Disc Medicine, Inc. (IRON) Earnings Call Transcript & Summary

Good day, and thank you for standing by. Welcome to the Disc Medicine Corporate Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, John Quisel, Chief Executive Officer. Please go ahead.

Great. Good morning, everyone. Thank you for joining. We're here today to discuss the regulatory update for bitopertin. But before we get started, I'll mention that we will be making forward-looking statements, and they should be taken in context with respect to materials that we filed with the SEC and is posted on our website. So I'll start by saying, I wish we were here today discussing better news. As you all saw last Friday, we received a complete response letter from the FDA noting that while in their view, there's sufficient evidence that bitopertin significantly lowers protoporphyrin IX or PPIX there was uncertainty in the regulators' minds about whether the reductions in PPIX were reasonably likely to predict clinical benefit. And as we'll talk about in a minute, that's the standard for an accelerated approval, to meet those 2 prongs. So Disc has been committed to bringing bitopertin to patients as quickly as possible. because we believe in the potential of this program and the importance of a potential disease-modifying therapy for the EPP community. We are deeply disappointed that this is happening today. But our commitment to bringing this program forward and pursuing an approval has not wavered. We believe the issue raised in this complete response letter or CRL is readily addressable with the results of the ongoing Phase III APOLLO study. And as you'll hear more today, we're delighted with the progress and rigor of that study. We expect data from APOLLO in Q4 this year. So we look forward to working closely with the FDA to support their review, and we're pursuing all avenues to support approval. So on this slide, we've summarized the details of the CRL. The full letter has also been published by the FDA on their website and by Disc in a Form 8-K. And it's remarkable actually to see this level of transparency. I think it's a new standard in the availability of these complete response letters to the public, and we're actually proud to be part of that. So I'm not going to rehash all the details here since it's all available to be read, a pretty brief letter. It's clear, and we believe readily addressable by completing and submitting the results of the Phase III APOLLO trial, which, as I mentioned, is well underway and progressing very nicely. This next slide is data from our Phase II AURORA study. This was central to the regulatory review -- this data has been presented extensively at scientific conferences and is now published in the Journal of the American Academy of Dermatology. This slide provides a brief summary, I'm not going to go through it all again in detail, except for a few highlights. I do want to note that we hit our primary endpoint of protoporphyrin IX reduction with high degree of statistical significance. And as shown on this slide, there was evidence of improvement in several endpoints that were designed to measure clinical benefit. There's a light blue line that shows an increase in placebo-corrected time and light. And below that on the same time line as shown with red hashes the phototoxic events. And I think that phototoxic events bar is probably the most remarkable data showing the reduction of phototoxic reactions in the 60-milligram dose group, the complete elimination of those attacks during the second half of the study. And there's a clear temporal relationship between the reductions of PPIX and the improvements in these clinical endpoints. I guess this was our view of the data. However, this study was powered to look at the protoporphyrin IX reduction, and these other endpoints, the so-called clinically meaningful endpoints. Some of them were statistically significant and some of them were not. And this is what probably created the room for debate and whether we'd satisfy the standard for accelerated approval. So let's talk about that standard for a moment. There are the 2 prongs. You have a surrogate endpoint in our case in protoporphyrin IX, which has been noted as being mechanistically compelling and the obligation is to achieve a clear statistical reduction in that biomarker, which we did, and that was acknowledged. The second prong of the analysis is whether that reduction in the biomarker is thought to be reasonably likely to predict clinical benefit. Now this is a very broad standard subject to a lot of different interpretations. And I guess, I think it's also remarkable to note as I've gone through the data, the stories in the media from patients about real changes in their lives, people going on beach vacations with family, spending time on boats for the first time in their lives, really very moving stories of recovery from a devastating disease. We know now from the complete response letter that the FDA did not ultimately feel that these lines of evidence met the current standard of reasonably likely to predict clinical benefit for the purposes of the second prong in achieving accelerated approval. I guess the policy debate about accelerated approval has been going on for years both in prior administrations and the current administration. And I think it is fair to say that recent decisions have indicated an increasingly stringent approach to this question of when an accelerated approval is appropriate. We, as a single biotech company, we can't set or meaningfully influence this policy. It's our job to do our best to bring promising therapies to patients as quickly and safely as possible. And we will continue that mission now by focusing on the Phase III APOLLO trial, which we hope will deliver inarguable evidence of the safety and efficacy of bitopertin for the EPP patients. And if we're successful in this, we'll be seeking approval through the traditional route rather than this accelerated route. So looking forward then, this slide shows the APOLLO trial overview. I think that is the next big question and what to expect from this important trial. We are happy to say that enrollment enthusiasm has been high, very high, in fact, and the trial will be fully enrolled in March, which is several months sooner than we'd expected. This means that we will be able to have or we expect to have top line data in Q4 this year. As a reminder, this trial is a randomized double-blind trial designed to measure both PPIX reduction and improvement in Sunlight tolerance as co-primary efficacy end points. And we reviewed and aligned with FDA on this trial design at our -- both our end of Phase II meeting and Type C meetings that were held in 2024. We're confident in this trial design for several reasons. The primary endpoints are robust and clinically meaningful. We have demonstrated statistical significance on protoporphyrin IX reduction in 2 studies now, both BEACON and AURORA in Phase II. And our light tolerance co-primary end points was designed by taking into account all of the learnings from our Phase II program as well as did a protoporphyrin IX mechanism of action and the behavioral dynamics that were noted in the AURORA study. We also have a very strong study design, which includes rigorous assessments of baseline like tolerance during screening, which we learned were -- was an important feature. And we've also introduced now stratification by geography. And these are both set up to minimize confounding factors in our analysis. The APOLLO study is also well powered, and we're happy to share that we have completed a blinded sample size recalculation of time and sunlight data that showed no increase -- no need to increase sample size. So that's a lot of jargon that means essentially the variability in our endpoints that we used to design and power the study appears to be sustained so far in the first 50 completers for the study so far. So actually, really good news there in terms of the way this study has come together in terms of rigor and our ability to capture reliable data sets. So we're very excited about the study. We have a lot of confidence in the design and chosen endpoint, and we'll look forward to sharing the data from it in Q4 this year. So on this next slide, to spend a little more time on the APOLLO endpoints. We have 2 co-primary efficacy endpoints. The first looks at the amount of time that patients can spend in light on a longitudinal basis, letting us evaluate improvements over time on therapy. The graph shows how bitopertin performed on this endpoint in the AURORA trial. And you can see that there is, and this is important to note, this is a post-hoc analysis. But had we designed the study this way, there would have been a significant difference between -- versus placebo, when you look at the time points after we know that PPIX has reached its new low point. And after the placebo effect, which is marked in the first couple of months of the study has waned. This endpoint showed statistical significance in the AURORA trial, despite only having 25 patients per arm, and it accounts for the amount of time it takes for the PPIX lowering effects of bitopertin burden to occur. So this endpoint has a greater than 80% power over a wide range of data scenarios in our 150-patient 2-arm study, APOLLO. So a very well-powered trial using these endpoints. Our other co-primary endpoint is reduction in protoporphyrin IX, which we have shown with a high degree of statistical significance in both the BEACON and AURORA trials 40% if you look at it versus baseline, actually closer to 50% if you look at it with respect to the placebo group. So really important reduction here in the disease-causative metabolite PPIX and a high degree of confidence that we will hit that part of the co-primary endpoint as well. So all in all, we feel we have two very strong endpoints here that we expect to successfully demonstrate the clinical benefit of bitopertin and its potential to be a transformational drug for EPP patients. So what does this mean for timing and next steps. We plan to request a Type A meeting to review our approach for resubmission and response to CRL, APOLLO is designed to demonstrate the clinical benefit of bitopertin in EPP patients. As mentioned, we are on track to complete enrollment of APOLLO in March and present top line data in Q4 this year. We'll then plan to prepare the package and resubmit. Typically, for a CRL response, the FDA has a goal date of 6 months for the review, which would put us roughly in the middle of 2027 in terms of when we could expect a decision on a traditional approval basis. So to reiterate, we are confident in this program. We believe that it can set a new standard of care for EPP. This is a debilitating disease that touches patients' lives every day. And so we've made every effort and pursued multiple avenues to expedite the process of making bitopertin available to the EPP community. This decision from the FDA is an unfortunate setback, but we remain committed to advancing the program and working with the FDA to support their review. We've heard stories through patient advocates, the investigators and in the media about how certain patients' lives have been transformed by bitopertin. We want to make it clear that helping those patients is our mission. And those who are currently on bitopertin through a clinical trial will continue to receive access to treatment while we respond to the CRL. And we want to thank really with deep gratitude all the people who've made this work possible, most notably the patients, the clinical trial participants who put their time and their health into this research effort. Their families who have to facilitate this, the broader advocacy community and the clinical investigators, all of whom have given so much of their time and energy to support this program over the past several years and continue to do so. In fact, without their support, we wouldn't be making this great progress on the APOLLO trial. Okay. So backing up to the overall corporate outlook, I feel that as a company, we are in great shape here to deliver across a wide range of programs. This is the so-called catalyst slide that we've shared before. with a few changes now responsive to this update. As I've noted previously, we are expecting top line data now from APOLLO in Q4 of this year, after which we plan to submit a response to the CRL by the end of the year. And with a 6-month review period, we would then expect an updated FDA decision in mid-2027. We are also very excited about the other catalysts we have coming this year for our other programs. For DISC-0974, we expect to have additional data from our Phase II myelofibrosis study in the second half of this year, followed by our objective is to have an end of Phase II meeting where we expect to align on digital trial endpoints with the agencies. And then we're super excited about the third program, DISC-3405. We expect to be able to share initial data from our Phase II study in polycythemia vera and we've talked about how the excitement for this mechanism has led to a very rapid trial enrollment there. And we've opened up our Phase Ib study in sickle cell disease patients, and we hope to have some data from that trial by the second half of the year as well. And all of this comes with being in a great financial condition. We have been and we will continue to be highly capital efficient. We do ensure that we're investing in activities that will we think create a great potential for creating value. And delighted to say that we'll be able to maintain our runway guidance of having cash into 2029. So really well funded to pursue all of the R&D programs that we have here. So that's everything I wanted to run through today. Thank you all for joining the call. We wish we had a better update today. But as I said, we are committed to getting bitopertin to patients and we are confident that we have a strong path forward to do so. With that, I will turn it back to the moderator to open up the Q&A. Thank you.

Our first question comes from the line of Roger Song with Jefferies.

Great. And thanks for providing confidence despite the surprising CRL. So maybe 2 questions from us. The first one is, can you just confirm this pain-free sunlight exposure in the PPIX co-primary endpoint will be likely to support the approval any indication during the review process, FDA has any different view? And then specifically, given this is a core primary endpoint, is that p-value 0.05 hitting both of them will be supporting the approval.

Yes. This trial design and the endpoints that were used here has been discussed with the FDA and are aligned with them. And I think, in fact, what we see in the CRL with specific references to the APOLLO trial would suggest that we have continued alignment there. So we're not aware of any change in FDA position on that. And yes, the 2 co-primaries, the protoporphyrin IX and the time in sunlight during month 6. These are independent. And so both need to hit p-value 0.05.

Got it. Just one quick one, if I may, is the -- in the CRL, they talk about the association between the PPIX and the clinical benefit. Is FDA looking for strategical significance, association between the 2 endpoints or they just looking at the clinical endpoint or some of the clinical endpoints are reaching the specific, so they think you lack of the association.

Yes. So the language that's there in the CRL is also all we know about the basis for this nonapproval event. So we're speculating in the same way you are. But it does appear that they were in the end if not in the beginning, looking for some kind of statistically significant, I guess, relationship between protoporphyrin IX and one of the various clinical endpoints. I'm not sure which one, to be honest. So it's something we'll try to understand better as we continue our interactions. Although to be honest, it's not -- I mean that's a feature of the accelerated approval path, which at this point is probably irrelevant now, we'll just be looking to get stats on our 2 coprimaries in the APOLLO trial. So it's more of a backward-looking exercise to understand what happened here. But right now, really, the CRL is the only information we have.

Got it. Exactly.

Our next question comes from the line of Tom Smith with Leerink Partners.

This is Pujan Patel on for Tom Smith. Could you please provide additional color on the powering assumptions for the APOLLO trial, specifically for the assumed treatment effect and the placebo response for the primary endpoint, the time and daylight endpoint?

Yes. Let me hand it over to Will to speak to that.

Sure. So we -- as John mentioned, we have in a variety of both variability and effect size scenarios have over 80% power that gives us a lot of confidence in the success of APOLLO. We haven't discussed the exact numbers that went into specific power calculations.

Got you. That's helpful. And then a follow-up on that. Do you plan to propose any changes to APOLLO during the upcoming Type A meeting as it currently stands?

Well, we're still trying to figure out. I mean, this news is really only effectively a business stable for us. So we're trying to figure out exactly how we want to approach that meeting. We don't have our final plan in mind. Modifying the APOLLO trial is not on the menu at least as we're thinking about it right now. But I don't want to -- yes, I mean, actually, it's just simply not on the menu right now. We feel like it's a robust trial. It's done very well. So I can't see why that would be part of the discussion. But to say generally, we haven't actually sorted out our final approach on that meeting.

Our next question comes from the line of Sean Laaman with Morgan Stanley.

Maybe just to double-click on the last question, John. What specifically will you seek to lock down in the upcoming Type A meeting regarding APOLLO's endpoint hierarchy analysis populations and success criteria, especially since you said the diary data can be analyzed in any way the FDA wants.

Yes. So I do think that's probably the primary purpose of the meeting is to just make sure that there's not some kind of misalignment around the data package that we'll plan to bring upon successful completion of the APOLLO trial. And to your point, I mean, I guess, on the off-chance there is some additional or different data analysis that the FDA has in mind. We believe we're really capturing through our diaries, et cetera, essentially all the information you would want to look at for this patient population. And if there's a different approach that's desired, then we should be well positioned to address that as well with what we think is a pretty the evidence so far suggests rigorously done and well captured data set. Again, I think that, that's an outside probability. We haven't had any sense of a difference opening up around the APOLLO trial design. But yes, that is probably the primary thing we think about.

Maybe just one other quick one, I hope. So the FDA called the 40% PPIX reduction at 60 mg is relatively modest and question whether that magnitude is predictive, what magnitude or threshold or distributional shift, you believe is clinically meaningful and how you demonstrate that prospectively, APOLLO and/or by bridging analyses from AURORA/BEACON?

Yes, there was a surprising comment. I think there's a lot of good evidence for why our reduction is quite meaningful. But Will, why don't you speak to that?

Sure. I think we look to the data to determine what is a reduction that is meaningful. And we've provided before evidence in the literature of women with EPP who would come pregnant and go into remission with about a 40% relative reduction of PPIX, experiment in Denmark with kind of mechanical extracorporeal reduction of PPIX of 30%, leading to very large increases in time and light. We have our animal model data, and we've shared the results of what happened in BEACON and AURORA showing light tolerance improvement. So I think our position as the data are telling us that bitopertin is achieving a level of reduction that has clinical benefits.

Our next question comes from the line of Kristen Kluska with Cantor Fitzgerald.

Sorry about the news, but I appreciate the positive attitude you have here today. I wanted to ask just on your confidence for the co-primary endpoint on time and light without pain, whether or not the FDA will maintain looking just at that final month. And then I think with the AURORA trial, people were probably really excited by the data in Beacon. And out of the gate, we're trying to test whether or not the drug works. So that we know the onset does take a couple of weeks here for the drug arm. Are physicians and KOLs kind of working with patients more to mitigate that high risk initially just given that -- it does take some time for the PPIX levels to go down?

Yes. So on the first point, and maybe I just need to be a little clearer because I hear everyone asking like, oh was there, is there an issue? Is the FDA going to change their view on the APOLLO trial? I mean I feel like I can lean in pretty hard on that and say there's just absolutely no evidence of that right now. But of course, we will have the Type A meeting and report back if there is something that's opened up there. But truly, I don't see any evidence of that. And I don't even really in the CRL see evidence of that. In fact, to the opposite, I feel like the CRL is essentially pointing to the APOLLO trial as designed as being the path to getting the data set that they would view as appropriate for supporting approval. So just kind of on that general lean, really, we feel good about the way the APOLLO trial is designed and the true to which it's embedded with the FDA. Your second question, a very interesting question, right? We know it takes a couple of weeks for protoporphyrin IX levels to reach meaningful reductions. And so, Will, maybe you can speak to this question of how investigators managing that, et cetera.

Sure. So one of the approaches to success in APOLLO that we took was doing things in a similar way to AURORA as much as possible. Of course, our analysis approach is different, given the placebo effect and looking at a time after that initial month or so of placebo effect time. But other than that, we have the same diaries and the same instructions. And so we think that's the best path to success is getting the same type of data that we did in AURORA and analyzing it in the way that we feel at month 6 is going to give the best chance to hit that.

Our next question comes from the line of Tara Bancroft with TD Securities.

This is Frances on for Tara. Can you just tell us a little bit more about the nature of the alignment you reached before the CRL. What -- given the recent events, what's your level of confidence in the current along with the FDA on the co-primary endpoint, specifically looking at those last 4 weeks. Kind of how important is total pain-free time in light given this was the approval precedent for SAS?

Yes. Like I said, in response to the prior question, we feel that it's fully aligned, both in the -- I guess, kind of 3 meetings on the topic, the end of Phase II in the fall of 2024, and then we had a Type C meeting that was dedicated solely to the topic of the APOLLO trial design and reached alignment there. In fact, that was kind of where the final alignment was reached. And then there was opportunity in the pre-NDA meeting over the summer, where there was no issue identified with that as well as throughout the NDA review, where I think the questions around the APOLLO trial have really just focused on this inquiry into whether it's well underway and how rapidly we expect to get the data on that -- from that trial. So really seeing no basis for a difference to have opened up there. But I guess I understand the sense of unpredictability here given the result that we have in the CRL. In terms of the SNES precedent, I mean, we haven't really talked about that since end of Phase II meeting. I think the FDA showed a lot of flexibility around endpoints here. We've seen that with other drug programs in this space. So I think it's to their credit they're clearly allowing sponsors to design endpoints that capture the appropriate biology for the drug in question. And that seems to have been applied to us as well.

Our next question comes from the line of Evan Seigerman with BMO Capital Markets.

I actually wanted to go back to some language you used back of November 2024 around the end of Phase II meeting. You noted that the FDA, you described the alignment for accelerated approval as potentially or is potential. Can you just expand kind of what led to the alignment between FDA and this medicine back in November of 2024. And might, what could have potentially have changed?

Yes, sure. So actually, it's pretty much the exact data set that I shared in the earlier slide in this presentation, that was available and presented to the FDA in the end of Phase II meeting, which if you'll recall, we went into that meeting offering of 2 alternatives. We provided a justification for why accelerated approval might be appropriate using protoporphyrin IX served end point. We also just offered up that we would pursue a traditional approval using the APOLLO trial as a Phase III trial. And the FDA at that time indicated interest in moving down the accelerated path, invited us to have a Type C meeting to discuss the APOLLO trial design as a confirmatory trial, which, of course, is an indicator of an accelerated path. After that, we had a meeting around the CMC package, and then a pre-NDA meeting where it was clearly asked and answered that we'll be filing an NDA -- I'm sorry, submitting an NDA on the premise of an accelerated approval. And then subsequent to that, we -- the NDA was accepted granted priority review again on an accelerated basis. So a rich record of the FDA aligning with us on this as the appropriate path for review. But I guess the important thing to say is that they -- none of that obviates the need for a review, right? And they have conducted that review and reached a different conclusion than expected, which certainly creates a lot of whiplash for everyone. I think that the general nature of NDA review is that you go from small sub team at the FDA focused on the package and forming an opinion about the appropriateness of the pathway that you're on and the likelihood of approval and then you get into a broader and broader set of people in the agency who engage and bring different perspectives and different standards. And I guess what we see here is a different standard that arose and ends up controlling the outcome. So I mean, I think that's how we see the arc of what went on here although, to be honest, we don't actually have a tremendous amount of information from the review process at this point.

And just as a follow-up there. In your kind of interaction with the regulators following the submission and the announcement of the commissioners prior to review voucher, could you give any indication that there was skepticism around the accelerated approval pathway, or did it seem that they were on board or just ask some questions. Just trying to get a sense as to where this changed?

Yes. So I don't think -- so there is an intense review process, a lot of information requests, essentially an entire NDA review packed into a relatively short period of time and actually a huge appreciation to the reviewers at the FDA for putting in that work and moving along quickly. There was no obvious skepticism of parent in the information request as we went along. And I think the first indication of potential challenges may have come, frankly, from some of the leads that we saw in the media, which was news to us. And I guess, in the end, spoke to the direction that things were going.

Our next question comes from the line of Danielle Brill with Trusit Securities.

This is Alex on for Danielle. You mentioned previously that you've been slowing down U.S. enrollment to satisfy FDA concern about patients potentially dropping out with the commercially available bitopertin. I guess now with the plan is changing, will you have the ability to enroll a sufficient number of U.S. patients to satisfy any potential regulatory concerns for full approval?

Yes. I mean we have -- we certainly have enough U.S. patients to satisfy any kind of regulatory requirement around that. I mean probably roughly 2/3 of the study is going to be U.S.-based. And we shifted enrollment over to Europe, which was kind of the plan. Anyway, those sites in Europe come online slower. So there was kind of a natural progression to the study towards greater European enrollment. And what we've seen is just this kind of overwhelming enthusiasm and eagerness from the various European sites to get patients on to study, and so there's not going to be any need to come back and reopen U.S. sites or whatnot, we're going to frankly struggling to manage the enrollment demand as it is just based on the European sites that are still enrolling.

Our next question comes from the line of Douglas Tsao with H.C. Wainwright.

John, I guess I'm just curious, during the review process, which was obviously very compressed, could you get a sense in terms of the issue of correlation between PPIX reduction and some tolerance that they were focused on the analysis of AURORA that you presented showing that sort of temporal relationship? Or were they just sort of looking at the data sort of at the study sort of as it was initially presented, which obviously sort of mask the underlying effect and sort of was ultimately a very complex data set.

I guess the general sense is that they were looking at everything and proving all aspects of the data and I guess behind the scenes forming their own opinion.

And John, just as a follow-up also, in terms of the commercial organization, obviously, as a company, you've been going at we see sort of preparing for a launch. Obviously, that's now going to likely be delayed some amount of time. Can you just talk about sort of what is going to happen with some of the infrastructure? And just does that -- or was the sort of spend sort of not material and not necessarily something that you're going to keep the sales team sort of in place for the MSLs because obviously there are other things for them to do.

Yes. No, it's a great question, very much where I think our heads are internally at the company is figuring out how to ensure that we continue to be capital efficient, that we do the things that we should do to ensure that when we do launch this drug is successful, but only do things that are clearly going to be value-creating in the long run. So that's the process we're working through, essentially reestablishing the business plan around the commercial push and I think there'll be some greater clarity on that soon.

Our next question comes from the line of Stephen Willey with Stifel.

Maybe just to build on the prior question. I guess, is there anything that you can say regarding just the prelaunch activities you're going to be prioritizing ahead of a potential approval in mid-'27, and how you might be looking to leverage this additional time to potentially improve the trajectory of initial uptake? And then I just have a follow-up.

Yes, it's a great question. And I think to give a little taste right, I think we have had some teams out in the field essentially using the claims database information as a call point list, right, to kind of go through each physician account that's listed in those claims data and check in to see and confirm whether there are patients actually being seen by that physician. And I think that kind of activity is unbelievably valuable for this kind of rare disease launch. I mean I think that our ability to get the word out to patients or, I guess, really to physicians who can then get the word out to patients. That's the way that we make this drug work, right, that we make -- give patients the opportunity to get it, they won't find out unless we're able to work through the physician community to get the word to them. So really continuing the work of validating those accounts which has progressed well, but it's still in the early days relative to the 14,000 patients that are in that claims database. If we can use this time to kind of solidify that and then launch with just a crystal clear account -- validated account list for our sales team, that would be, I think, incredibly value creating. So I think that's one activity that we would assume that we'll plan to execute on. And then other kind of related activities, that's something we'll have to think through and again, balance while I'm delighted that we are well funded. We also want to make sure that we're using those funds in a way that's just clearly value created. So figuring out the other activities we want to engage in how to staff those. That remains an internal question that we're working on.

Okay. That's helpful. And then is there anything more you can say just about the inputs that were used to conduct the sample size for calculation within the first 50 completers. Was this a blinded assessment of either co-primary? Was it just an initial look at endpoint, variability, patient dropouts, et cetera. I think just any color you can provide would be helpful.

Yes. Let me just first emphasize, it's absolutely blinded. We have no information about efficacy from that analysis. But to give you a little bit more color, I'll hand it over to Will.

Sure. So the analysis was prespecified to look at the time and sunlight diary data and looking at the variability. That variability is -- there was an assumption that goes into the power calculation if the design of the trial. And then this analysis tests that assumption of that variability in that time in sunlight diary data. And it said that we're -- the study is on track with the initial assumption of variability. So we did not have to increase the sample size from a statistical perspective. So the protoporphyrin IX is not part of -- not part of that assessment. We have high confidence in the ability to demonstrate a stat reduction there.

Our next question comes from the line of Derek Archila with Wells Fargo.

I just wanted to know how quickly you'll be able to request that Type A meeting, and I guess whether you'll wait for minutes before communicating the outcome?

Yes. So I think we'll move reasonably quickly, although actually we just -- we're -- as I mentioned before, we really just putting together our plan right now. And yes, we have typically wanted to get the minutes from meetings before we share anything with the public. So I assume we'll follow the same process. So of course, it can depend on what the outcome of the meeting is. But in this case, I would assume it's something we'd wait for the minutes on, which, as you probably know, typically is about a 30-day delay.

Our next question comes from the line of Rami Katkhuda with LifeSci Capital.

Okay. Just a couple of quick ones for me. I guess, first, has the FDA ever pointed to a minimum threshold of improvement in light tolerance that must be met for approval? And then secondly, can you also provide an update on the status of other NDA modules, including CMC and whether the FDA has commented on those aspects of the application?

Yes. Yes, good question. So no, no threshold for light tolerance was ever identified. And in terms of the other modules, yes, I mean, actually, we're really pleased with the way the CRL looks in that regard. It's intended to be a listing of items that are causing the FDA to be unable to approve the drug. And therefore, items that we should be addressing as a company. And there's no CMC or other issues raised on that CRL. So we interpret that as meaning that the interactions that we had around during the NDA review on those topics were satisfactory and that they're closed off. I guess just one thing I will say about CMC, while we had reached a line with the FDA on drug supply that would go along with the February launch time line, there are still some trailing PPQ activities with the commercial supply that will continue over the next few months. All indications is that those are going well and we'll be concluded successfully. But now that will become additional material that will probably, at some point, amended into the NDA filing. So I guess to summarize, everything appears to be aligned. All processes agreed upon with the FDA, all CMC aspects of review complete, except that there are some final activities that we have to close out. And those, of course, will get reviewed in the final version.

And I'm currently showing no further questions at this time. I would now like to turn the call back over to John Quisel for closing remarks.

Okay. Thank you, everyone. We appreciate your time today. Again, sorry, we couldn't achieve a better result. We're going to keep working on this. And hopefully, we have great data as we come in towards the end of the year. Thanks a lot, everyone.

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