... would love to, obviously, there's a lot going on at Apellis. It's an exciting time. You have a new drug launch, so I would just ask an open-ended question: Could you update us on current state of affairs at Apellis and the outlook for the rest of the year? And we'll dive into the Q&A thereafter. Thank you, Steven. Great to be here after Labor Day, and for the first time at Cantor. Congratulations. Thank you. So this is a very exciting time for us at Apellis. We are going into the later part of this year as the company that leads the field in complement in general, with two approved products on the market between Syfovre and Empaveli, and an exciting pipeline to look forward to. The key behind the science that we have is that complement factor C3 sits central in that complement cascade and allows the best possible control of all of the downstream effects of complement, regardless of what the source of activation is. Of course, we have been in the launch with Empaveli for PNH for a couple of years now, but now with this new approval in C3G and IC-MPGN, a lot of exciting things to look forward to and an incredible opportunity to make a big difference in the lives of the patients that suffer from this disease. With Syfovre, we are now in a period of stable growth. We have given guidance in the form of low to mid-single-digit growth for several quarters to come. But what's important there is that only a small number of patients have been treated so far, and the opportunity to really, I'd say, educate the retina community around the disease state, what it means for patients, what the drug can do for patients, and importantly, the functional benefits that are associated with the lesion size reductions that you see with Syfovre, on which more and more data matures, is also a really unique opportunity for us. Then, as it relates to the pipeline, we have one exciting phase II clinical trial that is currently ongoing, where we combine a subcutaneous injection with Syfovre, and that allows the... If the trial is successful and the program is successful, would allow us to reduce the injections from every two months to every three months, and of course, also looking for an outsized benefit in terms of both lesion size reduction and again, that functional benefit that we are looking for. We also have two phase III clinical trials in the kidney coming up in FSGS and delayed graft function. Those are going to start enrollment is planned for, again, the later part of this year. And then preclinical programs that are maturing as well, which we will be talking about more next year. All of this on the background of a stable financial situation. You may have seen what we did in terms of our royalty deal with Sobi that provides us with a solid balance sheet and kind of a great growth platform for us as we go into next year. It's a great overview, and hopefully, we'll cover most, if not all of that, in the 30 minutes we have. I do, of course, want to start with the C3G launch, though, and drill down on that. How is that going? It is going as predicted. What really stands out there is the unmet need that exists in C3G and IC-MPGN. When we meet with investors, we often get... You know, it's a new disease, right? The demographics are difficult to gather. I mean, you have to find out: where are these patients? Who are they? How many of them are there? But the one thing that I want people to remember is that doing a kidney biopsy, which is really kind of the criterion that you need to identify a patient as having a disease, is a serious intervention, right? I mean, a kidney biopsy is painful, can be dangerous, and is not done lightly by nephrologists. When we say the number 5,000 patients that we have identified that we believe are out there with C3G and IC-MPGN, that is based on highly robust data. It is also worth noting that if that biopsy is done, it's because the patient is highly symptomatic. The unmet need there and the symptomatic implications of having C3G and IC-MPGN are not to be underestimated. A really unique opportunity to make a difference. Obviously, in VALIANT, we had that broad readout where we did not just see these, you know, unique and first-in-class reductions in proteinuria, but had the trifecta of readouts also on deposition of C3 in the kidneys, proteinuria reduction, and eGFR stabilization across IC-MPGN, C3G, pre-transplant, post-transplant, pediatric, and adults. Really kind of everything has been covered there, and that really stands out with patients. Now we are building on other things that we think will further contribute, and one little element that I think is worth noting there is that the ability that you know that we have seen that we will continue to explore to potentially reduce concomitant medications, including steroids, is another really important opportunity for these patients. The launch is going as expected. You know, it will be a gradual uptake, of course. Patients need to get vaccinated, et cetera, but really happy where we stand. We've been speaking to nephrologists, obviously, and, you know, asking, "Have you prescribed Empaveli?" But also trying to draw some parallels from the Fabhalta launch, which, you know, has a few more months in C3G, but of course, is only indicated in certain populations of C3G, not in IC-MPGN not post-transplant. And yet the uptake seems strong. I mean, we can find doctors that have already prescribed it to 25% of their C3-eligible C3G patients. Is there any reason why demand in IC-MPGN or in adolescents or in post-transplant, the areas where Fabhalta is not even indicated, would be any different, stronger or weaker than the adult C3G population? That seems to be pretty, you know, eager for treatment here. Yeah. So it's a little bit early to kind of make those nuanced interpretations, but I'd say, what stands out for us competitively is not just the breadth, again, of the populations, as you mentioned, that we studied, but most importantly, the impact that it has on the kidney, right? I mean, so the trifecta of data, like we call it, and most importantly, how that C3 deposition in the kidney goes away completely in as many as 70% of patients after six months of treatment, and the continued benefits that you see after 52 weeks of treatment, that is really something that we believe we can build on. What expectations would you set for maybe Q4? I think Q3, I guess, the expectation would be, don't expect much. It's very early. Patients have to get vaccinated, et cetera, and then what metrics do you plan on disclosing? Can you just remind us of how we're gonna measure success of this launch in the back half of the year? Yeah, thank you, Steve. So in the first earnings report that we will have, we will just talk about patient start forms and payer uptake. Then afterwards, in subsequent quarters, we will expand from that, of course. Okay. The 52-week data that was presented at ERA, how can you leverage that in the market? I mean, just we've heard sort of competing views from some of the physicians we've been talking to. One being, I mean, look, there's actually experience with this, but also Fabhalta. I mean, we know complement in other diseases, PNH, for instance, you have a lot of chronic safety data. But then we've heard from some other physicians like, "Look, we only have 52 weeks of data. I don't know, maybe there's theoretically an infection risk long-term with chronic use." I found that very odd, and you also have a long-term extension study, right? Which will gather years of data. So, I mean, do you think that's... Do you think chronic use and taking people off therapy is something that's going to happen, or there's just no basis for expecting anything like that? And how can you leverage the long-term extension data that you're gonna get to assuage any of those concerns? Yeah. I think once patients are on treatments. And we've seen that in PNH, right? I mean, we see very good compliance rates, right? PNH is, of course, a different disease, but 97% compliance. It's hard to find in any disease state. And I think what really stands out from the experience that we've had with Empaveli, where we are now somewhere between 2,500 and 3,000 patient years of dosing, is not just the outstanding efficacy that we have observed, but also the remarkable safety profile of Empaveli. I think, you know, if we go back even five years only, and had said that the meningococcal infection rates with Empaveli, you know, would be. I mean, so far, no infections with encapsulated meningococcus. After that many patient years, where you would expect it to see, as is the case with C5 inhibitors, every one in 200-300 patient years, thinking that C3 could be potentially safer than C5, that is something that is, you know, really something that we can continue to work on and that stands out here. And all of that has everything to do with the mechanism by which pegcetacoplan controls C3, which is a buffered way of, you know, putting that complex interacting system of enzymes on ice, rather than trying to remove one element out of it and trying to control the whole thing that way. So that is, it's a mechanism that has given us those remarkable efficacy profiles in all these trials that we've run now, but also this remarkable safety profile that we've observed. Can you talk about just the reimbursement in C3G, just anything from a co-pay assistance or out-of-pocket sort of assistance effort that Apellis is doing, and maybe how that compares to Fabhalta? Because we've heard different things about just you know, Novartis making ways to ease access to that. And is there anything noteworthy here, or is this gonna be pretty straightforward, getting everyone covered? Nothing it's pretty straightforward. You know, it's the same. We've been you know, obviously, Empaveli's been on the market for a while, so we're pretty used to it, and it's a pretty similar. It's a very similar, you know, prescriber base, so. Okay. What about the receptivity of C3G patients, I guess, just based on the historical standard of care, the polypharmacology that they've sort of experienced historically, to an injection versus obviously the oral option? I mean, would patients sort of defer to the oral option, and have to be swayed by the efficacy data of pegcetacoplan, or do you think they're, in your, in the early experience that you have or just through the clinical trials, has there been any issue or resistance to the subcutaneous device? Yeah, no, it's, it is, it's actually quite, quite easy to self-administer this product. You know, everyone who's who has tried it, you know, it's, it's very easy to learn, and, and you get used to it, rapidly. I think what's interesting there is that, again, the most important element is the efficacy differentiation. But then the fact that in a disease like this, which are very serious conditions, of course, being able to control your complement system without having kind of the anxiety around compliance as well, is something that we've also heard from nephrologists. In other words, forgetting a pill, as we all know, can be very easy to do. With Empaveli, should you forget to self-administer or, you know, there's a delay because you're traveling, whatever it is, you can catch up for that for a couple of days and kind of go back on the schedule where you were, without affecting the efficacy profile. So again, I think it all comes down to what is the unmet need. How serious is this disease? And it's very serious for the majority of patients. And how well do you want to stabilize the trajectory for yourself, right? And those are the things that we can really detail on and plan to do so. The other thing that we've heard from nephrologists, which I think is very fascinating, is there's maybe a hesitancy in this disease to actually transplant patients, because they're just gonna be refractory, and there's actually- Yeah Nothing to do, and so you're putting them through a transplant, maybe essentially for not a lot of good reason. That's changed now, obviously, the Empaveli- Yeah can be used post-transplant, and so there would be actually more of an incentive to transplant a patient who could benefit from it. I mean, what, what's your thought on that? Are you hearing that as well, and do you think that just globally, sort of beyond Empaveli in isolation, but just the treatment paradigm for these patients, you can sort of improve and improve awareness of, and leverage that to build a brand in C3G? Yeah. It's hard to speculate on that, of course, but I think what really stands out here, and you pointed it out, is the excitement around what Empaveli can do in transplanted patients, period. I mean, that's the-- It's an area where most development programs do not even try to go in the transplanted population because it's complex and you know, more difficult to do operationally and also commercially. But in this particular case, the data really stands out that we've generated. And also, hand in hand with that, as we've talked about before, the impact that Empaveli has had on the xenotransplantation field, which is emerging- Mm-hmm ... of course, and where in all of the last transplants that were done- in the xenotransplantation field, C5 inhibitors were supplanted with Empaveli, which were, you know, organ-saving interventions at that moment in time. So these are all transplantation nephrologists and transplantation surgeons that, of course, are diving into the differentiation between C3 and C5 and seeing the impact that Empaveli can have. Maybe let's pivot to GA at this point. We can probably come back, and I certainly want to ask about some of the other opportunities in kidney later on if we have time, the phase III programs. But on GA, I guess first question is, when do you expect you'll start providing Syfovre annual sales guidance? Would that come next year? Yeah, that's a good question. We, you know, we did give some guidance in terms of injection growth. We said low- to mid-single digits, which tracks what we saw in the first and the Q2. You know, this is sort of the first steady, I would say, steady year. We had a, you know, two-year kind of launch period that had some competitive dynamics, some dynamics that were- There's a lot going on, yeah. ... that were unique to Apellis and Syfovre. So, I think it was impossible for us to consider giving guidance at that time. Now we're starting to see Syfovre in a steady place, which is really encouraging for us. Whether or not we can give guidance next year is a good question because it might be odd for us to give guidance on Syfovre, but not to do it with Empaveli, and, you know, people like total revenue guidance. I think you should do it. You know, it's a timing concept, but certainly, we're in a much better place to consider that going forward. Okay. You know, we'll try to give any metrics we can to help people understand what we think is gonna happen with Syfovre. Okay, and yeah, just to clarify, so the low- to mid-single-digit growth that you've spoken about, I mean, that's volume, right? And so- That's volume. That's volume. That's injections. Yeah. That is injections into the, you know, the patients. Yeah. I guess, how has the market share been tracking since the last update? 'Cause this seems there's always been a bit of a disparity between you and the competitor, Astellas, and what's been reported in terms of aligning on time, reporting new patient share versus total share, and it seems to maybe be ebbing and flowing among new patients. So what's the current status, if you could update us on any share that you'd be willing to comment on? Yeah. Well, you don't have to do mental gymnastics to understand the leadership position of Syfovre, right? Yeah. It's the market leader on new injections, on total in number of injections, on total market share, on revenue, on payer preference, on academic presence. I mean, That's currently, or that's just speaking sort of historically to the last six months or the last year? That is currently the case. Yeah. Yeah. The only metric on which we lost ground to our competing drug was in the summer of last year and the fall of last year, where on new injections, we fell behind them, and we ended up in a situation back then down to going as low as 60% of new injections to the competing product versus 40% for us. That flipped around completely since then and is now at about 55% of new treatments in favor of Syfovre. Just in terms of setting expectations for people, I mean, would there be reasons, I don't know, getting into new clinics or just the way that you've seen the sort of competing marketing efforts playing out, why that would continue to ebb and flow? Do you think it's stable now, or it's just gonna be fifty-five, forty-five in perpetuity? Or are there ways that either you or the competitor can actually sort of sustainably change that trend? Yeah. I think there's two important dynamics there. One is the generation of additional data. I mean, we have this, you know, amazing GALE extension study, right? Which has generated the largest data set by a mile in geographic atrophy ever generated. And that is something that allows us to have all of these presentations. I mean, every major retina conference, we have multiple podium presentations. At SRS, we had, you know, more than an hour completely dedicated to Syfovre. There were zero for our competing products. And that is, of course, because the data is not there for that competing product. That's something that will continue to stand out. The second aspect, and I think this is really important, is that we've not just learned about the efficacy of Syfovre in patients and continue to learn more, we learn a lot more about the impact that this disease has on patients, most importantly, on the functional impact that it has on patients and the functional benefit that Syfovre can provide to these patients, and that is something where, again, the competitive differentiation is very, very clear. So I think competitively, we feel incredibly good with where we are and where we are going. The important second piece to this, though, is growing the overall market, and that goes hand in hand with, you know, sharing those data, teaching physicians that these patients with geographic atrophy rapidly decline. You know, that it's not just best-corrected visual acuity, which is a poor measure. A little side note, I mean, we've spoken about this ad nauseam. I mean, patients with geographic atrophy can have stable, best-corrected visual acuity for years, while their overall visual function declines dramatically, and they lose more and more activities of daily living. That is something that we have an opportunity to use to let physicians understand what they can do for their patients. I have more market questions, but actually, on this point, I just wanted to pause because you mentioned the phase II program with the siRNA and then extending the dosing interval of Syfovre as a result of that. I mean, that's a sort of a line extension strategy for Syfovre. But it also feels like an opportunity where you, I mean, you're in clinical studies with Syfovre here, and you can generate more data, and you can address maybe some of the gaps that you think would exist in people's understanding of the profile. Yeah. I guess, how can you leverage that development program to your advantage for that combo product, but also Syfovre and compound...? I'm asking a lot of questions at once here, but just the development path in GA, has that changed at all since you ran the phase 3 DERBY-OAKS program? Do you have an understanding of how that's gonna- So it hasn't really changed- Okay. But we believe that it will change. Okay. Because, you know, right now, with artificial intelligence, with new methodologies in which, you know, because of our data, we are able to be the leader as well. We are now working on something called Functional OCT, where with a simple OCT measurement, you can actually determine what the world looks like, for that patient. Not just today, but if you have a patient with historical OCTs, you can go back and see, like, what the world looked like five years ago. This is how it has evolved over these years, and it's dramatic, right? I mean, it's not just, can this patient read letters on a chart? But, you know, what does the picture look like? How does that picture evolve over time? And it provides, most importantly, an understanding, not just for the physician, but also for the family members of that patient. ... to understand what they're going through, and then secondarily, of course, to understand what the impact of treatment will be. And I personally am convinced that in the very near future, in phase III clinical trials, when you use those functional endpoints, right, there's no more question on: Okay, what does lesion size growth reduction mean? What is that? How is that correlated, et cetera? That, I'm convinced, will go away and provide- You think regulators would be amenable to some of these new technologies that move past the eye chart? I mean, they already moved past the eye chart, obviously, in GA. Correct, yeah. This would be a functional- I am personally convinced that they will. I mean, already with the EZ zone analysis, which- Yeah ... to be clear, is not a functional analysis, it's kind of an interpretation of an anatomical endpoint, right? But that, in my opinion, clearly indicates that the FDA, and outside of the FDA, for sure, the regulatory agencies are interested in exploring how to measure function in GA. Okay, and are you using this functional OCT prospectively in the phase II program for this, or is this something to come? We are. Okay. And given what you said, though, about the fact that you can go back to old OCT readings, I mean, can you go back and readjudicate DERBY and OAKS and sort of see what the functional OCT data look like in those phase IIIs? We can indeed. Okay. And it is. It's remarkable. Much more to follow on that. Okay. Starting at Angiogenesis in February, we'll have more to present on that. Terrific. Okay. Back to Syfovre in the market, do you have a good handle on seasonality of this market at this point? Just thinking ahead to quarterly expectations. I mean, you set the volume growth, but there are some other dynamics, the paid versus unpaid vials, and that's been affected by, the patient, you know, copay assistance charities and the disruption there. So, I mean, just in terms of Q3, Q4, for Syfovre specifically, anything to note that you've learned? Yeah, we're learning a lot this year. Okay. Again, this is the first year that we've really had what I would call a steady state in the market. So I know, even with the copay assistance organizations being underfunded, that, you know, that throws another wrench into it. But we can get a sense, I think, based on how things go this year and, you know, get better guidance next year on what we think seasonality looks like, so. Just on that, the charity, I mean, is there any potential for refunding of the copay assistance charity or a new charity, specifically the one that would be dedicated to GA patient support? Look, at this point, our understanding is that the charity is closed to new patients, and we don't expect that to be a meaningful part of our, you know, business plan going forward in terms of expectations of patients on commercial drug, so. What would be the expectation you'd want to set for just unpaid vials and by number or by proportion to the total vials going forward? Yeah, that number was $13 million in the last quarter, in terms of dollars. That impact, that incremental impact of unpaid vials from this. We did say that we didn't expect that to change. I think it was a little bit less than that in the Q1, and it may even be more this quarter. I mean, it's something we can't really tell. It's-- We'll figure out what it is, but, Maybe a little more this quarter. You said slightly. Who knows, right? Who knows. It could go up, it could go down a little bit. It's gonna stay in that zone, right? Give or take a couple million, so. Okay. So on the pipeline, I mean, there's so much focus, obviously, on the commercial programs, that it's... I've done it myself here. I left five minutes to discuss your other phase III programs, and we talked about the phase II, but would love for you to set the stage, just the expected timelines on delayed graft function and FSGS as well. Just where we could see data and what do you think the opportunity is? Yeah, so these are two exciting phase III clinical trials that we kind of, of course, built on the data that we generate in VALIANT and C3G, where we saw kind of that exquisite target engagement that happened in the glomerulus. These two phase III clinical trials are on track to initiate in the second half of this year. You know, we're not guiding yet on when they will be completed or the designs, et cetera, but I think as opportunities to build on the franchise of Empaveli, really unique opportunities, right? I mean, with FSGS, probably as many as 13,000 patients in the U.S. alone, that could be candidates for treatment, and then with delayed graft function. You know, in deceased kidney donors in transplantation, you are probably talking a little north of 20,000 patients per year. Mm-hmm ... that would be treated for approximately three months, in case that they have DGF. So again, meaningful opportunity, and again, the biology behind it's firmly supporting what we're trying to do. Yeah. I mean, in delayed graft function, is there any precedent that you draw from in terms of conviction that complement inhibition, C3 inhibition specifically, is gonna be effective? You have all this experience in transplant. Can it be applied to DGF, and why? Yes and no, right? I mean, of course, we learned a lot from transplantation that directly will translate into that experience as it relates to safety, et cetera, of course, as well. But, you know, the role of complement in delayed graft function was already known when I was doing transplantation work twenty years ago, right? So it's not... You know, now I feel old. But, you know, really exciting fields, one that we know very well and where we think we can make a big difference. And I think in FSGS, I mean, we know some, and we'll learn more about just the regulatory path and expectations there, but in DGF, I guess it's maybe not as well understood or appreciated by folks, but there is a guidance document, I think, that exists for prevention sort of trial designs. But are you comfortable with your understanding of what it takes to get through the regulatory checks there? Yes. Okay. So again, kind of, you know, we, as competitors learn from us, we learn from our competitors, and that regulatory path is available and one that we think we can explore. Okay. So you mentioned upfront the decision to sell the remaining Empaveli European economics to Sobi. Would love just, Tim, to get your sort of postmortem on that. Why'd you do that? I mean, what the current state of the balance sheet and Apellis financially, how are you feeling? I mean, honestly, that seems like a lifetime ago. It was July 1st, and it seems like forever ago because we've got our C3G approval and everything in the meantime. But at the time, obviously, we were getting a lot of questions about our balance sheet, even though we felt we were in a very strong position. We ended the quarter with $370 million in the bank, and we thought that was great. I mean, we were and that would take us to profitability, but we still were getting questions, and we also had people kind of, you know, not being able to get their arms around the market opportunity. So doing this deal really shined a light on the opportunity and the value of even just that royalty ex US. And just to make one point, we did cap that royalty. So on an NPV basis, we have a very nice NPV for that royalty, and by capping it, we're able to capture the upside beyond, you know, the expectation of when that, you know, that will run out, and we've paid that essentially $300 million or whatever it is back, so. It was a nice deal. We feel very good about it. Yes. Yeah, we feel great. Was it competitive, or was it always Sobi knows what they have here, and let's just go at it? It was actually extremely competitive. There were a lot of third parties, but Sobi stepped up, and they obviously know the value of this program better than anyone, so. Okay. What would you fill out? You mentioned some preclinical programs that maybe will come to light next year or over time. Anything you can say about just areas of interest, mechanisms, what you've been working on behind the scenes? Yeah. So there are two important programs that we're working on. One is. Let me highlight one of them that we're very excited about, and that is the neonatal Fc receptor gene editing program. This is a program where, in our collaboration with Beam, what we've done is taken that receptor, and with the single base edits, be able to completely eliminate the recycling of immunoglobulins from the circulation, which, as we all know, of course, leads to a reduction of approximately 50% of IgGs in circulation without affecting albumin. So in other words, you know, with a single injection, you can have that treatment and have the impact and the benefit of that for the rest of your life. Now, of course, in gene editing and gene therapies, there, you know, there has been a lot of turmoil recently. What stands out here is that we use LNPs, not AAVs, to deliver the editing cassette, so that is important. And the second piece is that we are, with this program, not going after monogenic diseases, which, you know, has been the focal point of most gene therapies recently, and where, you know, the risk arguably is greater. So we're gonna, we believe we have a path forward, and we'll share more about that next year, to do this in a highly receptive population, where the safety, the risk-benefit profile will be very clear compared to what may have happened before. Yeah. Looking forward to that and thanks so much for a broad conversation. Thanks to everyone in the room for listening. Thanks to everyone on the webcast. Hope everyone enjoys the rest of the day at the conference, and join me in thanking Apellis for conversation today. Thank you, Steve. Thanks, Steve.