All right. Welcome everyone to the 41st annual JPMorgan Healthcare Conference. My name's Anupam Rama. I'm one of the senior analysts here at JPMorgan. I'm joined by my team, Malcolm Kuno and Priyanka Grover. Our next presenting company is Apellis, presenting on behalf of the company, we have CEO Cedric Francois. Cedric?
Thank you very much, Anupam, and thank you for inviting us. Good to do this in person again. In the next 20 minutes, I'm going to take you through the story around Apellis, what we have been doing in the recent past, and what we have to look forward to in the next year. These are our forward-looking statements. You can also find our SEC filings online. We have a lot to look forward to. The next month we have our PDUFA in geographic atrophy on February 26th, with the opportunity to deliver the first-ever treatment for geographic atrophy, one of the leading causes of blindness in the world.
We also have EMPAVELI that is currently in about a year and a half of sales, has had a great launch trajectory and is turning out to be a truly game-changing solution for patients with PNH as it relates to their condition, their anemia, and their quality of life. We also continue to focus on complement factor C3 and all that it can do across a wide range of therapeutic areas with 12 clinical and pre-clinical programs. 2022 was a transformational year for us. Of course, in geographic atrophy, we had our filings in the U.S. as well as in Europe. We had the commercial preparations to complete. We are ready to launch this drug in geographic atrophy in the U.S. and have also worked in Europe. Importantly, we recently announced that Dr. Caroline Baumal is going to become our Chief Medical Officer.
Caroline Baumal is a world-famous retina specialist. The way in which this happened is about a year ago, Dr. Federico Grossi and I, who co-founded this company with Pascal about 20 years ago, we decided that we wanted to have a retina doctor to help us launch this drug, 'cause it's such a specific field, and to have the power of her presence was deemed to be very important. We decided to do it now so that we have some time until the real approval date to get all of the preparations in place. Fede is going to help us with this. This is a great moment to thank him for the amazing job that he has done.
This weekend we're going to go to Hawaii all together, Caroline, Fede, and myself, to talk about geographic atrophy and what we can do with this product in this disease. When talking about EMPAVELI, last year we continued our launch trajectory with $65 million in U.S. net product sales. We submitted two supplemental NDAs and completed more than 800 patient years of systemic dosing. In the meanwhile, in the pipeline, we continued to progress our late-stage clinical studies with Sobi, our early-stage pipeline, and completed the enrollment in the phase II ALS study. Now 2023. This is gonna be an amazing year for us.
First of all, we are planning to deliver the first-ever treatment for patients with GA in the U.S. to prepare for our ex-U.S. approvals as well, to continue to maximize the value of EMPAVELI and to advance our early pipeline and the Beam collaboration. What is geographic atrophy? To understand this disease, I want you to think of the retina and of having a forest fire in the retina, where in a relentless process, you lose more and more photoreceptor cells. This process has no treatment available, and once you have it, your path is towards inevitably blindness if you live long enough. This is a disease in which many, many drugs have been tried and where we finally have discovered a pathway where something is possible to control the progression of this disease. We did this with intravitreal pegcetacoplan.
Here is pegcetacoplan, positioned to be that first-ever treatment, and there are three seminal features of this drug product that I want you to bear in mind. The first one, and in my opinion maybe the most important one, is that we have increasing treatment effects over time. The longer these patients are on treatment with intravitreal pegcetacoplan, the more the slowdown of this degenerative process becomes. We've evaluated that over 24 months in DERBY and OAKS, and it looks like an immunotherapeutic process that we will continue to evaluate in the GALE extension study. Importantly, we saw these increasing effects across two dose regimens. We have a dose regimens where patients receive treatment every two months, but we also have the ability to treat patients monthly if physicians choose to do so.
It is hard to overemphasize the importance of every other month treatment because it provides a benefit to patients and physicians of much more convenience with a benefit in terms of treatment effects that is pretty close to what you get with monthly treatment. In the meantime also, especially towards the end of that 24-month period, the convergence between the effect size on the foveal as well as the extra foveal lesions is fascinating to see, where from month 18 to 24 the effect size is more or less the same. These are the famous DERBY and OAKS studies. What's extraordinary about these two studies is that at 24 months they look remarkably similar, and the consistency for both dosing regimens is truly remarkable. What also stands out here again is that increased effect that we see over time.
If you quantify that in six-month segments, so 0-6, 6- 12, 12-18, and 18-24, you can see how in every six-month segments the effect on slowing down the lesion progression becomes more pronounced. Importantly as well is when you then look at how is the fire, what is the intensity of the fire in that segment from month 18 to 24, well, the slowdown there has become truly clinically meaningful. We see that for both subfoveal as well as non-subfoveal or extrafoveal lesions. We see that for monthly as well as for every other month lesions. These effect sizes in the range of approximately 30%. These two phase III clinical trials are the only ones to have shown such a slowdown in the progression of GA for both extrafoveal as well as foveal lesions.
You should expect that that treatment effect continues beyond year two in patients with GA who may be on treatment for 10 years, maybe 20 years or longer. We also had a favorable safety profile that we evaluated in a very large database of patients. 1,200 patients and nearly 12,000 injections were evaluated in these two clinical trials. What we found is that we have a safety profile that is best and most easily understood as that associated with an intravitreal injection, something we know very well from the anti-VEGF world. We also have a slowly increased rate of or slightly increased rate of exudations in these patients. That is something that can be controlled with anti-VEGF injections and that we continue to follow closely.
We are now ready to launch in this very important disease, which because of its prevalence, also represents, of course, a meaningful commercial opportunity for us. When we ran a global survey with physicians, with retina doctors, we found that more than 90% of retina doctors worldwide plan to use pegcetacoplan in their patients with GA. We have built in the past year a best-in-class team, highly experienced in the retina across all of these elements that are important in a successful launch. We currently have approximately 100 field-based employees out there doing the work. More than 90% of those come from companies that have profound retina and ophthalmology experience. These employees joined us because of what they have seen in the data package and the faith that they have in making a real difference in this disease.
In the meantime, the pre-launch activities are well underway. In med affairs, we have been working for a long time throughout 2022 on our presentations, on raising awareness, on teaching physicians and retina docs, as well as patients, what it means to be on treatment with a product like pegcetacoplan. On the commercial side, in September 2022, we really started amplifying our efforts. The one thing I want you to remember from the commercial efforts is that we have extraordinary access to the retinal practice. Retina docs want to see us and want to learn about this product. That is not very hard to understand when you imagine a patient that is on a path to blindness, that they have to see multiple times per day and for which currently nothing is available. Where do we stand?
We are positioned to be the first ever treatment for geographic atrophy as early as next month. With a compelling product profile to address an unmet need globally. With more than 90% of surveyed retina specialists worldwide planning to use this product in their patients, and a best-in-class field-based team deployed and ready for launch. Moving on now to EMPAVELI, our first approved product, and now on the market for approximately a year and a half. We've had a successful EMPAVELI launch, where it has been incredibly gratifying to see how this product elevates the standard of care in PNH. Many years ago, when we were doing our development, there was always a question as to what is the role of extravascular hemolysis in this disease? Is it safe to control this disease with C3? What is the difference that this is going to make?
The difference is absolutely extraordinary. If there's one number that I would like you to pay attention to on this chart, it is the fifth bullet point. We have 98% real-world patient compliance. It's hard to reach these patients. Many of these patients, unfortunately, get a little bit forgotten. They are on C5 inhibitors. They are, you know, hard to find. They need to be made aware that this is available to them. Once these patients are on treatment and discover what it does for them, the retention rate is absolutely extraordinary, and again, a testament to how much of a difference this product can make. We also have those two supplemental NDAs. What will they do?
The first one has a PDUFA on February 8th, next month. This gives us the ability to promote on the basis of treatment-naive data as well, data that we have established in the so-called PRINCE study and the 48-week PEGASUS results. We then also have the EMPAVELI injector that is going to come on the market at the end of March. Our PDUFA is March 15th. This was through a collaboration with Enable Injections. It allows these patients who self-administer this product twice per week at home to do this in a, what we call a needleless experience. These patients have no longer to manipulate any needles in order to self-administer this product, which will significantly improve the patient experience and the administration. Here, too, we have a strong safety profile. We have over 800 patient years of systemic pegcetacoplan exposure.
On this slide, the second bullet is the most surprising one. We have zero reported cases of meningococcal infection. With C5 inhibitors at this point in time, you should have expected to see a couple of these meningococcal infections show up already because it's considered to be a class effect. The way in which pegcetacoplan works, at least for now, seems to have an advantage in that regard as well. We are expanding on potential new indications. In the middle of this year, we are going to have the readout on our ALS trial.
We are enrolling very quickly in our VALIANT phase III clinical trial in IC-MPGN and C3G, and our partner, Sobi, is enrolling in the Cold Agglutinin Disease trial, as well as in the phase II trial in hematopoietic stem cell-associated thrombotic microangiopathy, where in the second half of this year, we will have the first data. Now, last but not least, our early pipeline, which in this year is going to move in meaningful ways into the clinic, and of course, our Beam collaboration. First of all, our molecule APL-2006, which we also call the ranibizumab molecules. This is a molecule that we developed by considering what happens with patients who are on treatment with anti-VEGF.
If you have wet macular degeneration and you are being treated with an anti-VEGF product, your chances of developing geographic atrophy within a seven-year timeframe are 98%. It's virtually inevitable. What we decided to do was create a molecule that would both control VEGF, could be injected, what we believe is going to be an every three-month procedure, and at the same time, control C3 so that we can hopefully avoid the development of geographic atrophy and have a next generation anti-VEGF molecule available to us. We have our next generation C3 siRNA program. This is a program to lower the levels of C3 in the body so that the twice-a-week subcutaneous administration that is currently needed with EMPAVELI can be reduced to something more convenient for patients.
In preclinical settings, we silence C3 expression by more than 90%, this drug product is planned to go into the clinic in the first half of this year. Last but not least, APL-1030. This is a molecule that allows us, via an intrathecal injection, to, for the first time, control C3 in the brain. This is a very exciting new frontier for us because we think of the brain or of the eye, I should say, as a window into the brain. When you look at the mechanisms behind complement and the reasons why we believe pegcetacoplan in the eye can slow down the progression of geographic atrophy, it shares so many commonalities with many neurodegenerative conditions, and some neurological diseases as well.
In the meantime, we also, as you know, in DERBY and OAKS, have seen these increasing effects over time, which gives us hope that there is something of an immunotherapeutic effect that we may be able to explore in these central nervous system conditions as well. This is another product that's moving forward very nicely and where we intend to be the first ones to explore this in the CNS space. Then we also have our Beam collaboration. As far as we know, the only gene editing program in C3 or in complement, I should say, six research programs in total on which you will hear much more in the future as well. This is what our pipeline looks like.
Really exciting to explore this unique target complement factor C3 across such a wide range of therapeutic areas and indications in the space of rare diseases, ophthalmology, neurology, and certain others outside of that as well. This is an extraordinary year for us. We look forward to sharing our data with you in the months to come. Of course, next month, the PDUFA date and the launch in geographic atrophy shortly thereafter, also to continue to see what we do with EMPAVELI and the advancement of our early pipeline. Thank you.
Thank you, Cedric. Lots of practice there. You got done five minutes early. Just wanna remind folks that a couple things. Number one, there's an ask a question feature through the digital portal book, and you can send that over, and I'll ask on your behalf based on this iPad. Then, you know, if you wanna get bold, there are microphone runners in the room, and raise your hand, and we will make sure we get your question answered. Cedric, on the PDUFA date forthcoming, just wondering how soon after approval could you launch? You said shortly thereafter. Is there a timeframe which you're targeting?
Yeah. We're not gonna be more specific than that, but we are, we will be ready to ship. We will, Adam has done a crazy good job of getting everybody ready. It will not be very long after the approval that we will be able to launch this product.
One of the controversies that we talked about in the back half of the year was the 24-month data being included in the product label and having that major amendment. Can you walk us through what the 24-month data do if they are fully included in the label versus the 18-month data?
Yeah. Our hope, of course, the reason why we did it is that we hope that it will be available in the label, and that's the label that we submitted to the FDA. The one feature of the 24-month data that is not very obvious at 18 months is the consistency between these two clinical trials. Even at 18 months, DERBY does not look as good as OAKS. For our sales force to go out and talk about that with retina docs, we felt that it would take too much time and too much explaining as to why these two trials are not exactly the same. As you've all seen at 24 months, that is clearly there. The second aspect that is really important to us, again, are these increasing effects over time.
From month 18 to 24, that is where it really starts showing up, right? I mean, these effect sizes that are close to 30% when we did our research with retina doctors, that is a number that virtually every retina doc, you know, becomes really excited about. These are elements. Those are the two most important elements that factored into our decision.
Questions from the audience. Oh, go ahead. Yeah.
You know, people have been worried about whether or not you have an Adcom and obviously the updates of the CMO in those years. Can you just address whether or not you still don't expect an Adcom and if there's any assurances that will not be required?
Questions around an Adcom and the CMO leaving.
Yes. The adcom. You know, the way in which this major amendment came about is we gave a call to the FDA. We said, "We would like to do this. Will you accept it?" Right. That was the first question. In those conversations, we also talked about the adcom, and we were told again that no adcom was planned for this program. Then with the chief medical officer change, this is something that got planned well in advance, right? I mean, Federico was, you know, it was always the plan that he would leave the company and that we would turn it over to a chief medical officer with retina experience. When we thought about the logistics and making sure that the team is kind of fully ready to operationalize this, right.
We said, we're gonna do it before the PDUFA. That gives us time to really hit the ground running when we're there. That's why we did it. From an investor perspective, this is of course not what you want to do because it creates uncertainty, but operationally, it's 100% the right thing to do for us. Again, Federico, you know, you all feel welcome to talk to him. You'll see him this weekend if you go to Hawaii. Has been an amazing project. Dr. Caroline Baumal, I think is gonna be the perfect person to launch this drug for us.
I guess while I have the mic, the other thing investors are really focused on is when you start labeling discussions, that being a positive indication that things are moving forward as you expected. When do you expect to start labeling discussions?
Well, it's typically about a month before the PDUFA date, right? That's the timing. We're not going to announce it when we are in labeling discussions. For SYFOVRE, it was III and a half weeks before our approval. I think it varies a little bit.
Thanks.
We do have a question in the question portal, which is, Cedric, does the new CMO have a different view on the value of having both monthly and every other month dosing in the label?
You know, I think you should all know that Dr. Baumal did not join us, you know, in the spur of the moment, right? She went through all of the documentation, she went through the data, and it is her belief in the product and the difference that it can make in this disease that led her to join us, right? This is something where every other month is incredibly important to the vast majority of these retina docs. We do want to have the monthly dosing regimen in the label so that physicians have the flexibility. That's the best way to think about it, is every other month is very attractive, but for certain patients, you may want to resource to monthly injections as well.
Other questions from the audience. You talked about every other month dosing. The other thing that could be differentiated in the label is having a broad label, such as with fovea patients. How do you think about that inclusion of that in the label, as well as one other controversy around fovea patients is what the uptake would look like in that segment?
I think, look, first of all, on a prevalent basis, approximately 60% of patients have foveal lesions. That's because there was no treatment available so far. At the time of diagnosis, as many as 85% of patients have extra foveal lesions that ultimately involve the fovea. When we enrolled our patients in our phase III clinical trials, if you wanna use that as a surrogate for the interest that patients have of enrolling in this trial, we had approximately the prevalent distribution. Meaning that, at least from a physician-patient interaction perspective, there was no preference for extra foveal patients to come into this study. Now, we expect both to be present in the label. Again, especially with the 24 month data, really the difference between the foveal and the extra foveal lesions becomes quite minimal.
Question from the audience. Go ahead, Brian.
Can you give your thoughts on intermediate AMD and whether or not this would be an opportunity you would pursue, and what would be the pathway to get a label in that indication?
Intermediate AMD is not an indication, intermediate AMD is not an endpoint. That is verbatim feedback that we received from the regulators. You know, I think quite frankly, that the FDA doesn't think about intermediate AMD as a different disease, therefore, I think, you know, we should not expect to have that language in a label either.
Hi, just a couple of quick ones. One, I don't know if you've talked about the peak sales and also what kind of a sales force in a sort of, steady state would you require to support that?
Yeah. We have in August, we hired the full sales force as I presented to you, right? We have approximately 100 field-based representatives across these various functions that are out there doing the work. We are not guiding on peak sales, you know, all of our analysts, including Anupam, have their views on that. Again, for us, the main focus is to get access to as many patients as possible as quickly as possible.
Questions from the audience?
Can I have this back up? Can we pass this down? Would you mind passing that down?
Thanks. Hey, Cedric. Thanks. I was gonna ask on the exudation part, one thing that comes up when I talk to the doctors is, they don't think it's a, you know, an issue to give anti-VEGF, but they're not really sure what the protocol will look like in terms of can we inject the anti-VEGF on the same day on the GA treatment, or should we stop the GA treatment for six months and wait how the exudation recover? Anything, I guess, internally you have looked at the data, and can you comment anything on that? Would that be in the label, and, would it be helpful for physician practices essentially?
Yeah. No. Thank you for that question. That's a very important question, right? In the clinical trials, it was done on the same day. In the real world, for now we plan on providing the flexibility to physicians to do it any way they want. They could do it on the same day, typically with about an hour apart between the two injections, or they could do it on subsequent days or even, you know, two weeks between them. We do not plan on providing kind of very clear instructions on how to do that.
Additional questions? Malcolm?
On monthly versus every other monthly dosing, would you expect any sort of switching between?
I think, look, as the data matures, right, and I think also a little bit based on what we see with anti-VEGF, some physicians may be tempted to start with monthly, and then after a certain period of time, switch to every other month dosing. Certainly, you know, based on the data that we have, and we'll present much more this year on that as we continue to evaluate it, that is a reasonable thing to do probably. But again, we need to gather more data and, but switching, I think, absolutely will be part of the, of the standard of care.
It could also go the other way, every other month to monthly.
It could go the other way as well. Yes. Mm-hmm.
Questions from the audience? I'm sorry if I missed this in the presentation, Cedric, Will there be any updated sort of DERBY, OAKS, GALE extension data in 2023? If so, when should, what timeframe?
Yeah. We're gonna continue to present on the DERBY trial. Some of the work that we presented in September at the American Academy of Ophthalmology that was really exciting is when you look at the retina and don't just simply talk about lesion size growth, but start dissecting out what happens at the photoreceptor cell layer compared to the retinal pigment epithelial cell, how that continues to progress, how these two cell layers may be impacted differentially. We will talk more about that in this year at meetings and publications. Of course, we have the GALE extension study, where in approximately 800 subjects, we continue to evaluate what happens to these lesions over time.
Maybe just switching gears a little bit. You talked about the EMPAVELI, PDUFA coming up here in February, PRINCE data, the 48-week PEGASUS data. How do you anticipate label expansion could change the ramp of the uptake of the drug?
I think it's just a matter. When you look at kind of the evolution of how the product came to the market, as we expected in the beginning, the patients that came on product with EMPAVELI were patients that suffered from transfusion dependency anemia and was a very important component also for ULTOMIRIS-treated patients, right? Approximately 75% of patients didn't come from Soliris, which is what we tested in our phase III, but came from ULTOMIRIS 'cause they suffer from the same shortcomings that C5 inhibitors have. We also, after that, started treating patients that did better, that may even have normal hemoglobin levels but do so at the expense of very high reticulocyte levels, right, and high bilirubin levels. Those patients too benefit greatly from treatment with EMPAVELI, which completely controls this disease.
The last piece is the treatment-naïve patients, so the first ones that come on treatment with this drug. That is currently approximately 10% of our new enrolled patients and kind of an example of how that evolution is taking place over time.
We've got another email in the question in the portal, which is, do you believe that the monthly dosing of pegcetacoplan in GA would have the same cost as every other month dosing to the patient, or would it be twice as much?
The way, without talking about pricing, but the way in which we intend to commercialize it is on a per vial basis. That would answer that question. Yeah.
Questions from the audience? In what segments in PNH has the product outperformed based on your expectations? You know, where has it lagged a little bit from your initial expectations, and how can you improve that?
I think, generally speaking, it has followed the trajectory that we expected. The important segments now to capture, you know, as well as possible are these patients that I mentioned that have more normal hemoglobin levels, as well as the treatment-naive patient segments.
I think one of the trials that you guys are directly responsible for is the MERIDIAN trial in ALS, right? That's part of the Sobi collaboration. What are the key points that provide some, you know, mechanistic rationale for C3 in ALS? Whereas, you know, other complement approaches have had sort of mixed failed updates.
C5 does not seem to work in ALS, right? I mean, that was established by Alexion, but then also, by UCD with their collaboration with the Rap product. There is a very important difference between C3 and C5, as we know from PNH. Specifically, the effects on neural degeneration also is quite different. This is a high-risk, high-reward project for us. Our internal probability of success is approximately 10%. It's a project that we believe is very important. Again, kind of reaching the motor endplate, which is where ALS specifically starts before it goes to the CNS, that is a phenotype where we believe we have a chance at getting something, so.
Do you think the endpoint that you're using, which is a CAFS, is heightened to probability of success versus using the more traditional, ALSFRS score?
Well, this is an endpoint that we got to in collaboration with regulatory authorities, right? It combines function as well as survival. Should we hit the CAFS score on the primary endpoint, that would be, of course, an extraordinary finding, right? Kind of a whole new light through which we then have to look at the commercialization of EMPAVELI. I think the more reasonable expectation is that we're gonna get a mixed picture, hopefully find responder populations, hopefully find something exciting, and then see what we do with that program moving forward, potentially with another phase III or a discussion with the regulators if the data are good enough.
Questions from the audience? Going back to pegcetacoplan and GA, what are the key sort of European timelines that we should be considering?
We filed. It takes approximately one year. The approval in Europe is going to be in the beginning of 2024. The CHMP opinion typically comes 67 days before the full approval.
Questions from the audience? On the U.S. pegcetacoplan launch, can you walk us through the process of how we should be thinking about a permanent J-code and timelines there?
We, you know, with the PDUFA on February 26th, we would apply for a J-code somewhere in March. In the beginning, we would work with miscellaneous J-codes, and then we would get a permanent J-code sometime in October. That's the schedule on which we will be. While we are working with miscellaneous J-codes, of course, that means that the retina doctors have to be comfortable that they will be reimbursed. They will typically try that a couple of times and then become more accustomed to it. Certainly in the beginning, that will be something that, you know, will make the ramp less strong than it could otherwise be until the permanent J-code kicks in in October.
Any final questions for Cedric? Okay. Thanks, everyone.
Thank you.