Ladies and gentlemen, thank you for standing by. Welcome to Disc Medicine's Phase II meeting for bitopertin and EPP. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to John Quisel, Chief Executive Officer. Sir, please go ahead.
Good morning and welcome to the Disc Medicine management call. Today, we will review the results of our End-of-Phase II meeting with the FDA with respect to bitopertin for the treatment of patients with EPP. As a reminder, this is John Quisel speaking, CEO here at Disc, and I'll be joined by Will Savage, our Chief Medical Officer, and Steve Caffé, our new Chief Regulatory Officer. Before we get started, I'll cover a few preliminaries. We will be making forward-looking statements, and these should be taken in context with respect to materials that we have filed with the SEC and have posted on our website. Additionally, bitopertin is an investigational agent and is not approved as a therapy in any jurisdiction worldwide. Turning to our agenda, I'll start off by saying that we are delighted with the outcome of the End-of-Phase II meeting.
It was a very positive interaction, and we are appreciative of the support that the FDA has shown towards the EPP patient community, as well as the recognized need for new therapies for these patients. We will walk through the set of data that we brought into this meeting, the results of the meeting, and our plans for further development. On this slide, we summarize the key points for today. First, we reached alignment with the FDA on all of our proposed study parameters, meaning that everything we went in with, we got, and we found a very collaborative and thoughtful agency. The FDA acknowledged that EPP is a serious and potentially life-threatening disease with significant unmet medical needs. The FDA agreed that the average monthly time in sunlight without pain at the end of a six-month treatment can be used as a primary endpoint.
As you may recall, this is one of the endpoints that we have a lot of confidence in. Even further, the FDA noted that the reduction in PPIX observed in our Aurora trial may be sufficient as a surrogate endpoint that is supportive of an accelerated approval pathway. This is an excellent result, and we will certainly delve more into that process today. Finally, today, for the first time, we'll introduce the Apollo trial. This will be our next clinical trial, which may be conducted as a post-marketing confirmatory trial, depending on our next interactions with the agency. The attributes of the Apollo trial are very much what we hope for. We can use the high dose, 60 milligrams, for a six-month duration, and we plan to be enrolling both EPP and XLP patients with ages 12 or greater.
From this design, you can see the level of alignment we have with the FDA in advancing this program. All of this is very exciting news. So let me now review the development program that has gotten us to this point. We've conducted three studies in EPP patients: the Beacon open-label study that was conducted in Australia in 26 patients, including 22 adults and four adolescents, all for a 24-week duration. Then we have the Aurora trial, which is our double-blind randomized placebo-controlled trial with a duration of 17 weeks that was conducted in the United States. In that trial, there were three groups of 25 patients: placebo, low dose, and high dose, 60 milligrams. And then lastly, we have the Helios trial. We haven't discussed Helios much yet, but this is our long-term extension study in patients from both the Beacon and Aurora trials.
All of these patients had the opportunity to roll into this long-term extension, so it's being conducted in the U.S. and Australia. We're really pleased with this study. It's going to give us a good look at the long-term safety of bitopertin, as well as long-term suppression of PPIX. What we've noticed is that greater than 80% of the patients from the Aurora and Beacon trials chose to roll over into the study, which is a nice result and provides some testament to the benefit that patients may be experiencing on bitopertin therapy. Next, I'll review the data package that we were able to bring into the End- of-P hase II meeting. This slide provides a refresher on the key data sets from the Aurora trial at the 60 milligram dose.
Shown in a condensed form here on the graph, we saw significant reductions in protoporphyrin IX levels, about a 40% reduction from baseline, and even greater reduction relative to placebo. This is the dark blue line on the graph. We also saw improvements in pain-free time in light versus placebo, and that's shown in the light blue line as a placebo-corrected increase in that value, and as you get out towards the end of this four-month study, that time in light reaches two times, or a 2x increase over the baseline in the treatment group for the time these patients are spending in light without pain. If you look at phototoxic reactions, which is really a hallmark of this disease, that data is condensed into the two bars running at the bottom of this figure.
You can see that there was a 75% reduction in the rate of phototoxic reactions versus placebo. Notably, in the last 60 days of the study, there were literally zero phototoxic reactions among patients in the 60 milligram dose group. Lastly, we look at quality of life using a metric such as PGIC, and on this endpoint, we saw 86% of patients reporting that their EPP was much better. This was prospectively statistically significant versus the placebo group. Collectively, this is a very powerful set of results. One thing that was remarkable and also confirmatory here is that these improvements in clinical parameters showed an association with the degree of PPIX reduction in these patients. One form of that association that is apparent on the slide is the time dependence.
You can see in the dark blue line, as PPIX levels come down to a new minimum at about six to eight weeks, that is associated with improvement in time in light. That's when the light blue line starts to show an increase. And also, it's associated with the disappearance of phototoxic reactions in the last 60 days of the study. Seeing this nexus between the reduction of PPIX, which, as a reminder, is the toxic metabolite that drives this disease, along with various measures of clinical improvement, that was very important to us and became a key factor in our discussion with the FDA. That's a quick refresher on the data that we brought into this End- of- Phase II meeting, and I'm happy now to introduce Steve Caffé, our Chief Regulatory Officer, to provide some details and perspective on the meeting results.
Thank you, John. As John said, we are very pleased that the FDA agreed with all the study parameters we proposed going into the meeting. I will now walk through each item in a little more detail. Regarding the primary endpoint for the study, the FDA agreed that the average monthly total time in sunlight at the end of a six-month treatment period is clinically meaningful for EPP patients and can be the primary endpoint. We feel this is a very robust clinical endpoint, which captures the clinical benefit of lowering PPIX. We also reached alignment with the agency that all other endpoints captured in the Beacon and Aurora trials, such as change from baseline in whole blood metal-free PPIX, incidence rate ratio of phototoxic reactions, and measures of patient quality of life, can be used in this study as well.
Given the consistency of clinical benefits and the acceptable tolerability profile of the higher 60 milligram dose across the Beacon and Aurora trials, we proposed to move forward with only the 60 milligram dose in this study. We also proposed proceeding with a six-month study duration. There again, there was alignment with the agency on these parameters. Finally, based on the data from the Beacon trial across different age groups and genetic subtypes of EPP, the agency agreed that the trial could move forward and enroll adolescents and adults with EPP, including those with XLP. In all, a very constructive interaction with the FDA, with a clear positive outcome on parameters of trial design. We are appreciative of the agency's guidance and feedback. Next, I would like to touch on another important aspect of our discussion with the FDA with respect to the possibility of an accelerated approval pathway.
As a reminder, this is an agency program which allows for early approval of a drug based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Subsequent full approval is subject to further demonstration of clinical benefit in a confirmatory trial. The agency did acknowledge that PPIX reduction could serve as a surrogate endpoint, which would support accelerated approval of bitopertin. The accelerated NDA submission would include data from all three clinical studies to date and a large safety database of more than 4,000 participants. Additional discussion with the FDA is needed to finalize the design of the confirmatory trial, and we expect to have an update on this discussion in Q1 2025. We're obviously very pleased that the agency was open to having this conversation about the accelerated approval pathway.
I will now turn it over to Will to provide more detail on the data we have shown to date and the confidence that it provides in the selected study parameters.
Thanks, Steve. We want to go into more detail on the primary endpoint here, which looks at the amount of time patients can spend in light on a longitudinal basis. This gives us the ability to look at improvements over time. The graph shows how bitopertin performed on this endpoint in Aurora, and you can see that there is a significant difference versus placebo when you look at time points after we know PPIX has reached its nadir and after the placebo effect has waned. We previously reported the analysis looking at the last two-week interval of the study, and in the six-month Apollo study, we plan to look at the last four-week interval. You can see that this statistically significant finding persists regardless of the interval chosen.
We have a lot of confidence in the robustness of this endpoint, which is why it is the endpoint we chose to bring forward to the FDA. Keep in mind that this endpoint showed statistical significance in the Aurora trial despite only having 25 patients per arm. This endpoint accounts for the amount of time it takes for PPIX lowering effects of bitopertin to occur, and it allows for the initial placebo effect to wane before efficacy is assessed. This endpoint also has more than 80% power over a wide range of data scenarios in a 150-patient two-arm study. We are also implementing some protocol measures that we feel further shore up this endpoint, including a rigorous baselining, which will allow baseline light tolerance to be factored into the analysis of the primary endpoint, something that we saw that was beneficial in our Aurora analysis.
We will also be stratifying patients in the study by geography to balance light exposure across study arms. So overall, we feel that this is a very robust endpoint and have confidence in its ability to demonstrate the clinical benefit of bitopertin. Here we summarize our upcoming Apollo study. We are planning for a study of 150 patients in the U.S. and Europe that will last for six months studying the 60 milligram dose of bitopertin in adults and adolescents with EPP and XLP. Our primary endpoint was discussed in the prior slide and will be the average monthly time in sunlight after six months of treatment. All other efficacy measures we studied previously will be captured as additional endpoints. Back to you, John.
Thanks, Will. So overall, we are incredibly happy with the results of this discussion with the FDA. It really couldn't have gone better. We aligned on the trial design we wanted, and on top of this, the FDA has acknowledged the possibility for accelerated approval using protoporphyrin IX as a surrogate endpoint. We're excited at this point to move this program forward. So in terms of next steps, we're planning a discussion on the confirmatory trial design with the FDA, and we'll expect to provide guidance on the results of these discussions in the first quarter of 2025. And our aim is to initiate this trial by mid-2025. And just a note there that given that we have a good feel for the endpoints and trial parameters based on this interaction, we're already operationalizing this trial and feel good about getting it going as soon as possible.
We will also be having discussions with the EMA before the end of the year to confirm the regulatory path forward in those countries. And we are continuing to move ahead with commercialization and launch preparations under the guidance of Pamela Stephenson, our Chief Commercial Officer. So that's the story on bitopertin and our End- of -Phase II meeting and some of our plans for the future. There are also several catalysts still coming this year. So I'll note just about a week ago, we presented our positive phase I single ascending dose data for DISC-0974 in patients with anemia of chronic kidney disease at the ASN conference. So that was an exciting and recent update. And then looking forward just between now and the end of the year for bitopertin, we expect to be providing some additional analyses from the Beacon and Aurora trials for DISC-0974.
We expect to provide complete phase I-B data in the MF anemia study that we have running. And then lastly, for our third program, DISC-3405, we'll provide healthy volunteer data from our multiple ascending dose study. So altogether, really exciting progress today on the bitopertin program, and yet still a lot of exciting progress across our entire portfolio to come before the end of the year. So thank you for your attention today, and with that, I'll hand it back to the operator for questions.
Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. One moment while we compile the Q&A roster. And the first question comes from Thomas Smith with Leerink Partners. Your line is open.
Hey, guys. Good morning. Thanks for taking our questions, and congrats on the great regulatory updates here. We had a couple of questions. I guess first, can you provide a little more color on how the FDA is getting comfortable with the use of PPIX reductions as a surrogate endpoint to support accelerated approval? Is this more on the basis of the literature or the data you presented publicly from Aurora and Beacon, or maybe data from those studies that we haven't seen yet? And then secondly, can you elaborate on what remains to be hashed out with FDA during the Q1 meeting? And can you comment on your level of confidence that you'll be able to move forward with the accelerated approval pathway versus the traditional pathway that you've been guiding to historically?
Okay. Yeah, thanks for the question, Tom. So as to the rationale and acceptance of the FDA around protoporphyrin IX as a surrogate endpoint, it is a mix of both the data that we've provided as well as extensive literature information, right? I mean, I think it's a matter of scientific fact that this metabolite protoporphyrin IX actually drives all the adverse consequences of this disease. So it's not just a biomarker. It's, in fact, the causative agent. And that's fully established in the literature. And then there have been a number of other associative studies relating PPIX levels to both sunlight tolerance and actually recently even to liver health. So there is a lot of development in the medical literature around the role and criticality of protoporphyrin IX and the importance of reducing that. But our data set provided a lot of information as well.
So I think it's the combination of all of that that was important there. And then the second part of your question was regarding the process here. I'm going to hand that over to you, Will.
Sure. So we think that the Apollo trial, which was accepted by FDA as an appropriate phase III trial, can also equally serve as a confirmatory trial. I don't think that there's too much that needs to be hashed out. What the request for another meeting reflects, I think, is that there wasn't, we had an End- of- Phase II meeting, and there wasn't the sufficient time to discuss a confirmatory trial. So I think we powered and designed Apollo for success, and I think it remains so designed as such for both confirmatory or phase III. So the only other point I'll say on the PPIX data, part of your question was, was there other data you haven't seen? I mean, we've presented the data that's the core of the argument from Aurora and Beacon publicly.
Great. That's super helpful. Yeah, appreciate the color there. And then just one other question on the Apollo trial. You mentioned you're more than 80% powered with the planned 150 patients. Can you just elaborate on what you're assuming for treatment effect and placebo response in these patients? Thanks.
Sure. Of course, we use the Aurora trial as the best predictor of what we would see in a phase III trial. We're not giving specific numbers out there, but with any power calculation, you do run a range of scenarios both in terms of treatment effect and variability assumptions. As I mentioned in the presentation, we have 80% power in a wide range of even downside scenarios.
Got it. That makes sense. All right, guys. Thanks for taking the questions. Congrats again on the updates.
Thanks, Tom.
And the next question comes from Roger Song with Jefferies. Your line is open.
Thanks. Big congrats for the regulatory update, and then thank you for taking our question. So maybe the first one I do want to just confirm and clarify. In terms of the accelerated approval path, just can you confirm you don't need any additional clinical data from additional clinical trial, including safety, exposure, and then the efficacy? So for the one Q, this update is really hashing out some of the detail for the confirmatory study, not related to the package you need for the accelerated approval. Thank you first.
Yeah, thanks. Thanks, Roger. Yeah, that's correct. The data we have in hand is the data that we would submit as part of an NDA to achieve this type of accelerated approval. The update that we expect to provide in Q1 next year would be kind of final design of the Apollo trial as a confirmatory study. And we expect at that time to be able to lay out a lot more detail around our path down this accelerated approval process.
Great. Super clear. And then so given you're about to get to the approval soon, much sooner than initially expected, so can you just give us some of the comments around the market opportunity, particularly around this clinically meaningful sunlight exposure improvement compared to placebo, how you compare to other EPP, either approved or pipeline in development, how you think bitopertin can become the future standard of care for this population? Thank you.
Yeah, thanks. So bitopertin has a remarkable mechanism, as we've already touched on, addresses the root cause of the disease at a molecular level. So we're decreasing the level of protoporphyrin IX, and that is the chemical that drives both phototoxicity as well as the accumulating liver damage that these patients have. And so, but for more, I think, detail around the commercial opportunity, I'm going to hand it over to Pamela.
Sure. Hi, Roger. And thanks again for the question. So in terms of market opportunity, what we've seen is the first thing I would just say is that EPP, there is a diagnosis code for EPP, and we've been able to utilize claims data to look at the number of patients in the U.S. And what we see is that there are 3,000-6,000 diagnosed and engaged patients in the U.S. And then that number would build to 14,000 if you include patients who are diagnosed but less engaged in the healthcare system. And what makes us just so excited about bitopertin is, as John mentioned, the fact that this would be the first product on the market to address the underlying cause of disease through this PPIX reduction. And so that gets us very excited about what's ahead.
Got it. Thank you.
Thanks, Roger.
The next question comes from Kristen Kluska with Cantor Fitzgerald. Your line is open.
Hi, good morning, everybody. Congrats on these updates. Great to hear that this drug could potentially be on the market a lot quicker than a lot of us anticipated. So wanted to ask you some questions specific to the Apollo trial. You did a great job for us at EHA this year, essentially demonstrating why the placebo responded the way it did and clearly showing the effects of the drug are quite clear once you hit that PPIX reduction of 20%-30%. So based on the trends that we saw at four months, I was hoping you can comment on what your expectation would be out to six months here. Would you expect that Delta to continue separating between the two groups, even if the data looks pretty stable from drug arm? Again, just what are your expectations with a little bit longer data set here?
Yeah, thanks for the question, Kristen. I'll hand it over to Will.
Sure. I think that when you look at the six-month data set, at the last two weeks under 60 milligram dose, you see an uptick. It's hard to know whether that's a treatment effect or just variability, but at a minimum, we expect the treatment effect to stay stable if not improved, and then on the placebo side, there is a trajectory of decreasing light exposure out to four months, and I would expect that trend to decrease between months four and six.
Okay. Thank you so much. And my last question is, I know when you have these discussions around confirmatory trials, the FDA, of course, wants to see evidence or a clear path to show that you're very serious about conducting the trial and a good amount of timing. So regardless of whether this ends up being a confirmatory study or if you run as a regular phase III study, can you give us some expectations for enrollment of this study and your confidence in telling the FDA why you'll be able to successfully complete such a trial if you go under accelerated approval? Thanks again, everyone.
Sure. So we think that trial overall would last about a year and a half with 12 months for enrollment. This is based on our previous experience plus other trials that have been conducted in EPP. And yeah, was there a second part of the question? I think we're, and obviously, with that trial underway in the middle of next year, it'll be underway at the time we're discussing approval paths with the agency.
Okay. Great. Thanks so much.
Thanks, Kristen.
The next question comes from Ben Burnett with Stifel. Your line is open.
Great. Thank you. And I'll add my congrats to the data and the update. I just want to kind of better understand the decision around the primary endpoint. Why did you and the FDA settle on the efficacy assessment over the last month as opposed to over the last sort of two-week interval that I believe you analyzed and presented at EHA?
Yeah, thanks for the question. And just to be clear, this endpoint as designed is precisely what we proposed to the FDA, and we're pleased that they accepted that in the context of the Apollo trial. So in terms of the interval of time, I'll let Will speak to that.
Sure. I think that four weeks guards against any unexpected variability taking hold at the end of the study. That's why we presented today the two-week and four-week analysis of the last month. Also, when you look at the proportionality of how much time on study, it maps pretty closely two weeks at the end of a four-month study versus four weeks at the end of a six-month study.
Okay. Great. And given the kind of sample size that you've proposed here, how long do you anticipate needing to conduct Apollo?
So, I think it'll be a year and a half, is our general expectation from opening till the last patient out. There are a large number of patients, as Pamela mentioned, in the U.S., plus we'll be opening in Europe. We have received a lot of enthusiasm from a number of investigators, and I think the patient numbers probably are not going to be what's rate limiting. It's going to be mechanics of opening sites and administrative things like that.
Okay. Super helpful. And if I can just squeeze in one last sort of clarification question. On Helios, is everyone dosed at the 60 mg dose, and do you have a sense as to when you would maybe provide an update of the Helios results?
Yeah. So people in Helios are on the 60-milligram dose. Although the trial's been ongoing for a while, we don't have a specific target for data presentation, but 2025 is a reasonable expectation.
Okay. Great. Thanks so much.
Thanks, Ben.
The next question comes from David Nierengarten with Wedbush. Your line is open.
Hey, thanks for taking the question. Maybe this is a minor detail, but the average monthly total time between 10 and 1,800 hours after six months. Obviously, we have a change of seasons. It's getting darker right now in the Northern Hemisphere. Are you correcting for that and kind of rolling starts in different geographies, or how are you making sure that there's actually sunlight until 6:00 P.M.? Thanks.
Sure. So one of the pre-specified subgroup analyses we presented in Aurora looked at seasonality and geography and showed that it didn't make a difference in terms of the outcome in terms of light tolerance. It is true that there is less light in winter as there is in summer, but that is true for placebo as well as those in active treatment. So it's proportional. We are stratifying by geography in Apollo, not to correct for anything, but just as an extra level of assurance. So we don't have any specific plans for timing enrollment. I think it takes care of itself when you balance active and placebo along the way.
Okay. And then maybe if I could squeeze one more in, maybe getting ahead of ourselves here, but would we get any updates on commercial preps, assuming you have an agreement with the FDA that this is an accelerated approval pathway? Would we get that in Q1, or how are you thinking about that scenario? Thanks.
Yeah, thanks, David. Yeah, I think as we get into Q1, we will be able to provide a lot more granularity about the path we're going down here in terms of when we expect to file an NDA, how that then links up to a potential PDUFA date. So I think all of that we'll be able to map out in pretty good detail.
Okay. Thanks.
The next question comes from Danielle Brill with Raymond James. Your line is open.
Hi, guys. Good morning. And let me add on the development. I guess first, just to be clear, is there anything left to align with the agency regarding the accelerated approval path, or are you just needing to iron out details around Apollo? And then I have a couple of follow-ups.
Yeah, thanks for the question, Danielle. Yeah, what you stated is our expectation. The request from the agency at the end of our end-of-phase II meeting was, "Come back, have another meeting. Let's talk about the design, kind of the final design of the confirmatory trial." That said, just to be clear, as we all know, the agency has discretion to make decisions as we go along based on the data that it has in hand, and I think nothing we're saying here is intended to kind of limit their authority or make presumptions about how this is all going to go, but the indications are all positive. We are on this path, designing the confirmatory trial, and expecting in parallel, we are working on the NDA submission that would be consistent with being on an accelerated path.
Okay. Great. That's helpful. And then I guess, what's the rate-limiting step then to filing? Is this getting Apollo up and running, CMC, or is it something else? And then just curious if during your discussions with the agency, there were any aspects of your proposed trial design that they were not supportive of. Thank you.
Yeah. So the trial design was fully supportive. There were no areas of disagreement around that. And in terms of rate-limiting step, you correctly note there are many, many aspects that need to go into an NDA filing. We're working on all of that. It is not a matter of getting the Apollo trial up and running. That's something we've been planning on for quite a while. The kind of acceleration in our system is now kind of driving towards the NDA and getting all those parts and pieces together. But we think all of them are well in hand. We'll be obviously looking to cooperate with the agency across all the different sections of the NDA: non-clinical, CMC, clinical.
And we do have to sweep in what is a very large amount of information that we have from Roche, which I think, as everyone knows, is a very strong part of this program that we have safety experience in over 4,000 people. But at the same time, it's also a very large administrative effort to pull all that information together. So I think those are some of the features that we're pushing hard on and moving quickly to complete the NDA filing.
Great. Thank you so much.
Thank you.
And the next question comes from Jeff Hung with Morgan Stanley. Your line is now open.
Congratulations on the progress, and thanks for taking my questions. For accelerated approval, has the FDA given any indication if there's a specific percent reduction in PPIX that they would look for? And then I have a follow-up.
Yeah. Thanks for the question, Jeff. So no, I think what we have is an indication that the degree of reduction we've seen, the robustness and statistical significance of that finding. As a reminder, the mean decrease from baseline is around 40% in the Aurora trial, closer to 50% in the Beacon trial. And that is associated both temporally and numerically with marked clinical improvements. So that package appears to be sufficient, is instrumental in opening the pathway that we're on. Obviously, that's going to be ultimately a review issue once the NDA is filed and the FDA has the opportunity to take the whole data package and apply their own analytics to it. But that's the expectation around that. The data we have in hand is sufficient to satisfy the requirements.
Great. Thanks. And then what is your current thinking on the bar for success on the primary endpoint for Apollo? Are you just looking for statistically significant difference, or is there a specific amount of time that would be considered clinically meaningful for that month? Thanks.
Yeah. I think statistical significance should be sufficient here.
Yeah. And our expectation would be to see differences like we saw in Aurora, which we're 2x improvement over baseline in the active group. So I think if we can replicate that, that's an easy win.
All right. Great. Thank you so much.
Thanks, Jeff.
The next question comes from Evan Seigerman with BMO Capital. Your line is open.
Hi, guys. Thanks so much for taking my question. On your interactions with the FDA, can you characterize what they want to see in terms of enrollment for the Apollo trial? I know a lot is debated around what 'underway' means when it comes to enrollment, but any color there would be great. And then secondarily, it's really great to see this alignment on approvability, but maybe talk about the feedback you've gotten from payers in terms of driving access and how that has helped align and inform the design of the Apollo trial. Basically, what do payers want to see from this trial so that they can be comfortable providing access to this drug? Thank you, guys.
Yeah. Thanks, Evan. Steve, why don't you speak to the enrollment question?
Certainly. So we've had the discussion preliminarily with the agency in the context of the accelerated approval pathway, which is the requirement to have a confirmatory trial underway at time of approval. So that's sort of the standard practice. Some say well underway, and we haven't completely defined what it means, and that's going to be part of the next interaction in finalizing the Apollo trial and presenting the plan for enrolling patients and completing the trial. But given the study, as you heard, we'll say will be about a year and a half in total, maybe at a quarter sort of at the end to analyze the data and write it up. I think in the context of an accelerated NDA submission, we're very confident that our plan to complete the trial in due course will be acceptable to the agency.
And then, Evan, the second part of your question was regarding what payers are looking for.
Yeah. Kind of the commercial side of things now that you have a trial underway or Apollo's design essentially kind of underway, what do they want to see?
Yeah. Sure. Evan, this is Pamela. And we've had discussions this summer with U.S. payers, and we're also engaging with European payers. And I'll say a couple of things regarding this discussion. The first is that they recognize the high unmet need and the burden of disease for EPP, which is a real plus. They've been well educated on that, and they're aware of the disease. And then second, I would say they appreciate the reduction in PPIX that we've seen with our phase II data, and they understand that linkage to patient outcomes because we've shared with them some of the data that John and Will have mentioned throughout this call.
So they really appreciate and value the fact that Bitopertin would be addressing the underlying cause of disease in terms of what's important in the short term with patient outcomes and even over the longer term in terms of things like liver health. So I would just conclude by saying they are not waiting for future data to come out from Apollo, but I think they are pretty comfortable with the data that we shared from phase II.
Great. Thank you.
Thanks, Evan.
The next question comes from Greg Harrison, Scotiabank. Your line is open.
Hey, good morning. Congrats on the update, and thanks for taking our question. Just thinking about in the case of an accelerated approval and depending on priority review, it looks like you could be on the market maybe near the end of next year or early 2026. First, is that possible? And then in that case, how would you ramp up your commercial capabilities to prepare for launch much sooner than previously anticipated? And where are you at so far with patient identification and other aspects of launch prep?
Yeah. Thanks for the question, Greg. Yeah. As to the timing of a PDUFA date, we won't really be guiding to that until the first quarter next year. Until then, you'll just kind of have to make some of your own assumptions about when we might file an NDA, then what kind of review you'd expect to come from that, and how that would all line up to a projected launch date. In terms of what we're doing to prepare for that, Pamela has been through this many times, so why don't you speak to that?
Sure. Yes. And I joined Disc again earlier this year, and I've been working really hard to prepare the organization no matter what scenario we are under, which pathway we are under. And I would say just a couple of things that give me confidence that we are well underway. The first is in terms of patient identification, as I mentioned earlier, there's a diagnosis code for EPP, and we've done a tremendous amount of analysis in terms of understanding where those patients are and how they map to accounts and how we can prepare in that way for the U.S. launch. And then the second, in terms of sort of the operating model that would be needed to support this launch, this is a rare disease. There are a concentrated number of patients at some specialized centers.
So again, we anticipate this being a pretty efficient sales team and commercial team that would be able to sort of cover the providers out there. And again, knowing where the patients are and sort of the degree of high unmet need recognized in the community, we're confident that we'd be ready in either scenario.
Great. Thanks so much, and congrats again.
Thanks, Greg.
The next question comes from Douglas Tsao with HC Wainwright. Your line is open.
Hi, good morning, and congrats on the progress, and thanks for taking the questions. I think, Will, you noted that in Apollo, there is going to be some mechanism, I think, to, I don't think you said stratify, but to adjust or account for patients' baseline sunlight tolerance, which makes sense. I'm just curious if you could discuss that in a little bit more detail to just provide some color for how that mechanism will work.
Sure. So in the analysis, our longitudinal analysis of the Aurora data, which we presented again this morning, that analysis has an adjustment or takes into account the baseline time in light on a daily basis during screening. So we are doing exactly the same thing in Apollo to make sure that we are comparing apples to apples when we look at active versus placebo and to even out the analysis, which is the standard approach for longitudinal analysis.
So Will, will this be done on an individual patient basis, or will it be sort of done on a population basis? And I guess it's because the endpoint itself is not the change, right, relative to baseline still?
So it'll be done. It's done on an individual basis. It gets a little involved to talk about the method of a longitudinal analysis, but basically, each patient gets their own trajectory plotted over the course of the study. And then the final analysis looks at the month six portion of that longitudinal line that's plotted for each patient. And that statistically drawn line accounts for where the patient started.
Okay. Great. Thank you very much, and congrats on the progress.
Yeah. Thanks, Doug.
The next question comes from Rami Katkhuda with LifeSci Capital. Your line is open.
Hey, guys. Congrats on the update, and thanks for taking my questions as well. Two quick ones for me. First, I know you touched upon this briefly, but can you remind us of your interactions with the EMA thus far and if you expect a similar expedited path to market in Europe, or if it's just too early to say? And then secondly, given that EPP and XLP are genetic diseases, could you potentially run a study in pediatric patients under the age of 12 in parallel with Apollo, or would that come later down the line?
Yeah. Thanks for the questions, Rami. In terms of EMA, we've done, I think, what would be standard in any program where you're intending to launch in both jurisdictions. We've had interactions with EMA periodically along the program. We have some sense of how they view things and have certainly seen some acknowledgment in those interactions about the importance of protoporphyrin IX. So we're anticipating to have a favorable and probably similar discussion with the EMA. I don't really want to make a bet about whether we get access to an equivalent type pathway there, but I do think I'm willing to bet that we'll have a very similar trial design and acceptance around the endpoints that we're using. But more to come on that, probably also roughly in the first quarter next year. Your second question was about pediatrics.
Can we get into the under 12 population essentially in parallel to what we're doing here? I think at this point, that's not part of our plan. We are still reacting to all of this information and thinking through aspects of our plan, so I don't want to make a final pronouncement on that point. We are acutely aware of how affected by this disease the younger population can be. We're trying to think about how to bring this drug to those patients as quickly as we can to address that unmet need. But as you know, it's often typical to explore older ages and confirm everything around safety and efficacy there before you go to the youngest patients. So we're trying to unravel that knot in the most humane way possible right now.
Got it. Thank you very much.
Thanks, Rami.
I show no further questions at this time. I would now like to turn the call back over to John Quisel for closing remarks.
Great. Thank you, and thank you, everyone, for joining in today. We're very excited about where we're headed with this program and look forward to future updates. Have a great day.
This concludes today's conference call. Thank you for participating. You may now disconnect.