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Wells Fargo Securities Healthcare Conference 2023

Sep 8, 2023

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

All right, everyone, I think we'll get started with our next fireside discussion. My name is Derek Archila. I'm one of the senior biotech analysts here at Wells. Very happy to have Apellis Pharmaceuticals and the team. We've got Cedric, the CEO, and we've got Tim, the CFO, here for the discussion. Gentlemen, thanks so much for joining us.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Thank you, Derek.

Tim Sullivan
CFO, Apellis Pharmaceuticals

Thanks.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

All right, well-

Tim Sullivan
CFO, Apellis Pharmaceuticals

Great to be back.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah, great to have you again. Well, I'm gonna turn it over to Cedric. He's gonna kinda give a kind of state of the business currently, and then we can kinda dive into questions afterwards. But, you know, Cedric, I'll turn it over to you.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Thank you, Derek. So needless to say, it was a busy summer for us, right? But I'm gonna start with what I think is really most important, which is that SYFOVRE off to a fantastic launch. And, in the summer, a little bit, you know, drowned out by the noise, this amazing efficacy profile that we see with SYFOVRE. So as you may recall, one of the cardinal features of SYFOVRE in the treatment of GA is that the efficacy increases over time, and when you get to the point between month 24 and 30, that slowdown in extrafoveal patients is as high as 45%. So that means that if you go on treatment with SYFOVRE, after 30 months of treatment, you have slowed down the disease by almost half. Right?

I think in a disease like GA, that is really, you know, kind of extraordinary news, and importantly, it's news that, you know, within all the noise, of course, with what occurred over the summer, is now starting to really become a focal point for physicians, for patients, and provides context for the other event that took place, of course. In the meantime, EMPAVELI continues to be a really important product in PNH. We also have our clinical trials in C3G ongoing and IC-MPGN, with a readout next year, where we think we're gonna have be able to make a really important difference. I mean, we had phase 2 clinical data that was, you know, remarkable in terms of its potential to control the disease, and that will allow us to build on that EMPAVELI franchise as well.

And then our research as well continues to progress very well. We had, you know, little notice, but in the spring, we had an IND, and are now in the clinic with an siRNA product that allows us to lower the levels of C3, and preclinically, our work continues to be very promising as well. So, as an organization, you know, all of you saw that last week we had to reduce our workforce. For me personally, one of the, you know, most painful things we had to do as a company, because you say goodbye to a lot of people that, you know, really helped us to get where we are today. But it was something important, you know? It was the prudent thing to do.

It was, you know, kind of refocusing the organization on its top priorities and lining us up for what is ahead. But it's rebuilding that company or continuing to build that company on a strong foundation of prescription behavior. I think that at the end of the day, I think the great win of the summer is that in July, we ended up in a situation where, very understandably so, the retina community was faced with a type of side effect that causes panic and fear because of something that happened a few years ago, right? And navigating that panic and fear was important.

You know, it was important to tell everyone, "Hey, yes, there is this side effect, but it is extremely rare, it is sporadic in nature, and it's not a side effect that's increasing over time." And we did all of that in the most possible transparent way with the retina community. And as a consequence, you know, our drug, SYFOVRE, continues to be prescribed in very high volume to patients. That allows us, of course, to look into root causes, move forward, navigate these waters, and we'll provide regular updates to the retina community to make sure that they understand it. But at the end of the day, what drove the amazing launch that we had and what drives this prescription behavior is the need that exists. I mean, this is a blinding disease where people lose vision.

People want to do something about this, and the risk of 1 in 10,000 of having a serious complication like this, you know, really, once you wrap your head around it and you take the fear factor out, that, "Oh, it may be much more than this," or, "There's something we don't know," becomes an entirely acceptable discussion point.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. Lot to talk about. I actually wanna start just in terms of the reduction in workforce. Was this something that had already kind of been, you know, kind of on your mind in terms of, like, looking at that and kind of the, the cost base of the business and, you know, kind of gaining the profitability? Or was this more kind of due to kind of the more recent disruption that you've seen kind of, you know, with the launch?

Tim Sullivan
CFO, Apellis Pharmaceuticals

Hmm? Yeah, sure. So, you know, it's a mix of things, right? But ultimately, you know, it's incumbent on us, especially when there's uncertainty that gets created, to make sure we're operating efficiently, and ultimately, that's what led to the decision, right? It wasn't any one thing. There were certainly areas that we had been looking to optimize over time. That just made it more of a kind of a priority, a timely decision, right?

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. Understood. Yeah, so going on to SYFOVRE, I guess, you know, trend-wise, you know, as you were saying, you know, people are still prescribing it, volumes... You know, how are they looking? I guess, how are they kinda trending since, you know, some of your more recent updates, in terms of, you know, switching the needle, and other things that you've been kinda communicating to the retina community?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Yeah. So we believe that there's a rate of approximately 1 in 10,000, as mentioned before. And I think what's important, and that's why we provide these regular updates, is that physicians, if they see that rate be stable, they'll be comforting. And that is because a couple of years ago, it started with 1 in 10,000, and then it was 1 in 1,000, and by the time it was all said and done, in no time, it was, you know, as, as high as 1 in 50 patients, right? And that was because with Beovu, at the time, you had a sensitization against the drug that was happening. So with every subsequent injection, things got worse. We don't have that. That rate is stable. It is where it is. So just in a status quo world, that will be totally fine.

Having said that, when we then looked at the two ancillary kits that we provide, where one of those kits has a 19-gauge needle, the other has an 18-gauge needle, we saw a remarkable association with the use of one type of needle. We also found that there were these structural abnormalities, these variations that existed within these needles, and those two factors combined led us to take the decision to take the field action that we did. Now, proving a negative is very hard to do. Is this the cause or not? We do not know, but out of an abundance of caution, we removed the needle, and the best way to find out if it was the cause is to now look in the next couple of months if that already very rare rate can be further reduced.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Were all the cases associated with or, you know, were those patients treated with that specific needle? Is that something you've talked about yet?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Yeah. Unfortunately, that is pretty impossible to establish because most practices will receive both types of ancillaries, right?

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

There are several cases where definitively we could bring it back to the use of that needle, and then there were others, and to kind of so to give you an idea about how we handle that, if we have a practice that has a case of vasculitis, we take we look at the, the number of kits available within that practice, and if there are 80% of one needle versus 20% of the other, then we split that one case of vasculitis into 0.8 and 0.2. Right? There's no assumption on causality. It's just a probabilistic analysis of being associated with the use of one needle or not.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. I know you guys are still, you know, doing your investigation, but I know that was kind of like one of the first kind of variables that you saw that was different than what you saw in the clinical trial. I mean, any other kind of learnings since, since then, and ultimately, I think you said you were going to put out another update prior to the third quarter earnings. Is, is that still correct?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Yep, that is correct. So, you know, between now and earnings, we'll provide another update, you know, focused, of course, again, on giving physicians-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

that comfort and knowing what's going on. And I have to say, our Chief Medical Officer, Caroline Baumal, has been extraordinary at doing that and creating that trust with the community. But yeah, that's kind of the next step for us.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

I guess when you guys talk to physicians, you know, as you kind of see the rate stabilize, and as you said, like, you know, you've now taken some actions here, how long before, you know, people will start to... or people who have not started using SYFOVRE or have stopped, will start again or start for the first time? Like, how long do they want to see that rate be stable?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

I don't think that there is a kind of an easy answer to that question, right? I mean, retina docs are humans, and they come in all shapes and colors. So, you know, you have some physicians that will never, you have physicians that still don't prescribe anti-VEGF, by the way.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Because they're not convinced of the benefit, so that will always be there. I think the key thing here is that the more experience you have, the more you understand the risk-benefit of this drug. We just crossed the 100,000 injection mark, which is a huge milestone for us, right? I mean, it provides you a very clear picture on, you know, what is the safety? I mean, we know, we know now what it is, right? I mean, that's the... And on the other side, we also know from the GALE extension study what the benefit is that patients can expect. That is all very exciting in a disease that until a year ago, or six months ago, right, was untreatable. That, at the end of the day, will, will carry us forward.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

I mean, now that, you know, obviously post ASRS, a lot of discussions, you guys are again in the field talking about it. Obviously, physicians are, you know, on notice that, like, they should be looking out for this, and ultimately, if they do see some inflammation, are they more quick to, you know, treat with steroids now? I know usually when they think of inflammation, it could be infection, but like, you know, have procedurally and just kind of like how docs are thinking about it now, they want to continue to use it because they think it's important. But, you know, have they put any sort of, you know, protocols in place, you know, if things are to go, you know, or start to see inflammation?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

The very simple answer to that question is no. I know that's intuitively where everybody wants to go. It's 1 in 10,000, right?

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Right.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

You just cannot do anything about that in terms of a real mitigation strategy. You cannot ask physicians to go and worry about that particular scenario and start taking steps that fall outside of the routine.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Hmm.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Infection and endophthalmitis, which has very similar outcomes in terms of vision, right?

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

I mean, it happens once in every 3-5,000 injections. You know, that—there's no, there's no reason to be afraid of that. You just have to know it, and then if it happens, and you're unfortunately within that position, then you treat it appropriately, and you hope for the best outcome. It's part of the risk profile, and you handle it appropriately. But for those very, very rare cases, you know, are you going to bring in all these other patients for another follow-up visit with the cost and time associated with it? Unfortunately, it's not worth it. You know, it's like,

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. And then is there like a specific characteristics around physicians who have stopped using it versus people who, like, are, like, for instance, like, are high-volume docs still generally, you know, using it and maybe only, you know, smaller, I mean, community retinal specialists are not using it because, you know, they either never started or they stopped because of the safety concerns?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Well, I think, you know, with every drug launch, with every new technology, you always have kind of the pioneers.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Mm-hmm.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

And then the people that are like: "You know what? I'm going to take a little bit of time." And what you have now is, I mean, the great thing, to some extent, of Geographic Atrophy is it's a slowly progressing disease. If you wait a couple of months, it's not the end of the world, right? So-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Mm-hmm.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

I think that kind of the urgency or the lack thereof is helpful. I mean, because we have huge practices doing, you know, large amounts of prescriptions, I mean, and that have had a great experience. I mean, many doctors tell us, "I prefer SYFOVRE, I love this product." Right? I mean, it is... So those are the things that will carry us forward, and people will step in line. Because if you're a retina doc and you're not prescribing SYFOVRE, 10 times a day, you're going to be asked about it. And 10 times per day, you have to explain to your patients why you're not doing it. And I think, you know, there are people that will do that the rest of their lives, but they're going to be a small minority.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Mm-hmm.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

And then there are a lot of people that will tell their patients: "Listen, come back in a couple of months. I mean, there were these cases that were described. I just want to be ultra-safe with you. In a few months, we'll revisit it." And in many ways, I think that the summer was, you know, within all of the misery, of course, like an ideal moment in time for that to occur. Because, you know, you can tell patients, "Take your holiday, come back in the fall, and we'll see again." So I think what's happening now is very helpful to us. It's happened with great transparency and a collaborative spirit with the retina community, with ASRS and others, and prescriptions continue to happen in high volume, which is the key behind everything.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. Maybe just in terms of, you know, obviously, trends are a little bit, you know, all over the place, just given some of the, obviously, the safety and your updates. But, you know, would we expect any type of seasonality in, you know, for retinal specialists, like, in this, like, latter part of summer, just in, like, the 3Q timeframe?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

In terms of prescriptions picking up?

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yes, prescriptions, yeah.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Um-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Or injections. Like, again, do they go on vacation? Do the patients go, and things like that.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

I mean-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Probably.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

So we don't have a precedent for it.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Right.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

So, you know, there's no way to know, but I don't know to-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

I mean-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Like, do we see it with other, you know, injectables, I guess?

Tim Sullivan
CFO, Apellis Pharmaceuticals

You'd expect things to be a little bit slower in August, as you would for a lot of these sort of, you know, people who go on vacation and so forth. So we had the ASRS right in the middle of July or late July.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah.

Tim Sullivan
CFO, Apellis Pharmaceuticals

Then we gave an update on what the first three weeks in August looked like. You can figure out what the demand vials were just by-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Mm-hmm

Tim Sullivan
CFO, Apellis Pharmaceuticals

... looking at the 2, you know, that time period and the 2, updates we gave. And then, you know, the last 2 weeks of August are the last 2 weeks of August, and what we're really looking for in terms of getting a little more certainty is going forward in September and October, there aren't really any holidays aside from the one we just had, any major ones. And, you know, and of course, on October first is when we get our J-code activated. We already have the J-code, but it activates on October first. So not only do we get a more normalized September going forward, we then get the new world normal, which is with the J-code. So, you know, we'll know a lot more by the time we, you know, have our earnings.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

To the point on the J-code, so, I mean, I know access has been pretty good, but I guess, you know, is there, like, a certain percentage of patients that remain or, you know, untreated largely because there's no J-code or the J-code hasn't been activated yet? Like, you know, what's kind of that maybe pent-up demand look like, at least you're hearing from some of the high-volume docs?

Tim Sullivan
CFO, Apellis Pharmaceuticals

Sure. I think, I mean, so anecdotally, the way, you know, our conversations are, you know, if you speak to 10 physicians, call it two are going to say, "I'm not doing it until the J-code comes." So there, there is an impact, and it's a real impact. That's a pretty, you know, small number to... You know, there's an error bar there, too. But there are definitely patients who are not being treated because of the J-code. You know, and that's, that we'll see how much of an impact that has.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

I mean, from that perspective of these, you know, some of these patients, and we've heard this, too, from KOL, saying, you know, X% patients are, you know, not being treated yet, waiting for the J-code.

Tim Sullivan
CFO, Apellis Pharmaceuticals

Sure.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Do you get the sense that, again, these patients are, you know, and these docs are setting appointments for them to start to come in, like, after the J-code? Like, is that-

Tim Sullivan
CFO, Apellis Pharmaceuticals

Mm-hmm.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Do you think that could be an interesting inflection point, you know, for SYFOVRE, you know, after?

Tim Sullivan
CFO, Apellis Pharmaceuticals

Yeah, I don't have an answer for that. I mean, all I can tell you is that for certain physicians, it makes life enough easier, specifically the smaller practices that don't have processes in place-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah

Tim Sullivan
CFO, Apellis Pharmaceuticals

... to deal with all the paperwork. They don't want the hassle, you know? So the answer is, I don't know about patients lining up for that, but for those doctors, the next time they see the patient, they're going to be willing to have the conversation, whereas they're not right now. I guess that's how I'd think about it.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Okay. I know there might be some noise, obviously, with what's going on, but, you know, generally, what are you seeing from patients, like, obviously getting, you know, subsequent injections and, you know, ultimately, kind of the, the cadence of, you know, monthly versus every other month, you know, so far?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Majority is every other month. I think that's the regimen that is very much enjoyed by physicians and patients. You know, in terms of the experience of being on chronic treatment, we have patients in GALE that have been on treatment for five years, right? So, and that have had a wonderful experience going through that for all of these years. So I think, again, it is a drug that needs to be given chronically. It is a drug that the longer you treat, you know, we've seen now up to 30 months, continues to slow down the disease more and more. And that's the treatment that benefits the patients. So yeah, every other month, I think, very important in terms of prescription behavior.

Tim Sullivan
CFO, Apellis Pharmaceuticals

I can add one point. Having spoken to a couple of our highest prescribers, almost unanimously, they say: "You know, I, I just can't see bringing my patient in every month.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Mm-hmm.

Tim Sullivan
CFO, Apellis Pharmaceuticals

So it's every other month is a very important regimen.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. And maybe we can talk also to, you know, some of your incoming competition with Astellas and IZERVAY. And I guess, I mean, have you—what are you kind of hearing, you know, from KOLs, or what are you kind of hearing about, you know, that launch and again, kind of like how people are kind of comparing the products now that, you know, post ASRS, I guess?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Yeah. I would say for we have every other month dosing-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Mm.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

you have 45% slowdown.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Mm-hmm.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

You have a safety profile based on 100,000 injections, right? Between the clinical trials and the real world. So you really know what you're going to get. I know our competition, and we wish them well, but 300 patients, more or less, 300 patients have been treated. We have data at 1 year, nothing beyond it, and we just don't know what the efficacy profile is going to be. But with every other month dosing with SYFOVRE in patients with extrafoveal lesions, we have better efficacy than monthly injections with IZERVAY. So it'll be interesting to see how it ends up.

Tim Sullivan
CFO, Apellis Pharmaceuticals

I would also add that in this population, efficacy is very important, especially over time, right? Because it compounds. And in this same population, Cedric mentioned, you get 45%, as much as 45%, we showed in GALE. That really means something over time. It's really hard to, you know, treat a patient for years and years and years if you're not seeing that extra, you know, dividend you receive, so.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

I mean, what level of promotion do you think they're willing to do for, for their product? And do you think, again, is it helpful for just kind of the class? Like, again, this is still a very new indication, you know, first drugs approved. Like, how do you think this kind of helps build the overall market longer term?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Look, duopolies can be very powerful because they raise patient awareness and physician awareness, so we're not worried about that. We think that there's plenty of demand for both products to be accommodated. You know, of course, we think it's much better for patients to use SYFOVRE, but -

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah, of course.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

But it's good. I mean, again, a few months ago, we had nothing-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

for this terrible disease.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

I know it's still very early on the launch, but, you know, kind of given the trajectory, and, you know, as it continues to resume here, has your thought on the overall market opportunity in GA, like, has it improved? Has it gotten better? Are you more bullish, you know, now that you've kind of seen this early uptake, versus, you know, prior?

Tim Sullivan
CFO, Apellis Pharmaceuticals

Yeah. What I'll say is our market research team was like: Well, maybe we, maybe it's a little bigger of a population than we thought it was. Which is kind of a, you know, I don't know how often that happens. I guess it happens, you know, occasionally. But, you know, we, they think they may have undershot the population by as much as 20 or 30% in the U.S., right? Who knows? But certainly the demand showed us that this population is very large.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Something that we suspected, which certainly is materializing, is that a lot of patients with geographic atrophy were not being seen at all or consistently by retina doctors. They may be with a general ophthalmologist who says, like: "Look, I can refer you to a retina doctor, but there's nothing to be done for you," right?

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Right.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

I mean, that was kind of the, again, the world until six months ago. That's changing, of course.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. Can you maybe talk about where we are with EU for SYFOVRE? And, I guess, how your, again, key learnings and some things that you've done here in the US, how much is really applicable there, just given the obviously different reimbursement schemes and obviously different countries?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

So the EU is something that we decided to do ourselves many years ago, and decided to do right. And doing right means really being conscious of challenges to reimbursement that exist in Europe, and approaching payers and educating payers about the disease and the impact of our treatment years in advance. That is something that was done exquisitely well, in my opinion, by our European team. So building the groundwork, not just for approval, which we are, of course, highly confident in, but also for reimbursement. Then, as it relates to approval, I mean, as you know, we expect to be approved early next year. That approval process has gone exactly according to plan. You know, it is. We have an enormous set of clinical data available to us.

You know, the recent events in the real world are, of course, part of the dialogue-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Mm-hmm.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

but we do not believe will derail us... and we look forward to making this product available to every patient who needs it.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. There's definitely been obviously dialogue, you know, with everything that's gone on with EU regulators-

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Mm-hmm.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

you ultimately don't think it'll, you know, impact timing or anything like that?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

No, we do not think it will impact.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. So in terms of, like, pricing in Europe, like, how do you think that will look? You know, obviously, maybe you kind of get the reference from Germany, but, like, ultimately, what's kind of your assumption around EU pricing?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

We haven't commented on that, and that's something you can kind of look to the anti-VEGFs for.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Okay

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

... an analog there, but we haven't commented on our pricing. You know, our first country where we will launch is expected to be Germany. Reimbursement there is immediate, so you know, we expect hopefully to have revenue as soon as we're approved, and we're expecting approval in the first quarter of next year.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Gotcha. Or maybe with the time remaining, we can shift to EMPAVELI and some other pipeline things. Spent a good, good amount of time on SYFOVRE, but, maybe just give us a sense of, like, your, your view now on EMPAVELI and kind of, you know, the current base business you have and ultimately, how, how you continue to grow that. I mean, you know, PNH is a small indication, but, you know, where do you actually end up... or where do you actually think you'll end up in terms of like, you know, kind of a peak opportunity within, within PNH?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Yeah. So, kind of the one metric that we always use with PNH is the compliance rate, right? I mean, 97% compliance is what we have with EMPAVELI. So patients with PNH on treatment with that drug are incredibly faithful to that drug. And that is a reflection of how much better they feel, the difference in quality of life that it makes to them, and also, frankly, the safety profile associated with this drug. I mean, we are, I don't know, the latest that we have, probably somewhere around 1,300 or so patient years of dosing, if not more. We should have seen by now, if the C5s are a proxy-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Mm-hmm

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

... many cases of meningococcal infection. We have seen zero, right? So and also, once patients are used to self-administering this product at home, which is, you know, twice a week, takes 30 minutes, it's absolutely not something that they consider to be burdensome or an issue. So in the near future, we're gonna get the orals come on board, of course-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Right

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

... and that will be severe competition for newly diagnosed patients. It will, you know, also be competition to switch over patients, of course, but we believe that the patients who are on treatment with EMPAVELI, you know, based on what we have seen, are gonna be very faithful to that. And, you know, I think, and this is important, the... We are kind of in that phase where enough patients are on treatment to kind of talk about it with their peers. So EMPAVELI is here to stay in PNH, provides a tremendous opportunity, with the only drawback being that it's, you know, less convenient, of course, than taking a pill.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Sure.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

But with a safety and efficacy profile that is now very well established and makes an enormous difference for patients. So in PNH, that's where we are. The next big frontier for us, as mentioned in the intro, is C3G and IC-MPGN. You know, these are devastating kidney diseases. Between the two, approximately 18,000 people in the U.S. affected by that. And that is a disease where, in young people, the risk of getting to end-stage renal disease is about 50% over 10 years. Also important is that if you get to end-stage renal failure and you then get a transplant, you have a 50%-70% chance of relapsing with that transplant. So there, too, we will have the orals to compete with, of course, but especially in IC-MPGN, we're ahead of the competition.

And if you think about, say, kind of the, the lifespan of a patient with that disease, if you are in the later stages of the disease, let alone once you are transplanted, convenience is far less important than having the best possible treatment. And the efficacy profile for EMPAVELI and C3G, IC-MPGN, I think, is going to really stand out. We know that from the phase II clinical trial work. We also know this from many compassionate use cases that we have seen in the real world, that we have, you know, we're able to honor in the past couple of years.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it, and maybe just take it back to PNH. So do you feel like that with the oral coming in, you know, you're probably... You're not gonna see people switch off of EMPAVELI, but, like, your, your ability to grow that in kind of, you know, newly diagnosed patients, do you think that's, you know, kind of negatively impacted? Should this be more of kind of a flat to, you know, modestly growing business? Like, how do you think about the profile now?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

It will, of course, be negatively impacted, right? I mean, if as a patient, you have a choice between an oral-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Sure

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

... and a subcutaneous, the vast majority of patients are going to choose the oral product. I do think that we need to see in the real world what an oral product will do for patients with PNH, right? Because, it's, it's one thing to take pills for kind of quote-unquote, "more innocent diseases," but taking a pill that you have to take twice per day for a disease that could be deadly, like PNH, where the pharmacokinetics, you know, -

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

... are kind of on a razor's edge. You know, there are... Look, in all of my subjectivity, if I had the choice, I would not take a pill. But, then I think you will find patients that prefer kind of the comfort of, "I do it twice a week.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Mm-hmm.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

I don't have to worry if I forget for a day to take it. I have a catch-up period of about one week if I'm late or I'm traveling," whatever it is. So there's two sides to this, especially in PNH, that I think we'll be able to take advantage of.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. Maybe just talk about, again, I think you have kind of a different delivery for EMPAVELI that you've been working on and just an update there. And, I mean, is there any push to, again, to, you know, do other types of formulations with, you know, kind of a C3 asset?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Yeah. So, you know, unfortunately, so this subcutaneous device, which we think is going to be very attractive to patients, makes it really easy to self-administer, you know, got delayed over and over again. We got another delay recently.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

So, you know, we still don't know when that will be available to patients. It's unfortunately and unwarrantedly not considered a priority, I think, within that division. So we're a little bit on the, you know, on the impact side of that. Not material, but, you know, it's just a shame because it's-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

something that we think will be impactful for patients.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

That's just an extension. They haven't communicated any sort of issues or anything to you guys around that?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

No, that's correct. Yeah. No issues.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Maybe with the last couple of minutes here, you know, obviously, you're the premier complement company, like, kind of thinking about, you know, earlier stage pipeline and, you know, kind of the next thing beyond SYFOVRE and EMPAVELI. Like, what are you, what are you looking at, like, kind of early stage, you know, kind of complement programs?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

Yeah. So we've done the... So as mentioned, we have an siRNA in the clinic that, you know, we'll be talking about data soon there. Very exciting program for us, and we'll talk later about what we're going to do with that siRNA program. Then preclinically, we've done a ton of work within the- within this favorite space of ours. The program that, you know, a lot of people may have forgotten we have that I think is incredibly exciting is our collaboration with Beam, where we have 6 programs around complement. So for the first time, edit the genes within the complement pathways, so it's very different from the, the monogenic-

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

approaches that have been pursued by the majority of gene-editing companies. Something that we look forward to sharing more on in the year to come as well.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

I mean, are you only looking to be focused on C3 largely, or are there other areas in the complement cascade that you know of, are of interest, depending on the indications you might pursue?

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

We're definitely C3-centric, but also C3 agnostic within the complement space.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Yeah.

Cedric Francois
Co-Founder, President & CEO, Apellis Pharmaceuticals

And then we have also what we call a C3+ approach, so synergistic pathways or additive pathways with complements are also things that we are interested in.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. And just, you know, maybe last thing, and I guess we started with, you know, some... the workforce reduction. We can end there, too. Like, how much of, you know, like, R&D and, like, that sort of, you know, component is impacted with, you know, the reduction in workforce?

Tim Sullivan
CFO, Apellis Pharmaceuticals

Sure. So development was one of the, you know, areas that was impacted. We don't guide on expenses specifically. What I can say is that, you know, we announced that we have approximately $300 million in savings through 2024, that versus what we were kind of budgeting, right? And also that our expense rate will go down and, you know, from this year, based on what we've done today and what we have in the plan. Certainly, if things change, European build-out and other things, it could go up a little bit. But, you know, from where we stand today, R&D, you should expect that to be a little less than it was this year.

Derek Archila
Managing Director, Senior Biotechnology Equity Research Analyst, Wells Fargo Securities

Got it. All right, gentlemen, well, we'll leave it there. Thanks so much for joining us.

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