Alrighty, let's get started. Thanks, everyone, for joining. This is the 44th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad: Priyanka Grover, Joyce Zhou, and Rathi Pinheiro. Our next presenting company is Apellis, and presenting on behalf of the company, we have CEO Cedric Francois. Cedric?
Thank you so much, Anupam, and what a great pleasure to be back here. Thank you so much for inviting us again. We have a lot to go through and a very exciting year ahead of us, so let's go straight in it. We will be making some forward-looking statements as per usual. So who are we? So Apellis is a company focused on the complement pathways, specifically on complement factor C3, which sits centrally in this complement cascade of immunity and which allows us to explore many therapeutic options across many therapeutic areas. We have growth drivers in the near term as well as in the long term, and we are a company that is currently self-funded. So let's talk about 2025.
2025, for us, was a building year in which we created a foundation around Syfovre and Empaveli and started thinking about what the pipeline for Apellis would look like in the future. With Syfovre, we have a steady, durable revenue stream that supports our long-term growth ambitions. It's a reliable revenue stream that will continue throughout the year. In 2027, we see renewed growth in the future for Syfovre based on several inflection points, most notably, as you will see in a couple of minutes, the coming on the market of the prefilled syringe for Syfovre, which makes it very easy to administer this drug in a retina practice, and then also the ability now to visualize and image the functional benefit that Syfovre gives to patients.
With Empaveli, we are in the middle of what we hope will redefine what a great launch in a rare disease in nephrology looks like. Empaveli is the approved product for C3G and primary IC-MPGN. Rare diseases in the kidney, but that over a course of approximately 10 years in these patients, who are typically young in their lives, adolescents, young adults, over the course of 10 years, in about half of these patients, can lead to end-stage renal disease if left untreated. Now, let's talk about the three pillars of our company. First of all, of course, Syfovre and what we intend to do there. So we are and continue to be the market leader in geographic atrophy with approximately 60% of the share of the market. We had continued total injection growth at approximately 17% growth year over year on injections.
We are in a preferred position with many payers. And very important with Syfovre, this is a drug that can be given every two months to convey the benefit to these patients. Now, what should you think with patients with geographic atrophy in terms of the population? And I think what you can see here is kind of a breakdown of the patient segments, showing you and explaining to you that we are just at the beginning of what we can do for these patients. If you break out geographic atrophy, this disease where slowly the retina degenerates into three segments, you have, on one hand, advanced geographic atrophy, patients that may be blind in one eye, are close to becoming blind in the other eye, where you're trying to make an intervention to slow that process down, but then also GA that can appear with wet macular degeneration.
So these are patients that have the wet form of the disease. They have exudations in the back of the eye, and they also have atrophy in the back of the eye. Many of these patients end up being co-treated with both Syfovre as well as the anti-VEGF treatment of choice of that retina doctor. And then we have early geographic atrophy. These are patients that are very early in the development of the disease. And as the drug becomes more used in the retina practice and better understood in terms of what it can do for patients, this is a patient segment that we believe will also break open. So let's talk about the first two.
In advanced geographic atrophy and in GA with wet AMD, where we have this important presence right now, in the first half of 2026, we should look at field execution and clinical evidence to grow what we are seeing in the markets. This is a place where we think we can really make a difference in the lives of patients. And in the second half of this year, we then believe that we can expand our share vis-à-vis our only competitor in this space. It is worth noting that this very difficult-to-treat disease continues to see failure after failure by potential new competitors because it is so hard to slow down the lesion growth in this particular indication, again, highlighting how important Syfovre is to patients.
In the second half of 2026, with the prefilled syringe, we believe that we will have a competitive advantage that will stand out as well. Now, talking about that clinical evidence, what you see here is the largest data set ever generated in geographic atrophy, where we followed patients for an entire period of five years of follow-up, where we look at these retinas in the back of the eye and determine how much we can slow down disease progression, and to put it very simply, with this treatment, you have the ability to slow down, over the course of five years, the progression of GA by one and a half years.
That is highly meaningful to these patients who are typically in their 70s or 80s, sometimes beyond that, where you have that ability to save that precious amount of time that you have left in your twilight years to continue to function well in the real world. The prefilled syringe, so this is something that we're very proud of. It is a very easy-to-use syringe in the real world, and it makes the flow in the practice so much better. Retina physicians are incredibly busy. They have to take care of a lot of patients, sometimes see 60, 70, 80, sometimes 100 patients per day. And the ability to have a prefilled syringe that makes it very easy and saves a lot of time to be able to fit into that flow is very, very important. This is a best-in-class syringe that we have created. The clinical trial is complete.
We will file in the first half of this year, and later this year, we'll provide with timelines as to when we anticipate this product to come on the market, and then let's talk something about that I'm particularly excited about, that ability, as I mentioned earlier, to image the functional benefit that Syfovre provides to these patients, so as many of you know, the primary endpoint in geographic atrophy, the way in which we've always studied this disease, is to look at the area of retina that is affected by the disease and try to slow down how quickly that area expands, but until recently, we didn't really have a sense of what does this mean in terms of how the patient can actually perceive the world. That is a huge challenge, not just for us, for the entire field of the retina.
With the data that we have created, we were able to leverage artificial intelligence to, for the first time, be able to do that. So what does that look like? So what you see here is something that we have named functional OCT, OCTF, and it allows you to take an OCT image. And this is important. This is not a new technology. So it's the standard SD-OCTs that have been taken in all of these retina practices for 10-15 years now. And you can translate these OCTs into a functional map of what the patient actually sees. So let me briefly now ask you to imagine yourself sitting in a retina practice where a retina physician takes an OCT from you and can say, "This is what the world actually looks like from that eye." And not just that.
If I have historical OCTs, I can go back in time and say, "That image of the world, this is how it has evolved over time." And it will make it so much more tangible, not just to the patient to feel seen, but to the family members, even to the retina physician that treats that patient, to understand what the impact of the disease is on that patient, to understand what the impact of treatment means for that patient. And we have even more fancy things coming up where we have an augmented reality headset that we're building that will truly make it possible for somebody else, a family member or a relative, to experience what it's like to live with this disease for their parent or family member. We also have our 3007 program.
With all of our bias, this is the most exciting developmental program in the retina. What we do here is a subcutaneous injection that can be given once every three months that reduces the systemic levels of C3, the target for Syfovre, by approximately 90%, and it gives a stoichiometric advantage to the drug that you inject in the eye, so what we try to do here is to reduce the injection frequency from every two months to every three months while conveying an outsized benefit compared to what we currently can do with Syfovre alone, so very exciting. It is currently enrolling, and data are expected in 2027, next year, so then moving on to Empaveli.
Empaveli was approved for PNH several years ago and is now approved for C3 glomerulopathy and immune complex membranoproliferative glomerulonephritis, IC-MPGN, which together represent an epidemiology of approximately 5,000 patients in the U.S. alone. We now also have two phase III clinical trials ongoing in focal segmental glomerulosclerosis and delayed graft function. Both of these trials are enrolling. That's another 30,000 patients that we have potentially access to. But for now, let's focus on C3G and IC-MPGN. So here, the launch is everything that we had expected it to be. The drug got approved at the end of July. We started launching this product in August. And as we are here today, we have what we believe one of the best launches, again, maybe the best launch in a rare disease in nephrology to date, again, making a huge difference in these patients' lives.
The label that we got in this drug was a reflection of the data that we generated in the so-called Valiant study, where we decided not to be bespoke to certain segments of these populations, but to really take a broad approach to adults, the pediatric population, both C3G as well as IC-MPGN, and to study the transplanted population, all of whom, or the majority of whom, tend to relapse after they get transplanted, as well as in a pretransplant setting. So where we are today, again, we have more than 5% penetration after the first full quarter. So when you think about that, out of these 5,000 patients, we believe that approximately half of these patients will end up being on treatment with Empaveli.
As we are today here, after that first full quarter, we believe that we are on a path to being able to accomplish that. We've also had a very good payer reception, which we believe is a reflection, of course, of the data. And with that, we have, again, one of these launches compared to other rare disease launches in the kidney that truly stands out. What are we doing for durable growth in 2026? There's the patient identification and activation. We want to improve the diagnostic ability to find these patients and know where they are, to drive the urgency to take care of these patients. Because you have to remember, in nephrology, urgency is not really something associated with that specialty.
We need to educate the nephrologist to make sure that these patients are treated well and to differentiate Empaveli competitively through its efficacy, safety, and real-world evidence. In delayed graft function, we then have the ability to do something in patients that get transplanted, as well as in this disease called FSGS. Let's dive briefly into these two indications. FSGS is a rare and progressive kidney disease that, quite frankly, in terms of the impact that it has on patients with nephrology, is quite similar to what you have with C3G and IC-MPGN, maybe even slightly more severe.
There are approximately 13,000 patients in the U.S., and we have a strong biological rationale to believe that our drug, which we know from our data in C3G, has exquisite target engagement in the glomerulus in nephrology, that we have an ability to do something about complement activation in these patients. As I said, we are enrolling that trial and really looking forward to being able to make a difference there as well. In delayed graft function, think about the 21,000-23,000 or so decedents, and that means transplanted kidneys from a deceased individual to a living recipient. About 30%-35% of these 21,000 patients have an issue where in the first week after transplantation, the kidney doesn't function very well.
That is associated with a long-term higher incidence of loss of these kidneys, and that is clearly associated with complement activation, again, something that we believe we can control, and this trial is also enrolling at this moment in time, then the last, and that is our pipeline. This is something that we are particularly proud of, has taken a little bit of a backdrop in terms of messaging compared to what we are doing commercially, of course, but something that you all should be looking forward to, and first of all, there is our so-called APL-9099 program. This is a gene-editing approach to disrupt the $20 billion FCRN market.
What we do there is we provide a single base edit in the liver of patients who have any of the indications where FCRN is a mechanism that we know is biologically active that allows us to reduce the IgG levels by approximately 50% while maintaining albumin levels. Importantly, we do this with base editing, not with CRISPR, and we do this with LNPs instead of AAVs, which is important because these are important safety advantages in the context of what in gene editing we have found in the past couple of years can be hurdle blocks. The IND is planned for the second half of this year. Let me show you briefly what we are able to do when we test this in a preclinical setting. Importantly, we don't have to just dose once. We can dose twice, maybe even more often if we want to.
And here you can see the durable response over the course of half of a year with a single treatment, or in this case, two treatments in NHPs while maintaining these albumin levels over time. So again, much more to follow in the second half of this year, but really excited about what we will be able to do for patients. So this is what our pipeline currently looks like. Really excited about 2027 and beyond. And this is the foundation that we have built in the last year and that we will build on for the foreseeable future. And with that, I want to thank you for your attention. Thank you, Cedric. I'll ask the first couple of questions, but there will be certainly an opportunity for folks in the audience to also ask questions. So I was just wanting to dig into first, we'll dig into Syfovre.
You mentioned in the presentation 17% injection growth. What's driving that quarter or over the quarter? And how do you expect that growth to continue? You talked about your initiatives in the first half, second half, 2027.
Yeah, thank you, Anupam. So I think what I would like to say about geographic atrophy, that is kind of the most important element about this disease. This is a devastating condition that happens to the elderly that is irreversibly and ultimately leads to blindness. So as such, it is incredibly important to have therapies available for these patients. Now, this disease gets treated in retina practices. And last year was a very complicated year in the retina practice because there is such high volume, as we talked about earlier, and so many patients need to be seen. Anything that can disrupt that flow can be very disruptive. Now, in the last year, there were several elements that disrupted that flow, including the fact that foundation money was no longer available for patients to be treated.
That meant that retina practices had to figure out how to deal with copay payments, etc., and because of that, a lot of retina practices took a pause on treating patients with geographic atrophy because wet AMD is really a medical semi-emergency. When you have a patient that comes in with wet AMD and they need treatment with Anti-VEGF, you cannot send them home. You have to find an alternative, whether it's a sample, whether it's switching to a generic. I mean, and that was a whole phase of settlement that in the last year had to take place. Recently, we are seeing physicians and retina practices figuring this out better. For us, during that period, our mission was to support patients, to support the retina practices. We did that as well as we could with our patient access program, with samples, etc.
But in the meantime, what was really important was that we saw how important treating patients with GA was because physicians decided to resort to samples, resort to whatever they could to take care of these patients. So again, we're very excited that this year these retina practices have found a new flow, a new rhythm that is more conducive. And we have a long path in front of us.
In the presentation, you talked a little bit about the prefilled syringe. Maybe could you expand on your market research on what a prefilled syringe could do to sort of maybe change the trajectory of this launch and flex this launch? How do we think about that?
Yeah. So currently, when you treat a patient with Syfovre, you have to take a vial out of the fridge. You have to thaw that vial. You have to wait for it to heat up. Then you have to draw a product that is quite viscous through a filter needle. Then you have to put on the injection needle, and then you have to put it on the tray. And then there's typically a time period between. So there's a lot of technician time involved. And again, this is disruptive to that flow that we were talking about. The prefilled syringe very much solves that problem. So it's really important to know that from the anti-VEGF therapies that are out there, that it really improves the quality of care and improves the flow in the retina practice and something that we look forward to be able to share with them.
We think that competitively will make an important advantage. We believe that also in terms of growing the overall market, it will make a difference as well.
Questions from the audience? Yeah, in front.
My name is Volker Wendel. I come from Sanoptis, a European-based...
Yeah, hello. Volker Wendel, Sanoptis, European-based ophthalmology group. And we would like to treat patients as well in Europe with Syfovre, but unfortunately, you didn't get the EMA approval. So what is your strategy regarding that topic?
Yeah, so patients globally with geographic atrophy are very important to us. In Europe, through the regulatory process, there was a concern that it was not possible to measure the functional benefit that the drug was conveying to patients. We believe that we are cracking that code. And so we believe that hopefully in the near future, there will be paths available in Europe, ex-Europe as well, to revisit kind of global strategies for us. So that's...
As a kind of, yeah, plan B, we heard that you plan to have national applications for some selected European countries. Is this still part of your strategy, or?
We continue to prioritize patients in Europe as well as ex-Europe. And hopefully, we will find a way to make Syfovre available, yes.
Additional questions from the audience? Yeah.
So going into the Syfovre results in the fourth quarter, you talked about sales being flat-ish. Ultimately, you were able to grow a little bit here. Can you just talk about what went well with the quarter? Was it mainly the samples? Were there kind of other aspects of demand that went well in the quarter?
Tim, do you want to?
Yeah, sure. No, as we looked forward to the fourth quarter, we saw very strong injection volume through the first, really for the first two months and even into December. What happened was there was a little bit more of a slowdown at the end of the month than we had expected, which led to basically a relatively flat injection volume over the quarter versus the third quarter. But it was really just the last two weeks. So otherwise, it would have had the expected kind of low to mid-single-digit growth.
Additional questions from the audience?
Maybe let's switch gears here to Empaveli. You said you had 267 patient start forms in C3G and IC-MPGN. Tim, you talked about a floor in the 3Q of 220. Was it 225, right? So what were the key drivers there in the fourth quarter? What is the patient phenotype that's going on? Anything you would highlight on 4Q?
So first of all, the key driver is the efficacy profile of the drug combined with the safety profile. I mean, Empaveli and the Valiant study showed a highly meaningful clinical benefit to patients, again, in this devastating disease. We saw a very important pickup in the pediatric population, where I think it's fair to argue that the urgency that is perceived is higher than it is in the adult population. We also see that urgency, obviously, in transplanted patients, where, again, you have to put that in the context of protocols, but we see this steady cadence that is picking up and that we're very happy with.
We also had our publication that came out in December in the New England Journal of Medicine, highlighting what we like to call the trifecta of the data for this indication, where on one hand, we saw the proteinuria benefit that we have in these patients that are unprecedented. We also see that when we look at biopsies in these patients, after six months of treatment, already in 70% of patients, there is no more trace of complement deposition in these kidneys. Hugely important and obviously correlated to what we know is driving this disease. And then importantly, even after six months, we saw the impact that it had on eGFR. And it's worth noting that the FDA, we were the only company to be accepted with six months' data to be reviewed and ultimately lead to approval. So the efficacy data is really what is driving this, of course.
That needs to be combined with the fact that there's a lot of education. There's also a big effort to find these patients. I mean, they're typically spread across the country, across many, many practices. Many nephrologists have patients that, because there was no therapy available, they've been tracking. I mean, kind of working on the diagnostic patterns, educating on reimbursement, etc., etc. That is the opportunity in front of us.
Questions from the audience?
What are going to be the key messages for Empaveli and C3G and IC-MPGN in 2026? And what is your understanding of maybe competitive counter-detailings?
So a little bit the same answer as I just gave, right? I mean, the trifecta of data, the fact that we got these approvals based on the data as it stands out, the publication that we have available to us, and the very meaningful difference that you can make in the lives of these patients. I think other things that stand out that are maybe less obvious but are really, really important is the exquisite safety profile for Empaveli. We are now well north of 3,000 patient years of dosing. Typically, for the class, you would expect to see a meningococcal infection every 200 to 300 patient years. We have seen zero cases of encapsulated meningococcal infection under Empaveli. I mean, that's something that really stands out.
There's also the fact that in the clinical trials, there are the concomitant medications, most notably steroids, which have a dramatic impact on these patients, as you can imagine. We're going to be diving into what we can do in terms of reducing and sometimes even eliminating those concomitant medications and the benefit that that provides to patients. So again, a really important opportunity for us to kind of highlight the benefit and the competitive differentiation of the drug.
Questions from the audience? Yeah.
Sorry, just wanted to move back to Syfovre in terms of the market share versus Izervae. What's the latest trend of the market share and what's your outlook for the market share in 2026 versus Izervae? And how's the feedback so far between Syfovre and Izervae from physicians?
Yeah, thank you for that question. So it's been relatively stable, right? So our overall market share, as outlined earlier, is at approximately 60%. The market share on new patients coming on treatment is a little bit lower, 50%-55%. That also has been stable throughout the course of last year. The reason why the market share is a little bit higher than on the new injections, we believe, has something to do with the fact that there may be a bit better retention on Syfovre compared to Izervae. That's what we believe. I think moving forward, what's going to be important is to highlight the long-term data that we generated to start talking about the functional benefits. And then, of course, as we discussed, the prefilled syringe, which we believe competitively is very, very important.
Yeah, go ahead.
How about the market share outlook for this year?
So we believe that, again, the prefilled syringe is something that will come later. Hard for us to determine at this point in time how long the regulatory review will be. I think for 2026, you should think about Syfovre as a resilient and durable business with growth opportunities that will start to materialize in 2027. Again, most notably, the prefilled syringe and then also the ability to image the functional benefit that the patients may have from this drug.
Izervae doesn't have a prefilled syringe coming up, right?
We have no insight into that. I think that's something that you have to ask us, tell us about.
Got it. Thank you.
Thank you.
Additional questions from the audience?
Cedric, just a quick one from me. On the broader Empaveli pipeline, FSGS, Delayed Graft Function, I think the slide said these are 2028-plus opportunities, but you just started these trials. How do we think about the enrollment curves and I guess maybe timelines of data? Because I'm assuming that is commercialization 2028-plus.
Yeah. No, thank you, Anupam. Look, it's a little bit early. We just started these phase three clinical trials, so we're going to see how enrollment goes. FSGS, I think, again, the data helps us that we have generated in C3G and IC-MPGN because you have the target engagement element there that kind of truly stands out. And delayed graft function doing work in transplantation, as you can imagine, is a little harder to do. So no guidance on what timelines look like, but very excited that they are in testing right now and to what may be a good outcome.
Any final questions from the audience? All right. Thank you.
Thank you very much.