Conference Transcript - ATYR 2025-09-15

Operator

Good morning, ladies and gentlemen, and welcome to ATIRE Farmer Conference Call to review the top-line results for the Phase III EFSOFIT study of EFSOFITAMOD and pulmonary sarcoidosis. At this time, all participants are in listening mode. Later, we will conduct the question and answer session, and instructions will be given at that time. As a reminder, this conference is being recorded for repaying purposes. It is now my pleasure to hand the conference call over to Ashley Dunston, ATIRE's Senior Director of Investor Relations and Public Affairs. Ms. Dunston, you may begin.

Ashlee Dunston, Head of Investor Relations

Thank you, and good morning, everyone. Thank you for joining us today to discuss the top-line results from our Phase 3 EPSO-5 study of EPSO-fitomod 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 ATAR 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 and such forward-looking statements. Please do the forward-looking statement disclaimer in the company's press release issued this morning, as well as the risk factors in the company's SSD 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 as only of the date they are made as facts and circumstances underlying these forward-looking statements may change. Except as required by law, ATAR Pharma disclaims any obligations to update these forward-looking statements to reflect future information, events, or circumstances. We are joined today by Dr. Sanjay 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. Bachman. I will now turn the call over to Sanjay.

Sanjay Shukla, CEO

Thank you, Ashley. 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 III EPSOFIT study of our lead therapeutic candidate, EPSOFITAMOD, 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 per kg of efsofitamide 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 milligrams per kilogram of esophitamide 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 milligrams per kilogram of F-sulfitamide compared to placebo. And a greater proportion of patients achieved both complete steroid withdrawal at week 48 with KSQ lung score improvement in the 5 mg per kg epsilfitamide arm compared to placebo. Now, lung function as measured by force vital capacity or FVC at week 48 was maintained. And finally, epsofitamide was well-tolerated at both the three and five milligram per kilogram doses with a safety profile consistent with that 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 F-silfitomod 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 three trial and largest ever interventional study conducted in pulling 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 efsofitomide across multiple clinically relevant efficacy endpoints, we plan to engage with the FDA to determine the path forward for efsofitomide in poling sarcoidosis. As a reminder, efsofit was a global phase 3, 52-week randomized double blind, placebo-controlled, multi-center study in 268 patients with pulmonary sarcoidosis. It consisted of three parallel cohorts, randomized equally to either three or five milligrams per kilogram of epsofenamide or placebo, dosed intravenously once a month for a total of 12 The primary endpoint of the study was steroid reduction at week 48. Additionally, clinical efficacy assessments included the KSQ lung score, FPC, 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. Steric 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 of PI was required to rescue based on this PGA. And 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 FEC, 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 per kg of sulfitamide, we saw patients reduced from a baseline of 10.7 milligrams of steroids down to 2.79 milligrams. For 3 milligrams per kilogram of esophidomide, 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 percentage, patients were able to reduce their steroid dose at the end of the study by 73.6% for 5 milligrams per kilogram of epsilfitamide, compared to approximately 68% for 3 milligrams per kilogram of epsilfitamide, and finally 63% for placebo. In our modeling, we assumed that patients on epsilfitamide would taper from baseline to an average daily prednisone dose between 1 to 4 milligrams. with placebo expected to taper to between 4 to 7. So 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-milligram-per-kilogram efsofitomide treatment group tapered to zero milligrams of steroids at week 48, and 51% of patients in the three milligram per kilogram efso arm also ended the study steroid-free. We believe that this is very good performance by the drug. However, we did not anticipate the 40.2% of patients on placebo would also end the study steroid-free. We modeled for 30% of placebo patients to taper to zero, 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 zero milligrams on their prednisone. So 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. We're administering the patient global assessment every two weeks to guide steroid titration. Well, 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 shorness 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. And 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 milligrams per kilogram F-safetamide had a clinical improvement of 10.36 points, And those on the 3-milligram F-sulfidamadol had an improvement of 7.33 points, compared to placebo, which improved by 6.19 points. Next, as a KSQ lung is a disease-specific measure of pulmonary sarcoidosis symptoms, we wanted to evaluate if complete with steroid withdrawal, i.e. removing all prednisone, would impact the KSQ lung score. So we used a responder analysis to assess patients that were steroid-free at week 48 and improved eight points or more on the KSQ lung. So I'll point out here that while the KSQ lung has been validated academically, it's currently undergoing validation for regulatory purposes. And preliminarily, we've established during this validation that the threshold for meaningful clinical change in the KSQ lung score is eight points. And this is consistent with the consensus among sarcoidosis experts that an eight-point improvement in the KSQ lung is a very meaningful change. So in this responder analysis, we saw that a greater proportion of patients were both steroid-free and achieved KSQ lung score of eight or greater, which is improvement, with 29.5% in the five milligram per kilogram EFSO arm. compared to 14.4 percent 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 five milligrams per kilogram of epsofetamide. I'll note that we also saw an improved result in the analysis, responder analysis for the three milligram per kilogram epsotreatment group with nearly 28 percent of patients responding. These improvements in steroid withdrawal and KSQ-long over placebo observed in both doses of efsopetamide give us confidence that the drug is providing meaningful benefits 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. And quality of life compared to current treatment and options is of high priority to patients with sarcoidosis. So this combination we are observing with F-Sofitobot 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 percent predicted FEC. And 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 FEC would potentially decline. And by rescuing patients with steroids, it's expected that FEC would actually improve. FEC percent predicted was largely maintained across all treatment groups, with a decrease of 1.8% for the 5 milligram arm, 2.7 for the 3 milligram EPSO 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. And these results for FEC are in line with what we expected, considering the steroid taper and rescue protocol. And 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 F-safinamod's value proposition, considering that current treatment options for polysacridosis typically have serious side effects and toxicity. Overall, monthly dosing of F-safinamod was determined to be well-tolerated at both the three and five milligram per kilogram doses, and the safety profile was consistent with all trials conducted to date. Adverse events or AEs were mostly mild or moderate in severity, generally assessed as unrelated to the study drug. And 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 anti-drug antibodies was small and also balanced between treatment groups. These findings are consistent with previous studies and reinforce efsofitamide'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 Cure and Pharmaceutical, our team at ATAR, 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 epsofetamide. 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 F-safetamide's favorable safety and tolerability profile, suggesting that F-safetamide 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 esofitimab in poloence arginosis, 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 Boffman, Emeritus Professor of Medicine at the University of Cincinnati and Chair of the Trial Steering Committee for the EPSO-FIT study. Dr. Boffman will provide some of his thoughts around the data and key takeaways for the

Robert Baughman, Analyst — KOL, University of Cincinnati

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 esophenamide has drugged activity in sarcoidosis. The best evidence for that is the steroid reduction scene beyond the reduction scene 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 esophenamide 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 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 its shift in clinical practice. I also viewed the high placebo response as likely as 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 F-zofitamide had in this study. If available, this drug would be a very helpful treatment option in my clinical practice. So, 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 F-zofitamide. And finally, I would like to say how remarkable it is that ATAR 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, and 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.

Sanjay Shukla, CEO

Thank you, Dr. Boffman. Now at this time, myself, along with Dr. Boffman and Jill, we're available to take your questions.

Operator

Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Our first question comes from the line of Derek Archula with Wells Fargo. Your line is now open.

Derek Archila, Analyst — Wells Fargo

Hey, good morning, and thanks for taking the questions. You know, first one, just for Sanjay, you know, I guess based on your conversations with the agency, I guess, how much flexibility do you think they're willing to extend here just in pulmonary sarcoidosis, not a lot of good treatment options, and can you just confirm for us that all the endpoints that you've presented today are pre-specified?

Sanjay Shukla, CEO

Yes, Derek, thanks for that question, and 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 sarcoidosis, so we're encouraged by all those interactions. You point out that there is really no really good available therapies, no approved therapies in sarcoidosis, so 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

Derek Archila, Analyst — Wells Fargo

our next steps here for this program. Great. And then just a follow-up, I guess, you know, any specific measures that you can call out, you know, within the KSQ lung kind of questionnaire that were really driving the improvements on the score? Another thing that we're also looking more

Sanjay Shukla, CEO

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. But the overall KSQ improvement I think is outstanding. I also think that the responder analysis where we look at KSQ of greater than eight, 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. So both really, really positive findings with regards

Derek Archila, Analyst — Wells Fargo

to the PRO. Great. And then 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 26? How are you thinking about the timing there? Thank you. We're going

Sanjay Shukla, CEO

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 epsofenamon. But I want to make sure that we have the best breaching book possible. I want to take some time, look at some things from a post-doc perspective, and then look to engage the FDA shortly after that.

Derek Archila, Analyst — Wells Fargo

Got it. Thanks, Anjay.

Operator

Thank you. Our next question comes from the line of Yasmeen Rahimi with Piper

Yasmeen Rahimi, Analyst — Piper Sandler

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 and kind of following up on Derek's question is, 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. So if you could just maybe talk about the work that's going to start imminently this post, this top line data that you like to complete before you meet them. And then 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? And 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 go forward and this could be an improved drug would be really helpful for us.

Sanjay Shukla, CEO

Yeah, I'll answer quickly the first part before turning it over to Dr. Boffman. 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 hope to present more of that at European Respiratory Society. Also cracking open some of the biomarkers, that's going to take some time. So 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, Dr. Baumann, I'll turn it over to you, Bob, now to discuss your opinion on this

Robert Baughman, Analyst — KOL, University of Cincinnati

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 starcoidosis are 1950s, prednisone being the prominent one there. So at this point, we're moving away from, in clinical practice and in clinical trial design for a four-spot of 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. So 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. So 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 body of life stable. We've just generated a couple 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 own quality of life better should be approved. But that's still the FDA's call.

Yasmeen Rahimi, Analyst — Piper Sandler

And 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.

Jill Broadfoot, CFO

Yes, thank you, Yaz. The last time we provided a corporate update, we had a total of $113 million in cash. So I feel confident that we're sitting, you know, 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.

Yasmeen Rahimi, Analyst — Piper Sandler

Thank you, and I'll jump back in the queue.

Operator

Thank you. Our next question comes from the line of Faisal Kershid with Levering Partners. Your line is now open.

Faisal Kershid, Analyst — Leerink Partners

Hey, thanks for taking the question. Maybe one for both Sanjay and for Dr. Boffman. Could you just speak to your hypotheses on how the placebo outperformed this way? Were these not the right patients? I thought these patients were supposed to be steroid-dependent. dependent, like how is, you know, 40% able to come off of a prednisone?

Sanjay Shukla, CEO

Thanks, Russell, for the question. As I mentioned, our view of this is largely driven by that, 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. And 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. So, you know, prior to the trial starting, if I could have told you that epsofitamide knocks your steroids down more than 75%, 50%, more than that, are getting off steroids and we're greatly improving your quality of life, that's exactly the patient profile, the TPP I would want in a label. So 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. But 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 EFSO to get a significant number of patients off. Bob, I'll turn it to you. You can talk a little

Robert Baughman, Analyst — KOL, University of Cincinnati

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 my seat can get off. And when I did with Janssen, the infleximab 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, very few on immunosuppressants other than prednisone. And they were on a lot more prednisone. So 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. And on top of that, they were now using more immunosuppressants like methotrexate. So in this study, more than half the patients were on methotrexate. So I think that that's part of the reason why the placebo patients get better. I can't overemphasize the importance of asking the patients every two weeks how they're doing in 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 their presence on men. We'd start moving that up, especially in the first six months, to having them come in every six weeks. But nobody was really making the decision every two weeks until just recently. And 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 that dose every two weeks.

Faisal Kershid, Analyst — Leerink Partners

And then 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? And then for Dr. Boffman as well, I think you had published a paper, actually, that said the MCID for kids healing is four points. So I'm curious, you know, how you interpret the results. And then for Sanjay as well, do you have a responder analysis for percent of patients able to achieve that four-point reduction for drug versus placebo?

Sanjay Shukla, CEO

Right. So let me just point out from the MCID you point out, that's from some work from Dr. Bering at King's College. While academically validated, I think we are getting more sophisticated. And what we're learning is when you look at group changes, this is really wonky with the PRO, but, you know, about two, 2.1 points looks like is what you'd want to see among group changes. but individual patient responder, it has to be much higher. And what we're learning is it should be closer to eight. So when you think about the group changes that we observed in this trial, yes, we saw a more than four point as, you know, leaning on the old MCID among the groups. That's great. But it looks like the threshold between groups, the MCID is probably going to suss out at about 2, 2.1. Bob can talk a little bit more about that. That's work that's ongoing. The eighth point is what you want to see if it's a true response. So the FDA likes to have a responded threshold. We've been working with them hand in hand. And 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. So 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?

Robert Baughman, Analyst — KOL, University of Cincinnati

Yeah, I think it's important that you rightly point out the KSQ MCIDs was a paper that I did with Syrindra who developed the KSQ. And four points was the minimal important difference. However, in clinical practice, we don't use KINGS, but when we look at trial results, people realize that there's enough variability that four points was maybe a little too low. And we just recently published the Delphi where we looked at 100 stakeholders, 30 experts, and came up that eight points and 12 points would be better cutoffs if we're gonna really say, This is truly an important effect rather than just seeing the variability of the patients responding. So that's why I think in the WASOC statement that's working its way through, we just presented the results of this task force that looked at as a recommendation is to look at eight points, not as four points as the minimal important difference in clinical care.

Faisal Kershid, Analyst — Leerink Partners

Got it. Thank you. And it sounds just a little bit like you're saying the responder analysis was successful?

Sanjay Shukla, CEO

using using the cutoff of eight in this and also the steroid free yes that that is that is i think one of our most you know strongest and outstanding findings and that i think 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. And I think, you know, Dr. Valkin would probably also agree that, you know, that finding is exactly what he'd want to see. Bob, I don't know. Got it. Yeah. Okay.

Robert Baughman, Analyst — KOL, University of Cincinnati

I think that 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.

Operator

Thank you. Our next question comes from the line of Joe Pant Guinness with H.C. Wainwright. Your line is now open.

Joseph (Joe) Pantginis, Analyst — H.C. Wainwright

Hi, everybody. Thanks. So two questions first. I don't want to harp on this, but regards to the placebo effect. So the every two weeks concept, so is that just talking to the variability of how patients feel? I know that's somewhat rhetorical. And do you feel that going forward that might be able to change patient guidelines in how you're looking at the frequency of steroid vapor?

Sanjay Shukla, CEO

Yeah, Joe, certainly this is a construct that's in the protocol. And, 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. Boffin can answer some of that. But 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 of prednisone. We're also taking a snapshot of about a year. So certainly looking at things in longer trials, you may see some of that smoldering light of fire. But, 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, you know, 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. So, Dr. Boffman, you can answer more questions around what you think this data will do to the treatment guidelines.

Robert Baughman, Analyst — KOL, University of Cincinnati

I've been actually treating patients with Sarkoic for more than 40 years, and I developed the treatment guidelines from 1999 and I chaired the recent ones that we published in 2023. And 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 of prednisone. Because we used to think it was a relatively slow process when you went down on prednisone. This study and others have shown that we can make that decision faster, and so things like the PULSTER trial, which led this one that 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. And so I think this is really going to drive the way we practice rather than necessarily trying to reflect what practice was 10 years ago.

Joseph (Joe) Pantginis, Analyst — H.C. Wainwright

I appreciate that. Thank you very much. And then my next question, and obviously, Sanjay, this can change, you know, a hundred times, you know, between now and your FDA meeting, but if you were in front of the FDA today, you know, what would be your potential wish list of what you might want to accomplish with regards to next steps or study design and changes you would make?

Sanjay Shukla, CEO

Well, I mean, 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, you know, 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. But 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. But what are the reasons behind that? And as Dr. Botham has pointed out, this two-week protocol assessment, it 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 can 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 current standard of care. So all things that, you know, right now we have to sit down with the agency and see what they think about the short-term ability here for us to, you know, get FSO over the finish line. But 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. Boffin 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.

Robert Baughman, Analyst — KOL, University of Cincinnati

Yeah, I mean, really, infleximab, Remicade is the drug that we first described in 2000. In the last 10 years, it has been the best drug for patients that are sclerorefractory who aren't getting better with just methotrexate. So that represents the significant proportion of patients with sarcoidosis chronic disease. And that is a much more toxic drug. You're probably aware of it in things like rheumatoid arthritis and Crohn's disease. And this drug, infliximab, is better than Humira, some of the other anti-TNF drugs. So having a drug that has a much better safety profile like this one is good. And the infliximab trial 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, Ken.

Joseph (Joe) Pantginis, Analyst — H.C. Wainwright

Appreciate the comments.

Operator

Thank you. Our next question comes from the line of Prakar Agarwal with Cantor Fitzgerald. Your line is now open.

Rakar Agarwal, Analyst — Cantor Fitzgerald

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 on the placebo on performance? And second question is, have you been able to tease out efficacy by patients who were on a higher quartile of baseline steroid across placebo in treatment compared to the average of 10.5 milligram? And I had a quick follow-up.

Sanjay Shukla, CEO

Yes, for that second point, Prokhar, we did look at, we've looked at 10 and above and below 10, as that was a 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, at those cutoffs. Now, looking more specifically into smaller 2.5 milligram or quartile elements, this is something we are going to unpack and look a little bit more closely at the to to the other the other question you had was if I understood correctly your your view was the ability to taper I think that's what you're getting at that did the placebo patients maybe need to take a little longer than 12 weeks it was that

Rakar Agarwal, Analyst — Cantor Fitzgerald

what you were getting at yeah yes yes yeah so another thing we're really

Sanjay Shukla, CEO

looking at closely, 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. And also then looking at ability to maintain zero for, say, a six-month duration. We're seeing differences emerge there that efsofitamide does a better job. So 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. So stay tuned.

Rakar Agarwal, Analyst — Cantor Fitzgerald

And can you talk about the timing of the SSC-ILD readout now and the read-throughs to that indication from these data sets?

Sanjay Shukla, CEO

No timing just yet. I think we'll come back to that But probably later this year, as I've said previously, once we have 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. So stay tuned once we look to finish enrollment in that trial. The SSC data will be approximately six or seven months after that.

Operator

Thank you. Our next question comes from the line of Roger Song with Jeffries.

Roger Song, Analyst — Jefferies

Thanks for sharing the data and taking your question. The first one I have is the variability and the kinetics. Since you've already taken to a lot of additional detail on the time course, just curious, one is how the deviation look like? Is that higher than your modeling? The other thing is that any time point, you see the statistical difference between the episode and placebo during the course of the one year, and I have a call-up.

Sanjay Shukla, CEO

Right. So your first point, I think, is more about, you said about the drug kinetics?

Roger Song, Analyst — Jefferies

Yes, drug kinetics and then stand deviations, yes.

Sanjay Shukla, CEO

Right, right. So the PK, we are doing some sparse sampling, and we are going to be looking more closely at that. So absolutely, looking at the exposure of the patients, that is something that we're going to look 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's 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. And 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. Epsilfitamide immediately started to make patients feel good. And 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 epsilfitamide significantly better, regardless of which time point you look at. So that's 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. And Dr. Boffman, you've seen some of that as well. I think you would concur with me with

Robert Baughman, Analyst — KOL, University of Cincinnati

Yeah, 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. And 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.

Roger Song, Analyst — Jefferies

Got it. And then in terms of the case QL, the endpoint, it is a pre-specified, do you have any alignment on the powering and then the way you design the trial, and the last question also related to regulatory, any potential subpopulation you will dip deep into to show the statistical significance even in the primary endpoint? Thank you.

Sanjay Shukla, CEO

Yeah, so the KSQ is pre-specified and all of the analyses that I presented today were pre-specified and well-powered. So 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. And as I said, preliminarily validated at this point, we're working on validating in parallel from this trial. So very much in line with the numbers that we want to hit as we validate the KSQ. And then from a powering point of view, very robust signals in both of those two endpoints. Your second question, Roger,

Roger Song, Analyst — Jefferies

can you just repeat that again yeah sure so any subpopulation population yeah yeah need a primary

Sanjay Shukla, CEO

endpoint yeah yeah so i think what we're we're going to be you know looking really closely at we've looked at things like uh duration of disease say more than two years less than two years uh we've looked at um uh we'll be looking uh we'll be looking at some populations of different PFT phenotypes. We've started by looking at mixed and restrictive patients compared to not mixed and restrictive. So those subpopulation, 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. So 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. You know, this sets us up to also have a real discussion around can esopharmide also potentially replace methotrexate because methotrexate does not seem to be, at least looking at this data, to be a drug that has, you know, a lot of primary efficacy, which I think I suspected, but these are the elements that we'd look to unpack as a drug. Epsafidmine is certainly safer than methotrexate, which comes with its own liver side effects. So these are the things that we're going to be looking really closely at, Roger, in the post-hoc data cuts.

Operator

Thank you. Our next question comes from the line of Brian Abrams with RBC Capital Markets. Your line is now open.

Brian Abrahams, Analyst — RBC Capital Markets

Hey, guys. Thanks for taking my question. And sorry the results didn't work out as you'd hope, but I appreciate you hosting this call and providing this really helpful context. Just kind of curious as we think about, you know, framing next steps, can you characterize your willingness to run another study in this indication? And 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 the subsequent study? And then how to follow up.

Sanjay Shukla, CEO

Thanks, Brian. And yeah, so just to be clear, you know, we're looking to engage the FDA about, you know, the potential for F-sulfitamide immediately being available for patients. So 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 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, but I do like the way the protocols run. I think what we 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? I think 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, you know, the more than 12% difference. You could model off that. I mean, this is probably the best natural history data ever in sarcoidosis. So now you can model off of this and model an end that, you know, you can hit that difference, provided it's a meaningful, important difference. But I also, I look at signals in KSQ that has to play a bigger role. I think we've already gone beyond steroid reduction. So now I think we're in a world where our drug and other drugs will, I think patients would demand steroid withdrawal. With regard to dosing, we don't, 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, you know, how the patients would feel and the centers. All really good points here if we are asked to do something, another trial. But 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.

Brian Abrahams, Analyst — RBC Capital Markets

Understood. No, that makes a lot of sense. And then 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 like quite early on. Thanks.

Sanjay Shukla, CEO

I think it's fair to say that if you remove steroids, you are going to feel better. But 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 efesafetamide. And that's apparent when you look at the KSQ differences and especially the responder analysis. So 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? And we've demonstrated that in this trial. So 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. but to really feel better, efsefitomib is the thing that is making the patient's quality of life better here with that difference that we observe.

Brian Abrahams, Analyst — RBC Capital Markets

Got it. Thanks so much.

Operator

Thank you. Our next question comes from the line of Yale Gin with Laidlaw & Company. Your line is now open.

Yale Gin, Analyst — Laidlaw & Company

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 retrospectively, as you go back to look at the Phase 2 readout, do you have any comments and thoughts on that? Then I have a follow-up.

Sanjay Shukla, CEO

Thanks, Yael. Yes, I mean, Phase 2 obviously had a different design, taking folks down to 5, and obviously we didn't have the rigor of the every two weeks with the PGA. But 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 Five certainly is always outperforming a placebo in all the assessments we're looking So a lot of, you know, 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 270, nearly 270 patients. So consistency in a much larger population that is now really well powered. I think this is why we like, we like some of the results in this trial.

Yale Gin, Analyst — Laidlaw & Company

Okay, great. That's very helpful. And 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?

Sanjay Shukla, CEO

Well, I think you have to look at, we have patient diary data for every single day. So the average dose is also best as the way the FDA wanted us to look at it. So point estimates, point-to-point variability, you know, I think that could be worrisome if we just take a point estimate. But I think the main point here is when you look at month-to-month assessments, as Dr. Boffman 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.

Yale Gin, Analyst — Laidlaw & Company

Okay, great. Thanks a lot and best luck for the meetings with FDA. Thank you.

Operator

Thank you. Our next question comes from the line of Sumit Roy, with Jones Trading. Your line is now open. Hi, everyone, and thank you for presenting

Sumit Roy, Analyst — Jones Trading

clear data. When you look at the curve between the placebo arm and the 5 milligram, 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 gas threat pretty much overlapping the whole time?

Sanjay Shukla, CEO

I'll be looking at the different cutoffs. We've looked at the whole trial. We've also looked at 12 to 48. So 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. And 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. And the other component is, did it take placebo patients longer to get to zero? So this is some of that time to event, the number of steroid-free days. Those are things that I will be looking at and hope to get that to you in the future.

Sumit Roy, Analyst — Jones Trading

Thank you. And one last question. In trying to reconcile the quality of life endpoint versus the primary endpoint, do you think the drug is clearly disease-modifying, and if there is any objective biomarker or something that you can use to show that this drug is effective in certain subpopulation as you dig through the data?

Sanjay Shukla, CEO

Well, 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. So I think it's yet to be determined. But certainly, yes, I mean, we are in many ways modifying disease by substantially reducing steroids, still maintaining inflammatory control, not worsening lung function. And I think patients would certainly say that it's modifying their life. And I think that's a significant concern and consideration for these patients. They've been on toxic prednisone for decades, and I think this is the first drug that I think really gives hope. It is going to change, I think, you know, treatment practices, and experts are going to look at this data and have to think differently. But I also think that tepsifinamide has demonstrated some things quite unique.

Sumit Roy, Analyst — Jones Trading

Great. Thank you again for taking the question.

Operator

Thank you. Our last question comes from the line of Dev Prasad with Lucid Capital Markets.

Dev Prasad, Analyst — Lucid Capital Markets

line is now open. Hi, thank you for taking our 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 SVC in pulmonary sarcoidosis patients in terms of capturing meaningful clinical benefit? And for Sanjay, KSQ demonstrated clear benefit in the trial, but how do you think the FDA will balance those quality of life gains against the FVC benefits.

Sanjay Shukla, CEO

Dr. Babin, why don't you go first and then I'll finish.

Robert Baughman, Analyst — KOL, University of Cincinnati

Yeah, all right. So, yes, I'm a pulmonologist, so we like numbers and we look at FVC. But if you ask the patient, and we did a few years ago, we published a study of 1,800 Sarkway patients. The number one priority to them as far as treatment was quality of life. Number two was functionality. Number eight on the list was the lowest one was pulmonary function tests. They really are less enthusiastic. And 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 inflexiomab, despite the fact that over the next 15 years, we've shown that that drug is an important part of therapy. So I think the FBC has been overblown up. The FDA has, I think, recognized that that's probably not the primary endpoint and the recommendations we're making now, is you should be looking at quality of life and steroid

Sanjay Shukla, CEO

Yes, Dr. Boffman, you exactly said what I would say. FEC, from a regulatory perspective, is falling much lower in its priority. We got wind of that years ago when we started after our Phase II 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 feel endpoint. They look for things in field function and survives. Right now, I think the drug of the disease is searching for even better functional measures. But in my view, the feel endpoint here that the FDA is focusing on and has guided us to focus on is kink sarcoidosis questionnaire. So I do think that this portends well for us that that's where we saw a signal.

Brian Abrahams, Analyst — RBC Capital Markets

Thank you.

Operator

Thank you. I would now like to turn the call back over to Sanjay Shukwa for closing remarks.

Sanjay Shukla, CEO

I just want to thank everyone's interest. Just 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. Epsofenamod 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. But 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, we really moved the fields forward. So I'll end there, and thanks, everybody, for dialing in.

Operator

This concludes today's conference call. Thank you for your participation. You may now disconnect.