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

All right. Good afternoon, everybody. Welcome to Cedric and Tim from Apellis, who are joining us this afternoon for a real world fireside chat.

Thanks, Jon.

Thank you, Jon.

All right. Well, let's start with EMPAVELI, if we can, and the ongoing launch in C3G and IC-MPGN. On the third quarter call, you gave some numbers. You said you're excited about this. We're going to get into all of those details. But first, Cedric, Tim, how is the launch going? Can you talk to us generally about where you are in the process right now and where you're excited to get next year?

Yes. Thank you, John, and thank you for inviting us again. This is a wonderful conference. So the launch is going exactly the way the commercial team had told us it would go. And that is really gratifying to see because it was a feat as many people on the buy and sell side will appreciate to understand the epidemiology of this disease, right? Patients with C3G and IC-MPGN, it's a rare disease, of course, are highly spread out across many, many nephrologists and knowing how many patients are really out there that we can serve and what the unmet need is, is difficult to establish. And I think that our business intelligence and our commercial team did an exquisite job of establishing that. They also did an exquisitely good job at predicting how the pickup would be of treatments and where we are headed. So all of that is in line -- very much in line with the expectations that we had internally. So I could not be happier, and I'm happy to hand it over to Tim to provide some additional color.

Yes, sure. No. I mean -- so in terms of that, again, we had a good sense of where that launch would be from our commercial team. The epidemiology, as Cedric said, is something we -- the 5,000 patient number is something that we had estimated at the beginning. It was a bit different from our competition. They thought it was quite a bit bigger, at least in terms of their number. And I think everything we've learned throughout this process and triangulating from a few different sources gets us right to where the number we thought -- where we thought it would be. So everything has gone exactly according to plan. And our goal is to redefine what a great launch looks like in rare kidney.

Okay. Fabulous. So let's get down to the specifics. So on third Q, you said 152 new patient starts in that quarter. You have line of sight to '25 coming through the end of the year. Can you walk us through the patient identification process at this point as we've moved beyond the patients that rolled over from the OLE as we're getting into fresh patients that maybe we've not previously identified or not previously treated at all. What are the bottlenecks here? And how do you get new patients into the funnel?

So multiple sources, right? I mean, through the patient organizations, through claims-based data, through our interactions with the major centers, et cetera. So there's not really a simple answer to your question. But I think one of the other metrics that gives me great comfort in where we are is that in July, we obviously -- we're not yet in the category of start forms or patients on treatment, but we had established soft leads and hard leads, a large bucket of patients that we believe are accessible to us. If you take the patients out of those buckets that have now transitioned into either start forms or on treatment, that bucket, the supply, the pipeline is richer now than it was in July, right? So not just are we putting patients on treatment at the pace that we had hoped we would, confirming the epidemiology, we also have the funnel that is being filled up and replenished at a rate, arguably even a better rate than we had expected.

Okay. Excellent. Obviously, both you and the competitor are relatively new launching into these indications, which as you said, are quite rare diseases. Should we expect -- how should we expect the cadence to evolve as physicians get comfortable with the data, comfortable with the drugs and start being more -- getting more on the lookout for these patients to put them on therapy?

Yes. So as we've always said, this is going to be a steady progress. Nephrology is not a specialty or a therapeutic area that's characterized by emergency settings, right? So nephrologists in general, will not be in a hurry to put patients on treatments. I will highlight that -- or highlight that if you take the 3 subsegments of patients being pediatric adults and then either one of those, but in the post-transplant setting is that in the post-transplant setting and the pediatric population, where, by the way, we are the only approved product, that, that urgency is notably higher than it is in the adult population. So again, all very much in line with what we had hoped and expected. And of course, this week, we are -- we have our publication in the New England Journal of Medicine kind of highlighting and demonstrating the really fantastic quality that we had from the data in VALIANT.

So we should talk about the potential impact from that publication. But first, you said there's more urgency in those pediatric and post-transplant settings where you have a unique label. And this is before launch, you were talking about as being a potential differentiator and opportunity to outcompete Novartis. Do you have an idea what percent of Novartis drug or what percent of these patients are being used off-label for them or how early adoption has gone in those specific indications where you have the unique label?

Low to very low. I think that not just does the data look very differentiated and has its unique positioning in the label. I think the appreciation for the severity of the disease in those particular patient segments is very strong and the importance of getting the best possible drug on treatment for these patients is also prioritized.

We had some feedback coming out of ASN, which you may have seen on last week. But I'm curious to get your take on the conversations that you were having with nephrologists at the meeting. What's the typical profile for folks that are actually actively prescribing EMPAVELI at this point? And who is still on the sidelines from a prescription perspective?

So I think that the -- again, kind of highlighting the pediatric nephrologist population is very well informed, highly motivated and understands the need for treatment in their patients. I would say, and I think Tim would agree, that is definitely kind of the population of physicians that stands out as most engaged at this moment in time. On the transplantation side, we actually have an engagement on the transplantation side that is pretty much in line with the epidemiology, meaning out of those 5,000 patients, about 1 in 5 are transplanted, and we see a good pickup there. But it is worth mentioning that in the transplantation world, things are very much done by protocol as well, right? So we expect that throughout the course of 2026, we will see a pickup there as the large institutions make that part of the standard of care of how you take care of a transplanted organ. And from there that, that will become kind of the ingrained way of taking care of [indiscernible] kidneys that were transplanted to patients with that disease. I don't know if you want to add something.

No. I mean what I would just say is that we're still in the early innings of all this. And what you see is there is a -- there are the people who have experience with the drug, and there's a big difference in having your hands on it and seeing what it's done to a patient and those who are kind of looking at the data and saying, that looks interesting, but we have a long arc to this disease. And we tend to move slowly and we tend to move in packs. Those were -- that was feedback from the nephrologists themselves. But I was also at a dinner where we had a nephrologist who had used EMPAVELI and had 3 patients on in the VALIANT study. And when she spoke about the impact on those patients, the other 2 nephrologists at the table who were very scientific and circumspect about doing anything too quickly, all of a sudden, they had some clear sort of interest that spiked, right? So what I'm telling you is that this is a process that will continue and the momentum will continue to build. And because we think we have really the first true effectively disease-modifying therapy in a disease like this and certain nephrologists look at this and said, I mean, I heard 2 say they've never seen a drug do what this did in a kidney disease, right? So that's the kind of thing as that starts to spread, we think that momentum will continue until it becomes kind of an established view on EMPAVELI. So it's just starting. It's interesting. It's great to watch.

All right. Well, we've talked about the broader arc here. Let's talk about some nitty-gritty in Q4 and as we head into the beginnings of Q1. It takes 4 to 6 weeks to go from a start -- a patient start form to a commercial customer. There's the guidance that you gave for line of sight in Q4 seems to suggest that cadence might be a little lighter than people were hoping for, at least some voices on the Street were hoping for coming into Q4. So I'm curious about the evolution of these things over time. Is there seasonality that we should be on the lookout for in a disease like this in terms of new patient starts? Is there an evolution that we should expect to happen over time in terms of conversion from a start form to a paying customer? And what does that cadence look like over the next just 1 to 2 or 3 quarters?

Well, you were the -- it was -- you mentioned also on one of your podcasts that expectations had sort of increased pretty dramatically the week before we announced. And look, the idea behind discussing our start forms was let's all take a breath. This is all a launch that we have to -- that like anything will take time. There is -- obviously, we mentioned a potential early bolus effect. We did say it was 225, we expected 225 or more start forms, and we continue to believe that guidance. And look, we think this is going extraordinarily well. We're very excited about how this launch is going. In terms of the things that are -- that we can do to optimize that 4 to 6-week time frame, the logistics of this are you have to submit the start form, you have to get vaccinated, right? And then you have to get payer coverage in place and everything else. So to the extent we can optimize that, we will. And we think that process as time goes on, will shorten somewhat. So the hurdles are not significant, but it does take a little time to get on the therapy. And then from a seasonality point of view, I mean, it's too early for us to tell, but we don't think there's a tremendous amount of seasonality to this.

Not necessarily. All right. Let's transition in the second half here to SYFOVRE to geographic atrophy, the other side of the business. I'll start with this. This is a market that the Street has stopped talking about as much and has revised expectations down pretty dramatically over the past couple of years. While you have maintained bullishness and you've maintained the notion that you think this could be a very large class and a very important class. So as the data has evolved and as physicians have had more commercial experience with the drug, has the medical perception of SYFOVRE, the perception of the prescribing community evolved to match your bullishness or involved to match your data from GALE in a way that you would have hoped?

Not yet, right? So I think that -- first of all, I think it's important that we place some context around this particular year of 2025, where the retina practices, which you have to think of like well-oiled high-functioning Ferrari engines, right? I mean these physicians see sometimes 100 patients per day, everything needs to run incredibly smoothly. When you throw a wrench in there, that can be very disruptive. Forget about SYFOVRE. We're talking about all patients. And in this particular case, what happened this year is that 1 in 5 patients historically depend on assistance from foundations to be able to afford their medication. That foundation money all of a sudden was no longer available. And especially on the wet AMD side of things, when you have patients with wet AMD and 1 in 5 all of a sudden comes in, they cannot -- there's no funding available to do the co-pay. What do you do as a retina doctor? This is a medical emergency when you have fluid in the back of your eye, do you resort to samples? Do you resort to generic Avastin? Do you -- so in this year, a lot of stuff had to be figured out on the wet AMD side to make sure that these patients were properly served. That affected us indirectly in a very meaningful way in the sense that geographic atrophy is not a medical emergency. It's important, but it's not from today to tomorrow. And a lot of practices paused on enrolling new patients with geographic atrophy. That does not mean that the disease has been impacted, right? It is just that this year, the retina community had to figure out how to handle this new dynamic. I would argue that from a perception standpoint, this was a good year for us in the sense that there is kind of a renewed interest in a new way of looking at geographic atrophy at this disease and understanding it, and we will be partners to the retina community to continue to do that. The patients population where we have found a solid footing is patients with advanced geographic atrophy blind in one eye, far advanced in the other eye, and you're going to try to rescue whatever is left, right? I think that is kind of the initial field where the drug now becomes much more widely adopted. That is a place where we have lots of plans to kind of consolidate our positioning. But there are -- and this is very important, 2 other large important segments of patients where a lot of work can be done. The second segment of patients are patients with early geographic atrophy. You're affected in your first eye. You still have good vision, but you're going to invest in trying to protect as much as you can. That is a patient segment where we know from the data that we can really help patients and physicians, and we need to work on bringing that to fruition. The third segment are the patients with wet macular degeneration who have geographic atrophy as a secondary manifestation of the disease. And there, too, the -- our drug is being used there, but there's a huge opportunity to help patients and expand the potential for this drug. So I think the message for 2026 and 2027 and beyond is we are kind of now working in a very like a level playing field where kind of there's room for a new appreciation for the long-term data that we have. I want to highlight the GALE data where we have now clearly shown with the largest trial by far ever run in this disease that over 5 years of treatment, you can save 1.5 year of vision, right? I mean that is very meaningful to patients. We have also developed a technology that allows you to show the functional benefit across the retina in these patients. These are all things that will take time, but that will impact this field, I think, in a meaningful way. And last thing I will say there is that in 2026, our main mission is, of course, it's always to improve sales on SYFOVRE, but it is to help physicians reimagine and rethink what it means to have geographic atrophy, what the functional decline looks like, what the impact is on patients. Because in all of the noise that we had in the past couple of years, that's been a little bit lost, and we have a real opportunity to reestablish that.

Okay. I wanted to dive in the first thing you said about the co-pay assistance foundation and the impact that's had on the entire retina community. Obviously, we've all been tracking the rate of samples that you give us every quarter, Tim, and we've all been curious about when those headwinds could clear out. But Cedric, it seems like you're saying there's a secondary effect, almost more important than just SYFOVRE being given out on samples, and that's the inability of the retina community to adopt a new treatment while their existing business is being thrown into [indiscernible]. Is that a headwind? I mean we don't have any line of sight on the foundation coming back to normalcy. Is there a line of sight on the retina community coming back to normalcy at that point, Cedric?

Yes. I think that has been a huge headwind for us this year. And one, quite frankly, that was less visible to us, right, in the beginning of the year, but that we came to realize as the course of the year progressed. We do not know what will happen with the patient assistance organizations. These are medical decisions. We'll see what happens. We have no expectation that, that will change. But what has changed is that these practices, they've now figured out how to speak about this, how to see these patients, receive them figure out, can they afford the co-pay, yes or no? How do we speak about this? Switch to patients that couldn't afford and needed Avastin have been switched. So there's slowly a new place of normalcy that is emerging. And in that place of normalcy, there is much more place for geographic atrophy.

Okay. And in that context, you mentioned a handful of potential tailwinds for 2026. You talked about this on the 3Q call. You talked about this just now obliely. You talked about a bunch of things here, the long-term data from GALE, the imaging, AI-enabled imaging. But one thing you didn't just mention, Cedric, that I wanted to make sure to ask you about is the effect of prefilled syringes. That's something else that you've spoken about coming in 2026 that seems to me to resonate very much with your message of well-veiled machine in retina practice. Is that something that you expect to be a major lever here? And if so, why didn't it come up in your answer just a moment ago?

It is, we think, going to be hugely impactful. And we know that from, again, what we saw in the anti-VEGF space, right? Fitting into the flow of the physician is the highest return on investment that you can get and the prefilled syringe fits in there. Right now, the SYFOVRE prescription means taking a vial out of the fridge, towing it, which can take anywhere from at least 30 minutes, but sometimes longer, then putting it into -- through a filter needle into a syringe, which takes about 30 seconds because it's viscous. And then you typically have to leave it on the fridge. So you can imagine that, again, from a flow perspective, that's not ideal. With the prefilled syringe that we have, we think that will improve dramatically and further increase adoption. In terms of timing, we just ran the clinical trial. I mean, we announced that, I believe it was in October. We now depend a little bit on the revision times that happened at the FDA after our filing. But again, this is not guidance, but I think towards the end of next year seems like a reasonable place for us to be able to have.

Towards the end of the year. This is not something that the competitor in this space has available at the moment.

Not at the moment. We have no visibility.

Yes. So we haven't heard about them trialing this. You haven't heard from your prescribers or anybody who's on your clinical study feedback that they've been working on something like this.

That's correct.

Is it possible that in '26, we'll finally see some differentiation in the market share here? It seems like there's been endless debates over who has the dominant position, but the delta seem to be very small in either direction no matter who you believe.

Well, I think there's no debate on who has a dominant position, at least on a total prescriptions basis. I think the new prescriptions did have some fluctuations. And that's settled out where we've been more or less in the mid-50% range. They've been in the sort of 45-ish percent range. And that's been pretty steady for really the whole year. And we don't expect massive shifts in either direction at this point, subject to other things like new innovations, prefilled syringes or other things like that.

Okay. And then lastly, just last couple of seconds here. Obviously, we have the RNAi, the LL-3007 in Phase I currently. What's the bar for success with the combination study? And what's the time line for that readout?

Yes. So with 3007, we aim to produce a subcutaneous injection that can be given at the same time or on the same day that the intravitreal injection is given. The objective is to go from every 2 to every 3-month dosing and to increase the impact that the drug has on specifically on the RPE cell layer. So that the lesion slowdown can go from 30% to a much more meaningful number. It has been fully thought through from a commercial perspective as well, meaning that if this works and it gets approved, you have a set of patients who are on every 2 months SYFOVRE. You can now bring them in every 3 months. You can increase the benefit from the drug and also do it in a way that does not hurt your bottom line.

Excellent. Well, I guess we'll leave it there. Thank you guys so much for joining us.

Thank you, John. Appreciate it.