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

Well, thank you, everybody, for joining us this morning. We've got Cedric and Tim from Apellis with us. Lots to discuss. So thank you so much for coming down to Miami for us.

Well, thank you, Jon.

Thanks, Jon.

Cedric, question number one. Could your GA drug peak below $1 billion Y-o-Y now.

You want to take that?

Certainly not our...

Basically, are we close to the peak already with the current run rate.

Well, That's definitely not what we believe, right.

Okay. And I guess what do you see and hear because we -- there's a lot of curiosity on this now.

I think that the aspect that is -- that people lose sight off a little bit is that there are 2 important factors that will drive this market in the years to come. The first one is that fewer than 10% of patients with GA have been treated so far. And the desire and the need for treatment by these patients is something that I think always has been underappreciated. I mean, when you're going blind, the fear that it brings to people is unimaginable unless you're in that chair. The second aspect, and I think this is important, is that this is, unlike wet AMD, not a disease with the same urgency to treat, right? So if you're a physician and you're a patient, and you have a drug that's new to the market, and especially when it's a drug that comes with a lot of stories and a lot of things, it's easy to say, like you know what, let's take a little step back and let's wait a couple of months to see what happens, right? What I've been very pleased with in the last 2 quarters is that in the background, right, the knowledge around the drug, the understanding of what it does has become much more stable, right? So the controversy is really getting out of it. And what's happening now is that we're seeing real-world evidence where physicians, in their own practices, on an intra-patient basis, see patients get better. That is something that will be published in the year to come from several groups that we are aware of. At the same time...

Wait, they will publish what their experience.

The real-world experiences, right? Where you take essentially the historical progression of geographic atrophy, you start treating and then you see how it essentially slows down the disease, okay? The second piece is that in the -- there's a segment of doctors that are not negative necessarily towards the drug but that are kind of sitting on the sidelines, they want to see how this all pans out, what's happening, et cetera, but they're open-minded. And the doctors that are younger, that have recently graduated or that are like having a new practice, especially those physicians, right, I mean it's a great opportunity for us to educate them and bring them along in the story. So we're super excited about 2025. We think...

So at the current less than $650 million run rate, you are still seeing sequential growth, which is like real volume growth.

Look, we saw 7% vial growth late last quarter. So we're still seeing vial growth. That's not the issue.

This is 7% net of any -- obviously, net of any discontinuations that may have happened.

Those were vials. That's vial growth.

And maybe expand on the discontinuations as well as -- like what would it be in the absence of -- like how much new patients...

From a discontinuation perspective, we don't specifically talk about the data, but what we've seen is basically in line with anti-VEGF discontinuation. So it's a pretty standard rate. And I think what you're getting to, this sort of concept of slowing really came from the fact that we had -- while we did have 7% vial growth, we had a big hit to gross to net. So the optics of the revenue were obviously flat. And of course, when heading into this quarter, we guided pretty conservatively because there were some dynamics we knew were going to just sort of continue to play out for the fourth quarter, but we said longer term, we see this market growing and substantially. It's just something we really didn't feel comfortable talking about sort of any kind of growth...

Beyond just your own product here, are there signs that the overall GA market is plateauing. To Cedric's point, you haven't treated the majority of patients, certainly, but it does feel to observers that the GA -- the new patient starts in GA across the indication are slowing down.

Look, in the third quarter, it didn't grow as much as it did in the second quarter, right? It was 15% overall vial growth in the quarter. So that's still pretty healthy growth when you -- I mean, it's not going to go to zero in this quarter in all likelihood, at least that trend doesn't suggest that. So look, I think there may have been some seasonality. There was August in that -- in there. We haven't had a number of years to look at this market and kind of project it out. And I think that needs to be taken into consideration when people take a view on the long term so.

And remind us your expectations into next year on a dollar sales perspective, are you guys commenting broadly? I mean you're obviously expecting growth. I think consensus is modeling it as such as well.

We haven't guided. And look, as we said, fourth, we really wanted to see how the fourth quarter played out in some of the beginning of the first quarter before we really decided to guide and that's certainly something we're definitely considering, but it probably wouldn't be until later in the quarter. It would be more likely earnings than it would be kind of early in the year. So obviously, there's a lot that's happened this quarter already, and we have to see how that all plays out.

Well, Cedric, maybe -- we have to ask you about that then. Obviously, your competitor did get a CRL for their label expansion, what does that mean for the market currently? I think expectations are that docs aren't going to change their behavior in the near term. Do you think that this has a major impact on your ability to build back market share over time?

Yes. So look, SYFOVRE is a drug that is meaningfully differentiated on efficacy, can be dosed as few as 6 times per year and has increasing effects over time. None of these things accounts for our competitor drug, which now also has that limitation that hasn't been resolved or being able to be dosed beyond 12 months. That matters, especially in the context of the payers, right? I mean the average cost of the drug for SYFOVRE versus our competitor is on [ paper ] health, right? I mean 6 vials per year versus 12. Even if there are off-label prescriptions, the cost per patient will be meaningfully higher for our competitor compared to SYFOVRE. That is something that payers know and many Advantage plans, January 1 are going to start placing SYFOVRE as the preferred drug. Driven by that, but also by the fact that the efficacy is differentiated even with every other month dosing compared to monthly so there's a clear differentiation there. What is interesting now is that we're not speculating on whether the 12 months will be reversed or removed in the end or not, that doesn't matter. But we will go into January 1 with a situation where recertifications need to happen and where patients beyond 12 months are at risk of not being recertified. There's also the risk, frankly, of clawbacks, where payers could go like and tell physicians, look, we paid you for a patient that you treated in month 13 or 14 that was off-label, we want that money back. That is a real risk that is out there. And there are small anecdotes already, of physicians not being paid. And when that gains traction, I think that would be...

You -- there have already been reports for patients not getting reimbursed post 12 months on Izervay.

That is correct.

Got it. Cedric, one of the dynamics we're hearing from physicians is younger retinal specialists so we're talking sub 45-year-old retina; specialists, they think there's too much risk in engaging with either your drug or Iveric drug, but if anything, maybe the other one is perhaps there is a perceptive safety. But in general, they just don't want to go near it for liability reasons. I guess how big a cohort is that of the total retina audience? And what type of -- it almost sounds to me like there needs to be a commercial strategy very specifically intended towards getting those guys comfortable because -- now I'm hearing this feedback from some of the highest volume practices out there, including some of the folks that hung in there back when things got really dicey last summer.

It's a big cohort, and it's a great opportunity for us, right? So because the facts here are on our side. Now we all know that emotion matters more than facts, unfortunately. But in this particular space where patients want to be treated, right? I mean you have a great opportunity to kind of turn these things around, right? That takes time, it's not easy. But the element that I think you need to bear in mind is that there is not like a negativity towards -- oh, this is terrible, it is more like we don't know what exactly is going on. So educating on physicians, and we've seen this in many kind of individual cases now, and I think and I hope and I expect that, that will pick up steam is they want to understand how rare these events are. Once they understand that half of these events do not lead to a bad outcome, once they put it in the context of the risk of [ infectious endophthalmitis ], which happens with every single injection, then you realize that, for example, dosing monthly for a year, the risk of infectious endophthalmitis and severe vision loss is higher than the first injection risk of vasculitis and dosing every 2 months.

Got it. Is there -- I mean, this probably sounds like an odd question, but is there any way to help some of these -- again, the risk they're pointing out is something very basic, which is they have a structural financial risk to their practice if they end up in a liability setting. Is there any mechanism, obviously, completely legally that could be structured to help them hedge against that in some shape or form?

Well, it's education and disclosure, right? I mean this risk is not different from the risk of having a patient with infectious endophthalmitis. I mean that is -- those are things that happen when you do intravitreal injections and it's important that you have a proper explanation to the patients of what that risk is. So in that sense, this is exactly the same. When you do the intravitreal injection, once in a while, it will go wrong. If you didn't tell your patient, you're liable, if you did properly tell your patient, you're not. So it's...

Got it. It's -- and my last one, -- these are not parallel, very different populations, Alzheimer's with the Leqembi launch, SYFOVRE in retina, completely different things. However, one thing I'm hearing from Biogen recently is because their drug does not have an immediate symptomatic benefit. What they're finding is as the -- as patients are approaching 6-plus months in, now they're starting to feel a difference in terms of -- because that's when the curves start to expand meaningfully versus the trajectory they were on. And their family members are starting to feel the difference, and it's incentivizing them more. I'm curious, is there any parallel like that in GA where, once you're hitting month 6 or month 9, somehow the conversation starts to change in terms of, oh, now I can feel some sort of difference versus the trajectory I was on.

Yes. Well, so...

And I know you had some of that follow-up data longer term, which was like 42% in some of those large deltas in the outer times.

Yes. So I mean these things are anecdotal. We have plenty of anecdotals like that, right? So I think that is absolutely there. I think what is very encouraging to us is that the physicians who are negative on our drug are physicians that don't use our drug. Physicians that actually have a lot of experience with SYFOVRE are very enthusiastic about it, and more and more enthusiastic, the more they use it. And those are the physicians that are now also bringing out these publications. And I think it's important to bear in mind also, if you take the last year, right, and we have conferences with very loud opinionated voices coming out. It was hard 6 months ago or until recently to go and stand up and fight that because the knowledge is -- that's not out there. But I want to point out that we have up to 42% slowdown in lesion growth in geographic atrophy. Had we said 5 years ago that we were going to have 42% slowdown in a neurodegenerative condition, people would have lost their **** -- that is a -- that's how good this drug is. And that is something that will -- that needs to come back into the picture. And I think that physicians as the -- with experience, as they disclose it, that will come around.

I want to just transition quickly, but just ahead of that, Tim, would you remind us where do we stand on the balance sheet? And where do we stand on your aspirations towards this being -- getting to a breakeven because I think those are also relevant considerations for the stock into next year.

Yes, we have just shy of $400 million on the balance sheet.

And how much is the debt? That's the part that confuses people.

Yes. So we have a couple of things. We have $100 million -- a little under $100 million in convertible debt. And then we have -- we obviously have the Sixth Street debt that we used to refinance the...

How big is that.

$375 million. And so -- so we have -- the way we have it right now in terms of our income statement is that if you look at our cash expenses and our net revenue, we basically are offset cash neutral. So right now, our financing consists of our interest expense and our working capital financing. So ultimately, from that perspective, we're almost there, right? It doesn't take a lot to change things. So.

Can you be a breakeven next year on an EPS basis as a company?

On an EPS basis, so -- we're not guiding to anything like that. But everything depends on revenue. Sorry.

Is there an aspiration to control cost to have an EPS breakeven next year? And maybe an EPS positive in 4Q or something like that?

No. I mean, strategically speaking, we get that, and that's something we will try to be as efficient as possible. But the simple fact is that we have incredible data in C3G. We have this incredible opportunity to expand our GA market. And not funding that would be an issue, right? And there are some additional trials we're considering in the kidney. I mean, obviously, the data we showed in C3G is so differentiated that if that -- if complement has the same impact in certain other areas in the kidney, we have to pursue those, right? So we're going to evaluate all those things and make sure we're as efficient as possible overall, but we're not going to commit to anything from a cash flow breakeven or EPS breakeven.

Well, let's talk about kidney then a little bit more since you bring it up. The -- I have a whole bunch of questions here, but you just said new trials and other indications. Let's be more specific there. How broad in kidney is complement going to be. Obviously, C3G is an entirely C3 driven indication, but as we look across kidney, there's...

IgA nephropathy.

Very competitive, and is it less complement driven? Do you expect to see the same level of impact in those indications?

Yes. So we are still doing the work on identifying which kidney indications we will be pursuing. But there are several indications where we believe the biology, the science and the profile and the competitive profile is there as well. So -- we'll talk more about this, but we have -- we're very excited about kind of the opportunity beyond C3G and IC-MPGN that presents itself. Again, needless to say, what stood out there was kind of the complete stabilization of the disease that we saw in these patients. That is something that makes us very excited about what we can do in these indications, but it also tells us how good the target engagement was in the glomeruli of these kidneys. And that is something that provides a great opportunity.

So the Novartis updated data at 12 months seemed to confirm sort of a mid-30s proteinuria benefit in that crossover arm. But obviously, that is apples-to-apples with their prior -- their prior disclosure. What's the impact of their 24-hour collection versus spot test? Would you expect spot test to be more variable. Are there -- is there a risk introduced to that very impressive proteinuria number from the method of collection?

No. So we had both -- I mean they confirm each other. The spot test is the one that's actually generally viewed as the more reliable one because it is always in the morning, especially when you have a pediatric population included in it. So again, the data -- but what really stands out here beyond proteinuria, that I want to point out, and I think it's critical is the difference in the histopathology, right? The fact that you can look at these kidneys after 6 months and see how they're -- in 70% of patients completely clear of C3 deposition. And by the way, to pathologists, it look like normal kidneys, which is why some physicians have used the C words, the good word for this indication. That is something that really stands out. And that's not something that we have seen with any other complement inhibitors.

Cedric, the big investor question I get constantly on this is how many patients are there? Is it 1,000? Or is it 10,000? I guess -- I realize where your guys bias at. How do we know -- do -- is there any patient registry you have access to, which already has a list of, let's say, over 2,000 because that would mean there really is over 5,000.

Yes. So first of all, we enrolled 124 patients in development. We also already now have more than 50.

How many were in U.S. Or what percentage broadly is in the U.S.

It's just under 50%.

That's correct. But the...

So you had 124.

Yes. So we also have more than 50 patients on expanded access already. And the way in which we did the math, the number 5,000 patients in the U.S. where that comes from is we went back 5 years and looked at patients that during that 5-year period had 2 confirmed diagnostic claims, right? So that's a pretty high standard. Our competitor has a number that is, I think, as much as 4x higher than that, that we believe, even though we don't know that for a fact, it's probably based on going back 10 years and a single diagnostic claim that is probably taking a little bit too far. Wherever the truth is, we stand firmly by the number of 5,000. We believe that, that is real. We believe that is a conservative number. And again...

Novartis thinks it's 20,000.

Yes, that's right.

Folks who think it's 1,000 are extrapolating from epidemiology numbers, incidence numbers from [ SemStudies ]. What's the risk in using that approach versus a claims approach.

Well, if it's 1,000 patients, then we were able to find 6% of all patients in the U.S. that are in trials, which would be quite remarkable.

This is not a centralized indication where there are a few centers of excellence where the majority of patients are treated. How challenging will it be to identify and find these patients, assuming a good review process and a launch.

It's a challenge always, right? I mean I think that there is a segment of patients that I think very quickly are going to want to be treated, especially patients that are transplanted that are at risk of relapsing. Those will be highly motivated patients that want to come on. Patients that are adolescents or young adults on their way to end-stage renal disease, they're going to be very motivated. But I think that these pieces are going to find their way, what's fantastic to see at ASN in San Diego in October, what the response was by that physician community. And again, I think the fact that you're not talking about a slowdown of a certain percent. I mean these kidneys at 6 months look like they're stable in that disease. That is very promising, right? That means that as a patient, you may never have to face end-stage renal disease, hemodialysis or transplantation.

Last question. I know we're at time. Proteinuria benefit. I know you guys are almost double what Novartis has. However, there was a difference in how the read was done, the 24 hours versus spot read. Can you remind us, on an apples-to-apples basis, because you haven't reported it like that, the endpoint that Novartis reported. Where do you guys broadly track on that endpoint on the spot rate on 24 hours.

We are pretty close to where we are with the spots.

So it's general range. .

Correct.

Do you have any plans to report that in the future if you measured it.

I don't think so. I mean look, we have the publication and it is in the same range so.

Yes, we also -- it wasn't our primary. So we didn't track it as rigorously as we did on the spot test. So it was -- it's in there, but -- and it's consistent, but it isn't something that...

Is the clinician feedback clearly that this is...

Clearly.

Clearly double, like is that up there.

Correct.

Excellent. Unless there's anything in the audience, we'll wrap it up here. It sounds like kidney is going to be a lot more in focus. So remind us, could you have a PDUFA date by late next year on this?

Yes. By late next year should be the minimum expectation here.

The minimum expectation -- so this could even be a more rapid, could it be a 2Q type turnaround? .

No.

No.

So our plan is to file early next year.