My name is Yasmeen Rahimi. I'm a Senior Biotech Analyst at Piper Sandler. Excited to have the team, oh, sorry, my hair is blocking it. The purse. Sanjay, it's so wonderful to have you. Lots to cover. A wonderful place to start off would be to kind of walk us through, since the EFZO-FIT data read out, at the top line, what additional data you presented at ERS that maybe investors may have missed. Maybe we'll start there. Sure. So at ERS, we presented our full topline results from the EFZO-FIT data. Previously, we had talked about the steroid reduction endpoint and what we saw there in the press release. In addition, at ERS, we presented data on three PRO instruments that were key objectives in the analysis to also look at KSQ Lung, KSQ General Health, and KSQ stands for the King's Sarcoidosis Questionnaire. We looked at those two PROs, as well as another PRO focusing on fatigue, the Fatigue Assessment Score. We also had more information around safety, looking at treatment discontinuations, ADAs. Those were the additional analyses that Dan Culver presented in Amsterdam. Okay. And team, obviously, one of the findings from the EFZO-FIT™ study was that the primary, there was a high placebo response and steroid dose reduction. I think it came in at 40% when assumptions were 30%. Have you been able to get a better understanding now that you've had some time to look at the results? What could have driven those high placebo responses? Yeah. So this was an unexpected element of our trial. The drug performed better than we would have even expected. We saw more than 70% reductions in steroids. We saw more than 50% of the patients get off steroids. So in our modeling, this was on the high end of what we expected. But as you pointed out, in the placebo group, we saw about a 60% reduction and about 40% of the patients get off steroids. So this was based on historical data with KOLs that talked about, and they continue to think that this was a very aberrant signal. So why did this occur? So a couple of reasons that we have been able to unpack, and we're still doing some analysis. First of all, our trial was a trial where we assayed these patients every two weeks. I would say we were the most rigorous and had the most rigorous protocol on steroid tapering ever really seen before in sarcoidosis. And the view from the experts is it wasn't very real-world in the sense that they see these patients sometimes two to three times a year, and we were checking on them every two weeks. By doing so, we were able to really fine-tune their steroid dose and drop it down by essentially checking on them so often. So that protocol rigor is a good thing, but it may have also highlighted the amount of overdosing that's occurring. Other elements we're looking at in our trial is, are there any regional differences, site differences? We're not seeing that so much. I think the field is really surprised and is currently changing treatment guidelines. And even just two weeks ago, I spoke to one of our lead investigators in North Carolina, and she said she's making immediate changes to patients who previously she'd been managing on 10 mg for five or six years, and right now she's telling them all, "I'm going to take you down to two and a half and five based on the aTyr data." So it truly is treatment changing. The guidelines are going to have to be updated. We continue to look at inclusion and exclusion differences, clinical characteristics. A little bit early to say right now if we can pinpoint a reason around this placebo response. But I will say that the one thing that everyone is pointing out is the PRO differences. We didn't see that in placebo. So this overall, "I'm feeling better, my fatigue is better, my cough and shortness of breath is better," that in conjunction with steroid withdrawal and reduction is only really occurring in the treatment population. That's why we feel very confident that we have clinical benefit here. We'd have to think about how do we mitigate some of these other placebo elements, which were only really observed when you think about steroid reduction, not with anything to do with symptoms or other measures. And maybe also if you could talk about the FVC data showing maintenance of lung function and the importance of contributing this to the total package. And obviously, the FDA is very FVC-focused, so would love to get your thoughts on that data point as well. Yeah. So FVC has been used for approvals, less reduction of FVC, I should say, for example, in IPF. Now, in IPF, it's a very restrictive disease, so FVC is the right PFT to look at. But there's a number of other pulmonary function tests, FEV1, DLCO. Depends how the patient presents. Are they presenting with obstructive disease where FEV1 is better, restrictive, FVC? Diffusion limited would be DLCO. SARC patients present with a number of phenotypes. We have broken out five different phenotypes, and this is part of the secondary postdoc work we're doing where we're looking at all of these different phenotypes. And this probably will be in subsequent publications and posters. What are we learning? FVC is not the same for all patients, which is why I think the agency has always said for sarcoidosis, it may not be the best endpoint to focus on as a primary. We've heard that time and time again. What did we see in our trial? We saw slight reductions in FVC, about 1.22% differences in a reduction of FVC. This is within our expectations because remember, we had a steroid reduction protocol. Steroids do a good job of propping up FVC. As you remove steroids, you might expect some amount of decline. We were hoping to only see maybe a nominal 1%-2%. That's what we saw. We wanted to avoid seeing these 4%-6% declines. That would be an unfair trade-off, removing steroids and seeing that amount of morbidity. But the experts have pointed out that this is within the normal variability. They're not too concerned about the decline that we saw in FVC. And if you really want to dig in deeper, the sharpest declines, or the greatest declines, I would say, were in placebo, not on drug. Okay. Sanjay, as obviously you guys have your FDA meeting in 1Q 2026, maybe help me visualize what are post hoc analyses that you have conducted, will be conducting in preparation for the meeting, and what are things that were pre-specified from the beginning that now materialized of getting those data that will be included. So if you could just walk us through what will the totality of the data package be to be presented to the FDA, and then specify what was pre-specified, I guess, and what was post hoc. Yeah. So the pre-specified endpoints, and we had a lot of them. So we had steroid reduction, steroid withdrawal. We were also looking at, as I said, the three PROs I mentioned, the KSQ Lung, the KSQ General Health, and the FAS, fatigue assessment score. We were also looking at all the safety measures, including treatment-related discontinuations, AEs, SAEs, ADA production. We were looking at FVC. So these were all pre-specified endpoints that we were looking at. Now, post hoc, as I said, we've started to dig into different subpopulations. So looking at different PFT phenotypes, as I mentioned. We're also looking at high and low dose. We had looked at a stratified analysis of greater than 10, lower than 10. In this post hoc, now we'll get even more fine-tuned. We'll look at what happened in those patients that came in between 5-7.5 and 7.5-10. We may learn some things there. There are some preliminary cues that the drug may work better in more severe patients, the more dyspneic patients, the patients that needed more steroids. But we have to verify some of that, so this could also shape our discussion with the agency that some of these post hoc subpopulations may give us a better clue into what's a more sensitive population of efzofitimod. Remember, this is the largest, the first ever, and the largest SARC trial ever conducted. So there's a bevy of information here for us to basically sift through. What else is coming is things like biomarkers. There's a lot to unpack with biomarkers. These are serum biomarkers, so we are looking at that currently. Those are all elements post hoc that could be part of what we want to discuss with the agency. As you guys are in full preparation with all this very in-depth data set that you're going to engage with the agency, what are the scenarios that you're—what are the possibilities that you are thinking about? And now that you've done the analyses, and I'm sure you shared it with some of the key opinion leaders, do they have any thoughts on their views on which of these possibilities could materialize? Even though they're not the agency, it's their opinion, obviously. Sure. Sure. So first, I'll talk about the experts. I mean, there's a range of opinions, but the majority view our data set as really demonstrating clinical benefit. In their mind and what was presented in Amsterdam, this is the first therapy in sarcoidosis that's showing quality of life improvement, and quality of life improvement through multiple prisms, and is also improvement that's quite durable. In that presentation, you'll see that the drug starts to improve quality of life, basically eight to 12 weeks after administration, and then we hold a very durable response. So it wasn't that just at week 48 we were showing statistical differences there. You pick any time point, you're seeing really significant improvement in all those symptoms compared to placebo. So their view was the drug did what we expected to do in reducing steroids. It did a great job of withdrawing patients, but then you couple that with the PRO. There's clear clinical benefit in their mind. Now, I think that prepares us well for a range of scenarios with the FDA. I can't get into right now what I think of handicapping with the FDA. I mean, there's changes occurring daily, literally daily. Today, there's another change at the FDA. I believe we will have the best and most robust comprehensive data set briefing book to present to them. It's going to be important with all the data that we have that we give that totality of information. We really get some crucial guidance on what are next steps for the program. I am very optimistic that we have a clear clinical benefit here. How the agency feels about that and where they want us to go or where they want to take us. I want to be open and ready for all options, but I do think that this is a very compelling program. And if you heard Dr. Baughman speak when we announced this program, he said he'd be using this in his clinic if he was still practicing at University of Cincinnati because there's such poor treatment options right now, and the options that are out there are not showing really any clinical and meaningful quality of life benefit for the patients. And so let's think about so if scenario one is they review the entire depth of the package and they say you have the green light to go ahead and file for a BLA, then you would obviously their disclosure will be you wait for the minutes to come back and say that you're good to go. And obviously, that would be incredible. That would, in my view, best case scenario, present that. If they say, "No, you do need to do an additional confirmatory study," do you think in that same discussion you can also figure out what the next study would be so that when you come back to us, to the street and investors and analysts, you could say, "Well, the FDA recommended based on the depth of the data, we look into a confirmatory study, and this confirmatory study would be X, Y, and Z." In my view, those are the two potential outcomes. A third outcome would be, "Let's meet again and discuss confirmatory." So help me understand if that's realistic, and is there an outcome that I'm not thinking about that is possible? You're thinking about it the right way. I want to have one meeting. I don't want to have two meetings. So part of the reason why we're taking some time here is I need to also have another trial ready to go. And that's what makes most sense to me. It also forces more of a decision-making around, "Okay, how do you really feel about the hierarchy we have here on endpoints? What our criteria looks like? What did we learn from the last trial? How do we tighten things up? What's the standard deviation from what we saw with the last endpoint? Here's the power." Get it all done all at once. So if we are asked to run another trial, we're ready to go. So the street then understands, "Okay, I know what I'm getting here. Here's what it looks like. Here's what the agency said, and aTyr is ready to go. That's the approach I'm taking here. So I want to be ready for all of those outcomes. I think the best way to be prepared is to cover all of those avenues as opposed to take a two-step approach. It'll also give us a little bit more, I would say, more or less that sort of emphasis around, "Okay, if you believe that there needs to be another trial, we're putting this right in front of you. So let's just get guidance on it right now so that we can be clear about next steps. Let's say it's scenario two and they say, "Yes, we agree you should do a confirmatory study." Given sort of these challenges with that there's not a standardized protocol to do steroid tapering in the real world, right, without being in a clinical study, is there an optionality? You You could propose a PRO as an endpoint or anything else? I feel like now it's insanity. Why do the same study with the same endpoint? In some ways, we blew out steroid reduction. Right. It just is not a good choice by the FDA. You're going to see now and look, part of this is evidence wasn't created before. We've created a high degree of evidence, is what they call for the treatment guidelines. So the treatment guidelines are now going to, whereas they previously said, "Get these patients to around 10 and keep them there." You're going to see a shift, and I predict they're now going to say, "Get to 2.5-5." And then what's going to be the evidentiary standard of that? Our trial. Our trial is going to demonstrate that. Now, if you wanted to go further with steroid reduction, you really are now within earshot of getting to, you can get to zero at this point. So you could take that approach of it's a complete steroid withdrawal trial, but let's also understand that most of this group of patients who previously were in that sort of 10 mg range is shifting. But you're also going to see an emergence of probably what I would call the true chronic steroid-dependent wonky patient who needs 10-15. So you're going to see the EPS start to resort itself. You talk about steroid reduction. I think we have been told we did a better job than ever seen before in managing steroids because we could see these patients every two weeks. I don't think that's real world, but you also can't back off of that and just say, "Okay, well, we'll apply a looser standard." I think if you look at an endpoint like KSQ Lung, you have to say to yourself, "Okay, that benefit you observed there, there's significant delta that you see between placebo and five milligrams in particular. How do you lean perhaps more into that?" That is a feels endpoint. The key criteria, the SSC criteria the FDA likes is a feels, functions, or survives endpoint. Survival endpoint wouldn't make sense in SARC. Functionally, I told you the PFTs are a little bit all over the place. So we have a feels endpoint. And I'll highlight here that we've spent the last several years working with the PRO division to validate the KSQ Lung while we're running this trial. So that's another reason for us to have a protocol sitting there saying, "Look, let's now talk about this. Is this now sufficiently validated for this to be a primary?" And if that is the case, endorse this protocol for an IND, and then that's very clear to everybody at that point. But if that endpoint is not validated, where would you like us to go? Because we have done a lot of work here. So this is why it's going to be a really crucial meeting for us. It's also why we're taking the time to really have a robust briefing book and be ready to go for all of those outcomes. Given that you have done a really great job on site selection and initiation and enrolling the study in the midst of COVID and everything, how much time savings is there? Let's say you would have to do a confirmatory study because I don't think it's fair to use the enrollment timeline. So I know you have EFZO-FIT as a timing of how long it would take you. How much would you save? Six months, a year? I don't know, or more beyond that? What I can say is it depends. Yeah, it depends on the size of the study. So you have to look at the size of the trial. You have to look at are you including a tighter population, which could be a little bit you could amplify a signal there. You got to be careful about chasing that, but that also can change your timelines because you now are looking for a tighter, more severe patient. You could open it up and say, "Look, the field has changed now, and everyone now is just looking for a steroid replacement-type therapy." That could also change your timeline. So a little bit early to say what timelines would look like. You have to think about what's the endpoint, what's the inclusion criteria, and then I'd be able to come back to you. I will say that after our data, we've had more interest than ever before by patients who want to get involved, who want the therapy now, but also if we were to run another trial, they have said, "We want to be involved." Why? Because they care more about the quality of life than anything else. PFT change is fifth or sixth lowest on their list. The top two things they want to see is, "Does a new therapy improve my quality of life, and does it get me off steroids?" And we've done both. So I do think that there are going to be opportunities to go faster. Everybody, investors will want us to go faster if we are asked to do something. But let me come back to you on what that trial looks like. Then I'll have a better handle on projecting timelines. Okay. And then, team, you have reported earlier this year interim data from the EFZO-CONNECT™ study, which was the SSC ILD. I don't know if there's additional disclosures that are coming and how you're thinking about development or right now focus is let's get ready for the FDA meeting and all hands on deck. We did guide recently that we'll finish enrollment in the first half of the year. And this is a tough trial to enroll because we're looking for a newly diagnosed ILD patient who had previous SSC, but SSC that they didn't have so long that they can't progress. We and other companies are looking at SSC ILD, looking for a very, very specific type of patient, a patient that is, frankly, going to decline in the first 6-12 months of having an ILD diagnosis. And there's very specific criteria around that. We will finish enrollment in the first half of the year. And as you pointed out, we saw in an interim look some real nice improvement in skin. No therapy has improved skin, which is the most important quality of life element for SSC patients. So what you're seeing here is also some concordance where quality of life seems to be where efzofitimod is really helping. Now, in that population, skin subscores in a small number of patients improved. I'd like to see that once we read out the full data set. But let's finish enrollment in the first half of the year. That's a six-month trial. And then you think about data in the second half of the year. Great. Well, Sanjay, very much looking forward to next year. Obviously, we were hoping we would celebrate, but I know you've conquered all kinds of roadblocks to your path. This will be another roadblock that I have no doubt you're going to be able to conquer. So we're very much wishing you the best of luck as you go into this meeting and honestly sending you the best positive wishes to come back with the green light to say, "Go file. Yay." Because I think if you look on the analyst side, we still have a very strong buy rating at our price target. We believe in you that given this drug's product profile and the hard work you've put into it. So, I just really, honestly, from the bottom of my heart, I am voting and praying and doing whatever to that it will all work out because I think you have a lot of positive data, and it's just now thoughtful preparation for the meeting. We feel the same way. There's a lot of good. We have to own the fact that we didn't hit the primary endpoint. We've said that. But I also think moving forward, there is, as I said, clinical benefit here to have a really robust discussion with the agency. And the idea here is we still believe Efzofitimod can be a substantial new therapy for sarcoidosis patients. They are clamoring for a better therapy, a better therapy that gets them off steroids, a better therapy that improves their quality of life. So yeah, we're sharpening our pencils, keeping our heads down, and we look forward to have a productive FDA meeting in Q1. Awesome. Let's thank Sanjay, and we can't wait.