Good day, and welcome to the Apellis update call. At this time, all participants are on a listen-only mode. Later, we will conduct a question and answer session, and instructions will be given at that time. As a reminder, this call is being recorded. I would like to turn the call over to Meredith Kaya. You may begin.
Good morning, and thank you for joining us to discuss our announcement this morning regarding the CHMP trend vote. With me on the call are Co-founder and Chief Executive Officer, Dr. Cedric François; Chief Medical Officer, Dr. Caroline Baumal; and Chief Financial Officer, Tim Sullivan. Adam Townsend, Chief Commercial Officer, is with the European team in Switzerland right now and unable to join the call this morning. Before we begin, let me point out that we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail. Now I'll turn the call over to Cedric.
Thank you, Meredith, and thank you all for joining us this morning. As announced in our press release, the Committee for Medicinal Products for Human Use, or CHMP of the EMA, informed us of a negative trend vote for our EU marketing approval application for intravitreal pegcetacoplan for GA following our oral explanation meeting yesterday. In short, this means that CHMP will likely formally adopt a negative opinion at its next meeting and not recommend EU approval of intravitreal pegcetacoplan for GA. We intend to appeal this decision. It goes without saying that we are extremely disappointed with this outcome and deeply saddened for patients. Geographic atrophy is a relentless disease that leads to the destruction of the retina and irreversible blindness. Patients lose their independence as they can no longer take on tasks which are crucial in their daily lives.
We are seeing firsthand in the U.S. how important SYFOVRE has been for this community, and there are over 2.5 million patients in Europe right now desperately waiting for a treatment. In earlier discussions with the CHMP and key retina experts, GA lesion size was acknowledged, quote, "as the most important anatomical parameter reflecting photoreceptor and RPE cell loss," unquote. The experts also agreed that microperimetry is an important objective functional measure. However, our understanding of the reason for the negative trend vote was because the rapporteurs have not accepted what we believe and what our expert advisors agree is clear evidence of a functional benefit. It is important to remember that GA is a category where no treatments in Europe are available.
Unfortunately, as we have discussed before, there are significant challenges with measuring visual function in GA, given the limitations with the tools we have available, such as best corrected visual acuity or BCVA. BCVA is measured by reading a chart with letters of decreasing size, as we have all done at our eye care provider. If you read this chart while looking through a straw, you will have perfect vision when measured by BCVA. However, imagine walking across a busy street in Paris, only looking through that straw. This is important because in GA, the vision seen through that straw is naturally preserved until the very end of the disease. Capturing this and other concepts of function requires a longer educational process. We obviously disagree with this outcome, and we firmly believe in the strength of the phase 3 results and the proven ability of pegcetacoplan to slow GA progression.
First, pegcetacoplan has demonstrated increasing effects over time in our clinical trials, substantially slowing GA progression in non-subfoveal lesions by more than 40% in year 3 in our GALE extension study. This means that the longer a patient is treated with pegcetacoplan, the greater the impact this medicine can have on the degenerative process. In addition, in a post-hoc analysis, pegcetacoplan halted photoreceptor loss, the cells responsible for vision within the first 6 months of treatment and up to 53% after 2 years. No drug in geographic atrophy has ever shown these magnitudes of effect. Second, pegcetacoplan has been shown to preserve vision longer in multiple post-hoc analyses, which several experts have agreed is robust and strong. In other analyses using microperimetry, pegcetacoplan was shown to preserve central vision longer and lengthen the time to severe vision loss.
And third, the safety profile has been well demonstrated in the phase 3 studies and in the real world. The unexpected events of vasculitis in the real world remain extremely rare at an estimated rate of approximately 0.01% per injection, with the last confirmed GA case dating back already to September. Regarding next steps, as I said, we expect the CHMP to adopt a negative opinion at its next meeting in January. We plan to appeal the outcome and seek re-examination of that opinion. This takes approximately two months. So we would expect a final opinion during the April CHMP meeting and an EC decision by early July. We will continue to work closely with the CHMP, the retina community, and patient advocacy groups, and remain steadfast in our efforts to bring pegcetacoplan to GA patients across Europe.
Our market research continuously shows how hopeful physicians in Europe have been around finally having a treatment for their patients. They see the irreversible damage that GA causes to the retina and how that poses a significant burden on patients' quality of life, underscoring how important early GA treatment is for their patients. I'd like to close by sharing my deepest gratitude to the patients, families, caregivers, and physicians that make up the GA community. I would also like to thank my colleagues here at Apellis for your tremendous work to date. I am so proud of your continuous efforts to bring the first potential treatment to people living with GA in the European Union. We are happy to take questions, but please understand that there isn't a lot more that we can say about the ongoing review. With that, let us now open the call for questions. Operator?
Thank you. If you'd like to ask a question, please press star one one. If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from Jonathan Miller with Evercore ISI. Your line is open.
Hey, guys. Obviously, very disappointing news. But I would love to get a sense, and I know you can't talk too much about the review, but what options are there for you on reexamination to change the narrative, to pursue a different strategy or to modify your communication to the agency? Like, how much flexibility do you have in approaching this from an angle that you think is likely to get you to where you need to be? Do you have a strategy for that next phase?
Yeah. Thank you very much, John. So that is, of course, a very important question, and I think there are two elements that are important in that context. Number one, you know, this was a, for lack of a better term, a relatively sterile process so far. I think that the voice of the retina community, of the patient advocacy groups, which we have experienced to be very strong, right? Will now be heard. I think, you know, there will be a much more important discussion around what is happening, not just kind of in a one-on-one interaction as it has been between the rapporteurs and us. You know, there will also be a change in the rapporteurs that we will get.
So, you know, there will be a new review cycle that we will go through, during which we can also really hone in on those aspects of the function that you know are clearly most convincing, in this context. And again, I want to point out here that there is obviously a functional benefit when you save photoreceptor cells, and that is something that led to the approval in the United States. That link, however, is difficult to understand, and you pair that with the fact that measuring function is so difficult because of the tools, or the lack of tools, I should say, available to us, that this is really an iterative process that takes time, takes a lot of, you know, explanations, bringing in experts to explain this, et cetera. So, you know, we're going to continue through this process.
It will, of course, be an uphill battle, but one where I think, you know, we have an opportunity to really clarify those points.
All right. Thank you.
Thank you. Our next question comes from Tazeen Ahmad with Bank of America. Your line is open.
Hi, good morning. Thank you for taking my questions. So I have a couple, Cedric. So this, this meeting that happened yesterday, this wasn't an advisory committee meeting per se, the way it is in the U.S., but in Europe, is there something equivalent that takes place before, like a scientific advisory meeting, perhaps? Did something like that occur, and do you have a sense of what might have been discussed if something like that did happen? And then secondly, you know, you've talked about the support that you've gotten from KOLs in the E.U., but how would you compare their influence with European decisions? We know that in the U.S., that can make a big difference in addition to advocacy.
But I think all of us are just trying to understand, because you did use the word sterile in the EU review process, and I think most EU review processes, you know, tend to be pretty cut and dry. So, you know, help us understand what gives you confidence that Apellis makes sense at this point. I know I asked a lot here. Thanks.
Thank you so much, Tazeen. No, look, I think, you know, the important point that you bring up here is, of course, that we are dealing with a brand-new disease indication, geographic atrophy. You know, which many people, including physicians that don't have the specialty background, right, have a hard time understanding the difference between wet AMD and geographic atrophy, right? So there's just a whole lot of education that needs to happen. To the point of the serial interaction, you know, during that process, it can be difficult for people to wrap their head around what this disease really means, what its impact is, et cetera, and kind of having organized feedback around-...
The impact of this disease, what these endpoints mean, the fact that measuring function is so hard, the organization around that is really not in place in Europe. You have to remember that in the U.S., the FDA has a division specifically dedicated to this. Of course, we've all spoken in the past about Dr. Chambers, who is a retina doctor himself. That is not in place in Europe. So it's just a much more iterative process. Expert advice does get brought into the equation, but not in a way that I think, you know, has been you know, as well organized and as representative of the vast majority of the opinions in Europe as it ideally should have been. And that's, of course, what we're going to be focused on in the months to come.
And just in terms of the influence that physicians will have at this point, can you talk about that?
Well, I think, you know, again, we will see now how the physician and the patient community in Europe will respond to this news. And I believe that, you know, that sentiment has not been fully taken into account yet in the review process, and it is, of course, critically important.
Okay. Thank you.
Thank you, Tazeen
Thank you. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open.
Good morning. Thanks for taking my question. Can you frame the nature of the discussions that led to a negative trend vote, what specifically with regard to evidence of functional benefit and did the rate of rare vasculitis impact the CHMP's view of the data? And then can you also help us understand precedent here, with regard to an approval post-appeal? And then finally, you know, what does this mean for cash runway? Were there any EU sales embedded in your assumptions for cash until at least Q2 2025? And how much EU infrastructure spend was included in OpEx? Thank you.
Thank you so much, Salveen. So, regarding the nature of the discussions, first of all, around the effect on lesion size, on slowing down the growth of GA, nobody argued with that, right? I mean, the data is extremely clear. It really comes down to discussion as to what is the functional meaning of that slowdown in the lesion size growth. And again, because we don't have the tools available, that is something that, you know, requires a lot of explanation. And the two points that, or the two, I'd say, measurements that are most prominently featured in that discussion are best-corrected visual acuity, which has the shortcomings that we just spoke about, and then microperimetry, where you have 68 points in the retina that individually are assessed for the ability of the retina cells in those points to sense light.
So the problem that you have in geographic atrophy is that you have. Let's dive into BCVA, for example. That is only the central vision. Remember that straw that we spoke about. Now, the patients where that central vision is affected need to have a lesion that's close enough to the central point of that straw and lesions that grow in that direction. And when you hone in on those patients, you will see the functional impact. But when you have all the patients that are not on that trend, they of course can overwhelm that signal. So that just gives a little bit of insight into why measuring function is so complicated. It's an iterative process.
The vast majority of the experts agree with us on the importance of microperimetry, and the importance of diving into kind of the regions where the disease impacts those points, but that takes time and takes education, which is what we're going through. On vasculitis, I want to again stress here that that was not a factor in the process that we went through. The discussion was squarely around what is the functional impact of these lesion size reductions that we have shown.
As it relates to precedent, and as I mentioned during the call, it's an uphill battle to go through an appeal process, but one that we look forward to engaging into and where, again, I think since there are no hard points to latch on to, the hard points or I'd say the very objective points like lesion size reduction, et cetera, we have clearly and without any doubt shown to be able to reduce that growth. It's more on the subjective interpretation of these functional endpoints, which is hard and takes time. As far as it relates to cash, I will hand it over to Tim.
Sure. Thanks, Salveen. You know, so while we expect the revenue opportunity in Europe to be significant, the ramp that we were expecting over particularly 2024 was not very large. But that was actually the infrastructure spend was quite a bit larger than the revenue we were expecting. Much of that, of course, was gated on the CHMP opinion and ultimate approval. So ironically, from a cash perspective, this actually is probably a lower cash usage scenario. But we won't give you any specifics, I think, until we know a bit more, which will be probably around our next earnings.
Thank you.
Thank you. Our next question comes from Anupam Sharma with JPMorgan. Your line is open.
Hey, guys. Thanks so much for taking the question. So were there any visual assessments beyond microperimetry and BCVA that was presented to the committee? And specifically on BCVA, what was presented? I think previously-
... At medical meetings, you've presented things like 3-line vision loss differences relative to sham, and showed some interesting data. Why was that not sort of more compelling, in your opinion? Thanks so much.
Thank you so much, Anupam. To be clear, the analyses that we have are very powerful, and they have been presented, and the majority of experts, you know, are very impressed by the data that we have, by the way. The problem that you have with these analyses is that they are post hoc in nature, right? If you take kind of a strictly censorious view of the validity of these data, you can say this is post hoc, you know, therefore it's, you know, it's something that was not pre-specified and is not as relevant. That is, statistically speaking, a reasonable view, of course.
But in this case, the problem that you have with these functional endpoints, again, is that the noise is so large that you kind of are stuck with post-hoc ways of looking at the data. So again, the data is very strong. Our experts agree with us on the strength of the data. To be fair, our interaction with the rapporteur, you know, had been very collaborative in nature, which is also why we, you know, we were probably overconfident ourselves, you know, in the process, I have to admit. I mean, we were taken by surprise by this, and you know, we're gonna have to take the next steps here. But I think that's really important.
Maybe, Caroline, you can speak a little bit more as well to, you know, your experience through this process, and specifically also what your feedback has been from the European KOL community.
Sure. Thank you, Cedric. You know, our European KOLs are very supportive and, really, you know, they are the experts in GA. I think that many clinicians, it makes sense that you would like to treat GA before it becomes extremely advanced. You know, it's very similar to glaucoma in many ways. And I think that, they're disappointed by this finding, knowing that, you know, this was the- would have been the first treatment for their patients who have been suffering from this blinding disease. So, I think that we'll be able to present this again and, hopefully, get something that will be better for patients and physicians.
I have taken our question.
Thank you. Our next question comes from Yigal Nochomovitz with Citigroup. Your line is open.
Hey, Cedric and team, thanks. Just a few more questions, sort of following up on all the themes that have been discussed. So first of all, did they actually tell you what the trend vote was? I mean, in terms of numbers. The reason I ask is because, you know, if there were a vocal minority that were supportive or that you believed could become more supportive, I think that would be important, if you could enhance the arguments for the, the visual benefit with more experts or with more data. So can you comment as to whether there were some that seemed inclined to understand your position but just needed more evidence or more understanding from experts?
Thank you so much, Yigal. So just, just to kind of explain what a Trend vote is, right? So it's essentially not an official vote. And also, to go back to Tazeen's question earlier, this is not like an outcome, right? It is more kind of like, this is how we feel as it goes into the real vote, which happens in the third week of next month. So nothing official has really happened at this point in time, but of course, it is a negative indicator as to what we should expect next month.
Okay. And when in this initial discussion, was it just the company, or did you bring external retina experts with you to the discussion to, you know, help drive some of the points you wanted to make, or would that only happen on the appeal?
So the oral explanation is one where the company, us in this case, goes to the CHMP. The rapporteur makes a presentation behind closed doors to the CHMP members. Then the company comes in, makes a presentation to the CHMP members. They then deliberate, and then they come back to debrief. So that's really the process. But again, the final vote is taken at the CHMP meeting of next month, not this one.
Okay. And do you expect that you're going to need just a better way to educate the rapporteurs on what the significance is of the visual benefit or how to understand it from the existing data you have? Or is the sense that you're actually going to need to generate new data and new patients to further bolster the arguments that you're making on the visual function?
Yeah. No, this is not about new data. This is again, around, you know, how, how do you view the connection between lesion size and function? But remember, function in this, in the case of geographic atrophy, is really hard to measure. The tools are not there. So, you know, it's, it's an iterative process with new rapporteurs, and I think very importantly, as mentioned earlier, now also a voice from the KOL community, from the patient advocacy groups, to talk about what function represents, right? I think that's really gonna be an important aspect of that.
Okay. Thank you.
You're welcome.
Thank you. Our next question comes from Steve Seedhouse with Raymond James. Your line is open.
... Okay, thank you. Good morning. I just want one clarification and then a broader question. My understanding is, even if you wanted to, you actually can't provide new data as part of the appeals process. I just wanted to clarify if that was in fact the case. And then the question is, obviously, you've done a lot of commercial prep work in Europe. You've articulated how big of an opportunity that could be. So if the appeals process is unsuccessful, just curious if you've already thought about reevaluation of pipeline, urgency to advance a new product into the clinic that could have a clear functional benefit, and if that would—if so, if that would be more likely to come from internal development or through external assets, so you'd do something strategically. Thank you.
Thank you so much, Steve. So first of all, on the appeal process, you are correct. There will be no new data included in the appeals process. We will get new rapporteurs. So I think that is something important, where you basically get a fresh look at everything, but viewed also with, I think, the important angle of expert advice and opinions on this that I think is really important to be able to interpret what it is that we have. Then, as it relates to how we move forward, you know, the impact on the cash runway is very small in the near future, but I will hand that over to Tim as it relates to the next steps there.
Yeah, so I mean, as I mentioned on a previous question, from a cash runway perspective, the cost that we expected to build out Europe was on a country-by-country basis. We were expecting to spend more, quite a bit more, than our near-term revenues. So from a cash runway perspective, it looks like we'll, in all likelihood, have a longer runway, you know, than when we originally guided based on this. But that, of course, depends on the scenarios, right? If we get approved in the middle of the year, based on the appeals process, you know, that's probably a smaller difference.
But ultimately, guiding on cash runway is something we'll do, you know, when we know a little bit more, and I think that should be around our, you know, our earnings call, our next earnings call.
Yeah, just to clarify, I was just asking about clinical development strategy, not cash runway. Do-
Yeah.
If this is unsuccessful, do you have pipeline assets that you would accelerate and try to get to that European market, which you've articulated is pretty large?
Yeah. Thank you, Steve. So we have very exciting things going on pre-clinically and early clinical as well. That, of course, we're going to be talking about next year. That will take time to get to the markets, but, will of course, be an important aspect of, of what we have for our growth as well. And I think noteworthy, I mean, most noteworthy, of course, is not just our early pipeline, but also the, the C3G approval for EMPAVELI that we expect, that we've spoken about before, where we think we have an important opportunity for, near-term revenue growth as well.
Thank you. Our next question comes from Phil Nadeau with TD Cowen. Your line is open. Phil, if your telephone is muted, please unmute.
This is Alex on for Phil. Thanks for taking my question. Just clarifying, so the opinion is expected at the meeting in January. I'm just curious if you could walk us through timelines again, what you expect in terms of appeals and re-examination process. Thank you.
Thank you so much, for that question. So the timeline is that the CHMP comes together on a monthly basis. The official, vote will take place in the third week of January. As we outlined before, we should expect that vote to be negative. We would then appeal within two weeks after that negative opinion, and that would place the next vote in April. So at that point in time, should the appeal be successful, the, vote would be overturned, hopefully, right, into a positive opinion, which would then lead to an EMEA approval in all likelihood, early July.
Thank you. Our next question comes from Derek Archila with Wells Fargo. Your line is open.
Hey, good morning, and thanks for taking the questions. Just two brief ones from us. I guess, through the recent process, can you talk to kind of the EMA's view and understanding of microperimetry as a measure for understanding the functional benefit in GA? And is that different, you know, obviously, than the US? And then, I know you're saying that there's not really going to be any new data, you know, when you get the new rapporteurs, but I guess, are there new arguments or information that you think that you just learned through this process with the previous rapporteurs that you want to focus on? Or do you think it's going to be kind of largely the same in terms of, you know, how you're going to present it? Thanks.
Thank you, Derek. So, the microperimetry data was very well received by the experts. I think that's important to point out, right? Now, the way in which all of that feedback is handled by the rapporteurs is, of course, also very important. And, you know, that is really where I think the... We have the elements on our side, we have the experts on our side. It's about how this gets interpreted and accepted by the other party, right? So, it's something that we need to just work through. What was your second question, Derek?... 'cause you were breaking up a little.
It was just yeah, sorry. Just in terms of, like, how you're gonna present the data, I know you said there's not gonna be any, like, real new information that you're gonna present, but is there new arguments or, you know, the way that you present it to the new rapporteurs, will it be any different, you know, than the previous?
Yeah. So we may, you know, the point that you're making is that you can indeed, when you resubmit or go through the appeals process, make certain changes, right? And focus on certain analyses more than others, and that's of course something that we intend to do, 'cause we learned a lot in the past couple of months. So there will be a refining process for sure. What exactly that will entail, you know, we're not going to talk about yet.
Got it. Thank you so much.
Thank you.
Thank you. Our next question comes from Justin Kim with Oppenheimer & Company. Your line is open.
Hi, good morning, and thanks for taking the question. Just a clarification, one, on microperimetry. Could you just remind us, I believe the microperimetry was assessed in only one study of the two DERBY and OAKS studies, and just what additional, I guess, longitudinal data exists in GALE and sort of how often that might have been measured?
Yeah. So the microperimetry is measured every six months. And you know, as you mentioned correctly, I mean, it's very supportive. You know, all of these data were presented, discussed, but I think, again, you know, you have to make sure that the rapporteur on the other side accepts them. Caroline, would you like to add something to that?
Sure. Just, our microperimetry data set was done in OAKS. It's actually the largest microperimetry data set ever done from a Phase 3 clinical trial with over, you know, 600 patients involved. And, you know, that's what really gives confidence in the results that we have. Of course, we've learned a lot about microperimetry since the study was started. It was really in its infancy and, you know, we're using methodologies to analyze our data that are used, you know, by the global microperimetry experts, and this is really, you know, emerging as the most meaningful way to evaluate geographic atrophy. So I think we're incredibly fortunate to have had this data on such a large data set of patients. But in addition to educating about GA, it requires a whole, you know, set of education about what microperimetry is.
And, you know, since it's not used by clinicians and also people who evaluate our data set are also not ophthalmologists, so, this requires a lot of work and education. And that's what we'll be honing in on even more in the future.
Okay, great. Thank you.
Thank you. Our next question comes from Ellie Merle with UBS. Your line is open.
Hey, guys. Thanks for taking the question. Just on the rapporteurs, given you mentioned there'll be a change in the rapporteurs and the re-review, just what's your sense on, like, how much of a difference there is between the different rapporteurs and, you know, how wide a range of opinions they have on, you know, the importance of functional versus anatomical endpoints? And then just a second question. If approved on the re-review, what's your latest thinking on payer reimbursement, based on, you know, GA lesion growth? And does the fact that it would be approved theoretically on an appeal have any impact on reimbursement and I guess perception when it comes to pricing discussions? Thanks.
Thank you so much, Ellie. So, look, I mean, the, you know, everybody through a process like that has good intentions, right? I mean, I think that's important to note. And a lot of work goes into this by us, by our advisors, by the rapporteurs, by the CHMP members, so we have nothing but gratitude for that. But, you know, it sometimes happens that people get entrenched views on certain things and, you know, it's good to have a fresh look at things, especially when it comes to elements like the benefit to patients, right? Again, I cannot overemphasize that measuring function is very, very difficult, arguably impossible, to do properly in geographic atrophy. So there's a lot of subjectivity that comes into play.
When somebody has a certain opinion about something and you don't have objective measures to, you know, get through that, at that point in time, opinion matters more than anything. Bringing in the overall view of the retina community, I think is gonna be important through this process. So that's as far as it relates to that. The impact on reimbursements, you know, we have right now no reason to believe that there will be one. This is, you know, par for the course through the European processes. The reimbursement, we've done a ton of work in the past couple of years, educating the payers, you know, talking to them about our programs. We have even presented to the European Union in Brussels about geographic atrophy.
We believe that we have done all the work there to give us the maximum chance at a proper reimbursement in all geographies.
Thanks.
Thank you. Our next question comes from Akash Tewari with Jefferies. Your line is open.
Hey, thanks so much, and, a few on our end, maybe not on the EU approval. Maybe just starting off, can you talk about how SYFOVRE discontinuation rate is currently trending quarter-over-quarter? Our math suggests that if you can drop it into the 20% range, it's possible you could have sales north of $100 million in 4Q. And just to confirm, was the EMA able to have access to any suspected cases of retinal vasculitis? And can you remind us how many cases are currently being adjudicated by the team internally? Thank you.
Thank you. I will hand it over to Tim on the discontinuations.
Yeah, sure. So we don't have perfect information on discontinuation rates, and that's something that we, you know, we follow, from an anti-VEGF perspective, it's probably around 20%, and we have no reason to believe it would be that different. You know, I can't comment on your other assumptions that get you to a revenue number, but, discontinuation rates is something we just don't have perfect information on. It's really just gathering anecdotal information from docs and so forth. So, can't give you any help on that, unfortunately.
With regards to vasculitis, all of the information that we have available is always shared with regulatory bodies, U.S. and ex-U.S., of course. The numbers are the same as we reported at our last call, which was 12 confirmed and 2 suspected, with the last confirmed case in September. Thank you.
Thank you. Our next question comes from Annabel Samimy with Stifel. Your line is open.
Hi, thanks for taking my question. Just going back to something that was asked previously, can you tell us what type of negative trends have led to appeals in the past, as is commonly done? What's the success rate, and what has proven successful and what has not proven successful? Do you have any analogs for this to, I guess, understand how successful you might be in your efforts here?
Thank you very much, Annabel. Good to hear you. So, look, it's not common to go through an appeal process. Companies, you know, often prefer to withdraw their application. But in this particular circumstance, you know, again, considering the nature of how we ended up with this trend vote is important. Going back to measuring function in GA is arguably impossible. So at that point, it comes down to opinion and understanding the opinion of the key opinion leader community in Europe is probably something that requires work and something that will be an important base for what we're going to be doing in the next couple of months.
Okay, great. Thank you. That's very helpful.
Thank you.
Thank you. Our next question comes from Joseph Stringer with Needham & Company. Your line is open.
Hi, good morning. Thanks for taking our question. Just curious, if you could expand a little bit more on the mechanics of sort of bringing in the overall view of the EU retinal community, potentially in support of the drug approval. What, what are the actual mechanics of that? Is that something that Apellis can do through additional presentations, conferences, raising awareness? Or is that something that those individuals or groups would sort of do on their own?
Thank you, Joe. I think that is a really important question, actually, right? You know, I want to go back to what I mentioned earlier. I think the key opinion leader community and us at Apellis are probably equally surprised with what happened yesterday. You know, this is not something that either of us saw coming. As far as it relates to what we can do in this position, you know, that is limited, of course, but as far as the KOL community is concerned, they're going to have to now voice how they really feel about things, right?
Hopefully that will reflect what we believe is their sentiment, which is one of shock, arguably even anger, that they may be in a position where the rest of their lives, professional lives, they will have to tell GA patients: There is a drug that can slow down your disease almost in half over the course of three years, but you will have to fly to the States to get it. And, you know, that is something that is very visceral, right? When you're actually confronted with that sentiment, and hopefully that is something that we can properly communicate.
Great. Thank you for taking our question.
Thank you. Our next question comes from Douglas Tsao with HC Wainwright. Your line is open.
Hi, good morning, and thank you for taking the question. So, Patrick, maybe just help clarify, because it wasn't exactly clear to me, was it a question that they didn't accept sort of your presentation of the functional benefit meaning, or was it that they understood your sort of measurement, but they just didn't think that SYFOVRE, or pegcetacoplan, sort of met the threshold that warranted approval? So, were they fine with the sort of analysis that you're presenting? Obviously, you noted they had some questions around post-hoc, but leaving that aside, would they have been okay with it, do you think?
Yeah. Thank you, Doug. So, you know, again, touching on the very important point, which is running a study on function as a pre-specification in a phase three clinical trial in GA is impossible to do, period. This is why the lesion growth endpoint became kind of the cornerstone of all of these geographic atrophy trials, right? So when we then talk about analysis on function, they are going, by definition, to be post-hoc analyses. And then it comes down to, you know, how open are you to that post-hoc nature, and how receptive are you to what is, at the end of the day, opinion, right? The only objective measure that we have are these autofluorescent images, SD-OCT, the microperimetry analyses, where we, again, in a post-hoc nature, look at it, et cetera. But, the only objective measure is lesion size growth.
There, of course, we have remarkable data, both in DERBY and OAKS, and then continued in GALE, with that lesion size reduction up to 40%, in non-subfoveal patients in the third year.
So, Cedric, to clarify, so they sort of recognize the value of the Microperimetry data, but they just simply... I'm just trying to understand how you could or, you know, just given the limitation that you highlight in terms of not being able to run that type of study on a prospective basis, how could you, or how could they- or what was their expectation for what somebody could do from a development standpoint or clinical trial design to meet their standard? Because it sounds like they're almost setting a bar that nobody could reach. Thank you.
Well, you put your finger on it. They, they did set a bar that nobody can reach, which brings into, you know, question kind of the whole process, right? But to your point, microperimetry was recognized as a valuable measurement. The post-hoc nature of the microperimetry analyses was not.
Ah, great. Thank you so much. That clarifies it.
Thank you. Our next question comes from Graig Suvannavejh with Mizuho Securities. Your line is open.
Good morning. Thanks for taking my question. Two, if I could. Just on, could you characterize for us, please, just European retinal specialists versus U.S. retinal specialists in terms of their prescribing patterns or habits, and whether they tend to be more open or adaptive to new treatments or less open or adaptive to new treatments, just given their nature? Sometimes European doctors have a different way of looking at things versus U.S. doctors. So that's my first question. And then my second question is, you know, we've done some proprietary analysis on requests or appeals in Europe, but it tends to be about a 25% success rate. So I'm wondering if you have any other analyses that suggest otherwise. Thanks.
Yeah. So, thank you, Graig. Look, European and U.S. doctors all have the same interest in mind, which is their patients. So, you know, I don't think that there's a point in making a distinction between that. This is a remarkable community that is incredibly communicative on a global basis, and ultimately always does what's best for patients. So there is, you know, there's no parsing out there, and that is ultimately what we believe will lead to our success. As it relates to the appeals process, you know, again, we're not going to dive into that.
All I can say is that we believe that the crystallization of what the retina community as a whole, especially in Europe, really feels about this peg product and its benefit to patients, is now going to become very important and hopefully will reflect what we believe has been an overwhelmingly positive attitudes. Caroline, I don't know if you want to-
Thank you.
Add something.
Cedric, I just want to add that my experience as a retina physician and now at Apellis with European doctors is that they are highly thoughtful and data-driven, and they find this data meaningful. Many of them are experts in microperimetry. One of the device that was used in our study was developed in Europe, so they have a high level of understanding of this, and they're data-driven, and they understand how this data is you know, shows reduced growth of GA lesion. I mean, it makes sense as a clinician to reduce the size of something before you go blind how that would affect our patients. We see these patients, and their lesions are growing, and they tell us they're losing vision every time, despite the fact that their central vision might remain stable.
So we know this from our experience. We know this from clinical studies, that central vision, the way we measure it, best corrected vision, is not indicative of how our patients are functioning. And I think that as someone who doesn't see retina patients all the time, that that is a more complex concept. But I think the European physicians are highly thoughtful and are very disappointed by this finding.
Thank you for taking my questions.
Thank you. There are no further questions at this time. I'd like to turn the call back over to Cedric for closing remarks.
Thank you so much. Well, in closing, thank you all for joining us today. We are around later. If you have any additional questions, feel free to reach out to Meredith. Have a wonderful day.
Thank you for your participation. This does conclude the program, and you may now disconnect. Everyone, have a great day.