Thank you for standing by, and welcome to the Apellis Syfovre FDA approval Conference C all. At this time, all participants are on a listen only mode. After the speakers' presentations, there'll be a question- and- answer session. To ask a question at that time, please press star one one on your telephone. As a reminder, today's conference is being recorded. I would now like to hand the conference over to your host, Meredith Kaya. Please begin. Thank you for joining us today to discuss the FDA approval of intravitreal pegcetacoplan, now with the brand name Syfovre, as the first and only treatment for geographic atrophy, or GA. With me on the call are co-founder and Chief Executive Officer, Dr. Cedric Francois; Chief Medical Officer, Dr. Caroline Baumal; and Chief Commercial Officer, Adam Townsend. Timothy Sullivan, Chief Financial Officer, will be available for the Q&A. Before we begin, I would like to point out that we'll be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional details. Lastly, please note that for this quarter, today's call will replace our normally scheduled quarterly earnings call. I will turn the call over to Cedric. Thank you, Meredith, and thank you everyone for joining the call. Today marks an extraordinary milestone for patients, for the retina community, and for Apellis. I'm thrilled to share with you that the FDA has approved Syfovre for the treatment of geographic atrophy secondary to age-related macular degeneration. Syfovre is the first treatment available for GA, a disease that relentlessly and inevitably leads to vision loss. This is one of the most important advances in ophthalmology in more than a decade. It is also the accumulation of more than 20 years of scientific research and a tireless commitment by our team to bring this important treatment to patients with GA. For those who have been living with this disease for years with no treatment options, we are privileged to finally change the course of GA forever. The approval of Syfovre is grounded in this medicine's proven ability to slow GA progression with a label that we believe details the significant value it offers to patients and physicians. First, most important, is that Syfovre has demonstrated increasing effects over time. This means that the longer a patient is treated with Syfovre, the greater the impact this medicine can have on the degenerative process. Second, the label offers flexible dosing. Physicians can decide the frequency of treatment ranging between once every 25 to 60 days based on the individual's needs. Third, Syfovre is indicated for all patients with GA, with or without subfoveal involvement. Fourth, Syfovre has a well-demonstrated safety profile in GA following nearly 12,000 injections over 24 months. This is a strong label, the inclusion of the positive 24-month efficacy and safety data in our label creates a very clear picture of what Syfovre can do for patients with GA. We are extremely grateful for our collaborative interactions with the FDA throughout this process. GA is a complex disease that the field has spent decades working to address. The effects we have seen with Syfovre, further validated by this approval, are a testament to our approach of targeting C3. We know that complement overactivation is strongly associated with GA progression. As you can see on the graphic on this slide, Syfovre acts centrally in the complement cascade, controlling all three pathways and all downstream effects. We believe this unique mode of action results in comprehensive control of the complement cascade. Now, before I turn it over to Caroline, I'd like to take a moment to thank the people who have been integral to getting us here. We are especially grateful to the patients with GA who participated in our clinical trials, their families, caregivers, and the healthcare professionals who also participated in the trials. I would also like to recognize our incredible team at Apellis. We are a small company in the world of the retina, but we have achieved what many of our larger pharma colleagues have not done. This road has not always been an easy one, especially over these past 18 months. For that, I thank you for your unwavering commitment to improving the lives of patients and your pursuit of the highest level of scientific integrity. It is such an honor for me to be on this journey with every one of you. With the approvals of EMPAVELI and Syfovre, we have only begun what we can accomplish together. Finally, I would like to thank our partners and the investors who have provided their incredible support to Apellis over the years. With the approval of Syfovre, we are transforming the treatment landscape for patients with GA. I will now turn the call over to Caroline. Caroline? Thank you, Cedric. Before I get into the label, I would like to say how proud I am to be a part of the team to bring the first and only FDA-approved treatment to patients with GA. As an investigator in the OAKS study, I have seen firsthand the transformative potential of Syfovre. I came to Apellis in large part because of this groundbreaking treatment. A diagnosis of GA is a life-changing event. I have personally seen how GA impacts the patient's vision and quality of life. GA takes away a person's ability to do the most ordinary daily activities, such as reading, driving, and even recognizing faces. One of my previous patients had progressed to the point where she could not even see the food on the plate in front of her. Of course, these impacts are both physical and emotional, and they affect not only the patient but also their families and their caregivers. Until now, there were no treatments to offer my patients with GA. As a retinal physician, having to tell your patients that they will ultimately go blind and nothing could be done about it was one of the hardest conversations to have. Thankfully, with this approval, this will no longer be the conversation. It is exciting and gratifying to now be able to offer Syfovre as a treatment for all patients with GA in the US The approval of Syfovre is based on positive results from the phase 3 OAKS and DERBY studies at 24 months in more than 1,200 patients with GA. Syfovre is approved for all patients with GA, regardless of lesion location or whether one or both eyes is affected. This speaks to the broad and representative population enrolled in our clinical trial. Importantly, it is also approved with flexible dosing once every 25 to 60 days. On this slide 9 are the results of the OAKS and DERBY studies at 24 months. As you can see, treatment with both every other month and monthly Syfovre resulted in a reduction of GA lesion growth in patients. Two things stand out in these graphs: the consistency of the data across both studies and the increased effects over time. These findings were pivotal in our decision to submit the major amendment in November. With this label, we believe we are now in the best position for our launch. On this slide is the slope analysis showing the effects in each 6-month segment. These data are in some ways the most important from these studies, as they show how the treatment effects evolve over time. We know, GA is not a one-year disease, so understanding how the treatment is benefiting patients today and what this could mean over time is incredibly important. You can see, Syfovre showed increasing treatment effects over time, with reductions in lesion growth as high as 36% between months 18 and 24 in DERBY. To see this type of disease modification is extremely rare and very promising. We have the opportunity to learn more about the effects of Syfovre over even longer periods of time in our three-year GAIL extension. Cedric noted, Syfovre has a well-demonstrated safety profile following approximately 12,000 injections. The most common adverse reactions reported in patients receiving Syfovre were ocular discomfort, neovascular, age-related macular degeneration, vitreous floaters, and conjunctival hemorrhage. Rates of ischemic optic neuropathy events are higher in the monthly group as compared to the every other month and sham groups. The rate and severity of endophthalmitis and intraocular inflammation were generally in line with reported studies of other intravitreal therapies. As with intravitreal therapies, there is always a warning for endophthalmitis. For inflammation, this is important information for prescribers and gives them assurance that they may restart Syfovre once events have resolved. No events of occlusive or non-occlusive vasculitis or retinitis were observed in our studies. While the US launch of Syfovre remains our top priority, this is just the first step in our efforts to bring Syfovre to patients with GA worldwide. We submitted the marketing authorization application or MAA to the EMA last December. We were pleased to hear that the EMA subsequently provided validation and that the application is now under formal review. We anticipate a decision by the European Commission in early 2024. In addition, we've also submitted a marketing application to Health Canada and expect to submit applications in Switzerland, Australia, and the U.K. later in the Q1. Before I turn it over to Adam, I also want to thank Federico Grossi. Fede, thank you for your support over these past two months as I have been transitioning into my new role. It is through your remarkable leadership that we have achieved this milestone, and I look forward to carrying on your legacy into the next chapter. I will now turn the call over to Adam. Adam? Thank you, Caroline. I'd like to echo the earlier comments around what a truly incredible milestone this is. There are more than 1 million patients in the US today who have been waiting for a treatment, and I am excited to share some details on our commercialization strategy. We have built a best-in-class field-based team with extensive experience in retina. They are all in place and laser-focused on bringing Syfovre to physicians and patients. We plan to launch in the next week or two once we have trained everyone on the final label and supply is in place for distribution. Our field teams will be calling on approximately 2,600 retina specialists and injecting ophthalmologists who treat patients with GA. We anticipate that retina specialists will initially prioritize treatment for those patients who have significant vision loss in one eye and foveal encroachment in the other eye. Wet AMD in one eye and GA in the other eye or bilateral GA. As these physicians gain clinical experience, we then expect them to broaden to more patients within their network. Turning to pricing and access. Following a thorough analysis, which included extensive physician and payer feedback, we priced Syfovre at $2,190 per vial. We believe this reflects its clinical profile as the first approved therapy to treat GA, whilst also remaining in line with pricing of existing anti-VEGF treatments. As described previously and considering the dosing flexibility, we believe this is a strong value proposition for physicians and payers. Our payer-facing team has been engaging with payers, educating them on the unmet need in GA, and has received positive feedback on the clinical profile of Syfovre. Over 90% of patients will be covered by Medicare, distributed almost equally between Medicare Advantage and fee-for-service. Keep in mind that this will be the first time that payers will see a treatment for GA come through their systems, which may result in some initial bumpiness, but should soon smooth out over one or two quarters. Like other buy- and- bill drugs, we will launch with a temporary J-code and are working quickly to obtain a permanent J-code. We plan to submit for the J-code within the next few weeks and expect to have it around October 1, 2023, based on CMS's quarterly cycle for J-codes. We anticipate measured adoption over this initial period, but then an acceleration in adoption once the permanent J-code is in place and physicians have more experience with the drug. Apellis is committed to ensuring that every eligible patient who may benefit from Syfovre will have access regardless of ability to pay through our ApellisAssist program. This patient access initiative is designed to help patients along their treatment journey by providing a system inclusive of insurance support, financial assistance for eligible patients, disease education, and ongoing product support. We look forward to keeping you updated on our launch progress as our experienced retina specialist team works to bring this transformative treatment to the GA community. I will now turn the call back over to Cedric for his closing remarks. Thank you so much, Adam. We are proud to bring Syfovre to the more than 1 million people living with GA in the US Syfovre's approval marks our second FDA approval in less than 2 years. This milestone reinforces the power of targeting C3 to treat some of the most challenging diseases, and we have only begun to unlock this potential. GA and PNH are only the start of what is possible with targeted C3 therapy, and we are focused on expanding our global leadership in complement. We look forward to advancing Syfovre and registrational programs with systemic pegcetacoplan across multiple rare diseases with high unmet need. Before we open the call up to questions, I would just like to once again offer my gratitude to all of the physicians and patients who participated in the clinical trials and everyone who helped Apellis get to this pivotal moment. While the list is too long to mention everyone, the following individuals also deserve a special thank you. Paulette and Bernard Berti, Natalis and Robert Scheuer, Nathaniel and Robert de Rothschild, and David Darst Sr. Additionally, there are a few people who are no longer with us, including founding investors Frederick Whittemore and Michael Gellers, Apellis toxicologist Ray Stahl, and one of Apellis' cofounders, Paul Olsen. Finally, last but not least, a special call-out to Gerald Chan, our board's chairman, and Morningside Ventures. You have supported us in this company since the very first day, and we are so incredibly grateful. Operator, please open the call to Q&A. Thank you. Again, ladies and gentlemen, if you'd like to ask a question, please press star one one on your touch-tone telephone. Again, to ask a question, please press star one one. One moment, please. Our first question comes from the line of Madhu Kumar of Goldman Sachs. Again, Madhu Kumar, your line is open. Hey, everyone. Thanks for taking our questions. Before I go to the questions, I want to congratulate you guys. This is a really exciting and important day, and I'm sure, like, you appreciate how big a change this is for people with this disease. I really appreciate you for kind of getting all this work done to kind of crossing the finish line here. You know, our first question really is how to think about, to the point Adam made about a temporary versus permanent J-code, how much of the kind of launch is kind of in a holding pattern until the permanent J-code happens in terms of kind of physician uptick? Like, do you have a sense of what fraction of physicians or what fraction of payers really require a permanence compared to a temporary J-code? Thank you, Madhu. I will let Adam answer that question. Thanks, Madhu. Obviously, you know, all buy-and-bill drugs will start with a temporary J-code. As said just recently, we're gonna submit in April for our permanent J-code, which we expect to get in October. We do expect that initial phase during the temporary J-code to be a little bit bumpy as physicians try and test reimbursement for their Medicare plans. I think some physicians will be successful during that period, but the permanent J-code truly unlocks the potential. We expect to see some acceleration after October once we get that permanent J-code. It's definitely something to be thoughtful about. We put our plans around that time period when we would have a temporary J-code. It's consistent for any buy-and-bill drug. We're still gonna be going out there talking to 2,600 retina physicians, getting them ready, and talking about this great drug. They will start to use this drug within 1 to 2 weeks, we believe. They will test the system for sure. That's a little bit on J-codes. Okay, maybe following up, a clinical question and a financial question. The clinical question is: how do you guys think about GAIL and the data that's gonna come out of GAIL in the coming years from that study, and how that influences the use of Syfovre? The financial question is: how are you guys thinking about kind of cash position and cash runway through this launch and kind of the path towards kind of breakeven basically and beyond for a drug of this nature? Thank you, Madhu. Well, let me briefly comment on GAIL, and then I will hand it over to Tim to talk about the financial side. The GAIL extension study, for those on the call that are not familiar, is a three-year extension study where the patient that came out of the DERBY and OAKS studies after two years, essentially engaged in another three years of follow-up. This is something that is very exciting to us because we will continue to image these patients and to look very importantly at the continued and hopefully increasing effects that we saw in the first 24 months as well. As mentioned before during the call, that is one of the most exciting features of this drug, especially the efficacy that we saw from month 18 to 24, where regardless of the type of lesion and with almost similar efficacy between every other month and monthly dosing, we already had efficacy or, and, or reduction in lesion size growth of approximately 30%. We will continue to evaluate that in GAIL and look forward to sharing that with you. Tim? Sure. Thanks, Madhu. You know, we've consistently guided to having cash into the Q1 of next year. We certainly hope with the potential of this product to gain a lot of leverage, relative to our operating expenses. We don't specifically guide, in terms of, either revenue or expenses or breakeven. We feel very confident that the amount that we need to get there is attainable and not as substantial as maybe some people think. Great. Thanks, guys. Thank you. One moment, please. Our next question comes from the line of Umer Raffat of Evercore. Your line is open. One moment, please. It looks like the line of Tazeen Ahmad is open. Your line is open, of Bank of America. Hi, guys. Can you hear me? Yes, Tazeen. Okay, perfect. Cedric, you told me back in January that the next time you would talk to all of us is when you got the drug approved. You kept your word. Congratulations. I maybe wanted to ask Dr. Baumal a question or two. This is the first time I think we're speaking to you in a formal setting. I just wanna ask, as a practicing physician, how would you expect to use Syfovre? A couple of details here. Is there, for example, a specific age group that you think is ideal? Is there a group that you think maybe could be potentially past the point where the drug would be helpful? Thinking about dosing frequency, can you tell us why having every other month on label would be important to you or any doctor? Thank you for the question. You're so right. I'm a practicing retina physician. I'm still also keeping my practice, and I've had the pleasure of joining Apellis with this breakthrough medication. I think that many of us will use clinical studies to help guide our treatment. One of the main things about DERBY and OAKS is that we have this very heterogeneous population of patients that were included with subfoveal and non-subfoveal lesions. I think that many patients who've already lost vision from geographic atrophy or even wet AMD in one eye will be very engaged to having this sort of treatment. I think many of my patients, even who are getting older, they have friends who have geographic atrophy, who have lost vision from geographic atrophy, and they're all excited about having a new treatment for this disease. One of the things to bear in mind is that geographic atrophy causes relentless, irreversible vision loss, and people are living longer, and we see more of this in the office. The other part was the age. I have to say that as a retina physician, age is something that we're used to. We treat patients with neovascular AMD who are over 90. We do surgery on patients of that age group, and we're really masters at giving intravitreal injections. I think that the Syfovre paradigm will fit nicely into the anti-VEGF injection paradigm that we already have. Was there one part I missed? About the how often given the label, I'm really pleased with the indication that we have in the label every 25 to 60 days. This is the flexibility that we like to have as retina physicians. Patients will be in this for the long haul. We will have this flexible dose. I think many patients will probably want to be injected every other month. We'll have more information from the GAIL data as to how patients do with different injection regimens. For example, if a patient comes in earlier, they're going to Florida or something happens in life where they want to be seen earlier than that, then they'll have options with this to have injections over that time interval. Okay. Thanks for that color. L astly, how important do you think it'll be to see a VA benefit over time in order to keep patients on therapy? We are used to treating patients based on imaging and OCT. We do this quite often in neovascular AMD. I think that having OCT and imaging ways to show reduced growth of lesions will be satisfying for many physicians and for the patients as well. Thank you. One moment, please. Our next question comes from the line of Umer Raffat of Evercore. Your line is open. Hi, guys. Can you hear me? Yeah, we can hear you. Okay. I don't have a question whether you're in labeling discussions anymore. But I did wanna ask you three things. One, you mentioned measured adoption in the early period. By my math, you need perhaps at least 10,000 patients in 2023 to make the type of numbers consensus bakes in right now. Do you think that's measured, quote-unquote? Second, expectations on monthly versus every other month, I feel like that's critical to the math I just went through. 50/50, or do you think most of the patients are monthly at the start? Third one is for Caroline. The retinal detachment disclosed on FDA label is, I think the number is 4%-6%. I feel like that's higher than what I had seen in your prior data disclosures on 24 months. Can you speak to how important that is commercially? Thank you. Thank you, Umer. I will first hand it over to Adam on the commercial side, and then of course, to Caroline. Yeah. Thanks, Umer. It's Adam. As said previously, we do expect slightly slower adoption. We use the term measured adoption within the initial phases of the launch, the Q1, potentially two quarters. As physicians are, you know, for the first time are going through all of the benefit investigations and prior auth for a GA product, they have to submit their claims, et cetera, and do all the paperwork. This is the first time that Medicare is seeing a GA product and paperwork. During that time, we will have a temporary J-code, and the feedback we get from physicians is that they'll be much more thoughtful in how they use the drug. They'll test and make sure that they get the certainty of reimbursement for the drug. It's a consideration that we need to take into account for the early stages of the launch. We believe that post-October the 1st, with the J-code becoming permanent really unlocks any of the gates that were holding physicians back potentially. We expect to see a big kick up towards the end of this year. That's answering the 1st part of your question. I can also answer the 2nd part of your question, which was monthly and every other month. I think you said 50/50. In our research that we've been doing with physicians, which we did at 12 months, 18 months, and 24 months, we found that we believe that every other month is a bit of a game changer in geographic atrophy. We think it's very patient- friendly. We think the efficacy of every other month is also very strong, and supported, that flexibility is supported in the label. All of our physician research, physicians like Caroline, point to every other month being the dominant player within the market, and we expect it to be 70%-80% of all of the usage. Every other month is a real game changer. The team's gonna be super excited to go out and talk about this new label and what a great drug, Syfovre can be for GA patients. Caroline? You had asked about, I just wanna clarify. It's actually vitreous detachment, which was reported at in the monthly, every other month in sham pools. Vitreous detachment is something that happens in elderly patients. It's not the same as retinal detachment. As a retina specialist, we see that all the time. It's when patients get floaters with age and the vitreous releases. That's why the rate is reported, and it's even 3% in the sham pools arm. I'm not concerned about that, and I know that my colleagues would not be. It's something that happens as a consequence of age. It happens more often in patients who get any type of intravitreal injection. We don't typically consider that a worrisome event. Caroline, maybe just to clarify, you're right. The table says vitreous detachment, but the first warning on the label says retinal detachment, and that exact number wasn't reported. I wasn't sure what that data was that made FDA write retinal detachment as the first warning. I was just curious what that data was on retinal detachment and how you think about that as a clinician, 'cause it sounds like they saw something. There is no increased incidence of retinal detachment with Syfovre. It's very rare after any type of intravitreal injection. If you see below the table, it mentions that retinal detachment was reported in less than 1% of patients. Thank you. Thank you. Thank you. One moment, please. Our next question comes from the line of Anupam Rama. Your line is open. Hey, guys. Thanks so much for taking the question and congratulations on the approval. Just a quick one from me. For Caroline, from a clinician's perspective, can you walk us through how you talk to patients about the concept of preserving vision versus, say, a gain of vision and how you think about patient compliance, with, you know, the broad dosing labels that you have? Thanks so much. Sure. Thank you for the question, Anupam. One thing that's important to note is that when patients have geographic atrophy, even if their visual acuity is stable, every single time that patient comes into the office, they will say that their vision is worse, that it is progressing. That's because the lesions are growing, and typically they only grow into the center of vision at the end latest stage of this disease. I think that many patients know that their vision is getting worse. The way that we measure visual acuity with Snellen acuity has been around for, you know, 100 years. You know, we need better ways that we can measure these things on patients. They know their vision's getting worse. They know that their field is getting worse. When I'm able to talk to them about a treatment to reduce the rate of growth of geographic atrophy, I think they'll be very receptive. Thanks so much for taking our question and congrats again. Thank you. Thank you. One moment, please. Our next question comes from the line of Philip Nadeau of TD Cowen. Your line is open. Good afternoon, ladies and congratulations. It's a great milestone for the company and the patients. A few questions from us. First, in terms of reimbursement, what payment terms will you offer to physicians? Will you give extended payment terms during the first several months before the permanent J-code is available? That's first. The second, Caroline Baumal, we'd be curious to hear how you think, a bit more about how you think physicians will determine the dosing interval that they wanna use. It sounds like convenience may win the day, are there any other factors physicians would look at that could cause them to give more frequent injections? Last question, also a medical one. In the prepared remarks in the slides, you do call out the rates of ION being higher in the monthly arm compared to every other month in sham. We also don't think we've heard you say that before. What's the significance of that and I guess, why call that out? Thank you, Phil. Great to hear you. Adam will start with the commercial question. Yeah. Caroline will follow up. Thank you, Phil. Appreciate the question. Obviously we did our homework, as you would expect, and we did a robust analysis of all of the services that physicians would expect from the previous wet AMD drugs and anything else that goes to a retina specialist. We've done our homework on all of those type of activities, and we're gonna be making sure that, you know, with a focus on making sure that every patient can receive Syfovre treatment. We're gonna make sure that we're as robust as we can be in meeting those needs of retina physicians within the US Now it's my turn. I think you asked multiple parts about monthly and every other month. The data is meaningful for both monthly and every other month, a little bit better for monthly. Every other month is also something as retina physicians, we're used to that treatment paradigm. That's what we try to get to. I think for, you know, retina physicians will base it on the individualized patient scenario. If the patient is monocular, has one eye, has a lesion that's close to the center of vision, maybe for that patient, they'll choose monthly. Maybe for someone else, they'll have a different paradigm. That's the best thing about this label, that we have this flexibility. I know that my retina colleagues are very creative and will find the best way to treat patients based on their individual scenario. With regards to ION, we've previously reported 3 serious adverse events of ION in the monthly arm, and the label also includes 4 cases of ION adverse events in the monthly arm and 1 case in the every other month arm. None of the adverse events were associated with significant vision loss. It's notable that the higher incidence of ION was associated with the monthly arm. All of these patients had associated comorbidities like hypertension and diabetes that are noted to be associated with ION. This is something for physicians to be cognizant of when they're treating monthly, especially for patients who have these underlying conditions that might put them at higher risk. Also importantly, across the DERBY, OAKS, and FILLY, there was a single AE event in the every other month arm and a single event in the sham control, and neither of these resulted in significant vision loss. That's very helpful. Congrats again, and thanks for taking our questions. Thank you. One moment, please. Our next question comes from the line of Steven Seedhouse of Raymond James. Your line is open. Thank you. Obviously, congratulations everyone. I wanted to ask, first on slide 13, where you sort of break out, you know, the priority patient populations. Can you put a number or a percent on that? How many patients comprise those four phenotypes that you call out? As you progress through the launch, maybe just you could comment on what we'll hear from you guys with respect to launch metrics and progress and how launch is going outside of earnings updates, if at all. Lastly, we've heard from some retina specialists that indicate, you know, basically like at a minimum, the first patient office visit for somebody with GA seeking this treatment could be like an hour and a half visit. Do you think the 2,600 retina specialists are logistically ready to handle 1 million patients coming through, or is this gonna be a big burden on offices? Thanks. Thank you, Steve. Great to hear you. My job's very easy today. The first question to Caroline, then Adam for the launch metrics and that first visit. I'll start with the timing of the visit. I think that maybe an hour and a half is a little bit on the long side. I mean, all of this depends on the sort of imaging that the patient will have when they come in to visit the doctor. With any new therapy, you know, it's always a very careful rated decision. As retina physicians, we're very used to this intravitreal injection paradigm. Whether this means adding more staff or having intravitreal injection clinics, I think that, I mean, all of my retina colleagues, I can see it from all the texts I've received, are all excited to have this new treatment option for our patients, and we'll figure out how to do it. I think some retina physicians are, you know, they're deciding how they're gonna monitor these patients. We always do OCT on patients whenever they come in. I think that that will be a great way to monitor these patients combined with. Also, again, our every other month dosing allows them some flexibility in terms of how they can schedule these patients, so it's important. Your initial question about the priority patients, obviously, again, based on our feedback with doctors like Caroline, physicians say that they're, you know, gonna prioritize the patients that are actually on their books, in their systems. They tend to be the patients initially who have severe and significant vision loss in one eye and probably foveal encroachment in the other eye, bilateral GA, wet AMD in one eye and GA in the other, also wet AMD and GA in the same eye. It depends on the size of a physician practice, but the majority of these patients, because of their vision loss, the SITS area can range anywhere between 20%-40% of the GA patients that these physicians see. A lot of these patients are obviously sent back to ophthalmologists, because until today, there was no approved treatment for geographic atrophy. This is where we believe physicians will start. We also know that physicians will start to squeeze patients out from ophthalmologists into their practice, once they've got through the bolus of patients within their system. The second part of your question was what type of metrics, so that you can all understand how we're progressing with the launch. We'll be providing net product sales and the number of files on a quarterly basis. We're also gonna look at some other qual type of metrics that give you some qual information on how we're progressing with payers and anything along those lines. The quant metrics will basically be net product sales and number of files. Thank you. Congratulations. Thank you, Steve. Thank you. One moment, please. One moment. Our next question comes from the line of Colleen Kusy of Baird. Your line is open. Colleen, good afternoon, and a huge congrats to the whole team. Thanks for taking our questions. Any post-marketing requirements that the FDA has communicated to you? Then in patients that have wet AMD in either the same eye or the fellow eye, are there any initial thoughts on how physicians will administer Syfovre as well as the bevacizumab in there? Thank you, Colleen. Great to hear you. There are no post-marketing requirements, and I will let Caroline answer the second question. We have a robust data from DERBY and OAKS to guide us on patients who develop exudative AMD or need to have anti-VEGF as well as Syfovre injections. I think that the best data that we have is that these can be done on the same day. It states on the label to wait for pressure to normalize after the anti-VEGF injection. The first time that physicians will have the ability to dose Syfovre and a wet AMD product in the same time. We do again expect initially one or two minor headaches are called. You know, as physicians get used to submitting their CMS form, they're using the GA ICD-10 code for the first time, the J-code and then a CPT code. I think we'll have some time to work through that type of initiative. I don't know, Caroline, if you wanna add anything from your practicing physician perspective. As a physician. We often inject both eyes on the same day. I think that we will be able to fit that into the treatment paradigm. I think that the billing issue will be solved. Awesome. Thanks again for taking my questions, and a big congrats again. Thank you, Colleen. Thank you. One moment, please. Our next question comes from the line of Justin Kim of Oppenheimer. Your line is open. Hi, everyone. Good afternoon, and congrats to the whole team. Maybe just one on the point of GAIL. I'm sort of curious how we should think about the US participation in the study, especially as sort of a commercial product becomes available and maybe a permanent J-code gets established later this year. Maybe as a quick follow-up to that, just kind of trying to work out how we should be thinking about these insights and, you know, in terms of, you know, what we've thought about previously, the fellow eye comparisons were pretty impactful and just wondering, you know, how much of this will be able to be looked at with the commercial product now available. Yeah. Thank you so much, Justin. I think I finally get to answer a question as well. I mean, GAIL, and many of you have heard us say that before, is one of the most valuable and most important things that we have done for this drug. The ability to continue to evaluate this drug over time is very important to us. You make a fair point, which is that, of course, patients that are in the study have to go through imaging, et cetera. It's certainly more burdensome to some extent to be in a clinical trial than it is to be on the standard of care. On the other hand, switching over from a trial to regular standard of care also comes with its hurdles, and I think many of these patients are now in the routines and used to being in the trial. We're hopeful that majority of them will decide to stay and help us understand the long-term impacts of treatment with pegcetacoplan for C3 glomerulopathy now. The fellow eye is just an absolutely fascinating observation that we have spoken about a lot in the past. Tomorrow at The Macula Society, we will also show data again on the fellow eye and hope for how over 24 months the fellow eye follows almost to a T what we see in the sham controls as well. Very exciting and a way for us to evaluate on an intra-patient basis how the drug does over time. That is something that, of course, to your point in the GAIL extension study, where the sham control patients go on active, will continue to be there. Some patients with bilateral GA, where only one eye is treated, the fellow eye, something very exciting to look forward to and we look forward to sharing more data on that. Okay, great. Thanks. Maybe one more, just follow-up. You know, with this approval, how should we think about 2006 and, you know, any updated thinking on plans for the sort of combination? Thank you, Justin. 2006 is a very exciting new molecule that we have developed. This is one molecule that combines the activity of pegcetacoplan slash Syfovre with an anti-VEGF modality and also a kind of a, I'd say, a half-life extending modality included within that same molecule. This molecule will go into the clinic towards the middle of this year. At the end of the day, will allow us to hopefully go as early as possible, treat patients who have primary wet AMD and find a way to reduce the incidence of geographic atrophy secondary to the treatment with anti-VEGF in those patients. Very exciting program that Apellis has told us they look forward to investigating and another next chapter for us as well. Great. Thanks for letting congrats again. Thank you, Justin. Thank you. One moment please. Our next question comes from the line of Yigal Nochomovitz of Citi. Your line is open. Hi. Great. Hi, Cedric. First of all, hearty congratulations on the approval and to the broader team on this incredible achievement. I did have a few questions. I think Adam mentioned the 70% to 80% every other month expected split when you surveyed physicians. Just wondering, is that a metric that you're gonna continue to report on the quarterly sales? You mentioned net product sales and dials quarterly, but in terms of the split on monthly and every other month, is that something we're gonna be able to track? With regard to the label, it says every 25 days minimum. I'm assuming that's just to provide for some flexibility since you can't get to 30 days exactly. Third, for Adam, on the pent-up demand with respect to the 2,600 retina specialists, could you comment to any extent on how many of those practices have specifically requested the drug so far? Thank you. Thank you, Yigal. I will briefly answer the second question and then hand it over to Adam. Again, the label having that flexibility from 25 days to 60 is fabulous for physicians and for patients, as Caroline alluded to earlier, right? We tested the drug with monthly and every other month, but considering how close the efficacy was between the two dosing regimens, in our interactions with the FDA, we found that this description of the label was the most appropriate. Adam? Sure. Yigal, you ask a great question. Obviously we, as we said, we'll deliver revenue numbers plus a number of files. Initially, we won't have a good idea on how those files are being used through. To our initial phases. What we'll do is we'll speak to physicians and, you know, talk to those 2,600 physicians and get some feedback from their offices. Eventually, we'll start to get a little bit more qual data on how it's being used. Within the initial phases, it'll just be vials. We won't immediately know if they use monthly or every other month or the flexibility of dosing. We'll have more qual type metrics that will talk to that as we get into the launch window. Your last part of your question was the 2,600 retina specialists and the pent-up demand. Obviously, our cross-functional field-based team has been in the market since last year doing disease state education. I have to say, the response to disease state education, the request for Apellis to go and educate offices and practices on the disease of geographic atrophy was hugely impressive. I think that's a great sign for how the practices and physicians and staff are getting patients ready. Also we've started to do those obviously at ophthalmology centers as well as optometrists, also identifying patients ready for today's approval. No surprise as we take our field-based teams, we educate them on the label. We then train them, certify them, make sure they go through all of the right certification, and we get product to the right site over the right destination over the next week or two. I do expect that, based on what we saw in disease state education, that we'll have some relatively rapid physician use. Thanks. Thank you. One moment, please. Our next question comes from the line of Derek Archila at Wells Fargo. Your line is open. Great. Thank you. Huge congrats to the team on the approval. Well done. Just a couple, you know, quick questions from us. Just, I think this one's for Adam, on the comments around every other month. The paperwork and test how long it takes for reimbursement during the temporary J-code time period. If in that time period they find a payer coverage or a patient demographic that gets reimbursed relatively quickly, they'll prioritize those patients for sure. I do think there'll be certain practices that will, you know, use that method to gain and see how long it takes to get reimbursement. I also see that patients will be moved towards physicians' offices towards October as well. You'll see a little bit of both. The permanent J-code is something that really unlocks the doors for the vast majority of physicians. Excellent. Well, congrats again. Thanks for taking my questions. Thank you. One moment, please. Our next question comes from the line of Eliana Merrill of UBS. Your line is open. Hey, guys. Congratulations. Thanks for taking the questions. Maybe just for Adam and Caroline, I guess, what are you seeing and I guess what do you expect in terms of new referrals into the retina practices? I guess, have you seen maybe any uptick recently in referrals and just your expectations for, I guess, this could grow with time just given the approval? Just, I guess, in general, how often do geographic atrophy patients see their doctors? Like, if you expect maybe like the patients to be called in with an approval or if they may be treated just at a typical visit and discussed then, in light of the approval. Thanks. I'll start with that. With regards to referrals, I think that we have done a great job of educating all eye care providers, not just retina physicians, but our cataract doctors, our general eye practitioners and optometrists all see patients who have geographic atrophy. There's been a lot of work done on education with regards to imaging in these patients. I think people are looking for this now and will be looking for it now that there's a treatment available and refer these patients to the appropriate source. I'll just add that since I am old enough that I was around when anti-VEGFs were introduced, it was very, very similar paradigm at that time. Patients with wet macular degeneration really weren't referred in. Over the first 5 years after treatment became available, patients became referred earlier and earlier, and we learned a lot about that. I anticipate that the same thing will happen, all the retina specialists are educated on this and are ready to treat patients. Hey, Eliana. It's Adam. Just to add to Caroline's comments, right? You know, we are starting to see based on our disease state education and the knowledge of GA and the, you know, the potential which actually happened today of an approved product, that optometrists and ophthalmologists are starting to identify that they can refer patients. The feedback initially from the 2,600 physicians is they have a bolus of patients already on their books so that as we've described before, they're going to prioritize those patients, but then they'll become quite sophisticated in how they pull patients up through the ophthalmology channel, et cetera. We expect that we can help facilitate that movement once they've got through the bolus of patients that currently sit on their books. Awesome. Thanks. Does that answer your question, Eliana? Yeah. Great. Thanks. Thank you. One moment, please. Our next question comes from the line of Annabel Samimy of Stifel. Your line is open. Hi, guys. Thanks for taking my question. Congratulations from me. I had a couple. Maybe this is for Caroline. We've heard a lot about compliance and the flexibility that you have with every month and every other month dosing. I guess I wanted to ask a broader question for GA patients in general. We all know that patients will not be feeling a benefit, rather they're preventing loss of sight. We're starting to hear from where we've heard from a few physicians that retention might be an issue as opposed to compliance, and maybe we get a flattening of a curve at some point. How do you think patients will remain on therapy when they're not feeling, just like in general, your patient base, how will they feel about staying on therapy? Will there be some level of injection fatigue like we've seen in wet AMD? Do you think that the replacement of patients from the optometrists and ophthalmologists will be fast enough and get into the retinal specialist office quickly enough to sort of offset that dynamic we've been hearing about? I guess it's more of a broader question that I'm asking. Second question just relates to the GAIL study. I know that we're gonna be seeing releases of some of the data, if there's any way you can provide us with some kind of timing of those releases, and if there's any additional metrics, things that you're exploring in the GAIL study that we haven't seen before, anything new that we might see from that study that could further inform treatment? Thanks. Thank you so much, Annabella. Look, as I've mentioned before, I mean, GAIL, very, very exciting for us, especially to continue to evaluate these increasing effects over time that we saw. I don't think I need to tell this audience how rare it is for a drug to have increasing effects over time, and that is something that we look forward to exploring. As it relates to releasing the data, we're not committing to anything, but we will probably synchronize this with meetings, maybe a press release if there's something particularly interesting, but, you know, no commitment at this point in time. Hi, it's Caroline Baumal. Regards to retention of patients, I actually think that injection fatigue is less of an issue in our patients who have macular degeneration compared to diabetics. The elderly patients, they really want the saved vision that they have. It's so tied to their independence. One of the benefits of Syfovre is that you can actually tell patients approximately if they're on the every other month dosing, you can actually give them a time point as to when their injections are. Anti-VEGF injections, sometimes it can be a little less, you can give them like, less of a standard because we do treatment extend, and if the disease gets worse, we, you know, we have a more of our own recipes. I think with this, so the patients know what to expect, that they will be motivated to be treated and to, you know, reduce the rate of vision loss. Okay. You mentioned earlier that you see retinal specialists becoming very creative with their injections. Can you share with us what kind of creativity you might expect? Well, many of my colleagues have injection clinics. They have patients come in. There's really a set paradigm where we see patients, do their vision, check their pressure, do a quick picture or an OCT, and then the patient goes right into the room and has an injection. This really fits nicely in with the flow that we have with anti-VEGF treatments. Great. Thank you. Thank you. One moment, please. Our next question comes from the line of Joseph Stringer of Needham. Your line is open. Hi. Thanks for taking our questions. 2 quick ones from us. Just given your expectations that the vast majority of patients will be covered by Medicare, what are your initial thoughts on what we can expect around gross to net? Secondly, following up on some of the earlier questions on dosing, could you provide your updated thoughts on what you think the average number of injections per year per patient would be? Understanding you alluded to that you think it's gonna be skewed more towards every other monthly dosing. If you take into account the various types of GA patients, how does that influence your estimate on that? Yeah, Joseph, it's Adam. I think there's some pretty complicated math that goes into that in terms of eyes treated, et cetera, and along those lines. You know, some of our initial treatment population, you might be treating 2 eyes per patient, et cetera, et cetera. I think it eventually will net out at what you would expect of, you know, approximately 6-7 potential vials per eye per year. That's after treating the initial patient bolus. As a reminder, some physicians will choose to start monthly vials based on the severity of the disease. Caroline, from your perspective, do you wanna add anything? Sure. I think, 6 to 8 is actually for example, for wet macular degeneration, that's on the lower side. Some patients get even more and patients are really able to stand the gain for that. I would anticipate somewhere between 6 and 8 per eye. Does that answer your question, Joseph? Yes, thank you. Very helpful. Thank you. One moment, please. Our next question comes from the line of Douglas Tsao of H.C. Wainwright & Co. Your line is open. Hi, good afternoon, and thanks for taking the questions. First, you know, there's a lot of conversation and focus on the visual, you know, for functional preservation, and what patients see and how that will affect adoption. You know, you presented earlier this year very interesting data on microperimetry. I'm just curious from Dr. Baumal's perspective, you know, how that will be sort of received by the physician community. You know, maybe for Adam, I'm just curious how we do plan to work that into the messaging from a sales force perspective. Thank you so much, Douglas. I think, look, the microperimetry data and really understanding what goes on with visual function outside of the lesion border, which is where the disease is progressing, right? It's very exciting work that we do with Sebastian Ernst from Vienna. That was presented at AAO that we will continue to do, specifically focusing on that area. That is going to be work to be followed. I don't know, Caroline, if you wanna add something in terms of, you know, how physicians look at that. I think it is interesting, but... Right. I think it's very compelling, the photoreceptor and RPE data done that show reduced rates of photoreceptor and RPE loss compared to sham-treated eyes and the microperimetry data. You know, as a, as a clinician, we know that functional data and as an investigator, I was an investigator in the study, so I will tell you that doing functional data tests on patients who are over 80 that are already have compromised vision due to a severe disease are very difficult for the patients to do these tests. As a retina specialist, I believe in the imaging data that I do. We treat other diseases based on imaging inputs that we see. I'm really enthusiastic with the reduction in GA growth rate. Okay, great. If I can, one quick follow-up. From a labeling standpoint, obviously you succeeded in getting a broad label. It does discuss both the benefits for foveal as well as subfoveal or extrafoveal lesions. Curious from a competitive standpoint, how do you think, or your, from your interactions with the FDA, how are they thinking about that relative to products where sponsors are focused only on extrafoveal lesions? The increasing effects over time, were very important in the approval process. Very important in the label. You know, the division has been very clear about the importance of the slope. These slopes are not just from 0 to 12 or 0 to 24, but specifically the piecewise linear slopes. It was our hopes that we would get those slopes in the label, and we did. We believe that those are critical elements of, explaining to physicians and to patients what the long-term benefit of this drug could be. Okay, great. Thank you so much, and congratulations. Thank you so much, Douglas. Thank you. I'm showing no further questions at this time. Let's turn the call back over to Cedric Francois for any closing remarks. Well, in closing, thank you all for joining us. This is an incredible day. The approval of Syfovre is such a major milestone for patients with geographic atrophy. We are around tonight. If you have any additional questions, feel free to reach out to Meredith. We have received questions about the tiki party next year, will happen. Thank you again for joining us today. Have a wonderful rest of the week. Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day.