Welcome everyone to the 30th Annual Credit Suisse Healthcare Conference. I'm Tiago Fauth, a Biotech Analyst here at Credit Suisse. We're joined today by Apellis. We have Tim and David from the company, and we're gonna have a fireside chat. If you guys wanna try to ask any few questions, if you can send them my way, I'll try to work those in. The email is Tiago, T-I-A-G-O.F-A-U-T-H@credit-suisse.com. We can get started. As usual, we can start bigger picture updates. Huge year for you guys. I'm sure you're tired of telling the story. You just had your earnings call, but if you can give us a brief introduction, kind of the key catalysts that you have in 2021 and the outlook going forward, and we'll take it from there. Yeah, sure. Just as a brief background, Tim Sullivan, I'm the Chief Financial Officer, and with me I have David Acheson here, who runs our U.S. commercial. I've been with the company for about seven years, and David has been building out our commercial organization in the U.S. for a little over two years. You know, at Apellis we are a leader in complement. Complement is part of the innate immune system, an old part of the innate immune system that when uncontrolled can result in many different severe diseases. Our focus is on C3, which is the central component of the complement system. We have a lead drug that was recently approved for systemic administration for paroxysmal nocturnal hemoglobinuria, which is the primary indication for systemic C5. At least historically, it was the primary and first big indication for the C5 inhibitor class. Our lead drug is a C3 inhibitor, but it's also a C5 inhibitor. As such, it has a very unique mechanism of action. It's a multimodal mechanism of action. It targets C3 as well as the downstream convertases, the C3 convertase, the C5 convertase, and as a result, has broad complement control. This year was a really big year for us, because we got approval in May for that drug, which we call EMPAVELI in the U.S. The trade name will be Aspaveli ex- U.S., but in the U.S. we call it EMPAVELI. In May, it was approved based on a phase III program that showed nearly 50% improvement in hemoglobin over the then standard of care, Soliris, in patients who were anemic while still on C5 inhibitors. We just finished our first full quarter, where we achieved $5.3 million in revenue, so a strong start to the launch. That's been a big year for us from a commercial perspective, making us a fully integrated biopharmaceutical company. We also had a huge readout in our phase III program for geographic atrophy. That happened in September. Geographic atrophy is the leading cause of blindness in people over 50 in the developed world, with about 1.3 million people in the U.S. who have geographic atrophy and around 2 million people in Europe, and then sort of 5 million globally in the developed world. The rest are in the rest of the world. We have those results. It's been a huge year for us on both scores. In addition to that, we also have four late-stage development programs for the systemic indication of EMPAVELI that are either ongoing or soon to be started. Those are in partnership with our partner for EMPAVELI, which is Sobi. Sobi has the ex-U.S. commercialization rights, and we are co-developing in C3G, cold agglutinin disease, ALS, and hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Together, those represent about 34,000 patients in the U.S., on top of the 1,500 patients or so that are addressable with a C5 inhibitor who have PNH in the U.S.. Then beyond that, we have research programs. We have several of those we talked about in our R&D Day this summer. We had four or five we talked about, which we can talk about more if you like. We also announced a partnership for gene editing with Beam for complement diseases. We're excited to take all of that forward into 2022. Cool. No, that's helpful background. Obviously the bigger focus recently has been on GA readout, right? Wanted to unpack a couple of things there, at least get your latest take on it. Again, you had recently presented a series of post-hoc analysis across that data to try to understand a little bit better the outcome. The phase II FILLY data set looked impressive, especially from an efficacy perspective. You had some differences between OAKS and DERBY- Yeah. In your phase III. Like, could you kinda just highlight at least the most important post-hoc analysis that you think kind of helps to elucidate that or any other factors that actually help to explain some of the disparities from a strong phase II to a phase III program that had different results between the two trials? Yeah, sure. It's a great question. It's the question, right? The question, right. Exactly. The one thing I would tell you is that I think what we always knew academically, but what we've really learned in our study, especially when you have, you know, a drug that clearly works. The question, right, when you have this type of data set is how do you figure out how well it works is the variability in the disease. I think that, you know, we did a number of post hoc analyses that we put out really pretty quickly, that kind of gave a little more color to the top line. The top line was all pretty much pre-specified. There was one analysis that wasn't pre-specified, but we showed the, you know, the two individual trials. We showed the pooled data, we showed the safety data, and we showed the extrafoveal data, which was a pre-specified analysis of approximately 460 patients or so, a pre-specified large analysis of extrafoveal data. But we also showed, I think probably the kind of data that helps you figure out where something happened. We can't actually necessarily attribute too much to one thing about what happened with DERBY, but we can kind of narrow in on where it happened. Primarily that was ex-US in DERBY, as you probably have seen from some of these analyses. But what we tried to do was to sort of level out the playing field. There were a couple of really important post hoc analyses. One was the fellow eye efficacy. That's probably the most important analysis. In geographic atrophy, when you have a patient who has geographic atrophy in both eyes, those lesions tend to grow at more or less the same rate. There's some small differences, but they grow more or less at the same rate. What we ended up showing in a post hoc analysis was you can see very clearly that when you give pegcetacoplan either monthly or every other month, you can get one eye to slow down relative to the progression of the other eye in these bilateral GA patients. That's a really important analysis because even in a study as big as DERBY, you could have these imbalances that can drive, you know, a complex result or a confounding result when you compare it to sham. Having this internal control for the bilateral GA patients gives you a second way to look at the data. One of the most important things about that is when you look at FILLY, DERBY and OAKS, those differences were highly consistent. Again, rather than worry about the baseline characteristics or drivers of the different progressions of the different groups, you have this internal control excluding the sham. Even in the sham, you can sort of show that these eyes tend to grow at the same rate when they're both untreated. That's really important. The second one would be the covariate analysis, which is a way to do that in a sham-controlled sense, but to normalize for these baseline conditions. Just to be very clear, what we saw, we had eight of these covariates that could drive disease in one direction or another. Eight of these. It's really hard to pre-specify or balance for these in trials. It's just a highly variable disease. You know, to add to that, when you look at the other really large phase III program that was run, which was the lampalizumab studies done by Roche, they had three that they talked about quite, you know, quite a bit. The largest one was GA lesion size, and the GA lesion size could, in the smaller quartile, would grow about 1.69 sq mm, but the largest quartile grew 2.31 sq mm. That's an enormous difference. If you have an imbalance in that alone, that can explain the difference when you compare one group to sham. The great normalizer, again, is the fellow eye analysis, and that's something that we gave, you know, way back in the day on FILLY. It's what gave us a great deal of confidence in our phase III program, and we showed it in DERBY and OAKS, and it's very consistent. For us, that's really the crux. These post hoc analyses are actually super meaningful, and they give real context to the top line and the other pre-specified analyses. Got it. That's helpful. And perhaps again, the phase III program was the first time we actually saw or at least that you explicitly analyzed a pretty distinct treatment benefit between foveal and extrafoveal lesions. Right. Was that something that could have been predicted prospectively? I'm curious what drove that analysis and if that could actually impact the potential addressable population at all or not. Well, again, based on our FILLY study that, you know, we wouldn't have necessarily predicted that. Again, these are small, these start to get very small numbers when you- Yeah. I mean, already FILLY is, you know, it's less than half the size of either DERBY or OAKS. It's 246 patients. It's approximately 80 per group. When you start to get to extrafoveal, the numbers start to be very small. What I will say is, I think, the biggest and most reliable natural history study is probably the lampalizumab studies. If you look at those, you know, the foveal versus the nonfoveal, the extrafoveal grew at pretty different rates. You could definitely tell that one grew faster than the other, but we couldn't tell necessarily whether our drug would work better in one or another. The answer is no, we couldn't tell. Got it. Now that you have established that benefit, is it more about just having greater efficacy in faster-growing lesions and having some benefit in slower-growing lesions? Is that the right way to think about that distinction mechanistically and biologically? Or is there any other way to assume that the response was greater in that subset? I think, you know, it's clear that there is a bigger benefit in extrafoveal, but we also think there's a meaningful benefit in the foveal lesions. It's really. You know, we looked at a really diverse patient population in this study. We enrolled all comers. Whether they had, you know, as long as they fit that, you know, one to seven disc area enrollment criteria in terms of lesion size, didn't matter if they had fellow eye CNV. It didn't matter if they had foveal or subfoveal. We really wanted to look at an exemplary population, and we think, you know, overall, yes, extrafoveal does benefit probably. You look at this, it looks much more like FILLY, right? It looks much more like the 20%-29% you saw in FILLY. This is 23% every other month, 26% monthly. These are really strong and clinically meaningful data. We also think, you know, there needs to be a solution for these patients who still retain vision, especially those who are losing that last portion of their central vision. You know, it's important to give them an option as well. Okay. That's fair. Yeah, and honestly, again, relative to initial expectations perhaps, DERBY and OAKS did show a pretty amenable safety profile, right? Sure. Can you contextualize the rate of inflammation that you saw? How does that compare to other intravitreal therapies out there? And just to be clear, just there's some variability depending on how you want to classify CNVs or the exudations. How comparable is the FILLY data versus DERBY and OAKS? Or how much does that criteria change based off of some of the learnings from the FILLY study? Okay. I'll start with the first part of that question, which is the rates of the other kind of AEs you typically see with an intravitreal administration, and this goes for the VEGF inhibitors, right? The rates of endophthalmitis and the rates of intraocular inflammation. In both cases, those were generally in line with the reported studies for other intravitreal therapies. I don't think anybody. We've never certainly been, you know, heard anybody raise a flag around those. You know, we had a little bit more of that in the endophthalmitis in the FILLY study than I think we had two cases or something, so people were initially worried about that. Just the small sample size, yeah. Small sample size and who knows. I think to some extent, the same goes for what happened in FILLY. In FILLY, after 12 months, we had 16% exudation in the monthly arms, 6% in the every other month, and 1% in sham. Those numbers, I think, raised some, you know, concern around the safety risk for administration of pegcetacoplan, and maybe in some cases, people thought it may limit the use. Those again, were pretty small numbers when you start to have an incidence of this type of AE, but FILLY was designed, you know, or was enrolled at a time when the lampalizumab Roche study were being enrolled, and those studies excluded patients with contralateral history of CNV. We ended up getting in the FILLY study, we think, a higher proportion of patients. We had roughly 40% of patients who had a history of wet in the contralateral eye. What we know is that those patients have roughly 4x-5x higher rate of exudation in the eye that doesn't have that history, right? We had a huge number of patients, and we think that's what probably drove that. Once you went into the phase III studies, we had a more normal 20%. We also had a situation where the treating physicians were not the same physicians that were calling the exudations. In both cases, both in FILLY as well as in DERBY and OAKS, those are physician-reported, how they're reported, how they're diagnosed, how they're called, it's all the same. We did change the terminology, though. Initially, we called those, and I think it was a real disservice not only to us, but to the, you know, to the situation, we called those wet AMD. wet AMD. I think you remember that, right? I totally remember that. Just, uh- We spent a lot of time discussing. Talked about shooting yourself in the foot with terminology. That was not, you know, the wisest of choices because we are the ones who coined it. You know, these were all generally small exudates, right? We ended up calling these exudations, which is what they really are. These were not classical CNV. In fact, in FILLY, we had all of these cases that were diagnosed as having officially CNV were occult, so they weren't classical, the kind that you think of when you think of a massive leak in the eye. Yet that terminology implied that. You know, we ended up reclassifying these as a name, as, you know, exudative AMD or exudative, events. Yeah, we changed the name, but everything else is the same. I don't know. I appreciate the clarification. Sure. Obviously, I mean, the big question is the regulatory plan going forward. You guys did speak to that in last earnings call. You do expect to have a meeting with FDA pretty shortly. The idea there is just basically try to understand if you're either gonna need the 24-month data or to run another trial. Is that kind of the expected outcome of that meeting? How explicit do you think you are gonna get in terms of guidance on the potential approvability of the regulatory package as is, given that I don't know how much data you can actually provide ahead of time for that discussion. Yeah. Well, look, I mean, in our interactions with FDA, and it's like everybody else, those are very much standard. What we do is we prepare a very detailed briefing book on the data we have available for FILLY, DERBY, OAKS. We say, we think this is the package that, you know, gives you the visibility and the understanding. These are three, we think, large well-controlled trials. These are the things that we think, you know, are valuable for potential approval. And then, you know, we have a discussion, and hopefully they will agree with that. And the implication being, if they do think that, we wouldn't need to run another study or, you know, we wouldn't need to wait for, let's say, 24-month data to incorporate that into the NDA. And, you know. I think there's certainly, you know, a lot of investor speculation around that, but it is diametrically opposite what our view is on this. You know, I think that regulatory clarity, depending on what it is, could go a long way to dispelling those, you know, those concerns. Yeah, absolutely fair. Perhaps somewhat related to that. Again, you had a couple of different data points. You do believe the totality of the data kind of supports an approvable product. Relative to your initial expectations for based on the FILLY trial, has anything changed relative to the potential market opportunity or how broadly addressable it could be for geographic atrophy? Again, there's always some expectations of perhaps a lower benefit with a larger sample size. Curious how you feel about that product profile that you have right now that you think is potentially approvable, and how that will do commercially relative to your initial expectations, if that changes at all. Maybe the demand is inelastic, right? I'm curious in that spectrum how you feel about that. Commercially, we don't believe that the data. Actually, the data has been very well received at The Retina Society, ASRS, or AAO this week. It's been super exciting because remember, this has not been done by anyone up to this point in time, right? We don't think the addressable market changes for us because we've got foveal and extrafoveal data. 85% of the patients, the fast progressors that you talked about earlier, are extrafoveal or have extrafoveal lesions. We think that market in both situations is gonna remain the same for us. The other thing too is just keeping in mind compliance. I think, you know, one of the things that we're hearing from these physicians is there's been zero choice for patients today. Patients want treatment, physicians want to help the patients. We believe compliance, whether it's every month or every other month, is going to be suitable, and patients will stick to it. We don't look at the market any different than we did before the data read out. As a matter of fact, I can tell you commercially, we're more excited because we're talking to customers now and physicians that are telling us they're excited that we're coming with something. Got it. No. Perfect. Appreciate those for color there. Yeah, I know we spent a lot of time discussing geographic atrophy, but I do want to highlight some other aspects of the business. I think your first update this last quarter for the PNH has been really well received, right? There was a lot of speculation relative to which patients would actually utilize this drug. Some questions about the delivery device and the dosing regimen. Would love to get a little more granular on any sort of feedback that you've received so far. And how much do you think there's gonna be a read through from this first quarter of launch relative to how the expected ramp up should look like? Yeah. No, that's great. Thank you. First of all, we're very excited about where EMPAVELI has taken off in regards to our initial few months of launch. It's still early, right? And there's still a lot to be done. Let me just level set a couple things around the marketplace and how we looked at it from a patient perspective. There's about 1,500 patients in the space that are treated for PNH today. About 500 of them are high on transfusion dependency and low hemoglobin, so less than 10, which is about a third of the total patient population. That's been our initial significant focus. Well, remember though, the label is very broad, so we can go for low hemoglobins, we can go for anyone else who wants to go on the product that feels like they can benefit from it, and we can also have an opportunity for naive patients to step in and be treated right away. Which is also we've seen some chart forms that have come through for naive patients as well. About the majority of our patients are coming over as a C5 switch. About 70% of them are coming from ULTOMIRIS, which is really good news for us. And I can tell you anecdotally when you talk to patients, we actually had a patient speaker who's been moved over to EMPAVELI for the company at last week. Her hemoglobin was a seven. It's now a 13.5. Okay, think about that. She just started treatment within the last couple of months. The stories that she can tell you what she's able to do, and her quality of life is significantly different than it used to be. When you think about some of the pushback that you were asking around in regards to treatment at home, sub-q, self-infusion, those type of things, we've got a whole nurse team. We've got a group called Apellis Assist that's attached to our specialty pharmacy. We've got a nurse team that goes into homes and trains. As soon as the patient sees it, understands it's not a large needle, it's very small, it's easy to do. Within the majority of patients are trained once and they are okay to go on their own. Sometimes we'll do a second training via a webcast or something like that, from the care educators to one of the patients. It's been very good. The other thing that's real positive is our compliance rate has been very high. We haven't had a lot of patients that have come off the product. We've been super excited about that. I think for the next quarter, it's always that quarter that's a little bit weird because you've got holidays, you've got Thanksgiving, you've got Christmas. I think we're gonna continue to see growth and the work that we're doing, the move that we've started to make with the product. I always caution everybody that the fourth quarter is a little bit unpredictable. I feel really good about finishing the year strong and going into 2022 with a really strong start. That's fair. Perhaps kind of a quick follow-up to that, just related to the new potential on body pump that you guys are expecting to develop. It doesn't seem like there is any urgency perhaps on bringing a new pump device for delivery. If you do choose to go that route to give more options to patients, what would that look like? It's just mostly gonna be a human factor study kind of bottleneck. I'm curious how that would look like actually in practice. Well, Tim, you may wanna jump in on the front end of that. On the commercialization side of it or the patient desire for it, we believe that there's a definite opportunity there. You know, the patients, this will give them additional flexibility than they have today, the ability to do a wearable, go about your business, and then be dosed the way you need to throughout the week. The flexibility continues to remain that we can do more for patients in that situation. We're hopeful that under the work that we're doing late 2022 or early 2023, we've got the opportunity to review that further and have that product available. I don't know, Tim, if you wanted to add anything to that. No, that was perfect. I would agree with that. You know, we're anticipating filing for approval on that, you know, late 2022. You know, we'll see what happens there. But we think that could be a, you know, a nice thing to have. But really it comes down to efficacy, as David was saying. Perfect. No, that makes sense. Perhaps in our last few minutes, I wanna talk a little bit about the clinical pipeline, right? Again, you do have multiple programs ongoing right now. Has the current I mean, you expect to get some visibility on the regulatory pathway going forward pretty shortly. As of now, has that outcome kinda changed the potential prioritization between all those programs and execution? I know a lot of those are actually executed by Sobi, from a practical perspective. What you have clinically on the systemic side in terms of those multiple indications, which ones are more interesting? Which ones do you think are gonna be a higher priority? Or is everything kind of moving along in tandem and they're all pretty compelling opportunities by themselves? Look, the way we look at those pipeline opportunities and the way we've always looked at them is, you know, based on everything we know, these are areas where we think targeting complement, the way we target complement, which we think is the most powerful complement controlling mechanism, either commercial or in the pipeline, we think these are diseases where this control of complement, the way we do it, will show a meaningful difference. That actually starts with GA, but when you look at C3G, ALS, CAD or HSCT-TMA, all of these things are areas where we think, you know, targeting C3 has some distinct advantage. For us, right, what happens in GA doesn't really impact what we're doing on the systemic side. We're moving ahead on all of those, and we believe in all of them quite a bit. Actually, when you think about it, those are significant increases in patient populations vis-à-vis the, you know, the. The PNH population. PNH population. There was a lot of debate initially just focused specifically on PNH. Of course, if you have five products competing for the same 1,500, of course, you were the only C3 kind of in the mix, right? There was some differentiation there. Point well taken nonetheless. Perhaps just some final thoughts on financing and runway. Honestly, again, recently you guys had an R&D Day that had a pretty comprehensive vision across multiple different new avenues of growth and new areas in complement, honestly, that could be explored. How are you guys thinking about bringing forward some of those programs? Any meaningful changes to timelines as of now? Honestly, everything is kinda still ongoing until you get some regulatory visibility, and then if necessary, you make some choices based off of that. Curious how you're thinking about building out the business in the future as well. Look, we feel really good about the topic that seems to be taking up most of the air in the room. We feel really good about, you know, our potential to, you know, get pegcetacoplan approved in GA in the second half of next year. As a result, we're keeping the gas on everything. You know, one of the true differentiators of this company, and it's really been underappreciated, is that research engine, right? We have, you know, five or six different modalities for targeting complement for a variety of different diseases. I mean, the impact of an uncontrolled complement system for everything from nephrology indications to hematologic to CNS and beyond, you know, we believe very much in those and, you know, and in the multiple ways we can target those. You know, and that I think the statement was really made with our Beam collaboration, and nothing has changed. I mean, we have a strategy and we're sticking to it. Fair enough. I guess we can kind of conclude on those remarks, but again, I appreciate you guys taking the time to talk to us and join our conference. Appreciate all the insight that you gave us today, and have a good rest of the day. Thanks, Tiago Fauth. Thank you very much. Thanks. Have a great one. Take care.