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

Alright. Thanks, everyone, for joining us this morning at the Goldman Sachs Global Healthcare Conference. We could not be more pleased to have the team from Apellis Pharmaceuticals with us today. Telling us about the story, I mean, pretty slow, nothing's really going on for you guys these days, right, just filling out. Kidding, obviously, this is really -- this is like the important time for the company. So we're really excited you guys join us today.

Thank you, Madhu.

Awesome. So let's start with a discussion of your kind of major C3 drug pegcetacoplan, I'm going to call it PEG for short, in geographic atrophy, also known as GA. So start by kind of walking through at a kind of high level, the mechanistic rationale for targeting complement C3 in GA?

Yes. Thank you, Madhu. So if we think about complement and the role that it plays in geographic atrophy, it's good to go back as much as 15 years. In 2005, for the first breakthrough out of the human genome project and these GWAS studies was an association that was discovered between at the time complement factor H and macular degeneration. And those GWAS studies kind of went all over the complement pathway with the year became more -- with the years became more validated. And here we are today. It takes time to do drug development, right, with several drug development programs in complements. And still the question, what is really going on in the retina? Why would this proportionate activation of complement contributes to the development of this disease? And when you think about geographic atrophy, we always like to compare it to a forest fire in your retina where slowly and progressively and irreversibly you lose photoreceptor cells, which then ultimately can lead to blindness. And to understand why complement is important in the retina, it's, I think, interesting to go back to what we saw in PNH, right, where we discovered how C3 is this large protein that's in circulation in the body and binds covalently irreversibly to all the cells in the body like red paint. And when it does that, a cell has the sacred obligation to clean up that paint from the cell surface. Because if you don't, you become visible to monocytic cells that will literally eat you up. And when you think about the retina, specifically, what we believe is happening there is that retinal cells, like all those other cells accumulate that product on the cell surface but the cleanup requires cellular mechanisms that compete with the visual cycle. And so these cells essentially are prone to becoming overstressed, not being able to clean up the red paint. Actually in the first stages of the disease, they start neglecting the visual cycle. But once that red paint starts accumulating, the process gets started and this progressive process, seemingly irreversible continues to spread. By controlling C3, like we do in PNH, we go kind of at the heart of where this mechanism is active. We believe that, thus far, the only way of controlling that accumulation of that red paint in the retina is by using pegcetacoplan, which we inject either monthly or every other month in these patients and where we had, of course, the promising data that we showed in the FILLY, DERBY and OAKS.

Yes. So I want to get into that data from FILLY, DERBY and OAKS. I want to actually take a brief segue following on what you said from a discussion we had with a kind of generalist investor a few days ago. Basically ask the question, to your point, if we've known for 15 years, the complement components have these genetic polymorphisms associated with geographic atrophy. And we've had complement drugs for the better part of 13 years. Why has it taken so long to target complement in geographic atrophy?

Because complement is complex, right? So -- and I think because the first drug that was on the market was a C5 inhibitor, Soliris, a fantastic drug for PNH that was life-saving that had, by itself, also its shortcomings. We've been -- we're kind of breaking open now what can happen when you go upstreams. What has been tested so far in registrational testing in geographic atrophy has been lampalizumab, which was an anti-Factor D inhibitor and which failed in Phase III clinical testing. That probably is related to the fact that Factor D is exclusive to the alternative pathway, and that the classical path, we believe, is important and again, that red paint accumulation. Then when you go to C5, there was a drug in development by Novartis, the LFG program, where an antibody against C5, one inject is intravitreally was not able to reduce the growth of geographic atrophy in patients. And that is probably because controlling C5 has again no effect on that accumulation of C3 the way we establish that very clearly in PNH. So I think, unfortunately, it's been a bit of trial and error. But there's a very clear rationality around why C3 is the important place to go and how we believe the data was generated that we did.

Okay. Great. So with that context in mind, can you walk through the existing clinical data that you mentioned earlier for PEG in geographic atrophy from FILLY, DERBY and OAKS?

Yes. So the FILLY data came out in 2017 was kind of the genesis also for our IPO in those days. It was the first time where we or anybody for that matter, was able to show any large well-controlled and adequate study that you could slow down the growth of geographic atrophy. At the time in FILLY in the monthly arm, the effect size at 1 year was a slowdown of 29% compared to the sham control. We then had the 2 Phase III clinical trials, DERBY and OAKS, where the top line data were released in September of last year. Where in OAKS, we showed with high statistical significance that we could slow down the progression with a smaller effect size, a little bit north of 20% compared to what it was in FILLY, but with high statistical significance. And then in DERBY, of course, as many of you know, where we narrowly missed the primary endpoint in that study. So the question that emerged in September was very much what went on here? What happened to DERBY for us to have missed that primary endpoint even if it was directionally supportive. And what we discovered and what I think by now we've established quite clearly is that we had very aggressive, rapidly progressing patients in the active arm compared to the sham control. And when we came to that realization in September, we said, well, look, as a check off the box exercise, right, if you want to have 2 positive studies, well, guess what, we have the FILLY trial, which was a Phase II clinical but which was adequate and well controlled. If the FDA were to agree with us on that point, that we have the check box having 2 positive studies. We went to the FDA, they agreed with us, and we announced that in the beginning of November. The next step for us, which came around the holidays in December, January, we said, look, if it is true that we have more aggressive patients in the active arm in DERBY, then with time as time progresses, a catch-up should happen. Like for example, in DERBY, if you just look at 2 months, right, when the drug really hasn't had a chance to show its effect yet, right, you already see there how the patients are progressing much more quickly in Derby. And then if you want, it's playing catch-up, right? So we hypothesized and this is what materialized that the p-value at 18 months in DERBY would flip towards statistically significant, even though that's a nominal p-value, but it kind of would tell us what was going on. So that was very exciting. We announced that in March. And we're going to, of course, have the 24-month data where hopefully, that trend continues to materialize.

Okay. And I want to get a level set for everybody in the landscape of therapeutic interventions in GA, has there been an agent that has succeeded in 1 trial, 2 trials, 3 trials?

Well, no. It's been quite.

Has there been anyone who succeeded in one randomized trial?

So there's the GATHER1 trial that was run by Iveric. They now have the GATHER2 studies. So we will find out the data I suspect somewhere in September, that is a C5 inhibitor. And of course, we wish a very good luck with that trail. There was also a Phase II clinical trial run by Genentech called the MAHALO study, with this drug called lampalizumab that was many years ago. And in that study, similar to what Novartis saw with their anti-C5 in their Phase II clinical trial, it became quite clear how you can be subjected to these imbalances between groups, like we saw in DERBY as well, right? For random reasons because there are just too many factors that drive the growth of geographic atrophy, you have to be able to kind of separate biological activity from trying to understand what the effect size is in these patients. Because when you run multiple trials, you can different outcomes, right? And if that's in a Phase II study in a small study, you can easily, of course, get pulled in the wrong direction.

Sure. So in about the efficacy profile for PEG in GA. How do you think about its activity in patients who have extrafoveal and foveal disease? And I guess, again, for level setting, maybe you could kind of better define what extrafoveal and foveal disease represent?

Yes. So this is an interesting phenomenon. So in geographic atrophy, we sometimes get the question, why is visual acuity not considered relevant endpoint in geographic atrophy. And the reason for that is that in geographic atrophy, the disease typically starts outside of the fovea. In other words, in the periphery of the macula. And there's a phenomenon called foveal sparing, where the fovea most often is the last piece of the retina to perish. So it's protected a few ones by mechanisms that we don't fully understand. What that means is that patients, when they are initially diagnosed, they are typically in 85 -- as high as 85% of cases, extrafoveal patients without foveal involvement. Towards the end of the disease, then the fovea becomes involved and then you have what we call foveal patients. What's interesting here is that on a prevalent population, so if you take all patients with GA, the majority, approximately 60%, are foveal patients because there have been no drugs, right? So -- but what it means from an implementation in the market setting is that with a good extrafoveal readout, you get access to patients early on in the disease. And where if you treat for many, many years, you probably get the most benefit. And what we saw in the DERBY and OAKS trials was a larger effect size. I just want to combine, if we put the 2 trials together, the effect size was approximately 26% slowdown on extrafoveal patients with multi-treatment, 21% with every other month treatment. But what we also see is a clear effect on foveal patients, where the growth is typically slower. And again, for reasons that we don't fully understand once the fovea is there, the growth is a little bit slower. And there, the impact is for -- what is fascinating, and I want to point that out here is that as we dose longer, and as we now are in the second year of dosing, the effect size on foveal lesions actually seems to amplify, whereas extrafoveal seems to be more stable. So it will be interesting to see what the 24-month data gives us.

Absolutely. So beyond efficacy, can you walk through some of the considerations around PEG tolerability profile in FILLY, DERBY and OAKS. And I think the key investor questions are around things like choroidal neovascularization, endophthalmitis and ischemic optic neuropathy.

Yes. So we had -- so very briefly, a distinction that is important to make is corneal neovascularization versus exudations, right? So CNV is blood vessels in the retina. Exudations are when these blood vessels actually exude. We report what's called exudative AMD, because when physicians or investigators in our trials discovered any type of CNV that was visible on OCT or fluorescein angiography that was reported. And those are the patients that require anti-VEGF treatment. Some investors ask us about nonexudative CNV. This is something that with special techniques you can detect and analyze, but these patients typically don't get treated with anti-VEGF. So they're kind of irrelevant in the context of the readout. We read out these events the same way across FILLY, DERBY and OAKS. And the safety profile that we had, I would argue, was better than what many expected. Because in FILLY, for many reasons, we have more cases of exudations because of the phenotypic distribution that we had there. But the bottom line is and kind of the easy way to remember it is that at 18 months in the sham control, we had approximately 3% of patients at -- in the -- every other month treated patients, 6%; and in the monthly dose patients, 9% of excalation rate. These events can be treated with anti-VEGF and are generally not viewed as a concern by the retinal community.

Can we maybe follow up a little bit on endophthalmitis and ischemic ocular neuropathy as well?

Yes. So there, we are treating with kind of the natural side effects that you have associated with intravitreal injections, right? So the endophthalmitis rate that we had was 4, 2 of that were clearly defined and 2 that were suspected to be cases of infectious endophthalmitis which is a very bad scientific, right? I mean it can be something that leads to significant vision loss. And that is a rate over approximately north of 9,100 intravitreal injections, which is an occurrence that is in line with what you would have with anti-VEGF injections. We also had 3 cases of, what you call, ischemic optic neuropathy. This is something that is associated with patients that have typically hypertension, especially when it is combined with diabetes. We had one case in the first 12 months. We had 2 case between months 12 and 18. And so far, we're now almost at the end of 24 months cross fingers, we haven't seen an additional case. And those cases that we did have were associated with that predisposition. Based on what you see on an anti-VEGF-treated population, we would have probably seen approximately 1.5 cases. So we had 3. So it's something that we continue to follow and monitor. But for now, not something that we are overly concerned about.

Okay. Good. It's all very helpful. So then given all the clinical data, which you've got a very thorough job explaining, could you highlight the remaining kind of regulatory path for PEG in GA, kind of where are we now and where are we headed in the next couple of months?

Yes. So we recently announced that we have submitted our file magnificent insight, something about 1.3 million or 4 million pages. And that's, of course, because we have a lot of patients and a lot of imaging data, et cetera. But it's a package that came together very nicely. And again, I want to point out that what was important to us and what we proposed to the FDA at the pre-NDA meeting was to include the full 18-month data package both on efficacy as well as safety. We requested priority review with what is called a type 3 submission. And what is a type 3 submission? It means that you have an NDA, a new drug application, but not within new chemical entity. Because pegcetacoplan, which is the active ingredient in our drug -- hopeful drug in geographic atrophy is the same active ingredient that we developed and that got approved, of course, in PNH. So that means that should we get priority review, which we are hoping and believe we are going to get that would be 6-month review period from the time of submission. So early August, we expect to hear back from the FDA as to whether we will get the priority review and should there the case we could have a PDUFA as early as the end of November.

Excellent. So one of the key debates we get around the PEG filing to your point is the likelihood of priority or view. So do you feel confident that you're going to get it. So what are the kind of basis set for that confidence?

Quite frankly, the historical precedent, right? So vision loss, needless to say, is viewed as rightfully so as an incredibly damaging elements to our health. And every drug in the retina in the past 20 years has received priority review. COVID is kind of the x factor in that. Will that have an influence or not? We think that based on the discussions that we've had based on the fact that the FDA in the retinal division right now doesn't, so we believe it's not overloaded, that it is a reasonable expectation to have.

Okay. The other kind of key debate we have around the NDA filing is the likelihood of having an advisory committee meeting. So how should we think about that? And how do you think about kind of the likelihood of an adcom?

Yes. So our going assumption is that there will be one. This is a new indication. It's a new drug, and we're preparing completely for it. Again, COVID is the x factor there. I think pre-COVID, it would have been given that this would happen. With adcoms these days being virtual, et cetera, we'll see if that effectually will come to be, but our going -- running assumption is that there will be one.

Okay. So to that end, what will be the kind of likely points of discussion in the adcom in the kind of like crystal ball that we're forcing you to gaze in right now?

Yes. So we -- look, when you look at the safety profile for the drug, we believe that the safety events are largely related to the intravitreal injections in line with anti-VEGF. There are, of course, the exudation rates, which remember, are adverse events, right, not the severe adverse events and treatable. So we don't think that, that will be something controversial. I think a point of debate is the effect size. I'm trying to understand the fact size, what does that mean for patients? And there, quite frankly, it's important to bear in mind that this is not a treatment of 1 or 2 years in most of these patients. If you have geographic atrophy, you're in all likelihood going to be on treatment for 5, 10 years or longer. And when you understand what that means in the context of being treated and the amount of retina real estate that you can save in patients, we believe that while it can be a point of debate when you really think about it, it's not that controversial.

Okay. So then you mentioned earlier the 24-month data for PEG in GA coming in a few months' time, what could we be looking for that data, both in terms of efficacy on GA lesion growth. But in terms of other types of points of assessment for patients with GA.

Yes. So on an efficacy standpoint perspective, we, of course, continue to see the effects to grow over time, right? So the longer you treat, the more retina you save. That's kind of the simple math behind it. It's easy to talk about percentages. But when you think about the real area of retina that you save, if you take OAKS, for example, at 12 months, we had 0.41 square millimeters of retina that were preserved compared to the sham at 18 months that was 0.66 square millimeters compared to the sham. You start extrapolating that over time. It becomes really meaningful. Put that in the context of less than 2 square millimeters of retina being responsible for all of our central vision, which we used to read, to do all of our daily activities. So that's kind of what we think is going to be very important to look at the 24-month time point. We are also going to do the functional analysis on the endpoint. So it's now the official analysis of what happens to function. It's important to bear in mind that measuring function in the retina is very difficult, which is why the anatomical endpoint, which is a direct measurement of photoreceptor cell death is viewed as so important from a regulatory as well as from a KOL perspective. What we have from a visual function perspective is visual acuity, which is really only measuring the foveal acuity, going back to earlier in GA less relevant. We have microperimetry, which measures 64 points in the retina, which is interesting. But there, of course, you're limited as well in terms of the resolution. We then have quality of life questionnaires, and we have reading speed. So all of these will give context to what is happening. From an FDA perspective, the clear link between photoreceptor cell loss and loss of vision is accepted as the primary driver, which is why we did not have to wait for the 24-month data. With EMEA, the relationship is considered to be more important between function and photoreceptor cell loss anatomically, and the 24-month data will be included in the full submission, which will happen in the second half of this year.

So to that end, have -- I mean you obviously engaged with EMA into that second half submission. Have they given you any sense of like what you need to no pun intended see from that functional endpoint data to kind of define the drug's activity on functional vision.

Yes. I'll start with what you don't have to see.

Okay.

No pun intent is that the -- for example, visual acuity, right, is something where you shouldn't expect to see anything on most of these functional endpoints. You shouldn't expect to see anything that's going to be significant and clinically meaningful. It will give kind of a directional understanding as to what you should expect over time, right? So understanding the relationship between visual loss. So you're going to look at certain populations, what happens to the effects on the lesion size reduction. How does that relate to visual acuity, how does that relate to other things. Understanding that is going to be important from an EMEA perspective. But at the same time, EMEA is also very much focused on the long-term implications of treatment. And we've had many -- of course, many conversations and interactions with the European KOLs, and they are exactly in line with what the American KOLs believe the importance of this drug it is.

Okay. So then kind of thinking about beyond the regulatory path, I'm going to start with the kind of almost simple minded question. Who is the product profile for a patient taking PEG in GA?

Yes. So I love this question. Because I think there are kind of 2 typical product profile that emerge when you speak to key opinion leaders. The first one is kind of the intuitive one, which is I have a patient who is blind in one eye, has geographic atrophy in the fellow eye [indiscernible] studies. And that is encroaching on the fovea. So other patient is literally at risk of blindness. And I'm going to try to do anything I can to stop that. I'm going to dose monthly, I'm going to be aggressive. And that's the objective. Where is that is intuitive? It just takes too long in the drug doesn't have an efficacy profile where it shuts down everything, right? You may benefit still. But in many ways, you can think about that as too little too late. On the other hand, if you think about patients newly diagnosed where with every other month dosing, you have close to 90% of the benefit that you have with monthly dosing, right? You have a profile where I'm newly diagnosed even in my first day, right? I'm going to now make an investment in 5 or 10 years of dosing, get the maximum benefit from this treatment, right, which compounds over time and with a dosing regimen that is viewed as being highly attractive. And with KOLs, generally, you start with the first profile and then they grow into the second one. So I think the adoption is going to focus on those 2 areas first.

So to that end, I mean, people throw around this big number, 1 million people with GA in the U.S., 5 million worldwide. Among those 2 groups, blind in one eye is like I get a first phase group, extrafoveal and both eyes in the second base group. What is your understanding of the kind of split of patients from that like 1 million patient number? What percentage are in those 2 buckets versus then the kind of the rest of the groups that are kind of like not in those 2 buckets?

Yes. So on the bucket of blind in one eye and GA in the fellow eye risk of going blind, of course, the numbers that we see are as high as 40% -- somewhere in the 30% to 40% range on the prevalent population. So this is a really meaningful and desperate population where hopefully, we will be able to do something to slow down that process.

And then the kind of extrafoveal in both eyes, what do you see is that population?

Yes. So extrafoveal either in one eye or in both eyes is depending on the -- again, the incidence versus the prevalence. On newly diagnosed patients, about 85% of patients start extrafoveal. On the prevalent population, 60% of patients are both extra and foveal involved. And in the context of treatment, it's important to remember that we are filing not just for extrafoveal. We ran these studies on all patients. We see a clear effect on foveal patients that actually compounds more over time vis-a-vie extrafoveal patients. And think about that incident population. If they go on treatment and the foveal were to become involved, you're, of course, not going to stop treatment, right? So I think including all of that in the product profile is going to be important.

Okay. Great. Moving beyond GA because you do have a company outside of geographic atrophy, believe it or not. Could you please give us an update on how the launch of Empaveli is going in PNH? And what factors give you confidence in that drug, both as a kind of later line but also first-line therapy in PNH?

Yes. So we're very excited about what is going on there. I'm going to hand it to Tom to talk a little bit more about.

Launch has been very strong. I'll answer the latter part of your question first, which is, I think, the important part, which is why we think this can be the first-line therapy in PNH? Obviously, our clinical data to date, the head-to-head study against Soliris, where we had 3.8 grams per deciliter improvement, the safety profile that we've been generating over time. And really the sort of the experience that the community that's prescribing and also patients, how they're doing on Empaveli. So the compliance has been greater than 95%. The feedback we get from doctors is incredible. And ultimately, why we think this can be first line, not just today because of that efficacy profile on that improvement over C5 inhibitors, but also the PK profile. This is a drug that you take twice weekly. If you miss a dose, it is fine. We obviously expect orals to -- the data that come out from Novartis with their Factor B inhibitor at some point at the end of this year. But ultimately, what we view is that having that security of being covered in terms of your protection from a hemolytic event or some sort of stroke that's ultimately what we believe to be the ideal profile for a PNH patient who could die if they don't get their dose, right? So that's why we think it should be a first-line treatment. And secondly, how the launch is going. Look, it's been extremely gratifying to have 19 of the top 20 payers have us on formulary. Again, as I mentioned, the compliance has been excellent. Feedback has been great. And ultimately, we're seeing that on a day-to-day basis with start forms and also physicians on REMS. So we've had greater than 150 start forms and over 170 physicians sign up for REMS. So these are very strong metrics. But ultimately, it's a very different thing from, say, the retinal community where the community is very tight knit and the patients are easy to find. These are kind of one z, two zs, right? So there's a little bit more of a challenge in getting to some of the patients in the U.S. If you look at -- we had one doctor, for example, who had, I think, 27 patients with PNH. And that doctor had not seen one of those patients in over a year. So it's a little bit more work, and it's a 1 patient by 1 patient strategy, but it's ultimately something where when people get experience, when the physicians get experience with the drug, they're incredibly impressed and they obviously want to have that for the patients that need it.

So thinking about the point you made about the kind of oral alternative pathway drugs how do you think about the need to kind of close the uptake gap ahead of a potential approval of those drugs? I remember, I believe a couple of years ago, Peter Hillman said that it would be hard to switch someone off a drug like Empaveli onto an oral pathway drug because they just don't do anything extra? By the way, where do that guy ever end up.

Yes. Well, obviously, you've seen Pete Hillman has joined Apellis, Cedric had the great idea of when he hired Pete, and Pete should tell the story, but I'll tell it but he said, Pete, I want you to come in and look at all of the data we have generated, right, not just the clinical data that you already knew because he was the lead investigator in our PEGASUS study, but also all of the data we've generated, all the safety data, all of the efficacy data. And if this isn't the best drug in your view for patients with PNH, we don't want you to come in and try to market this with us. Ultimately, he's such a high integrity guy that he -- we understood that he wouldn't probably be able to come aboard and market Empaveli if he didn't really believe it was the best drug for these patients. So we did that, and obviously, he joined, and we think that's obviously in and of itself, a very strong statement.

Okay. So thinking beyond PNH, how do you think about the state of Empaveli label expansion into other rare blood disorders like cold agglutinin disease, bone marrow transplant TMA, C3G in the kidney, ALS in the nervous system? Like how do you think about kind of the broader opportunity for Empaveli in orphan disease?

Yes. So I think that -- I mean, we're really excited about these opportunities. As you know, Empaveli was the first drug -- first component controlling drug in approximately 15 years to be approved. And with T3, it's just the tip of the iceberg as to what we can do, of course. So we're exploring this in all these new indications that you've mentioned. Our C3G trial, an indication that we're really excited about, which is combined with immune complex membranoproliferative glomerulonephritis, IC-MPGN. It's a Phase III trial that we just started. It is enrolling. We think it will enroll very well. And we think it as a high chance of showing great efficacy in these patients. So that's happening. We also have in cold agglutinin disease, of course, a trial where Sobi is right now working on finding the first patients to enroll, and we'll see where that goes. ALS is a trial that completed this enrollment at the end of the first quarter, beginning of the second quarter and where in next year, we'll have the readout. And then in HSCT-TMA, there's also an ongoing Phase II clinical trial run by Sobi, where we believe we have a good chance of showing efficacy.

Okay. So now looking outside of pegcetacoplan as a chemical entity, I'm going to ask you to do the dangerous game of picking among the remaining children, which one do you love the most? What is your favorite of the next-generation drugs you guys have in development that you're planning to put in the clinic in the next 12 to 24 months?

Look, they also have a very important strategic purpose, right? But let's start with kind of our program with siRNA, which as an objective has to lower the levels of C3 systemically in the body so that we can reduce the treatment frequency with Empaveli. Currently, that is self-administered at-home test per week subcutaneously, we believe that could be as little as once a month, once -- at least every 2 weeks, maybe once a month subcutaneous. That's a product profile. If you combine it with the efficacy and the safety that we've seen with Empaveli that would be really, really powerful for these patients, not just PNH but the other rare diseases as well. With APL-1030, we have a drug that for the first time will allow us to control C3 in the red. I mean opening up neurology with complement, which everybody in the field of complement knows is an extraordinary opportunity. We also have our daily anti-Factor B, which we are working on, which we believe we'll be able to compete very well with LNP023 and the various indications where it's being studied. And then last but not least, our 2006 molecule, which combines anti-VEGF with anti-C3, that is for patients with wet AMD because those patients with wet AMD almost inevitably will also develop geographic atrophy. And having a drug that could prevent that from happening would be highly attractive, and I think be viewed as a next-generation anti-VEGF.

Yes. Can we dig into that one a little bit more? Like how are you thinking about the product profile for that drug and what the kind of trial design feature would be as compared to like the standard wet AMD trial? Is there a layer of adding in kind of GA incidents as part of it? Like how should we think about kind of the broader opportunity for that agent?

Well, think of developing a drug for wet AMD with visual acuity being the primary endpoint as it has been for every drug in development. And they're a very well-established regulatory path. But where as a secondary measure, of course, you will also look at the development of geographic atrophy. And where, again, if you look at the visual acuity loss in patients with wet AMD, that also seems to be correlated to the development of GA, which in those patients, unlike primary GA seems to disproportionately involve the foveal.

Excellent. So then finally, and this is the question we're asking every company, and again, it feels kind of stupid asking this question to you guys. What is the reason to own Apellis stock now in the next 12 months?

For me, the fact that we have the great fortune of being in late-stage development. I think our industry right now is unfortunately suffering from kind of the excitement that we think we rightfully had around all the new mechanisms, the platforms that became available, et cetera. But where the question that needs to be asked, which is how much revenue can be generated with these drugs? How long will it take to bring these drugs to market is sometimes neglected or was sometimes neglected, and we're kind of having come to Jesus moment without red. What we have and that we feel very strongly about is that with our geographic atrophy program, should we have approval and in synergy with our launch in PNH, which we continue to believe is going to go very well, we'll have a drug that will meet an unmet need, that is, quite frankly, tremendous where the physician population that needs to be targeted is very small for a specialty. And we're launching a drug, I think, is ideally positioned to build on an ecosystem around anti-VEGF injections that we can very nicely move into. And then, of course, while we don't pay that much attention to it next year, you should also think about all of these programs that are going into new development now with what we believe are transformative new frontiers for complement. And to top it all off, of course, our collaboration with [indiscernible] and gene editing in the next year, you should expect to see lots coming out as well.

Well, thank you so much for your time, Cedric. It was great to have you here.

Thank you so much, Madhu. Thank you.

Thank you.