Good morning, ladies and gentlemen, and welcome to aTyr Pharma conference call to review the top-line results for the Phase 3 EFZO-FIT™ study of efzofitimod in pulmonary sarcoidosis. At this time, all participants are in listening mode. Later, we will conduct a question and answer session, and instructions will be given at that time. As a reminder, this conference is being recorded for replay purposes. It is now my pleasure to hand the conference call over to Ashlee Dunston, aTyr Pharma's Senior Director of Investor Relations and Public Affairs. Ms. Dunston, you may begin. Thank you, and good morning, everyone. Thank you for joining us today to discuss the top-line results from our Phase 3 EFZO-FIT™ study of efzofitimod in pulmonary sarcoidosis. Before we begin, I would like to remind everyone that except for statements of historical facts, the statements made by management and aTyr guests in responses to questions on this conference call are forward-looking statements under the Safe Harbor provision of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Please see the forward-looking statement disclaimer in the company's press release issued this morning, as well as the risk factors in the company's SEC filings and included in our most recent annual report on Form 10-K and quarterly reports on Form 10-Q. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, as facts and circumstances underlying these forward-looking statements may change. Except as required by law, aTyr Pharma disclaims any obligations to update these forward-looking statements to reflect future information, events, or circumstances. We are joined today by Dr. Sanjay S. Shukla, our President and CEO, Jill Broadfoot, our CFO, and Dr. Robert Baughman, Emeritus Professor of Medicine at the University of Cincinnati. On the call, Sanjay will provide an overview of the results of the study. Dr. Baughman will provide some additional commentary around the results before we open up the call for any questions, which can be addressed by Sanjay, Jill, or Dr. Baughman. I will now turn the call over to Sanjay. Thank you, Ashlee. Good morning, everyone, and thank you for joining us for our conference call. We're here today to discuss the top-line results from our Phase 3 EFZO-FIT™ study of our lead therapeutic candidate, efzofitimod, in patients with pulmonary sarcoidosis, a major form of interstitial lung disease. Earlier this morning, we issued a press release summarizing the top-line results for this trial. We reported that treatment with 5 mg/kg of efzofitimod positively impacts quality of life and maintains lung function while reducing or withdrawing steroids. The study, however, did not meet the primary endpoint of change from baseline in mean daily oral corticosteroid, or OCS, dose at week 48. Some additional key findings include 52.6% of patients treated with 5 mg/kg of efzofitimod achieved complete steroid withdrawal at week 48, versus 40.2% on placebo. A clinical improvement in the King's Sarcoidosis Questionnaire, or KSQ, Lung Score, change from baseline at week 48 was observed for 5 mg/kg of efzofitimod compared to placebo. A greater proportion of patients achieved both complete steroid withdrawal at week 48 with KSQ Lung Score improvement in the 5 mg/kg efzofitimod arm compared to placebo. Now, lung function as measured by forced vital capacity, or FVC, at week 48 was maintained. Finally, efzofitimod was well tolerated at both the 3 and 5 mg/kg doses, with a safety profile consistent with what we've observed in all trials conducted to date. This study demonstrates that patients with chronic symptomatic sarcoidosis can be managed with substantially lower steroid doses than previously thought without the fear of worsening disease. In spite of a higher than anticipated placebo response, we found that treatment with efzofitimod was associated with a greater amount of steroid reduction, including steroid withdrawal, a clinical improvement in the quality of life for these patients, and a maintenance of lung function. This is the first Phase 3 trial and largest ever interventional study conducted in pulmonary sarcoidosis, and the data generated from this study is likely to inform treatment practices for all sarcoidosis patients moving forward. Based on these consistent findings, which we believe indicate drug activity for efzofitimod across multiple clinically relevant efficacy endpoints, we plan to engage with the FDA to determine the path forward for efzofitimod in pulmonary sarcoidosis. As a reminder, EFZO-FIT™ was a global Phase 3, 52-week randomized, double-blind, placebo-controlled, multicenter study in 268 patients with pulmonary sarcoidosis. It consisted of three parallel cohorts randomized equally to either 3 or 5 mg/kg of efzofitimod or placebo, dosed intravenously once a month for a total of 12 doses. The primary endpoint of the study was steroid reduction at week 48. Additionally, clinical efficacy assessments included the King's Sarcoidosis Questionnaire (KSQ) Lung Score, FVC, complete steroid withdrawal, all at week 48. In terms of the trial design, the study included a protocol-guided steroid taper in the first 12 weeks of the study, followed by continued taper or rescue until week 48. Steroid taper and titration were guided by the Patient Global Assessment, or PGA, which was administered every two weeks. If there was any clinical worsening, the Principal Investigator, or PI, was required to rescue based on this PGA. If there was improvement, the PI was required to taper. Before we present the results, it's important to note that key demographic and baseline characteristics were generally balanced across all treatment groups for demographics, including age, sex, weight, race, and for disease characteristics, including FVC, duration of disease, and dyspnea. We'll start with the primary endpoint of steroid reduction. When we looked at baseline steroid use, treatment groups were mostly balanced with a mean daily steroid dose of 10.51 to about 10.7 across treatment groups. The primary endpoint was calculated as the change from baseline in mean daily steroid dose at week 48, with the week 48 point calculated as an average between weeks 44 to 48. For 5 mg/kg of efzofitimod, we saw patients reduce from a baseline of 10.7 mg of steroids down to 2.79 mg. For 3 mg/kg of efzofitimod, there was a reduction from a baseline of about 10.5 down to 3.5, and placebo reduced from a baseline of 10.7 down to about 3.5. If you look at the amount of steroids reduced from baseline as an overall%, patients were able to reduce their steroid dose at the end of the study by 73.6% for 5 mg/kg of efzofitimod, compared to approximately 68% for 3 mg / kg of efzofitimod, and finally 63% for placebo. In our modeling, we assumed that patients on efzofitimod would taper from baseline to an average daily prednisone dose between 1 to 4 mg, with placebo expected to taper to between 4 to 7. The drug performed accordingly to what we projected. However, we did not achieve statistical significance, as the placebo tapering outperformed even our most aggressive modeling. Another important assessment of steroid reduction in the study was patients that achieved complete steroid withdrawal at week 48. We saw 52.6% of patients in the 5 mg / kg efzofitimod treatment group taper to 0 mg of steroids at week 48, and 51% of patients in the 3 mg / kg efzofitimod arm also ended the study steroid-free. We believe that this is very good performance by the drug. However, we did not anticipate that 40.2% of patients on placebo would also end the study steroid-free. We modeled for 30% of placebo patients to taper to 0, which was well above the 10% that most experts said they would expect to see in this 12-month study, while forcing patients down to 0 mg on their prednisone. 40% of the placebo patients tapering off steroids majorly impacted both the ability to hit stat-sig on the primary endpoint of steroid reduction change from baseline and also the steroid-free response. We believe the high placebo response was driven by several factors, but most notably the implementation of our rigorous protocol for administering the Patient Global Assessment every two weeks to guide steroid titration. This has now been proven highly effective at managing steroid doses in sarcoidosis patients. Now let's turn the findings to the KSQ Lung Score, which is the main patient-reported outcome, or PRO, we used in the study, as it is viewed as the most sensitive quality of life assessment for sarcoidosis patients. The KSQ Lung measures disease-related symptoms such as cough and shortness of breath. This score is a leading indicator as to how patients felt while undergoing treatment. Patients completed these symptom assessments at baseline, monthly during the study, and at the end of the study at week 48. We're very pleased with the findings for the PRO in this study. There are a few ways that we looked at the KSQ Lung Score, which were all pre-specified. First, we compared the change from baseline at week 48 across treatment groups. Patients on 5 mg/kg efzofitimod had a clinical improvement of 10.36 points, and those on the 3 mg efzofitimod arm had an improvement of 7.33 points compared to placebo, which improved by 6.19 points. Next, as the KSQ Lung is a disease-specific measure of pulmonary sarcoidosis symptoms, we wanted to evaluate if complete steroid withdrawal, i.e., removing all prednisone, would impact the KSQ Lung Score. We used a responder analysis to assess patients that were steroid-free at week 48 and improved 8 points or more on the KSQ Lung. I'll point out here that while the KSQ Lung has been validated academically, it's currently undergoing validation for regulatory purposes. Preliminarily, we've established, doing this validation, that the threshold for meaningful clinical change in the KSQ Lung Score is 8 points. This is consistent with the consensus among sarcoidosis experts that an 8-point improvement in the KSQ Lung is a very meaningful change. In this responder analysis, we saw that a greater proportion of patients were both steroid-free and achieved KSQ Lung Score of 8 or greater, which is improvement, with 29.5% in the 5 mg / kg efzofitimod arm compared to 14.4% in placebo patients. This means that you have about 2.5 times better odds of being steroid-free and have improved quality of life if you take 5 mg/kg of efzofitimod. I'll note that we also saw an improved result in the responder analysis for the 3 mg /kg efzofitimod treatment group, with nearly 28% of patients responding. These improvements in steroid withdrawal and KSQ Lung over placebo observed in both doses of efzofitimod give us confidence that the drug is providing meaningful benefit to patients. We believe these are very important findings, as steroids are known to have side effects that can greatly impact patients' quality of life as much, or even more so, than the disease itself. Quality of life compared to current treatment options is of high priority to patients with sarcoidosis. This combination we are observing with efzofitimod is a very important and outstanding finding from this study. Now let's take a look at FVC, which is one of the main lung function assessments used in the study. FVC is highly variable in sarcoidosis, and there's limited natural history data to provide a predictable rate of decline. We were looking to assess the change from baseline to week 48 for the absolute% predicted FVC. For context, remember, steroids are used in these patients to help control inflammation and stabilize lung function. By decreasing steroid use, it's expected that FVC would potentially decline. By rescuing patients with steroids, it's expected that FVC would actually improve. FVC% predicted was largely maintained across all treatment groups, with a decrease of 1.8% for the 5 mg arm, 2.7% for the 3 mg [efzil] arm, and 2.1% for placebo. Though we see a slight decline, we see it across all treatment groups, and this decrease is well within the normal range of variability. These results for FVC are in line with what we expected, considering the steroid taper and rescue protocol. The stability of lung function while removing steroids in this patient population is a notable finding. Finally, let's review the safety findings, which are a key part of efzofitimod's value proposition, considering that current treatment options for pulmonary sarcoidosis typically have serious side effects and toxicity. Overall, monthly dosing of efzofitimod was determined to be well tolerated at both the 3 mg/kg and 5 mg/kg doses, and the safety profile was consistent with all trials conducted to date. Adverse events, or AEs, were mostly mild to moderate in severity, generally assessed as unrelated to the study drug. Serious adverse events, or SAEs, were very limited and balanced between treatment groups. The proportion of patients with treatment-related SAEs and events leading to discontinuation and the proportion of patients who develop antidrug antibodies was small and also balanced between treatment groups. These findings are consistent with previous studies and reinforce efzofitimod's favorable safety profile, making it a desirable option for patients. Before I summarize the key findings from the study today, I wanted to take a minute to thank the patients, investigators, patient advocacy organizations, our partner, Curin Pharmaceutical, and our team at aTyr Pharma, who all contributed to this landmark study. We're incredibly grateful for your participation, and the data generated is a major contribution to sarcoidosis research and sarcoidosis care. Although we didn't meet the primary endpoint of the study, we do see drug activity and clinical benefit for efzofitimod. This is evidenced by the benefit observed in substantial steroid reduction, meaningful clinical improvements for KSQ Lung, and preservation of lung function. Additionally, this study reinforces efzofitimod's favorable safety and tolerability profile, suggesting that efzofitimod has the potential to be a safe and effective treatment option compared to current standard of care for patients, particularly for those that require chronic therapy. We believe the totality of this data warrants engagement with the FDA to determine the path forward for efzofitimod in pulmonary sarcoidosis, as there are and remains an urgent need for a safe and effective treatment to address the unmet needs of this underserved patient population. We plan to review the full results of the study to obtain additional insights, and we're scheduled to present at the upcoming European Respiratory Society Congress in Amsterdam at the end of the month. I'd now like to turn the call over to Dr. Robert Baughman, Emeritus Professor of Medicine at the University of Cincinnati and Chair of the Trial Steering Committee for the efzofitimod study. Dr. Baughman will provide some of his thoughts around the data and key takeaways for the study. Thank you, Sanjay. I'm happy to provide some of my thoughts around the study results, and there are a few key takeaways from my perspective that I would like to highlight. First, I believe that efzofitimod has drug activity in sarcoidosis. The best evidence for that is the steroid reduction seen beyond the reduction seen with placebo, which comes with significant benefits, such as improvement in quality of life as measured by the KSQ Lung. I'm particularly enthusiastic about the improvement of the KSQ Lung in patients that received efzofitimod and were able to get completely off of steroids. Quality of life is so important to sarcoidosis patients, and steroids typically have a negative impact on quality of life. I know my patients would be thrilled to take a drug that gets them off of prednisone and makes them feel better. Second, I'm quite surprised by the high placebo response with regards to steroid withdrawal. I've treated over 2,500 sarcoidosis patients in my time and have been involved with many of the past sarcoidosis trials. I would have expected less than 10% of placebo patients would have been able to become steroid-free. I would have also expected more relapses when the steroids were withdrawn. Because this was not seen, it confirms that we have become increasingly aware of patients that we treat have been receiving excess prednisone. However, the amount of excess observed in this trial is historically notable. I think it reflects the rigor of the trial and the shift in clinical practice. I also view the high placebo response as likely a function of the study design and the protocol, which, in my opinion, was excellent. Like many clinical trials, it was more rigorous in clinical practice as we typically do not assess these patients every two weeks, as they did in this trial. However, the ability to get more patients off of prednisone using this rigorous protocol will be useful as we develop future clinical guidelines for the treatment of sarcoidosis. Third, I'll remind you that the drug is safer than what is currently used. The most commonly used drugs for sarcoidosis are prednisone, methotrexate, and Remicade. All of these have significantly more toxicity than efzofitimod as in this study. If available, this drug would be a very helpful treatment option in my clinical practice. In many ways, considering the clinical benefit observed in this trial, as well as the robust safety profile compared to current standard of care, I think that there's a strong rationale to seek approval for efzofitimod. Finally, I would like to say how remarkable it is that aTyr Pharma was able to conduct and complete this large global randomized controlled trial that had a rigorous steroid withdrawal protocol. This is something that really hasn't been done before in sarcoidosis to this extent. So far, even just the top-line results have given us significant new information that will advance the field. Overall, great job on this study, and I look forward to seeing more of the data when it's available. Thank you. Thank you, Dr. Baughman. Now, at this time, myself, along with Dr. Baughman and Jill, we're available to take your questions. Thank you. To ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Our first question comes from the line of Derek Archila with Wells Fargo. Your line is now open. Hey, good morning, and thanks for taking the questions. First one just for Sanjay. Based on your conversations with the agency, how much flexibility do you think they're willing to extend here? Just in pulmonary sarcoidosis, not a lot of good treatment options. Can you just confirm for us that all the endpoints that you presented today are pre-specified? Yes, Derek, thanks for that question. That last point is really important. These were pre-specified. These are not post hoc. We haven't even started really the post hoc look at the data. The fact that they are pre-specified is really another level here why I think we're really prepared to engage the FDA. The FDA has been great to work with thus far with this program. Frequent interactions as we talk about our trial, talk about the design, look to validate King's Sarcoidosis Questionnaire. We're encouraged by all those interactions. You point out that there is really no really good available therapies, no approved therapies in sarcoidosis. I do think that they're going to be a collaborative partner, and we're looking forward to engaging them. These results on their own really merit a really good discussion with regards to what our next steps here for this program. Great. Just a follow-up, I guess, any specific measures that you can call out within the King's Sarcoidosis Questionnaire Lung kind of questionnaire that were really driving the improvements on the score? Another thing that we're also looking more specifically, the KSQ Lung is an amalgam of cough and shortness of breath endpoints. Teasing out exactly which of those six questions, for example, you know, the drug was most sensitive on, that is something that we will look at more closely. The overall KSQ improvement, I think, is outstanding. I also think that the responder analysis where we look at KSQ of greater than 8, better than we would expect to see that kind of response in the steroid-free patients. That's a much more rigorous, even higher bar composite, and we show the greatest amount of statistical difference in that analysis. Both really, really positive findings with regards to the PRO. Great. Last one for me, just in terms of getting a Type C meeting on the books with the FDA. Is this something that you suspect you can complete and get minutes by before the end of this year or early 2026? How are you thinking about the timing there? Thank you. We're going to move to engage the FDA as quickly as possible, but I also want to make sure that our briefing book, we have a really good look at all of our data. The totality of the data, as I point out, gives us a high degree of conviction for efzofitimod. I want to make sure that we have the best briefing book possible. I want to take some time, look at some things from a post hoc perspective, and then look to engage the FDA shortly after that. Got it. Thanks, Sanjay. Thank you. Our next question comes from the line of Yasmeen Rahimi with Piper Sandler. Your line is now open. Yes. Good morning, team. Thank you so much for the presentation and obviously the strong data with the sad part of the primary endpoint being missed due to high placebo. Thank you, Sanjay, for clarifying that these were pre-specified analyses. Kind of following up on Derek's question, as you're engaging with the agency, what are some of the important analyses that you hope to complete before you engage, you know, that you like to present to the FDA? If you could just maybe talk about the work that's going to start imminently post this top-line data that you'd like to complete before you meet them. The second question is for our KOL. I know you're not the FDA, but given this product profile and drug activity with quality of life improvements, what would you say? Why wouldn't this warrant the FDA to say this is sufficient for a filing package? What would that probability be? I know this is your opinion, but given the depth of this data and the high unmet need, if you could just maybe help us understand what the probability of FDA allowing the company to go forward, and this could be an approved drug, would be really helpful for us. Yeah, yes. I'll answer quickly the first part before turning it over to Dr. Baughman. We have a large, and I would say, healthy number of pre-specified tables here that are going to give us a really good ability to have good discussions with the FDA. Many times, sponsors, I think, come to the FDA with a lot of post hoc analyses. That's a lot softer, in my opinion, and probably not the right way to go. We pre-specified a number of these endpoints, so that's going to really help us. There are some other things that we're finalizing here. You know, other quality of life, fatigue assessment score, for example, things of that nature, we'll help to present more of that at the European Respiratory Society. Also cracking open some of the biomarkers, that's going to take some time. Those are the other types of assessments that we want to make sure we really have a good look at before we approach the FDA. Regarding your question directly to Dr. Baughman, I'll turn it over to you, Bob, now to discuss your opinion on this drug and the FDA. Yeah. Thanks for the question. I think that nobody knows what the FDA is thinking about things in general, and certainly, this is a problematic area for the FDA. I've been with them for a couple of different drugs besides this one. You've got to remember that the only drugs approved for sarcoidosis are in the 1950s, prednisone being the prominent one there. At this point, we're moving away from, in clinical practice and in clinical trial design, forced vital capacity because, frankly, there isn't that much difference even with the best of drug in totally treatment-naive patients, which is not what we see in clinical practice. We're looking at quality of life and how to best measure it and getting rid of the prednisone in patients who are on it. The clinical trials that are out there that have been recently completed, they're ongoing, are all designed to look at getting people off of prednisone and improving, like this study, or at least keeping the quality of life stable. We've just generated a couple of different consensus statements among sarcoidosis leaders, and we're hoping that that's going to convince the FDA that a drug like this or other drugs that are able to show you can get people off prednisone and keep their quality of life better should be approved. That's still the FDA's call. Okay. If I may ask one question from Jill. Jill, if you could just maybe remind us what the cash runway is, and now with the sort of timing of engaging with the FDA, getting the minutes back would be helpful. Yes. Thank you, Yas. The last time we provided a corporate update, we had a total of $113 million in cash. I feel confident that we're sitting in a very good position, but we will be updating that when we report, updating our guidance, I should say, when we report our Q3 corporate update. Thank you. I'll jump back in the queue. Thank you. Our next question comes from the line of Faisal Khurshid with Leerink Partners. Your line is now open. Hey, thanks for taking the question. Maybe one for both Sanjay and for Dr. Baughman. Could you just speak to your hypotheses on how the placebo outperformed this way? Like, were these not the right patients? I guess, like, you know, I thought these patients were like supposed to be steroid dependent. Like, how was 40% able to come off of prednisone? Sure. Thanks, Faisal, for the question. As I mentioned, our view of this is largely driven by the protocol, the rigor of the protocol, the ability to manage these patients to be able to effectively every two weeks, which is a bit of an artificial construct. This has reaped tremendous dividends for all patients in this study. When we look at the relative disease characteristics, these patients are sick. They are steroid dependent. At least in this one-year trial, this is the data that we produced. Again, it outperformed any of our models, even my most aggressive model. Prior to the trial starting, if I could have told you that efzofitimod knocks your steroids down more than 75%, 50% more than that are getting off steroid and we're greatly improving your quality of life, that's exactly the patient profile, the TPP I would want in a label. We're digging in more into the reasons. There could be some things we're looking at, at background immunosuppressants. I do not think this confounds the signal and changes anything, but there's a notion that background immunosuppressants may have helped the placebo population, but that's yet to be determined. I really want to dig into that a little bit more. As you pointed out, these are steroid dependent patients that were enrolled in our trial, and we've shown a remarkable ability through the combination of our protocol and using efzofitimod to get a significant number of patients off. Bob, I'll turn it to you. You can talk a little bit more about that placebo response. Yeah, I think this is important to realize that there's a shift. I mean, since 2000, there's been nine clinical trials that have been published that looked at steroid tapering and looking at how much they can get off. When I did the, with Janssen, the Infliximab trial, Remicade trial in 2006, we had, you know, this, we didn't steroid taper in that trial, but we had a lot of people on prednisone and very few on immunosuppressants other than prednisone. They were on a lot more prednisone. What's happened over the last 20 years is people have been going down on prednisone. Even though the investigators were reluctant to think that would happen, it did indeed happen. They were able to get off easily. On top of that, they were now using more immunosuppressants like methotrexate. In this study, more than half the patients were on methotrexate. I think that that's part of the reason why placebo patients did better. I can't overemphasize the importance of asking the patients every two weeks how they're doing in the directing therapy. We simply didn't do that in our clinical practice. Certainly, 10, 15 years ago, we would have patients come in every three months and only reduce the prednisone then. We started moving that up, especially in the first six months, to having them come in every six weeks. Nobody was really making the decision every two weeks until just recently. This trial, I think, is going to push people to start having things like phone apps and stuff like that to ask patients how are they doing and thinking about going down the dose every two weeks. Got it. That's helpful. One follow-up on quality of life. Sanjay, can you talk to us about how you think investors should think about the quality of life outcomes on an absolute versus placebo-adjusted basis? For Dr. Baughman as well, I think you had published a paper, actually, that said the MCID for KSQ Lung is 4 points. I'm curious how you interpret the results, and for Sanjay as well, do you have a responder analysis for a% of patients able to achieve that 4-point reduction for drug versus placebo? Right. Let me just point out from the MCID you point out, that's from some work from Dr. Behring at King's College. While academically validated, I think we are getting more sophisticated. What we're learning is when you look at group changes, this is really wonky with the PRO, but you know, about 2, 2.1 points looks like is what you'd want to see among group changes. Individual patient responder, it has to be much higher. What we're learning is it should be closer to 8. When you think about the group changes that we observed in this trial, yes, we saw a more than 4 point as, you know, leaning on the old MCID among the groups. That's great. It looks like the threshold between groups, the MCID is probably going to suss out at, you know, about 2, 2.1. Bob can talk a little bit more about that. That's work that's ongoing. The 8 point is what you want to see if it's a true response. The FDA likes to have a responder threshold. We've been working with them hand in hand. This also matches what, more or less, the consensus of the world experts, the WASOG statement, which I'm not sure is out yet, Bob. Think about it two ways, that from a group perspective, the drug is really moving things in a significant fashion, and then from a responder threshold, which has to be higher, yes, no, we're also successful with that KSQ 8 threshold. Bob, do you have additional comments? Yeah, I think it's important that you're rightly pointing out that the King's Sarcoidosis Questionnaire minimal clinically important difference was a paper that I did with Surinder Birring, who developed the King's Sarcoidosis Questionnaire. Four points was the minimal important difference. However, in clinical practice, we don't use King's, but when we look at trial results, people realize that there's enough variability that 4 points was maybe a little too low. We just recently published the Delphi where we looked at 100 stakeholders, 30 experts, and came up that 8 points and 12 points would be better cutoffs if we're going to really say that this is truly an important effect rather than just seeing the variability of the patients responding. That's why I think in the WASOG statement that's working its way through, we just presented the results of this task force that looked at it. The recommendation is to look at 8 points, not at 4 points. It's the minimal important difference in clinical care. Got it. Thank you. Just to clarify, you're saying the responder analysis was successful? Using the cutoff of 8 and also the steroid-free, yes. That is, I think, one of our most, you know, strongest and outstanding findings. That's really what patients and providers want. They want to be able to get off steroids, and they want to make sure that their quality of life is significantly improved. We've demonstrated that through this composite. I think Dr. Baughman would probably also agree that finding is exactly what he'd want to see. Bob, I don't know if you're. Got it. Yeah. Okay. I think that at the lower bar would be getting them off prednisone and just keeping their quality of life stable. As a bonus here, you're showing that people are actually improving their quality of life, over 30%, almost 30% of the time, or over 30%. Got it. Thank you for taking the question. Thank you. Our next question comes from the line of Joe Pantginis with HC Wainwright. Your line is now open. Hi, everybody. Thanks. Two questions. First, I don't want to harp on this, but regarding the placebo effect, the every two weeks concept, is that just talking to the variability of how patients feel? I know that's somewhat rhetorical. Do you feel that going forward, that might be able to change patient guidelines in how you're looking at the frequency of steroid taper? Yeah, Joe, certainly, this is a construct that's in the protocol. Look, we've proven that if you can assay these patients, if you can talk to them every two weeks and assess them, you can do a much better job. Is that reflective of clinical practice and how things will move going forward? It will be tough if Dr. Baughman can answer some of that. I do think that this is a smoldering disease. By having frequent touch points like that, perhaps you can really have your finger on the pulse with prednisone. We're also taking a snapshot of about a year. Certainly, looking at things in a longer trial, you may see some of that smoldering light of fire. Again, that 40% was much higher than we had modeled for. If the modeling had hit even our higher 30% dose, 30% placebo response, we'd be fine right now with regards to the primary. I think moving forward with regard to treatment guidelines, I do think personally that this is the highest degree of evidence produced in a long time, and it's going to have to be incorporated in the treatment guidelines. Dr. Baughman, you can answer more questions around what you think this data will do to the treatment guidelines. Yeah. I've been actually treating patients with sarcoid for more than 40 years, and I developed the treatment guidelines from 1999, and I chaired the recent ones that we published in 2023. What's happened is that we used to tell patients, you know, come back in three months, and then we'll talk about changing your dose to prednisone. We used to think it was a relatively slow process when you went down on prednisone. This study and others have shown that, you know, we can make that decision faster. Things like the Pulsar trial, which led this one, it came out before this one, it's clear that we can make the decision every two weeks, maybe even sooner than that, but I think two weeks is a reasonable amount of time. I think this is really going to drive the way we practice rather than necessarily trying to reflect what practice was from 10 years ago. I appreciate that. Thank you very much. My next question, and obviously, Sanjay, this can change 100 times between now and your FDA meeting. If you were in front of the FDA today, what would be your potential wish list of what you might want to accomplish with regard to next steps or study design and changes you would make? I think the first point of view is to take this data, which I think is the best data set produced in a long time for sarcoidosis with no therapies available, and have a discussion around how do we seek approval here. Whether that's immediate or stepwise, that's what we have to determine. That's what we have to really strategize around. The fact is we have a lot of good data here. It gives us a lot of conviction around the drug. Yes, the primary did not hit, so we have to own up to that and address that. What are the reasons behind that? As Dr. Baughman has pointed out, this two-week protocol assessment is not right now part of clinical care and practice. It may need to be incorporated in that direction. I'll remind everyone too that this is a drug that could be administered once a month through a one-hour IV infusion. Thus far, tracking to really good safety and tolerability. I view it as a maintenance therapy that could fit really well into the current standard of care. All things that, right now, we have to sit down with the agency and see what they think about the short-term ability here for us to get efzofitimod over the finish line. It is going to require a really engaged conversation where we need to look at the totality of the data we've produced and put it up against what's available out there right now, in particular from a safety perspective. Dr. Baughman can comment a little bit around his experiences with drugs like Infliximab and from a safety perspective, how our drug stacks up. Bob, I don't know if you want to say something there about that. Yeah. I mean, really, Infliximab, Remicade is the drug that we first described in 2000, and in the last 10 years, it has been the best drug for patients that are steroid refractory who aren't getting better with just methotrexate. That represents a significant proportion of patients with sarcoidosis chronic disease. It is a much more toxic drug. You're probably aware of it in things like rheumatoid arthritis and Crohn's disease. This drug, Infliximab, is better than Humira, some of the other anti-TNF drugs. Having a drug that has a much better safety profile like this one is good. In the Infliximab trial, it didn't look that much better than this one. In fact, it didn't improve quality of life in the Infliximab trial like we did here, like you did here. Appreciate the comment. Thank you. Our next question comes from the line of Prakhar Agrawal with Cantor Fitzgerald. Your line is now open. Hi. Good morning, and thanks for taking my questions. Maybe a couple on pulmonary sarcoidosis. How did the ability to taper even beyond the 12-week tapering protocol impact the trial results and the placebo and performance? The second question is, have you been able to tease out efficacy by patients who were on a higher quartile of baseline steroid across placebo and treatment compared to the average of 10.5 mg? Just add a quick follow-up. Yes. For that second point, Prakhar, we did look at, we've looked at 10 and above and below 10 as those are pre-specified stratification. We're not seeing differences there in the conclusions. The drug does not work any better or any less regardless of those cutoffs. Now, looking more specifically into smaller 2.5 mg or quartile elements, this is something we are going to unpack and look a little bit more closely at. The other question you had was, if I understood correctly, your view was the ability to taper. I think that's what you're getting at. Did placebo patients maybe need to take a little longer than 12 weeks? Was that what you were getting at? Yes. Yes. Yes. Yeah. Another thing we're really looking at closely is the ability to taper. What we're observing is our protocol has been able to rigorously get folks down. The rate and speed in which placebo compared to our drug is something that we're really looking closely at. We're also looking at the ability to maintain 0 for, say, a six-month duration. We're seeing differences emerge there that efzofitimod does a better job. We'll look at things like steroid-free days, ability to taper, time to clinical worsening. These are also things that we're looking at very, very closely here. Stay tuned. Yes. Can you talk about the timing of the SSC ILD readout now and the read-throughs to that indication from these data sets? Thank you. No timing just yet. I think we'll come back to that probably later this year. As I've said previously, once we have a better line of sight to complete enrollment in that trial, we'll have an idea on when it reads out. That's a six-month trial. Stay tuned. Once we look to finish enrollment in that trial, the SSC data will be approximately six or seven months after that. Thank you. Our next question comes from the line of Roger Song with Jefferies. Your line is now open. Thanks for sharing the data and taking on questions. The first one I have is the variability and the kinetics. Since you are already taking to a lot of additional detail on the time course, just curious, one is how the deviation looks like. Is that higher than your modeling? The other thing is, at any time point, do you see the statistical difference between the EXO and the placebo during the course of the one year? I have a follow-up. Thank you. Right. Your first point, I think, is more about, you said about the drug kinetics? Yes, drug kinetics and then standard deviations. Right. The PK, we are doing some sparse sampling, and we are going to be looking more closely at that. Absolutely, looking at the exposure of the patients, that is something that we're going to look at very closely. This is standardized weight-based, but could we also tease out some differences in an exposure response? This is something, Roger, that will be important for us to look at for sure. That is not obviously a top-line analysis, but the PK characteristics and the ability to potentially see an exposure response is something that we want to have done here as well. I just don't have that right now, but that will be something that will be very important. Your second question is, I think what you're getting at is durability. When I think about this drug, I can see some data that will probably be presented at ERS in my mind. Quality of life, for example, was just remarkably consistent. Efzofitimod immediately started to make patients feel good. When you look at all the time points, our statistical difference observed is not just an anomaly of week 48. Really, across the trial, we're seeing the quality of life of the patients on efzofitimod significantly better, regardless of which time point you look at. That is data that we hope to present in Amsterdam, follow-on visualizations looking at point-to-point variability. I think the drug is demonstrating a very, very durable response and certainly a very durable quality of life trend. Dr. Baughman, you've seen some of that as well. I think you would concur with me with regard to that assessment. I think the fact is that you're seeing a response that looks pretty apparent in the first 12 weeks but doesn't go away with time. You don't see a decay in that. I actually like the fact that all the endpoints are going together. There's not an endpoint that's sitting out there that's going in the opposite direction. Got it. The incidence of the King's Sarcoidosis Questionnaire, the endpoint, it is pre-specified. Do you have any alignment on the powering and the way you designed the trial? The last question also relates to regulatory. Any potential subpopulation you will dig deep into to show the statistical significance even in the primary endpoint? Thank you. The King's Sarcoidosis Questionnaire (KSQ) is pre-specified, and all of the analyses that I presented today were pre-specified and well-powered. The fact that we showed the statistical differences in overall KSQ and also in the responder, this is a well-powered signal based on the size of our trial and at thresholds that are meaningful. As I said, you know, preliminarily validated at this point. We're working on validating in parallel from this trial. Very much in line with the numbers that we want to hit as we validate the KSQ. From a powering point of view, you know, very robust signals in both of those two endpoints. Your second question, Roger, can you just repeat that again? Yeah, sure. Any subpopulation? Subpopulation, yeah. Yeah, need a primary endpoint. Yeah. I think what we're going to be looking really closely at, we've looked at things like duration of disease, say more than two years, less than two years. We've looked at, we'll be looking at subpopulations of different PFT phenotypes. We've started by looking at mixed and restrictive patients compared to not mixed and restrictive. Those subpopulations, that analysis is starting and ongoing. As I said, this is some of the post hoc work that now we'll dig into to determine if there are some populations where we have a different signal. That is part of the post hoc analysis that's emerging. As I mentioned, background immunosuppressant use with methotrexate is something I'm looking really closely at because there's a notion, as I said, that placebo may have benefited from that. This sets us up to also have a real discussion around can efzofitimod also potentially replace methotrexate? Methotrexate does not seem to be, at least looking at this data, to be a drug that has a lot of primary efficacy, which I think I suspected. These are the elements that we'd look to unpack as a drug. Efzofitimod is certainly safer than methotrexate, which comes with its own liver side effects. These are the things that we're going to be looking really closely at, Roger, in the post hoc data cuts. Got it. Thank you. Thank you. Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is now open. Hey, guys. Thanks for taking my question. Sorry the results didn't work out as you'd hoped, but I appreciate you hosting this call and providing this really helpful context. Just kind of curious, as we think about framing next steps, can you characterize your willingness to run another study in this indication? If you were to, can you talk about maybe some of the changes you might consider to endpoints? Might the design include perhaps a less rigorous, more real-world check-in protocol versus, you know, every two weeks? Could you consider dosing higher? Did you see any patterns of AEs that would preclude you from dosing up in a subsequent study? I had a follow-up. Thanks. Thanks, Brian. Yeah. Just to be clear, we're looking to engage the FDA about the potential for efzofitimod immediately being available for patients. We'll be looking at any and all opportunities for that. In the event that we would be asked to run another trial, whether confirmatory, whatever nature of that trial looks like, you point out several things that we'd need to really dig into. I don't necessarily think about assaying the patients less. Loosening that criteria certainly, I think, would yield greater deltas. I do like the way the protocol is run. What we'd really want to focus on is the placebo population. Are there things with the IE criteria that could be tightened up to squeeze some of that signal? That would be something that we would look at really closely. How do we even further fine-tune the patient population to enhance that delta? One could say that just the delta we've established, the more than 12% difference, you could model off that. This is probably the best natural history data ever in sarcoidosis. Now you can model off of this and model an end that you can hit that difference, provided it's a meaningfully important difference. I also look at signals in KSQ that have to play a bigger role. I think we've already gone beyond steroid reduction. Now I think we're in a world where our drug and other drugs will, I think, patients will demand steroid withdrawal. With regard to dosing, we have a good safety profile. I think you bring up a good point. Could the drug be administered more frequently? Could we go to every three weeks infusion? We'd have to weigh that against how the patients would feel and the centers. All really good points here if we are asked to do something, another trial. Our viewpoint is we want to take this data set and see what can immediately be done for patients who are really in desperate need of a better therapy. Understood. That makes a lot of sense. Maybe just one more question. Did you notice any correlations between the improvements on KSQ Lung with steroid reductions or withdrawal? I guess I'm sort of wondering whether the quality of life improvements that you're seeing are driven primarily by greater steroid reductions or perhaps a secondary drug effect, especially considering what you mentioned that these were seen quite early on. Thanks. I think it's fair to say that if you remove steroids, you are going to feel better. I think what really is something that we have focused on is the degree of quality of life improvement is quite substantially different between those placebo patients that remove steroids compared to those that remove steroids on efzofitimod. That's apparent when you look at the KSQ differences and especially the responder analysis. I think it's fair to say that any and all of us, if we took less steroids, we're going to feel better. The question is, are you substantially or statistically better than your placebo counterparts? We've demonstrated that in this trial. I think it's a combination, but I also think that this is why I view it as the protocol effect, the rigor of our protocol reduces steroids. To really feel better, efzofitimod is the thing that is making the patient's quality of life better here with that difference that we observe. Got it. Thanks so much. Thank you. Our next question comes from the line of Yale Jen with Laidlaw & Co. Your line is now open. Good morning, and thanks for taking the questions. Just two here. The first one is that since we already have the Phase 3 data, in retrospective, if you go back to look at the Phase 2 readout, do you have any comments and thoughts on that? I have a follow-up. Thanks, Yale. Yeah. I mean, Phase 2 obviously had a different design, taking folks down to five, and obviously, we didn't have the rigor of the every two weeks with the PGA. When you look at that data, look at quality of life, again, a very consistent signal that we observed in that trial. It's safe, similar to that trial. We consistently in that trial showed a dose response. I think it's at least from my preliminary view, we're seeing something similar in this trial. Five certainly is always outperforming placebo in all the assessments we're looking at. A lot of consistency from that trial. That was a smaller trial. I think that was one of the things that we were heavily criticized. Now we have a signal in nearly 270 patients. Consistency in a much larger population that is now really well-powered, I think this is why we like some of the results in this trial. Okay. Great. That's very helpful. One more question here, which is that the endpoint has been adjusted toward the average of four weeks versus, I guess, the last weeks of the study. Do you see that have any impact on the readout? I think you have to look at we have patient diary data for every single day. The average dose is also this is the way the FDA wanted us to look at it. Point estimates, point-to-point variability, you know, that could be worrisome if we just take a point estimate. I think the main point here is when you look at month-to-month assessments, as Dr. Baughman pointed out, we have a lot of durability here. The signal is not bouncing around at the visits. Quality of life, in particular, immediately, patients start to feel better, and they continue to feel substantially better compared to their placebo counterparts all throughout the year while maintaining zero steroids, so zero to low steroids. Great. Thanks, Rob, and best luck for the meetings with the FDA. Thank you. Thank you. Our next question comes from the line of Soumit Roy with Jones Trading. Your line is now open. Hi, everyone, and thank you for presenting clear data. When you look at the curve between the placebo arm and the 5 mg, was there a difference between 12 to 24 weeks versus 24 to 48 as this is the longest trial ever in this indication, or was that pretty much overlapping the whole time? I'll be looking, Sumit, at the different cutoffs. We've looked at the whole trial. We've also looked at 12 to 48. Stay tuned. I think what you're getting at is, are there windows? Does the drug start to work better towards the end? Right now, we've just looked at overall, and we're also looking at 12 to 48. I need to look at some other windows. This goes back to an earlier question that can the drug seem to allow patients to taper faster and cleaner? That's something that I think is going to be really important. The other component is, did it take placebo patients longer to get to zero? This is some of that time to event, the number of steroid-free days. Those are the things that I will be looking at and hope to get that to you in the future. Thank you. One last question. Trying to reconcile the quality of life endpoint versus the primary endpoint, clearly, do you think the drug is clearly disease-modifying? If there is any objective biomarker or something that you can use to show that this drug is effective in certain subpopulations as you dig through the data? I definitely think it's treatment-modifying. Disease-modifying gets into looking at other elements, other functional elements, maybe radiographic. That's something we didn't assess in this trial. I think it's yet to be determined. Certainly, yes, we are in many ways modifying disease by substantially reducing steroids, still maintaining inflammatory control, not worsening lung function. I think patients would certainly say that it's modifying their life. I think that's a significant concern and consideration for these patients. They've been on toxic prednisone for decades. I think this is the first drug that really gives hope. It is going to change. I think treatment practices and experts are going to look at this data and have to think differently. I also think that efzofitimod has demonstrated some things quite unique. Great. Thank you again for taking the questions. Thank you. Our last question comes from the line of Dev Prasad with Lucid Capital Markets. Your line is now open. Hi, Thank you for taking the question. I have a couple of questions, one for our KOL and one for Sanjay. For KOL, how do you view the relative importance of KSQ versus FVC in pulmonary sarcoidosis patients in terms of capturing meaningful clinical benefit? For Sanjay, KSQ demonstrated clear benefit in the trial, but how do you think FDA will balance those quality of life gains against the FVC benefit? Thank you. Dr. Baughman, why don't you go first and then I'll finish? All right. Yes, I'm a pulmonologist, so we like numbers and we look at FVC. If you ask the patient, and we did a few years ago publish a study of 1,800 sarcoid patients, the number one in priority to them as far as treatment was quality of life, and number two was functionality. Number eight on the list, the lowest one, was pulmonary function tests. They really are less enthusiastic. I think, as I said, if you look at the trials that we've completed, the improvement in forced vital capacity has been minimal. That was the biggest result with infliximab, despite the fact that over the next 15 years we've shown that that drug is an important part of therapy. I think the FVC has been overblown. The FDA has, I think, recognized that that's probably not the primary endpoint in the recommendations we're making now. You should be looking at quality of life and steroid withdrawal. Yes, Dr. Baughman, you exactly said what I would say. FVC from a regulatory perspective is falling much lower in its priority. We got wind of that years ago when we started after our Phase 2 data. It's clear that quality of life and steroid replacement reduction, this is the way at least I read the FDA is interested in. The KSQ lung is a field endpoint. They look for things in field function and survival. Right now, I think the drug of the disease is searching for even better functional measures. In my view, the field endpoint here that the FDA is focusing on and has guided us to focus on is King's Sarcoidosis Questionnaire. I do think that this portends well for us that that's where we saw a signal. Thank you. Thank you. I would now like to turn the call back over to Sanjay S. Shukla for closing remarks. I just want to thank everyone's interest. A lot of great questions today. Obviously, not exactly what we wanted, not what the company wanted, not what investors wanted. I do want to just highlight here, though, that for patients, specifically those patients who are listening, those that were in our trial, you contributed to something here, landmark. The medical evidence that we're producing here is going to make you feel better. Practice patterns are going to have to acknowledge this excellent evidentiary data set that we've created. I think it's going to positively benefit your care. Efzofitimod is still in the mix here. As I said, we plan to really fight for you, fight for patients, and work closely with the agencies around the world. I did want to tip my hat to the patients out there and really thank them for their interest and those that participated in our trial. You really moved the fields forward. I'll end there, and thanks everybody for dialing in. This concludes today's conference call. Thank you for your participation. You may now disconnect.