Apellis Pharmaceuticals, Inc. (APLS) Earnings Call Transcript & Summary

All right. Good morning, everyone, and thanks for joining us at the Goldman Sachs Global Healthcare Conference. We're really thrilled to be joined this morning by the team from Apellis Pharmaceuticals to get an update on things kind of at an really interesting crossroads for the company. So really just so thrilled to have them with us today.

So let's start at a big picture level. So if, Cedric, if you can walk through the current clinical pipeline and the current kind of technological approach Apellis has for the treatment of complement-mediated diseases, that would be great, particularly focusing on ongoing and upcoming clinical trials.

Sure. Thank you so much, Madhu. So for those people new to Apellis, to understand the company, it's important to understand that we target the complement pathways, but specifically, we target the central target within the complement cascade called complement factor C3. C3 allows someone to control the complement cascades completely, regardless of what the source of activation is or what the downstream effects of complements are. The way in which we have developed our molecules in the past couple of years was initially focused on, on one hand, going after systemic indications like PNH and on the other hand, controlling complement locally in indications like geographic atrophy. And where we currently stand, and like you said, kind of this pivotal transformational year for us at Apellis is we have 3 things coming together. The first one is already behind us. On May 14, we had our PDUFA. And we got approved for our subcutaneous product called Empaveli, which controls C3 systemically in the whole body in a disease called paroxysmal nocturnal hemoglobinuria, PNH. We got approval for that indication with a label that allows us to treat all adult patients with PNH, including with instructions on how to switch over from the current standard of care, whether that is Soliris or Ultomiris. Now the second important event for us is going to be on June 30 of this month. We are going to have an R&D Day, and we will announce soon that, that will happen at the Apella in New York. And what we will talk about there is essentially, of course, the Empaveli launch, but also what we are doing with the systemic products in new indications. We currently have 4 registrational programs ongoing in ALS, an ongoing registrational Phase II clinical trial and then registrational programs in C3G/IC-MPGN, in cold agglutinin disease and in hematopoietic stem cell transplantation-associated thrombotic microangiopathy. What we will also talk about on June 30 is then, of course, the GA readout, what to expect, what we will do in the top line data. And then last but not least, we will talk about all of the innovation that we have been working on. So we've had a lot of preclinical programs that we've kept a little bit away from the broader public for many years and that we are ready to talk about now, all of that to really show the depths, both horizontally and vertically that we have in controlling this important C3 target and the promise that, that holds therapeutically for patients across a wide range of indications.

Excellent. So on that first point, about the Empaveli launch. So let's start by talking about the data you guys have for Empaveli in PNH. So really, can you walk through the existing results you guys have presented so far from the Phase III PEGASUS and PRINCE trials and how they influence kind of the market opportunity for the C3 drug?

Sure. Thank you for that question. So I'll quickly first review the clinical data, and I will then hand it over to Adam Townsend, who's on the call with us and is our Chief Commercialization Officer. So the trial that kind of really, for us, established the clinical profile of Empaveli in PNH was the Phase III PEGASUS study. The PEGASUS study was a very broad study that aims to accomplish 3 things: first of all, we wanted to show that Empaveli could be a drug for PNH, of course. Secondly, we wanted to show that Empaveli was a drug that would be superior on hemoglobin levels compared to Soliris, which again, is the standard of care in this disease. And then thirdly, and this is important, is we also asked ourselves the question what is it going to be like for patients with PNH who is on treatment with Soliris or, for that matter, Ultomiris and who is being told, we have a drug that may better control this disease, would you like to try it? And at the time, realized that we wanted to make it possible for these patients to understand, not just what a switchover would mean, but also what switching back would mean so that you always have kind of the feeling that what you're doing is not a risky proposal for your health. And so what we did in the PEGASUS study, which was quite unique, was we said, take patients on Soliris, 80 in total; switch all of them over, all 80, on to Empaveli, at the time called pegcetacoplan, on top of Soliris; and then after 1 month of combined dosing, split it in 2 where half of the patients continue on monotherapy with Empaveli, where the other half of patients had to go back to where they were before they had gone on 1 month of treatment with Empaveli. Again, to show that, that could be done safely. After 4 months of monotherapy, these patients were then also allowed to switch over back to Empaveli. And one of the beautiful results of PEGASUS for me was that 39 of 39 patients that were in the control group stayed in the study. So that after 4 months, they will have the chance to go back on to Empaveli. So that was something very important for us as well. Those data were so convincing, where we had 3.8 grams per deciliter superiority on hemoglobin levels, including also kind of the broad safety profile, that the regulatory process went forward solely based on the PEGASUS study and led to the approval subsequently last month. But we also then have the PRINCE study, which was -- on which we released top line data within, I think it was about 10 days of the PDUFA date. And the PRINCE study is a treatment-naive study. So here, instead of taking patients with PNH who are in -- who were not doing well in hemoglobin levels while being on treatment with Soliris, this was a treatment-naive study, so patients who had not received the C5 inhibitor before and where we tried to determine what does Empaveli do in a treatment-naive setting. And it further confirms, again, what we had already shown in PEGASUS and which will now be further subject to full presentation coming up later this year, probably at ASH. And then I will call Adam...

Okay. Great...

Sorry. Adam, if you want to talk briefly about the commercialization and the preparation, please.

Yes. Thank you, Cedric. Thank you, Madhu. So I think we're in a really, really great place with the launch of Empaveli. And one thing based on the data that Cedric outlined, one thing we thought prior to launch was that we expected physicians to identify the patients with the highest unmet need. So I'm sure everyone knows there are about 1,500 C5 treated patients and about 150 PNH-naive patients. We, in our conversations prior to launch, thought that physicians would start with the 1,500 C5-treated patients and 1/3 of those patients who have a low hemoglobin, and they're continually needing to top it up with transfusions. And we are seeing that play out now that Empaveli is commercially available. So again, the hematologists have identified patients with the highest unmet need and they're going to start with those patients, and I think, then, we will see the transition as we get through the launch to the broader treatment population. The label is very impressive to physicians. The data, particularly around transfusions, the superiority of hemoglobin is resonating incredibly well. They are very happy that we got a broad label, and I think we have a real opportunity to continue to elevate the standard of care for PNH patients.

Okay. So with that in mind, how should we start to think about the cadence of the Empaveli launch, particularly in terms of things like payer interactions, start forms and reimbursement?

Yes. Thanks, Madhu. I'm thrilled to say after a couple of weeks, we're exactly where I expected and hoped we would be with the Empaveli launch. We're seeing early indicators of demand from some of the really big institutions in the countries and some of the PNH experts. We're also getting our prior auth process very smoothly and very quickly. And that, to me, is a great sign of the benefit that people can see around switching to Empaveli. The patients who are now on Empaveli have had a great on-boarding, especially with the training on how to self-administer and self-infuse. It's very positive feedback that we're getting from the patients and also the support services that we offer those patients. As I said previously, the physicians are very happy that they have a broad label, they now don't have to [indiscernible] we'll see 5 switches. Everything is covered by the label. And our payer interactions have been going full steam. We expect to make great progress within the next couple of months to try and remove any potential slowdowns and blockages. We've been showing the whole wealth of our data to those payers. And as I said, all of our PAs are getting approved very, very smoothly. We're exactly where we are from a launch cadence and kinetics perspective. We've had physicians sign up for REMS. I know that process is working. We continually get them daily. We've had start forms come in, and that process has been working very well. So I'm thrilled to say that patients are going to soon see the benefit of Empaveli. And everything that we expected to happen is happening. So we're in a really good place a couple of weeks into the launch.

Okay. Excellent. So shifting gears, let's focus on the kind of remaining major clinical readout for you all this year, which is the Phase III DERBY and OAKS trial readouts for pegcetacoplan in geographic atrophy. So let's start by walking through the disease progression for GA, how prevalent the disease is, and what are the current treatment options for patients with those eye disease.

Thank you, Madhu. So the numbers that we always use is that there are 1 million patients with geographic atrophy in the United States alone. There are approximately 5 million patients globally. And what you think about in the context of that disease is, I'd love to use the analogy of a forest fire. Imagine in the back of your eye, the retina, slowly dying in a progressive degenerative process. Where it typically starts in one little spot, sometimes a few, and from there, like a forest fire, expands. And you can see that when you look at the back of the eye, like indeed a batch that gradually becomes larger, and they call it geographic atrophy because when you look at the back of the eye, it literally looks like a lens map where, unfortunately, the black spots of "lens" are areas where the retina is gone. There are currently no treatments available for geographic atrophy. It is a disease that has been really one of those, I think, staples of important and very prevalent diseases with devastating consequences, for which no therapies have been discovered and where, unfortunately, a lot of developmental therapies have failed in the past. So it's a very important program for us, a very important program for patients and one where we hope we'll be able to make a big difference.

Okay. Excellent. So with that in mind, can you walk through some of the rationale that exists for targeting complement specifically in disease like GA?

Yes. So the story around complement in geographic atrophy or in macular degeneration, in general, I should say, is now about 15 to 16 years old already. I mean, it takes a long time for drug development to happen. But it really started with the first breakthrough out of what we call the genome-wide association study, so the human genome sciences project, where it was discovered that patients with macular degeneration have an association with mutations within the complement pathways. And from there forward, people, us and many others included, have tried to tame complements in the retina. That is not easy to do. And specifically, if you go over that complex cascade, we believe that targeting C3 in the center of that cascade is particularly important. And the reason for that is if you kind of take all of the literature and knowledge that is available in macular degeneration, and you think about why is complement a problem. And probably, in our opinion and our hypothesis, it comes down to the following: C3 is something that throughout the whole body is continuously deposited on all cells. You should think of it like a paint job. And it binds covalently and it has a tendency to self propagate. So once C3 binds, it wants to bring in its friends and bring more C3 to cover the cell surfaces. Now we have very good mechanisms on the cell surface to control that. But when those mechanisms fail, you get an accumulation of that paint and macrophages use that as a signal to phagocytose and remove those cells. It is that particular mechanism that in the retina, we believe, becomes disregulated. Because the mechanisms that are needed to remove that C3 paint products from the cell surface are really the same and similar cellular mechanisms that are shared with the visual cycle. So at some point, the cell starts competing between doing its job with the visual cycle and doing its other very important survival job, which is to clean up that C3 product. And that overload at some point becomes too much. That is when the cells start dying. And probably when the cells start dying, it kind of triggers a vicious cycle, again, the forest fire, lighting the fire, if you want, where it then starts progressing. When you want to correct that, and I think this is very important, it is not just sufficient to kind of try to "inhibit complement." We believe it is very important that you flip from having more deposition than what you can remove towards having more removal than what actually deposits. And that is something that we believe pegcetacoplan showed very convincingly with its result in Phase II, and which we hope to replicate in our 2 Phase III clinical trials.

That's great, Cedric. So like we think about this question a lot. I think that rationale makes sense. And then kind of the question that naturally arises is, as you mentioned, complement in GA has been around for 15, 16 years. And probably drug development for a complement and GA has been around for at least half that time. So how do you think about the kind of prior failures that have occurred for complement-targeted therapies in geographic atrophy and macular degeneration?

Yes. Thank you, Madhu. So there are 2 kind of going -- I mean, we are very fortunate because we learned a lot from these other studies, of course, within the complement cascade. And the theory that I just explained to you bears into mind the previous failures. So on one hand, we have anti-C5, which has failed before, both when antibodies were injected intravitreally or when antibodies were administered systemically in the form of Soliris. That means that probably that point is too far downstream in the cascade. And then, of course, we had a very large and what many people were hopeful for would be a successful program with Roche's lampalizumab, which went into a Phase III registrational program with close to 2,000 patients and which unfortunately failed. So I think lampalizumab is especially important because there you have a drug that targets the alternative pathway, so 1 of the 3 pathways of activation and which did not do sufficient in terms of reducing the growth of GA. The reason for that, again, is that we believe that the leakage from the classical pathway, specifically, kept too much C3 depositing to make that switch that I was talking about. So if you reduce how much C3 is depositing but not to the extent that it allows the cells to catch up and start removing product, then it won't be sufficient. And that, we believe, was the difference between pegcetacoplan and lampalizumab.

Excellent. So with all that context in mind, it'd be great if you can walk through the existing clinical data for pegcetacoplan in both Phase II studies, kind of the follow-up studies that have happened in geographic atrophy patients.

Yes. Thank you, Madhu. So the so-called FILLY study, which was our Phase II clinical trial in 246 subjects in 3 groups, is really one of the -- in my opinion, one of the most impressive trials we've ever done in the sense that in a very complicated disease state, from every possible angle in which this study was analyzed, we found convincing data to tell us we are doing something right and it is worth doing a Phase III clinical trial. You have to remember, as a little side note, that in 2015, as a little company in Louisville, Kentucky and with access to relatively little capital, we had to think far ahead. And in a disease like GA, where everything had failed, we told ourselves, okay, we're going to do trial. What we cannot afford is to get a half-baked answer. Whether it's negative or positive, we need to know. And that was very much the spirit on which FILLY was designed. A, we did what was, at the time, the largest Phase II clinical trial ever done, 3 groups of approximately 80 patients: a sham control; patients dosed monthly with intravitreal injection; and patients dosed every 2 months with an intravitreal injection. We took then for the readout the exact same way of measuring the progression of GA as what we knew was expected at the time from Roche with lampalizumab in their Phase III clinical trials, so that we knew we would have the imprints for a Phase III clinical trial. We then took the exact same patient population that we expect that we were going to use in Phase III, always bearing in mind that we wanted that Phase III, both in design and demographic, to be as close as possible to what would hopefully become a successful Phase II clinical readout. And then to kind of enumerate for you the many, many reasons why that Phase II clinical trial was so successful. First of all, of course, we met the primary endpoint with statistical significance, both for the monthly as well as every other month dosed individuals. That was in a two-sided ANOVA. We then saw something, which for us is important, we saw an increased effect over time. So in this study, we took a measurement at 0, 2, 6, 12 and 18 months and we looked at the size of the dead retina and how fast that was progressing, which, again, is the acceptable registrational endpoint with the FDA as well as with EMA. The -- we looked at the progression and found that there was an increased effect over time, which goes hand-in-hand with the mechanism. If you reduce that C3 deposition in the retina, you shouldn't expect that to make a difference from one day to the next, like a steroid to it. This is something that takes time for homeostasis in the retina to restore itself. So we saw an increased effect over time. Then we asked ourselves the question, what in the past has led studies to be confusing or mislead huge companies like Roche? And that, at the end of the day, comes down also to cohort behavior, right? Once the set of patients is moving at a certain speed of retinal degeneration, they tend to continue to progress at that speed. If that turns out to be in a misleading range, you have a problem. So we said, "Well, how do we avoid that? Let's do the following." After 1 year, we are going to stop dosing with our drug. And then at 18 months, we're going to take another look to see if these patients start progressing more quickly again, and that was the case. And then we said, "Well, what else do we have?" We have the group to group comparison, of course, but we also have patients with bilateral geographic atrophy. And that is important because it's well-known from natural history that patients with bilateral GA tend to progress at identical rates between the treated eye and the contralateral eye. So we said, "Hey, if we take all of our patients with bilateral GA, of which there were many, we have a brand-new set of control eyes, the contralateral eye, how does that behave compared to the treated eye?" First of all, in the sham, identical progression, as you would expect. And then in the every-other-month as well as in the treated -- monthly treated individuals, we saw a trend and a statistically significant reduction in the growth rate as well. Not just that, but we saw, again, that increased effect over time, with most of the effect happening from month 6 to month 12, and where in the monthly dosed individuals, you saw close to a 40% reduction in the growth rate in the treated eye compared to the contralateral eyes of the exact same patients. And then the last piece that I would like to mention here is that -- and we presented this last year at the Retina Society presentation, is that you can look at the area of dead retina and how fast that progresses. But you can also go to the band outside of the dead retina, in other words, the retinal cells that may not be dead yet, but they're not looking good. They're sick. Are those cells more likely to be protected by exit pegcetacoplan compared to cells under control? And that, too, in a statistically significant way, was the case. So all of that combined gives us the confidence that we have that something real is happening with pegcetacoplan.

Excellent. That's a great run through all that data. So on this study, the question, I think you probably get the most, and I'm sure it's a question you all get all the time, which is the occurrence of new-onset exudations in the FILLY trial. And so what do you make of it? How do you think about it versus kind of the broader patient landscape in GA? And how do you think -- if it's a kind of real phenomenon, how it will be managed in kind of practical clinical practice?

Yes. So first of all, I want to make a mention of something that many -- that confuses many people. And it is the difference between CNV, which stands for choroidal neovascularization, and exudation. CNV are blood vessels that are present in the retina where they are not supposed to be. So in the retina, you're supposed to have blood vessels in the choroid or in the retina, all the way on top of the retinal cell layers. If you have vessels sitting in the middle, that's not a good thing. And these blood vessels tend to be leaky. So CNV, so the measurement of blood vessels is actually very hard to do. The measuring of exudation is very easy to do. And we have a technology called SD-OCT that allows you to do that with very high sensitivity since the past 15 to 20 years. The quantitation, the amount of exudation that you have in the retina is very important. It can be very little exudation, with little impact on vision. And where you could argue, does this need to be treated with an anti-VEGF or not, all the way to kind of very meaningful exudations that if you don't treat them, leads to blindness very quickly in these patients. It's important to note here that in the Phase II clinical trial, all of the exudations that we saw were mild in nature and did not lead to significant vision loss. So that is very important point #1. And that is the reason why our Phase II clinical trial was allowed to complete and where our Phase III clinical trials have no change in terms of patient demographic and why this has never been a safety concern. It is the nature of the exudations that matters. The second piece is that from the analysis that we have done, it looks like there was an imbalance between the patients that came into the study already having a baseline wet AMD in their contralateral eye and the patients that came into the study with pure geographic atrophy in both of their eyes. To put that in numbers, 38% of the patients that came into the FILLY study had came with wet AMD already in their contralateral eye and GA in their study eye, which is compared to the 20% of the overall macular degeneration population. So why did we have close to twice as many patients from that demographic as you would have expected? That's because, at that time, we were competing with enrollments with the 2 Phase III clinical trials of Roche, which excluded those patients. So to put that in context, those subjects have about a threefold higher rate of developing exudations in their study eye than patients that come from a pure dry background. So we kind of -- it was something that was already skewed to come in much higher numbers. And the last piece, and this is very, very important, and I cannot overstress this, is that exudations in patients with GA are not unusual, right? We did a retrospective analysis on 69,000 patients with geographic atrophy. And if you have pure GA, the incidence of getting exudations over the course -- or wet AMD, I should say, over the course of 2 years is 8%. If you are a patient like the 38% of patients that we had with wet AMD in one eye and GA in the contralateral eye, it's 22%. So that's the context that matters there. These are not different diseases. These are different phenotypic manifestations of the same disease. And what we saw in our study, in all likelihood, that goes back to the first comment I made, is that we have patients with preexisting neovascular CNV membranes in the retina that did not show up as leaky at the start of enrollment that may have become more leaky during the treatment with pegcetacoplan, which then showed up. And there are other factors that we published in a paper in February that people can look at that contextualize all of this. But going back to point #1, this was not a safety concern for physicians or patients or the FDA, which is why this Phase III clinical trial enrolled at rates that were the highest of any GA study ever that had been done for GA, could have enrolled as fast probably as 9 months. So again, giving insight into how the investigators look at this.

That's very helpful. So the other, I think, major question grouping we get around the GA trials is what is the impact of the COVID-19 going to be? Basically while we're all sitting on our computers rather than sitting in Southern California right now, while missed doses related to the pandemic, how they could influence how the trial performs. So how do you think about that? And how do you think about kind of how to assess that impact practically for the trial?

Yes. So with that question, Madhu, again, of course, a very important question, which in March and April last year, had me wake at night. I mean, what is the impact going to be on the crown jewel of Apellis. What we did at the time was take all the measures to control and make sure that as many injections as possible happened. There were, of course, a high number of missed injections. But in the FILLY study, we had the backstop of having had a lot of missed injections as well because of exudations, for other reasons, because in the Phase III in GA that happened, so we had a really good database to fall back on to see what is the bandwidth that we have. And when I want people to think about the Phase III clinical trial is that if you want to be as little sophisticated as possible about this, think about the following. First of all, the 2 Phase II -- Phase III clinical studies were very, very well powered. So we went from 246 patients to 1,256 between the 2 studies, so approximately 600 patients in each of the OAKS and the DERBY trials. But also remember that in FILLY, both every other month as well as monthly showed statistical significance. So if you want to be very basic about this, 6 instead of 12 injections in Phase II already showed something, right? So that is the -- and remember, just for the monthly injection, if that were to be the only thing that works, that will be sufficient for approval. So I think just from that standpoint, it can give you kind of a sense as to why we feel so confident about the readout. But the other important thing to bear in mind is that if you compare the number of missed injections in DERBY and OAKS compared to FILLY, it's actually quite comparable. We did it in a very thorough fashion, where we didn't just say how many, but also how does this apply to individual patients compared to multiple patients; where during the treatments, of course, these missed injections take place; were they sequential or a sparsed out, all of that, of course, matters. But we feel very, very good about the readout of this trial at the end of the third quarter.

Excellent. So kind of following from that, let's get a little more granular about thinking about that top line data. So really granularly, what exactly, though, should we expect at that top line data release from DERBY and OAKS in terms of both efficacy and safety?

So at the end of the month, again, on the 30th of June, we will dive a little deeper into that as to exactly what to expect. But the top line is going to -- we will, of course, give investors and physicians and patients what matters the most, which is to show whether we can reduce the growth of atrophy in these patients. And then also what the basic safety profile looks like. Also to elements as it relates, of course, in the context of exudation.

Okay. And then kind of following from that, to what extent do you expect to be able to provide interim data from later time points in DERBY-OAKS? Because I mean the top line data, the 12-month time point that, obviously, the trial goes to 24 months to ones that we provide kind of later patient data that's on an interim basis from DERBY-OAKS at that late 3Q readout.

Yes. So again, we'll provide a little bit more color about how that top line -- how that will work in the context of top line at the end of this month. But it's important to note here that, as you mentioned, this is a 2-year study, not a 1-year study. Even though we measure out the -- or read out the primary endpoint at 12 months. We are super excited about the 24-month period of this study because, as mentioned earlier, and using the analogy of the forest fire, in Phase II, we saw that increased effect from month 6 to month 12 compared to 0 to 6 months. And the question is, is there room for even further improvement from months 12 to 24 compared to from 0 to 12? This is a slowly progressing disease that takes years to really kind of come into full swing. And it may take also quite a bit of time for that to really go into a new homeostatic state and get the full effect from the treatment. So month 12 to 24, it's very important for us from a clinical benefit. Not necessarily from an approval standpoint, but also to understand how much can we really do for patients if they are compliant over longer periods of time.

Okay. And then there is one last question. Are there other aspects of DERBY and OAKS that we haven't mentioned so far that are important that could indicate either potential underperformance versus FILLY or outperformance versus FILLY?

Well, I think that -- look, in DERBY and OAKS, the primary objective for us is to have the data to develop and create the first treatment for this disease. What that comes down to is to show that we can have a protective effect on the ongoing destruction of the retina. And we measure that, as we've mentioned a couple of times now, by looking anatomically at the growth rate in these patients. Other things that we will look at that, in the longer term, will be relevant are functional endpoints. So we have 2 important ones that are measured between OAKS and DERBY. The first one is reading speed, where, again, it's very difficult to put stats on that because reading speed is -- has a lot of variability. And it definitely -- studies are, of course, not powered to measure that. But to have a directional sense of what happens to reading speed is going to be very interesting to see. The other piece is called microperimetry. And microperimetry is a technology where you don't look at the central portion of the vision, but you look at the areas around that central portion. And why is that important? Because in geographic atrophy, there is a phenomenon called foveal sparing. So many people ask us and ask himself the question, why does the visual acuity change so little in geographic atrophy? And the answer to that is, well, VA doesn't change very little, it changes typically abruptly. Because visual acuity is what is measured on a Snellen chart in what most people have -- some done in their lives, which is to read whether you can read letters on a wall. Well, to read letters on the wall, all your reading need is the very central portion of your vision, not the periphery around it. And as it turns out in geographic atrophy, in most patients, that central portion of your vision is actually maintained and protected from GA until the very end when it does become involved, and when all of a sudden, your visual acuity goes off the cliff, right? So when you look at the average loss of VA in patients with GA, it comes down to, simplistically stated, approximately 1 line of vision or 5 letters, right? 1 line on that chart over the course of 1 year. But it is very much skewed by those patients within a trial or a cohort of patients that go off that proverbial lift rather than an average decline. And it's that piece of the biology or the progression of GA that makes it so important to look at things like microperimetry and reading speed. And it is also the reason why for the FDA, the only thing the FDA says is it matters to them because it is evidently correlated. It show us that you can save photoreceptor cells, which is why that anatomical endpoint is so relevant and important and acceptable as the only primary endpoint in these GA studies.

Excellent. And so I'll conclude with 2 straightforward questions. First one is, can you remind us what your cash runway is and what development programs that runway assumes?

Thank you, Madhu. I'm going to hand that over to our CFO, Tim Sullivan, to answer.

Thank you, Madhu. So we look at our cash runway in 2 ways. One is positive GA and one is if GA were unsuccessful. When it's is positive, our cash runway is actually a little bit shorter due to the global build-out of commercialization [indiscernible] including the specialty describability ]. So in that scenario, we'd have a -- at least cash into the third quarter of 2022. And then if for whatever reason GA were not positive, that cash runway is actually quite a bit longer. So we feel very good about where our cash stands today and heading into the DERBY and OAKS readouts. And really, that cash runway encompasses, obviously, the PNH launch, geographic atrophy readout, the DERBY and OAKS readout, our ALS Phase II pivotal program as well as the new programs in cold agglutinin disease, C3G and IC-MPGN and then HSCT-TMA, not to mention the other goodies that Cedric is going to introduce in June at our R&D Day.

All right. Excellent. So I'll stop with our last question, which we ask every company, but honestly, like it's a stupid question to ask you all, why should someone own Apellis stock in the next 12 months?

Well, I think we are in this unique situation right now throughout kind of the history of our company where, on one hand, we have an approved product, where I think we -- as a team, we did a very good job not just creating an approved product in PNH, but one that is really well positioned to elevate the standard of care in that disease and to explore as a "platform in a drug," right? I mean, not necessarily a term I like, but to explore that in the many, many indications where complement is very clearly involved, some of which we have already established proof-of-concept in. And so Empaveli is a drug that we believe will benefit a lot of patients across a broad range of indications. And it provides kind of the perfect backdrop against which you can now look at what more there is. With geographic atrophy, we have what I would very subjectively argue is one of the more important readouts, clinical readouts this year in all of biotech where we have an opportunity to make a difference in the specialty for millions of patients worldwide, where nothing is available for one of the leading causes of blindness, I mean, something that has been in the making for 15 years, quite frankly. And where we take that responsibility very, very seriously and one where we are not just ready to take a positive readout and run with it and make a potential drug available to patients globally as quickly as possible, but also to really explore this new part of biology in the retina. And then the last piece, again, something we're going to talk much more about on June 30, is what else is there for complement because for all of the great things that have happened, and just not just apply to Apellis, but it is just the beginning of what this piece of innate immunity can do in terms of correcting and treating many diseases across many therapeutic areas.

Excellent. Well, on that note, I will thank the Apellis team for joining us today. It's been a real pleasure. And I thank, everyone, for joining us on today's call today, the Goldman Sachs Global Healthcare Conference. Thanks very much, everyone.

Thank you so much, Madhu. Thank you for those listening.

Thanks, Madhu.