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

Welcome, everyone, to the 39th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by Tessa Romero and Matt Bannon from the team. Our next presenting company is Apellis. And speaking on behalf of the company, we have CEO, Cedric Francois. Before I turn it over to Cedric, just wanted to highlight for those on the webcast, you can submit a question using the ask-a-question feature in the portal, and I'm happy to ask a question on your behalf. With that, I'll turn it over to Cedric. Cedric?

Thank you so much, Anupam, and what a pleasure to present again at the JPMorgan conference this year, obviously, under very different circumstances. But thank you for all of those attending virtually to the presentation on our company. On Slide #2 -- all right, I'm having some technical issues here. But on Slide #2, you can see our forward-looking statements. And then moving on to Slide #3. To understand Apellis, it is important to [Technical Difficulty] All right. I'm very sorry. Am I back in the meeting?

Yes. Cedric, you're good.

All right. Great. I thought 2021 was going to be better for that but. All right. So starting again, my apologies for that. So I'm on Slide #3, starting off with our strategy. So to understand Apellis, it is important to know that we have 3 important objectives as a company. The first one is to establish systemic pegcetacoplan as a disruptive therapy across rare complement-driven diseases. The second key objective of our company is to be #1 in the retina. And the third objective for our company is to develop new technologies to control complement, something that we haven't spoken a lot before, but that you will hear a lot more about in the year and the -- in the years to come. The 2021 key milestones associated with this strategy on systemic program is the PNH launch in the first half of 2021. We have our PDUFA date on May 14 and look forward to having the first drug available by our company should that approval come in paroxysmal nocturnal hemoglobinuria. We also have 4 additional registrational programs that will be in development this year. As it relates to the retina, in the third quarter of this year, we will have the results of our Phase III clinical trial in geographic atrophy. This is going to be the seminal and changing event for our company, where we have a unique opportunity not just to introduce potentially the first drug for geographic atrophy, but also to acquire a place in the retinal practice where this disease is something that retinal specialists see sometimes as much as in half of their patients. And then last but not least, we haven't spoken a lot about research before, but we have been very active in the past couple of years on a number of fronts, which you will hear more about in this presentation as well. We are advancing 3 new compounds into clinical development in the next 24 months. On Slide #4. Complement, one of the oldest parts of our immune system, is important in a wide range of serious diseases. Currently, at Apellis, we are active in neurology, ophthalmology, nephrology and hematology. Initially with systemic pegcetacoplan and pegcetacoplan injected intravitreally in the case of ophthalmology. On Slide #5 is a highly simplified overview of the complement pathway. What is important to remember from this pathway is that it is incredibly complex, similar to the clotting cascades and an interacting network of more or less 30 proteins, mostly driven by serine proteases. That in order to control it, it's important to act at multiple points within that cascade. And pegcetacoplan, even though we call it a C3 inhibitor, is a molecule that latches onto that interacting network at 4 distinct points. It prevents C3 from binding to cell surfaces and then also once -- and should C3 binds to a cell surface, also inhibits the C3 convertase activity as well as both of the C5 convertases. It is that broad control of complement that we believe has led to the impressive efficacy results that we have seen in the many trials that we have run so far. On Slide #6 is an overview of where we are currently working with pegcetacoplan, which has the potential to be a disruptive therapy in a number of these indications. Starting off with our systemic program. Pegcetacoplan, injected subcutaneously twice per week, has the potential to help more than 275,000 patients globally. Currently, we are developing this molecule in paroxysmal nocturnal hemoglobinuria cold agglutinin disease, hematopoietic stem cell transplantation-associated thrombotic microangiopathy, immune complex membranoproliferative glomerulonephritis and C3 glomerulopathy in the kidney and then ALS where we started a registrational study a couple of months ago as well. We also had this distinct pleasure of announcing our partnership with Sobi, a Swedish company, in the fourth quarter of last year. This has already turned out to be a fabulous partnership for our company, where Sobi is taking on the ex U.S. development in these indications, first of all, the commercialization in PNH, but then also the operational clinical development in the hematological indications CAD and HSCT-TMA. Importantly, the intravitreal product that we have for the administration in the eye in geographic atrophy is still entirely owned by the company. And to place pegcetacoplan from a safety perspective in context, we currently have more than 250 patient years in systemic indications and more than 750 patient years of exposure intravitreally. On Slide #7 is then an overview of where these programs stand in development, and important for 2021 is we have a Phase III clinical trial that will start in the second half of this year in cold agglutinin disease. We have a Phase II study starting in 2021 in HSCT-TMA and a Phase III study in immune complex membranoproliferative glomerulonephritis and C3G. On Slide #8, then diving into the first key milestone of this year, the PNH launch in the first half of 2021. This is going to be our first launch and, first of all, a quick recap as to why pegcetacoplan is such a potentially life-changing drug for these patients. So PNH is a disease of the bone marrow, where because of uncontrolled complement activation on the surface of red blood cells, patients end up having a lethal disease that can be controlled for its lethality with a C5 inhibitor like Soliris or Ultomiris. And these drugs fortunately have been available for approximately 15 years for these patients and changed completely how these patients can look forward to surviving, quite frankly. But in spite of that, because the inhibition of complements happens too far downstream, these red blood cells in these patients are still exposed and vulnerable to complement activation at the level of C3. The result of that is that about 1/3 of these patients continue to require multiple transfusions. 1/3 of these patients may not need transfusion but continue to be severely anemic. And another 1/3 of patients, in spite of having closer to normal hemoglobin levels, only get there at the expense of maximum output of red blood cells from the bone marrow. This is something that we attempted to control. And 1 year ago, when we presented our company to you at this exact same conference, we had just released the data from our Phase III clinical trial called PEGASUS, of which you can see a summary on Slide #10. This was a head-to-head study to find out if we could improve on the shortcomings of C5 inhibitors in paroxysmal nocturnal hemoglobinuria. We enrolled 80 subjects. And after a 1-month period in which we added pegcetacoplan on top of treatment with eculizumab to see if these patients would get better, we then separated the groups and evaluated over a 4-month period of monotherapy how patients would fare. After those 4 months, we read out the primary endpoint. And then there was a 32-week extension label, open label in which patients could continue on pegcetacoplan alone, including the control group. And on Slide 11 is a summary of the results, which again, have been presented last year here and at different conferences. We showed superiority of pegcetacoplan over eculizumab of 3.8 grams per deciliter on hemoglobin levels alone. We also showed that 80% of patients were transfusion free compared to only 15% of patients on eculizumab. We showed the normalization on lactate dehydrogenase, which is a marker for intravascular hemolysis, of 71% of patients on pegcetacoplan versus only 15% on eculizumab. And we showed, importantly, a 12-point difference on the FACIT-fatigue score, which is a scale that we use to measure how patients suffer from anemia, so they're fatigued. And on Slide #12, you can see how that effect was durable, including in the extension period from week 16 to week 48 data that we presented in the fourth quarter of last year, and again, kind of showing that what we saw in the clinical trial was consistent, durable over time and continue to be -- continue to have a favorable safety profile. On Slide 13 is also something important that we presented at the American Society for Hematology, where we did a meta-analysis in the literature to find out what would happen with other C5 inhibitors like Ultomiris, so the study was run at Soliris. This is on Ultomiris. And what we found was that in this meta-analysis, when you compare pegcetacoplan to ravulizumab instead of eculizumab, that we had 76% more patients who were stable on their hemoglobin; 71% of patients more transfusion free; LDH normalization, 64%; and a 9-point difference on the FACIT-fatigue score versus Ultomiris. On Slide 14, in the past 2 years, our Chief Commercialization Officer, Adam Townsend, and his team have done a tremendous effort to prepare to make this drug available to as many patients as possible. That meant a concentrated effort in medical affairs, marketing, value-added access and sales, where we are truly committed to elevating the standard of care in PNH. That is illustrated by the fact that we already have an ongoing expanded access program available for patients in the United States, where we have been educating the physicians as to the need that exists and have very heavily engaged with the patient advocacy groups and the patients to make sure that everybody knows what to expect. On Slide 15 is then a summary slide of these additional registrational programs. Going back to the 250 patient years of safety that we currently have with systemic pegcetacoplan. The safety that we had with this program was comparable to what you would find with C5 inhibitors, with the notable piece of information that after that many years of exposure, we have still not seen a case of meningococcal infection. It is too early to draw any conclusions from that, but it is worth mentioning that when you are on control with a C5 inhibitor, you would see meningococcal infection every 100 to 200 patient years. So we are in a very good spot from an exposure perspective. And that is something that we aim to carry forward in these additional indications. In all of these indications, there are either no approved therapies or therapies like in the case of ALS that have not -- that have only shown a slowdown but definitely not a stop or reverse of disease progression. All of these are diseases that affect a large number of patients, and we look forward to hopefully making a difference here as well. On Slide 16, then moving forward to the second key milestone in 2021. Of course, the readout of our Phase III clinical trial in the third quarter. On Slide 17, a brief overview of what geographic atrophy represents. The best-known form of macular degeneration is wet AMD, where we have drugs like Lucentis or Eylea. There are drugs that in this form of macular degeneration are able to seal the blood vessels that grow into the retina that are very leaky and that when left untreated leads quickly to blindness. So these drugs, like Lucentis and Eylea, are site-saving drugs but these are not therapies that interfere with the disease process itself. And that is worth mentioning because 98% of patients with wet AMD that are on treatment with anti-VEGF agents after 7 years of dosing will also develop geographic atrophy. That, in addition to the 5 million patients globally that have the pure form of GA. And the best way to think of geographic atrophy, is a forest fire in your retina, where it starts in a certain spot, sometimes multiple spots and from there gradually expands at a rate of 1 to 4 square millimeters per year until patients go blind. On Slide 18, you can see what that visually represents to patients. So you see there on these pictures on the right side how essentially you get a dotted image. And to understand the impact of this disease on patients, 2/3 of GA patients become ineligible to drive within 2 years of diagnosis. And something worth mentioning here as well is that visual acuity, which in wet AMD is quite a good marker of disease severity, is a poor marker of disease severity in geographic atrophy because the very central point of vision in GA is often spared until the very, very end. So imagine reading a chart at the ophthalmologist, looking through a tube, you could do that well, but then imagine going through supermarket with a view that you have on this slide. Then on Slide 19, I want to take you through kind of the 3 important steps in the run-up to that geographic atrophy study. First, of course, the readout of the primary endpoint in 2017 in the FILLY study. This was a life-changing event for our company. What we had done is run what, at the time, was the largest Phase II clinical trial ever run in this disease. Huge [ comment ] for a small company like we were at the time, where we studied 3 groups of patients, approximately 80 in size each, a sham control and then patients receiving drug intravitreally either monthly or every other month. We did that for a 1-year period, read out the primary endpoint, then had a 6-month period in which patients stayed in this study without receiving drug and then had another points of readout. And on Slide 21 are the 5 important take-home messages from the FILLY study. First of all, we met our primary endpoints, both for monthly as well as for every other month. Number two, we had a dose response with what looked like a more impressive result for the monthly dose individuals compared to every other month. Number three, we had an increased effect over time, something that you should expect based on the pathology of this disease, especially in the area around the dead retina. It's not like the retina is dead or alive. It's dead. It is hurt and injured, but still there. And then it is alive and arguably not sick yet. So when you start treating these patients, you should expect that over time, these cells that are in the danger zone also start essentially getting better. We saw that in our study. The sham group behaved exactly as expected, which in the past in other studies has been an issue. And last but not least, not only did we see effect between the 3 groups, we also observed an effect in the treated eyes of those patients that had bilateral GA compared to their contralateral eye, further lending credence to the results that we had in this study. On Slide 22 is then an image of the primary endpoint in the study. Again, going back to that very important point that the rate of progression in our sham control set at 0.35 millimeters, which was more or less identical to the rate of progression in the Chroma and Spectri studies, 2 very large Phase III clinical trials, which unfortunately failed for lampalizumab, but were close to 2,000 patients progressed at a rate at least in sham of approximately 0.342, so very close to what we had in our clinical trial. Moving on then to Slide #23. When we did the eye-to-eye comparison. First of all, in the sham control, in line with what we had expected from natural history, patients with bilateral GA tend to progress at identical rates between the 2 eyes. And that was the case in our sham control as well. And you could say, well, that is a great way of analyzing the data, why not make that your primary end point, intra-patient control? Well, we don't do that because when you inject 1 eye with a drug, the contralateral eye can benefit from that. And in our study as well, we had something that looked like a fellow eye effect, where the sham control in the 2 active arms was not exactly moving as fast as you would expect. But in spite of that, we saw a trend for an effect and a statistically significant effect in the monthly dosed individuals and the trend in the every other month dosed individuals. But what you should most pay attention to here is that here, exactly like in the group-to-group comparison, the effect really kicks in from month 6 to month 12, where in the monthly dosed individuals, the slowdown is close to 40% in the treated eyes compared to the contralateral eyes. On Slide 24, the safety take-home message was in line with other studies using intravitreal administration, where the most important serious side effect is endophthalmitis that you can get when a pathogen finds its way when the needle goes into the eye. That also happens when you have anti-VEGF injections. And the rates that we had in this study, which was 2 cases of infections, endophthalmitis, out of approximately 1,400 injections, was in line with other studies. There's also the case of the exudations in this time. What I want you to remember of the exudations that were observed in the FILLY study is that these were small exudates. These were not cases of classical CNV, which is what a retinal specialist typically thinks of when they hear wet AMD. Classical CNV are new blood vessels growing into the retina. They leak very heavily. If you don't treat them with Lucentis or Eylea, patients go blind. Small exudates are the types of exudates that you can actually follow, don't necessarily have to treat but can treat. And when you do, it typically goes away. In our Phase II clinical trial, we have some investigator advice that we think has influenced the readout there. But importantly, we do not believe that in the Phase III clinical trial, we will have the type of incidence that we had in the Phase II clinical trial. And most importantly, because of the size, so that the lack of severity of this exudate, this has never been and will not be in our Phase III clinical trial, we believe, a safety concern for this treatment. On Slide 25 and the second important finding, which was presented as a late-breaking abstract at EURETINA last year in October. Presented on Slide 26, as already briefly alluded to earlier, when you go outside of the area of dead retina by 500 microns, you can see that the cells are already sick. They haven't -- they're not dead yet. So they're not showing up as "atrophy," but they are injured. And when we look at these cells and find out how do those cells fare when we treat these patients with intravitreal pegcetacoplan, well, in this post-hoc analysis, we found that we have a significant reduction in the rate of progression from what we call intermediate AMD or nascent geographic atrophy to the full atrophy. So again, further lending credence and conviction that what we observed in the FILLY trial was real. And then moving on to Slide 27 and the top line Phase III results that you can expect in the third quarter of this year. These are going to be 1,256 patients split between 2 studies in a Phase III program that by design was meant to be as close as identical to possible through our Phase II clinical trial: the same patient population, the same way of measuring these lesions. We had great p-values. Everything was robust. We decided to keep those things the same. We have, of course, better quality, more measurements. It is a 2-year study. Even though we measure out at 1 month, we do continue to have these patients randomized for a full 2-year period and take another look after that second year. Worth mentioning here as well is that the endpoint analysis is going to be on the absolute lesion size versus what we did in the FILLY trial, where we did a square root transformation. And for those of you interested in that, it is worth mentioning that there is no difference post-hoc between that way of analyzing. It's just that the FDA in the Phase III clinical trial wanted to go with the absolute lesion size. Also a question that we often get is what was the impact of COVID on this study. We, of course, had missed injections, especially in the spring when the first wave hit. We got this under control very quickly. We made deliberate and concerted efforts to make sure that it was easy and comfortable for patients to go to the retinal practices, which are typically based in an outpatient setting. And even with the second wave, we did not see a change. Now in the Phase II clinical trial, we had quite a few missed injections, and to some extent, associated with these exudations that we saw because patients who were on anti-VEGF treatment in the Phase II did not continue to receive pegcetacoplan in the Phase III clinical trial. Patients who do receive anti-VEGF would continue on pegcetacoplan as well, 2 drugs in combination. So we knew from the Phase II clinical trial that we had a lot of tolerability for missed injections. And by doing the analysis in the Phase III compared to the Phase II, we feel very good about the quality in these Phase III clinical trials as we go into the readout. And then moving on to Slide 29. We are advancing 3 compounds into clinical development in the next 24 months, centered on 3 objectives. On one hand, less frequent dosing. Imagine having the results and the clinical benefit that we saw in PEGASUS with something that would be much more easy for patients than a twice a week subcutaneous administration at home. Secondly, a pan-AMD therapy. As already mentioned, in wet AMD, treatment with anti-VEGF does not slow down geographic atrophy. How can we go after that very important patient population and provide a solution for that and beyond that an intermediate AMD and avoid the development of advanced AMD altogether? And last but not least, neurology, where we believe that C3 plays a critical role in many neurodegenerative conditions, and you can expect to hear a lot more about that in the months to come. So what do we have in stock for you in the next year? 2021 is a transformational year for Apellis, where we will really move forward from the preparation that we did in 2020. So in the first half of 2021, have the readout of the PRINCE study. The PRINCE study is a treatment-naive trial that we ran in PNH for a number of reasons, initially because we didn't know what to expect. At this point in time, I would say, kind of the only backstop that we may still need for a label expansion, but we don't believe we will. We believe that we have a broad label available to us purely based on PEGASUS, but PRINCE is there. The data will be available in the next couple of months, and we're very optimistic that we can repeat what we saw in PEGASUS in a patient population that is much more representative of the overall treatment-naive population. Then the potential FDA approval of pegcetacoplan on May 14 of this year, the start of the Phase III study in nephrology in C3G and IC-MPGN and data from our Phase I/II study in COVID-19. We completed the enrollments on our COVID study last month, and you should expect data on that this quarter as well. We have not spoken a lot about this, but we are convinced and have become increasingly convinced over time that complement plays a key role in the thrombotic microangiopathy associated with the mortality in this disease. And we are very hopeful that with APL-9, the molecule that we studied there, we may be able to provide a benefit to these patients, should they end up in the latest often lethal circumstances. In the second half of this year, we then have, of course, the GA readout, the potential EMA approval for pegcetacoplan and PNH, the start of the registrational programs in CAD and HSCT-TMA, the completion of the enrollment in ALS and the submission of an IND for new technology to control complement, the first of 3 in the next 24 months. And on Slide 32, again, to remind you of our strategy, where, on one hand, we aim to have -- to establish systemic pegcetacoplan as a disruptive therapy across rare complement-driven diseases, PNH, in 4 registrational programs to start with to become #1 in the retina with a key treatment available, the first one in this disease, hopefully, in geographic atrophy to the retinal specialist and then to develop these new technologies to control complement with a focus on complement factor C3. And with that, I thank you for your attention. I apologize for the technical issues at the beginning, and I'm happy to take any questions.

Okay. Just to -- a reminder to everybody on the webcast, if you want to submit a question, please use the ask-the-question feature in the portal. Cedric, if you want to introduce the broader team, we can get going.

All right. Wonderful. Well, so on the call here with us, we also have Tim Sullivan, our Chief Financial Officer; and Adam Townsend, our Chief Commercialization Officer, who can answer any questions you may have around that.

Our first question actually comes from the portal, which says given the fact that there have been some allergic and anaphylactic reactions to COVID vaccines being attributed to PEG components, what can you tell us about sort of the immune response to PEG component of pegcetacoplan APL-2?

Thank you, Anupam. So that is a very good question. We have, of course, been tracking that very closely and investigating that. What gives me great comfort is that the cases that we have seen of these anaphylactic reactions have been sporadic and have been on the first administrations of the product. So it is not -- if there were to be a sensitization to PEG that happens, you would expect that to happen on the first injection and with the booster of the vaccine to lead to many more cases of anaphylaxis. And at least from what we have heard so far, that is not the case, which makes us comfortable and confident that we are not kind of introducing an anti-PEG immune reaction in the global population, which, of course, would be a huge problem for us.

Okay. And maybe thinking about PNH here, the PDUFA for pegcetacoplan is in mid-May. So what's the baseline assumption for the breadth of the label? What are some of the key marketing initiatives going on in PNH related to pricing, market access, sales team build-out, segmenting the physician population, that type of activity?

Thank you, Anupam. I'm going to hand that one to Adam, if he is on.

Yes, absolutely. Thank you, Anupam. So we're in a really good place with the commercialization to get ready for the PDUFA on May 14. So we've completed nearly all of our launch readiness projects. So we have mapped out our demand forecast. We have our physician and patient segmentation complete. Our campaign and message testing has been completed with physicians and also with patients. We've got a very high level of patient journey, and we've also got feedback on what we believe our patient offering and support will be. Our field force is basically fully recruited. They will be all online and members of the Apellis team by the end of January. We got nearly 2,000 resumes for rare disease and oncology hematology salespeople over the last couple of months, so there's a lot of interest in joining our company and joining our team. We obviously -- we've been in the field for the last 6 months virtually and where possible face to face through our field-based medical affairs teams and also our market access teams. And they've been having great discussions to allow us to get ready to get all perfect for our May 14 PDUFA. So we're in a really, really excellent place for PNH commercialization.

We've got a question in the portal here about kind of the recent M&A activity in the complement space and how, if at all, that changes your commercial outlook for APL-2 in PNH.

Adam, do you want to take that?

APL-2 PNH, obviously, we are ready to launch in the U.S., and we should be doing that quickly and we have our partners, Sobi. So it hasn't changed anything about our plans for commercialization.

Got it. Tessa, I'm going to -- Tessa Romero from the team has some questions.

Yes. So now just a quick one. As we're thinking about the PRINCE Phase III treatment-naive PNH readout, I think guidance is 1 half of this year, can you just walk us through sort of what would be -- what you're looking for -- what you're looking to see in that readout? I think that there are 2 components of the primary endpoint being hemoglobin stabilization and then LDH normalization, so -- I'm sorry, LDH reduction. So could you perhaps maybe walk us through sort of a win scenario there on PRINCE?

Yes. Thank you so much, Tessa. So the win scenario is to control PNH with -- this is not a head-to-head study versus the C5 inhibitor, of course, but with a clear and convincing appearance of better control of PNH. It is worth mentioning that with C5 inhibitors, approximately 15 years ago, the "new normal" on LDH levels became 1.5x the upper limit of normal, which is, of course, not normal. But that became the standard for PNH therapies to try to get below that. So for us, it's important to get as many patients as possible under the upper limit of normal in LDH. I'd say that's the key one to look out for.

Maybe a couple of questions on geographic atrophy. Cedric, in your presentation, you talked about the change in the way the FDA is measuring the primary endpoint. So maybe you can walk us through any rationale for why that -- the FDA made that change.

Yes. Thank you, Anupam. That's a great question. So a couple of years ago, it became very clear that using visual acuity in geographic atrophy was going to make clinical trials very difficult. Because visual acuity, again, going back to that point of the central vision, you should imagine change is very little. And then once the fovea becomes involved, you go off a cliff and you lose 30 points. On average, a GA population will lose approximately 1 line per year, but that is driven by the outliers within that population. There was then a consortium that was organized between the FDA and the NIH, led by Wiley Chambers. And at the end, Wiley Chambers had a very famous proclamation where he said, I think we can all agree that a dying retina is a bad thing, alluding to the fact that you can measure a dying retina either using autofluorescence or SD-OCT. And that if you can reduce the rate of photoreceptor death, that, that should be acceptable for a group.

We got an e-mail question in the portal, which is on geographic atrophy. "Based on the data today, what segment of the patient population is this a clear treatment option? How big is that segment? And are you providing any sort of kind of peak revenue opportunity for GA that we should be thinking about?"

Yes. I will hand it over for Adam for a little bit more color on that. But I would start off by saying -- I assume that the question is referring to, if you are a patient with GA in 1 eye versus both eyes versus you're blind in 1 eye and have it in the other eye versus it has involved your fovea. There's a lot of kind of different ways in which GA can manifest itself. But before I give it to Adam, imagine yourself sitting in a practice with a retinal specialist who tells you your photoreceptor cells are slowly dying. That is an irreversible process, and every cell that is gone will not come back. We have something that can slow that down by, conservatively here based on FILLY, we could say, 29%. But if we are correct about the close to 50% in the second half of the first year, which you would carry forward potentially into the second year if you can slow it down by 50% or more, it's -- there's absolutely no question in our mind that most patients would choose that solution. And I think that is something that is reflected also in our discussions with physicians. And Adam, I'm going to hand it over to you to give some of our feedback that we have received.

Yes. Cedric says it very well, right? So one thing we found within our research is that there is a willingness to treat patients because there's no current therapy. And consistently, we get from retina specialists and ophthalmologists that the primary endpoint is the right endpoint for us to be looking at. And on average, 20% less lesion growth would motivate them to use within all of their GA patients that were suitable for the treatment. We've also found that patients are even more willing to accept the treatment, right? And we get a lot of feedback about comments on I want to preserve my vision. I want to make sure that I can see my grandkids for as long as possible. So if you're looking at 1 million patients alone in the U.S., 5 million globally, you can start to see how the product will be used by retina specialists and then injecting ophthalmologists. Now we have obviously done some segmentation work, and we can go into the details of the segmentation about whether the lesion is central versus noncentral and the impact in the fovea, et cetera. And you'll find that across the patient segments and physician segments, there's still a very strong passion to want to get this product to use.

Got it. Okay. Cedric, Tim, Adam, I want to thank you guys so much for taking the time, and thank you so much for a really productive session.

Thank you, Anupam, and thank you to everyone for coming.

I hope you guys have a great rest of the conference.

Thank you. Thank you, Tessa. Thank you, Anupam.