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

Good morning, everyone. I'll just read this research disclosure. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. Well, welcome, Cedric and Tim, fantastic to have you, and congratulations in terms of product approval and launch.

Thank you.

Before maybe jumping into some granularity in terms of what's been happening over the past couple of months, it'd be great just to spend 2 minutes on the background of the company, and then we'll dive in on SYFOVRE.

Yes. Thank you so much, Jessica. Well, obviously, we had a very busy summer with the challenges that we had to meet. But what we like to think about is the efficacy profile that also came out this summer around SYFOVRE where one of the core tenets of the drug, which is the fact that the longer you treat the patient with SYFOVRE, the more you can slow down the progression of GA further continue to materialize in the GALE extension study. So where patients who had been on treatment for 2 years went into an extension study continues to receive the drug, and we disclosed the 30-month data where between months 24 and 30, the slowdown of the growth was almost reduced to half of what it was at baseline. It's an incredible benefit to patients, of course, something that we're incredibly proud of and that physicians are also very excited about it. So in the meantime, EMPAVELI continues to be an extraordinary drug for patients with PNH with a remarkable safety profile. I mean, we are now probably slowly gearing up to 1,500 patients years of dosing with EMPAVELI. And it is a drug where we have not seen a single case of meningococcal infection yet, something that I think was generally believed to be a class side effect, but not with EMPAVELI, and a drug where we have about 97%, 98% compliance rate in PNH. So something that really benefits patients tremendously. And where we have the C3 glomerulopathy and ICMPGN trials also ongoing with data coming out next year. Exciting things there as well and then our preclinical work with our first IND as well for siRNA, which is now in the escalation phase. So that's kind of the flash around everything that's going on. Of course, in the meantime, over the summer, we had to deal with these rare events of vasculitis that were described. So maybe a bit of background around that. Vasculitis can be best thought of as the very advanced form of inflammation that you can get when you do an intravitreal injection. And when you have vasculitis, that can sometimes lead to very severe vision loss, right? There's a particular sensitivity in the retina community to that term vasculitis that was caused by another drug that came on the market a couple of years ago and where patients in increasing numbers were developing that particular competition. I think it's important to note because very understandably, so the retina community, the physicians that treat these patients, right, have that memory of back-in in the very recent past, having these cases that started with a few and then more and then more. And then it was, quite frankly, something that had a very negative impact on patients and on the physicians that treated them. But the real important element that we had in the summer was, yes, we have these very rare cases, but physicians have to know and understand that a very rare incidence was indeed a very rare incidence and would not increase over time. And so that is something that we wanted to build on. We built trust with the retina community. We're very transparent. We showed everything. We work together with the ASRS as well in terms of explaining these cases and what they are. And that we provided our update in August, of course, where we continue to track with very thorough pharmacovigilance, what is really going on and where we feel very confident around this rate of 1 in every 10,000 injections. In the meantime, also in August, in our root cause analysis we discovered something that, and I want to be clear, we cannot say it's the cause of vasculitis but something that we found to be associated, which is that there is a 19-gauge needle that is provided to physicians to draw the product out of the vial into the syringe that is then used for the intravitreal injection. And that filter needle we found to have material variations in the manufacturing of the filter itself inside the needle that gave us cost for concern. So we took the action of removing that needle from the shield. And we're going to find out but with time, whether that has an impact on the rate of these cases or not. But as a base case, I think the key thing here is that we believe that this rate fits very strongly around 1 in 10,000 injections. And that is a rate that is viewed as acceptable, but the vast majority of physicians and most importantly, patients. So as we now move forward, the key thing is our drug continues to be prescribed in high volume that allows us to evaluate things like that needle that allows us to evaluate and continue to offer this product to patients and make the difference that it does.

Great. Well, thank you very much for that, Cedric. Maybe any questions on that topic because, obviously, very important in terms of what's been happening at the company.

Yes. So thank you, [ Chris ]. It's a very good -- very, very good question. So the question was whether the needle was already being phased out. The needle was not being phased out, but we launched in the beginning with the 19-gauge needle. And then in the spring, we introduced the 18-gauge needle. And the reason why we had 2 filter needles was to make sure that we would have supply to meet the demand and have redundancy in providing these needles to the physician community. So there is a coincidental because that's really what it is kind of introduction of the 18-gauge that came later and that became the predominant leader -- needle, sorry, in the summer. And then when we took the field action, we decided to make sure not only that we would no longer distribute the 19-gauge needle, but also we'll remove these 19-gauge needles to the extent that we can from the physician practices.

And then from a case rate, you're going to be anchored by the bolus of cases [indiscernible] as you go forward, are you able to say like since August [indiscernible] 20,000, 30,000 nominator grew now anchored by let's just assume that go down, are you able to -- or are you limited based on ways to operate [indiscernible] early case.

Yes. I mean that's -- there's 2 ways of looking at and to your point, you do a cutoff where you took action and see if there's a difference before or after. We'll definitely do that. But we'll also look at it in a holistic fashion. I think what's important here, and this sometimes often I think gets underappreciated is when you have a safety event in the real world and you issue an alert around it, the way ASRS did in the beginning of July, very often, more often [ turns up ]. There's a whole bunch of stuff that you don't know that all of a sudden comes to the surface. It was really remarkable. And I think kind of a testament to the retina community and how they report that the difference between what we knew and what we found out was very small. And then when we work with ASRS, we can disagree on, is this a case of vasculitis or advanced IOI because you have to remember that the term vasculitis is not really well defined and you show it to 5 retina docs, they're all going to have a different opinion about it. And at the end of the day, the visual outcome is what truly matters, right? I mean that's the -- so we don't always agree on is this vasculitis and IOI, what is it, but we were very close to each other, the ASRS and ourselves. We were all aware of the same cases, and that's something that continues to be the case. So I think for the benefit of patients, having thorough insight into what happens in the real world is key, and we clearly have that.

And when would we expect another update in terms of [indiscernible]

Yes. So we'll provide regular updates to the retina community, which we promised them and which we, of course, want to do. And in conjunction with that, we'd, of course, also update the investor community. We'll have one update before our earnings, then earnings. And then after that, I think we'll find a regular cadence to come back to this subject. But again, if it is a rate of 1 in 10,000 overwhelming majority of retina docs consider that part of the risk. It's worth noting that infectious endophthalmitis, which you can have very similar outcomes in terms of vision is a risk of 1 in 3,000 to 5,000 injections, and that is absolutely part of the risk profile of getting anti-VEGF injections or in this case, anticoagulant drugs as well.

Yes. Great. Great. You mentioned, obviously, the relations with the physicians. I mean it's been 6 months. Maybe you could touch on how physicians are identifying patients in addition to the safety that you mentioned, but importantly, the efficacy results that you've had and how the physicians have been embracing your product.

Yes. So I think it's -- when you go into a new indication, especially one as large as this one, where there has been nothing available before. Of course, it's under a gigantic magnifying glass through it, as it should be. What stands out here and which is probably the most underappreciated element is how bad this disease is, how impactful this disease is to patients and how that generates a desire to slow down this disease. And again, the ability to be able to slow down this disease by close to 50%, right, after 30 months of treatment is an incredible benefit to patients and patients that are losing their vision want to receive that treatment. Where it gets complicated, of course, these increasing effects over time, it's not something that is intuitive. Very few drugs do that, actually, right? So in the first year, you're still within a range where you could say, well, "well, is that -- we need that good," but it's a drug that most patients are going to be treated with for many years, maybe even decades. So as the physician community gets to know and understand this product, the way in which it works, the safety profile, combined with the unmet needs that exists in that patient population. We think there's kind of a very important stable of treatments that will be there for a long time.

Well, maybe this is a good time just to reinforce the clinical data that you have presented in the 30-month clinical trial data, which was also recently...

Yes. So it was -- we run, of course, a very comprehensive clinical trial program. We have about 24,000 injections that were done in our clinical trials. We're just in our Phase III clinical trial, we had 1,200 subjects on treatment, where we have the GALE extension study as well. By the way, we never saw a single case of vasculitis in our clinical trial work. So that's something important to point out as well. And as mentioned earlier, the cardinal feature of the fact that the longer you treat these patients with this drug, the more you can slow down the growth of geographic atrophy. There's also something else that's important that we found out more recently when you -- this is imposed drug analysis, but fascinating work that you can do with the new imaging techniques that are available and using artificial intelligence. And it's the fact that the protective effect of SYFOVRE on specifically the retina cells, so the light sensing source in the retina is pretty much complete from day 1. And I'm going to dive into that very briefly because it's just a fascinating observation, including for retina physicians. If you think of the retina as not just grass, like a lawn, but as the soil under the lawn and the grass on top of it, that's what you could think of as an analogy for the retinal pigmented epithelial cells and the photoreceptor cells. When you have geographic atrophy, you obviously have a hole in the ground, but you also have an area around that hole where you have the soil without the grass. And then what we measure with autofluorescence in our clinical trials is the size of the hole and the rate at which the hole grows larger. But then when you look at the graph, you can actually see that the grass stops dying immediately and pretty much completely with the drug. And then when the soil as it continues to grow, reaches the grass, then they die in conjunction with each other. That's a fascinating observation that we have the ability to visualize. And again, one that teaches us a lot about what we can do in this disease and provides hope for future treatments that could even be more complete than what we have right now.

Great. And in terms of the delivery, I mean, physicians have a choice with respect to every other month, monthly, how are they thinking about that?

Yes. So that was something -- I mean, we all are, and I am particularly proud of the way in which the clinical program was run, right? I mean, we had 1,500 subjects in total with EMPAVELI and the 2 Phase III clinical trials. We tested all forms of geographic atrophy regardless of where the location in the eye is. And typically, the distinction that we make is patients with subfoveal lesions where the central vision is already affected. And then patients with what we call extrafoveal or nonsubfoveal lesions which are in the periphery. All of these patients were assessed. And then as you mentioned, the posology were both with monthly and every other month, we found this profound efficacy profile with increasing effects over time, quite close in terms of pharmacology. It's not that monthly gives you twice the effect. You get a little bit extra, but every other month is very good and is for sure the predominant way for physicians to treat patients. And in our label, we got the flexibility between 28 and 60 days. And we see this in our high-volume prescribing practices already happening now. The flexibility that, that provides to a physician to say, I'll see you in -- and a lot of them say, I'll see you in 6 weeks, right? Then you go to the front office, you try to find a time that matches and you have 2 weeks up and 2 weeks down to work with. And if you go on a holiday, your physician is not around or whatever it is, you have maximum flexibility to continue to receive what has clearly been established to be an efficacious profile for the drug.

Fantastic. Maybe we should just touch on reimbursement payers, upcoming J-Code, the ramifications of SYFOVRE.

Yes. Thank you. Tim?

Yes, sure. So we're expecting our J-Code to become active on October 1, which should ease reimbursement for really all physicians. And that will probably get some portion of physicians who've waited to begin to prescribe. But so far, we've had great reimbursement success. In that 1 or 2 exceptions that have required a little extra work. But for the most part, we've been very satisfied with reimbursement already. But again, the J-Code probably is important for some of the smaller practices, some of the ones that have less infrastructure to deal with the reimbursement hassles pre J-Code, which should have some impact.

Great. Fantastic. And you've been invaded in terms of your marketing, perhaps you want to touch on the Henry Winkler campaign and its ramifications.

Well, I should probably do that because he didn't know who Henry, who was a year ago. Well, we got Henry Winkler over here, I was very excited. We were in this meeting, and they showed us the Henry Winkler ad and said it was like blank. This is Henry Winkler.

It's been great.

So you said, he's the Fonzie.

The Fonzie. Yes.

And it's right a blanks there.

They don't show Happy Days in Belgium. Anyway, so it's been an extraordinary success, right? I mean, first of all, Henry Winkler himself, when we tested a bunch of celebrities, he ranked higher than anybody they had ever seen in terms of how the target audience responded to a single celebrity. I mean they were -- it was like 99 out of 100, they've never seen it. And that's because he's such a well like guy and really across all age groups. And so I don't know, I hear all the time. I just saw your ad with Henry Winkler, got me -- actually, we had -- I don't know if I can tell this story, but Dick Van Dyke got his eyes checked because he saw the Henry Winkler ad. So there you go, pretty successful.

Fantastic, fantastic. Maybe just in terms of additional clinical news flow. I mean you mentioned, Cedric, with respect to acuity or functional data being important to the physicians. What should we expect over the next 2023, 2024 in terms of this continued rollout of clinical data that has been really robust today?

No, thank you for that. So the -- first of all, on the visual function, there's still a bit of a misconception out there that we don't have a functional correlation. We have already established that, right? So we -- the first data that we presented was approximately a year ago where we looked into the microperimetry data that we had generated in 1 of our 2 Phase III clinical trials. So what is microperimetry? The best way to think of that is a grid of 68 points in the back of your eye where you shine a laser with increasing intensity and the patient can see the dots then clicks on the button. And in geographic atrophy, the problem that you have is when a patient comes in, right, you have an area where the retina has already perished. Those dots are gone, and they're not coming back. And then you have the area where within the period of the trial, even 1 or 2 years, the zone would never grow into. So dots that sit outside of that are also never going to be affected regardless of whether your drug works or not. So you have to hone in on the zone where the dots have an opportunity to be affected and look at whether the drug impact that or not. And so we showed clearly there last year that we have an impact on those dots in those zones with the same increasing effects over time that we have when we look at the lesion size growth reduction. And then we looked at patients specifically for visual acuity. And that was challenging because, again, if you have a patient where the central vision is already affected, which was 60% of the patients that we enrolled, then visual acuity, which is your ability to read letters for which you only need your central vision will already be impacted. So what we did is we said, let's take the patients where the lesions have not impacted central vision yet and where the lesions are close enough to the central portion that they have an ability to impact visual acuity. And there, we saw that we could save these patients a line of vision after 2 years of treatment. But again, very impactful and with a very clear readout. Now we're going to have the 36-month data in GALE, so that's very exciting. It's going to come out later this year. That is 3 years of full treatment with SYFOVRE, we're going to look at all the endpoint again. Look at this increasing effects over time. Beyond 3 years, I think the effect is going to -- or not the effect, but the size of the patients that we're going to have in the extension is going to start dwindle down, you have to imagine that patients in GALE have to go on these visits, not just to get an injection, but get all the exams. They get tired of that. There's a commercial product available, why would they do it. So I think the 3-year will probably be the final point in time there we can definitively look at and establish what this drug can do for patients in the context of these trials. But really excited about that. That's going to come out later in the fall.

Fantastic. And in addition to clinical updates on the patient numbers, revenues, what should we expect through the remainder of 2023?

Tim?

Yes. I mean those are the big ones, right? We're going to continue to give updates on vials and on revenue. We're not prepared to do any guiding yet or anything like that. So those are the 2 basic metrics.

Right. Okay. Fantastic. And I guess just lastly, there's a new competitor out there in the marketplace. Any feedback in terms of how that's impacting dialogue with physicians, sales, et cetera?

Yes. Look, it's great to have a treatment for these patients available, right? I mean, with SYFOVRE established a profile that we understand very well. We are north of 100,000 injections now. So there's super robust data sets in tens and tens of thousands of new patients that have been treated. That gives us a profound understanding of what this drug can do. You combine that with a very robust work that we did in the clinical trials, and having the benefits of up to 45% slowdown after 30 months of treatment is something that, again, there's life changing and sight changing for these patients, something that we think is going to make all the difference.

And just make sense to remind people how large, unfortunately, the patient numbers are here for geographic atrophy. I mean sometimes we lose sight of how significant a problem this has.

Yes. I think the launch surprised us a little bit. Surprised everybody a little bit and gave us a sense that maybe the market size is even bigger than we initially thought. We always anchored to this 1 million patients in the U.S., 2 million in Europe. Our internal -- our internal assumptions have gone up a little bit on that, maybe kind of 20%, 30%. I still have no idea whether we're accurate on Europe, but that's what we're going to assume 2 million for now, but we think the population is bigger than what was initially thought.

Any other questions on SYFOVRE? We will move on to EMPAVELI. No. Okay. Well, great. I think you touched on in your opening remarks, Cedric, with respect to the fact you've got another product out there and it's doing extremely well. Maybe we could touch on the launch there and what you're seeing from the field?

Yes. Thank you. Yes. So as I mentioned in my intro, EMPAVELI is a treatment that makes enormous difference in the lives of these patients with PNH. In the next couple of months, we're going to get another product on the market, which are the oral Factor B inhibitors are the first one that is going to come on the market. That, of course, provides an important convenience benefit to patients with PNH. And I think for newly diagnosed patients will provide important competition, but I think importantly as well, a great option for patients that are in need. Specifically in PNH, though, I think it's noteworthy that the risk benefit of taking a pill twice a day with a tight pharmacokinetic window is not something that is there for everybody, right? So you could say, well, I don't want to take a subcutaneous injection twice a week. Again, the patients that are used to it have no issue with it at all, and they can forget to take it. They can forget to take it for a day, 2 days, 3 days, probably up to a week. Having that flexibility and that confidence is something that we find patients to really enjoy and appreciate. So I think there's an audience for both these products. We'll see where it falls out. But at the same time, of course, in the past couple of years, we've established that remarkable safety profile for the drug combined with its efficacy profile. And I think in PNH, EMPAVELI is there to stay as a stable of treatment for many years. It's also, of course, interesting and important that we have discovered that extravascular hemolysis, as we, of course, had always hoped and postulated. [indiscernible] is a really important contributing elements to anemia and transfusion dependence in these patients. And because unfortunately, PNH is a rare disease, because unfortunately, therefore, there are not a lot of patients they may get a little bit less attention. The hematologists generally may not think too much about PNH. Novartis is going to help us with that, right? So in terms of providing the best possible care for patients, I think this is a good thing. The next indications, C3G and IC-MPGN, we are very excited about. I mean there's about 18,000 patients between these 2 indications that right now typically get diagnosed in early adulthood during adolescents, at a 50% chance of developing end-stage renal disease over the course of 10 years. There's nothing available for these patients. Once they are transplanted, 50% to 70% relapse because the same reasons that caused the kidneys need to fail genetic reasons because the kidneys to fail in the first place will also affect the transplanted kidney. So again, there, we will have the competition from the orals. But I think the later you get into the stage of development, if you get towards end-stage renal disease, let alone when you're transplanted, convenience is less important than tight pharmacological control and a broad benefit. And when we look at the Phase II clinical data that we have in these indications, it's extraordinary. And we also have a lot of data from the real world where EMPAVELI has been prescribed to patients with this disease on a compassionate use basis with similar outcomes.

And when would we anticipate clinical data on these additional indications?

So next year, we'll have the clinical data. Yes.

Fantastic. Okay. Great. And then lastly, I think you took some very proactive steps in terms of a restructuring recently. Tim, I wonder if you could comment on that.

Sure. So through the beginning of the year, we've been guiding to having cash into the first quarter of 2025. And then with the uncertainty, obviously, is incumbent on us related to making sure we have that runway to really optimize our expenses. And so we had to take that decisive and difficult decision to reduce the workforce by about 25%. And reduced spend overall for next year, resulting in savings through 2024 of about $300 million. And then over the next kind of month or 2 as we get our certainty around the revenue and the slope, we'll be able to guide to that runway around earnings -- at earnings efficiency.

Great. Thank you. We've got about a minute left. Cedric, any final comments to the group here?

No. Thank you for inviting us to come here, and we look forward to an exciting fall and next year as well with the continued development. Thank you.

Thank you very much. Thank you.

Thank you, Jessica.

Thank you.