Good morning, and welcome to the Annexon investor event. At this time, all attendees are in a listen-only mode. A live question-and-answer session will follow the formal presentations. To our covering analysts, please use the raise hand feature to be added to the queue. As a reminder, this call is being recorded, and a replay will be available on the Annexon website following the conclusion of the event. I will now turn the call over to Douglas Love, Chief Executive Officer of Annexon. Please go ahead, Douglas. Thank you, Wilson. Welcome, everyone, and thank you for joining us this morning. We are pleased to be advancing towards the readout this quarter of the month 15 primary endpoint for our ARCHER II phase III trial in geographic atrophy, and we appreciate you listening in as we provide an overview of this promising program and what to expect with the readout ahead. We will be making forward-looking statements this morning, and you can refer to our SEC filings for more information. Next slide. Joining me on the call this morning is retina specialist Dr. Roger Goldberg of Bay Area Retina Associates, who will share clinical perspectives on the GA marketplace. We are also joined by Dr. Lloyd Clark, himself a retina specialist and our SVP of Ophthalmology Strategy and Innovation, who will walk through the ARCHER phase II data and ARCHER II phase III trial design and execution. Lastly, joining us for Q&A is Dr. Ted Yednock, our Chief Innovation Officer and one of our retina biology experts. Next slide. Regarding this morning's agenda, we will spend approximately 45 minutes in prepared remarks on the GA market and our vision-sparing pivotal program, and we will then invite you to join us for a Q&A session. All righty, next slide. Before diving into the meat of the program, I would like to quickly provide a little background on Annexon for those who are less familiar. Annexon was spun out of Stanford University based on discoveries there on the role of C1q as the initiator of harmful classical complement inflammation in a host of neuroinflammatory diseases. Built on more than two decades of research on C1q and classical complement biology, Annexon's novel platform is designed to stop neuroinflammation at its source in the body, brain, and eye before tissue damage becomes irreversible. By providing comprehensive protection against harmful complement inflammation, and consistent with our mission to help millions live their best lives, we have intentionally focused on preserving function or independence for those living with devastating neuroinflammatory diseases. We are encouraged by what our platform has demonstrated thus far and even more encouraged by what is ahead. Next slide. Today, our complement platform is translated into two late-stage programs with blockbuster potential in large underserved markets. GBS is our most advanced program, having demonstrated the first winning placebo-controlled dataset in this devastating disease in nearly half a century. Thereby blocking C1q inflammation in the body and brain, tanruprubart has protected peripheral nerves and function, and approximately 90% of treated patients in our pivotal phase III trial improved by week one, which gave them a 2.5x greater likelihood to being fully recovered from acute paralysis by week 26. Tanruprubart treatment has also shown unprecedented outcomes in the ongoing U.S. European FORWARD study, where 100% of patients have responded to treatment thus far. The net-net is that by stopping C1q inflammation where it starts on diseased tissue, that can result in profound functional outcomes. We have filed for approval for the treatment of GBS in the EU, and we anticipate filing the U.S. BLA this quarter. Today's event, however, is focused on the program on the right, our GA program, where we're targeting C1q in the retina with vonaprument to preserve synapses and neurons necessary to protect against vision loss. Our phase II GA trial is the first and only to show significant vision preservation in a randomized sham-controlled study, where we protected vision on several measures, as well as photoreceptor neurons responsible for visual acuity. ARCHER II is a highly differentiated phase III study with vision as the primary endpoint and why we're here today. We want to ensure that you understand this first-in-kind vision-sparing pivotal program that is unlike any prior approaches. Next slide. One other thing. It's important to note that we didn't simply advance from phase II to phase III. We made the ARCHER II phase III trial better by incorporating key learnings from the phase II and other programs to conduct what may be the most comprehensive and informed vision-sparing pivotal GA study to date. ARCHER II has been intentionally designed to maximize the probability of success by replicating the vision protection demonstrated in the phase II study, and as Lloyd will describe, the phase III trial is deliberately studying patient populations likely to lose vision over the course of the trial, coupled with patient populations where vonaprument has shown a dose-dependent treatment effect. We're particularly encouraged by the breadth and depth of patient populations where vonaprument has shown robust activity, which is exceedingly important in a disease such as geographic atrophy. It's also noteworthy that the phase III trial is larger, longer, and better powered than the phase II, all of which we believe enhances the likelihood of success when we report out on the 15-month primary analysis later this quarter. With that backdrop, I'll now pass the mic over to Dr. Roger Goldberg to provide an overview of what vision protection means to GA patients and physicians. Dr. Goldberg? Great. Thank you so much, Douglas, and great to be here, really to discuss where we are right now with geographic atrophy from a clinical perspective, what I hear from my patients, and what it would mean if we had a drug available that could actually slow down or reduce the risk of significant vision loss in geographic atrophy. If we could go to the next slide, please. We have two FDA-approved medicines, SYFORVE and IZERVAY, and they have been available since a couple years now on the market, a couple years now, I think 2023, 2024. There is still a huge unmet need, however, because although these two agents demonstrated the ability to slow down the growth of geographic atrophy, they have not been able to show down any protection of vision, of actually preserving the vision. GA, despite these therapies, is still a leading cause of blindness in the elderly. I hear literally every single day about the impact that geographic atrophy has on my patients' lives, their ability to function independently. Although here it says on the top right of the slide that the average age is 79 for a patient with geographic atrophy, I will tell you clinically, there is a huge range. It is not uncommon to see patients with GA in their 60s, still highly functional, but seeing that progression from intermediate AMD into the advanced dry form of AMD, which we call geographic atrophy, and seeing patients on the other end, 90-year-olds also with geographic atrophy. So a huge range. With that huge range, I would also comment, is a huge range in the functional capabilities of people when they walk in our clinic with geographic atrophy. I have 90-year-old patients who still drive and kind of live a really robust and full life and are frankly quite worried about their vision because the rest of their body and brains are still functioning quite well. So, there is a huge variability in terms of the severity of the disease, the age of the patients, and we know with this rising baby boomer population that the incidence of GA is only going to increase here in this country and frankly throughout the rest of the world as well. If you go to the next slide, please. This is some survey work done actually for an FDA panel to try to incorporate the patient voice as we think about designing clinical trials for geographic atrophy. One of the things you will notice that patients do not care about is lesion growth. That is never something that comes out of a patient's mouth is, "Well, how is my GA lesion growing?" What they care about is their vision and the way that they use their vision. We hear things all the time about difficulty recognizing faces, of course, driving in this country. I am in the San Francisco Bay Area. Although we have public transportation, I would say this is, other than frankly probably New York City, we do not have a really robust public transportation system in this country. Patients really rely on driving. You see here reading or watching TV. I hear a lot about this. Patients kind of sit there and scratch their head and say, "Geez, I even upgraded to a larger TV, and I am still having trouble. I cannot read the news ticker that comes across the bottom of the television." On the right, I would say, is more of the emotional component, and this survey, I think, replicates many other peer-reviewed publications that show this high concordance with geographic atrophy, vision loss, and depression. They basically, it is this feeling and concern about losing their independence, the stress of the unknown. How quickly am I going to lose my vision? Is there anything I can do about it to slow that down? Caring for their family, obviously losing the ability to drive, all these things that I think couple into a concurrent epidemic in this country in older people is this epidemic of loneliness. When they have vision loss associated with their geographic atrophy, they actually tend to withdraw a little bit, and it exacerbates their ability to socially interact with others, and I think exacerbates the loneliness that is also going on here. A lot of these things, of course, as you can imagine, are multifactorial, but point being, huge and profound impact on the patient's quality of life. If you could go to the next slide, please. This is not only a significant but a rapidly growing unmet need. In the U.S. there are about 1.5 million people affected by geographic atrophy. Actually, slightly more than that in the EU, two and a half million people, over eight million people worldwide with geographic atrophy. Of course, here in the U.S. we do have two FDA-approved medicines. In Europe, no FDA-approved medicines, nothing available really outside the United States. We are talking about one in 100 patients over the age of 50 of Americans have advanced AMD, and this incidence is projected to increase again, as that baby boomer population hits older age and as lifespans continue to increase. So, it is really important to keep people as functional as possible over that lifespan. If you go to the next slide for me. The ARCHER II study, I know Lloyd is going to talk a lot about that in the next section. The primary endpoint of this study, unlike the SYFORVE and IZERVAY studies, which was anatomic, this is functional, and it uses the proportion of patients losing three lines of vision or 15 letters. That has been a gold standard, and the reason the FDA uses 15 letters or three lines of vision on the eye chart is that is a well-recognized standard for significant vision loss or on the other hand, significant vision gain. We know visual acuity, when you are talking within a few letters, can be a little bit of a noisy endpoint. Sometimes patients do not recognize, let us say, three, four, five letters of vision change. But 15 letters, the reason the FDA has long accepted this, and you can see actually this same endpoint, proportion of 15-letter losers, was the primary endpoint in the LUCENTIS trials, the original drug for wet AMD. So, it is a well-established endpoint. You can see here, even the studies that use mean best corrected visual acuity change, this is what we're used to talking about, this is what we're used to thinking about, and frankly, this is what we care about. It's a lot easier to talk to a patient about, "Hey, this is a treatment that can improve your vision or help protect against vision loss." You can see here the NA there listed against SYFORVE and IZERVAY. Those had an anatomic primary endpoint looking at the growth, the change in the size of the geographic atrophy, but they were not able to either show or establish any functional benefit in those studies, in the two years of those studies. We're talking about, of course, significant vision loss of independence, the ability to read, to drive, and the independence that you lose when those things happen. The way they've defined it, Lloyd's going to talk a little bit about this in his section as well. Again, you basically confirm the 15-letter loss at two consecutive visits, and then we know that this is a kind of a true and real and stable effect, and it's a way to kind of further validate and kind of remove the noise in any visual acuity endpoint. Finally, if you could go to the next slide for me. As we've talked about, SYFORVE and IZERVAY, I think because of the lack of vision protection and vision benefit, coupled with, frankly, the safety issues that particularly arose with SYFORVE, but have also been reported with IZERVAY, we're talking about roughly 10% of the patients with geographic atrophy in the U.S. are actually being treated today. That is in part because to sit there and talk to a patient about, "Hey, we can slow lesion growth, but we can't have an impact on your vision, and by the way, you're taking some significant risk." Both SYFORVE and IZERVAY are pegylated molecules. They have this large peg that helps keep them in the vitreous. A lot of us hypothesize that this is associated with some of the safety issues that are seen with SYFORVE and IZERVAY. Both SYFORVE and IZERVAY, I should mention, are 100 μL injection volumes. Our standard anti-VEGF injection volume is 50 μLs. In general, I would say less is more, because every time you're injecting into the eye, you're temporarily increasing the pressure in the eye. What's nice about vonaprument, in addition to obviously being a visual acuity, a functional endpoint, is it's a 25 μL dose. It is a Fab fragment antibody. This is basically the same as LUCENTIS. I think all of us in the retina community view LUCENTIS as the gold standard from a safety standpoint on the anti-VEGF side of the ledger. There's a lot of kind of confidence and trust in the Fab kind of type of platform for treating retinal diseases. It's not pegylated. It's got a low viscosity. We saw in the phase II ARCHER 1 study that it was very well tolerated, in addition to having this profound protective effect on visual acuity. So, I think there's just a tremendous amount of excitement in the U.S. I know my European colleagues, where they have nothing right now to treat geographic atrophy, are perhaps even more excited because in Europe, they require a functional endpoint to receive FDA approval, or to receive EMA approval. I think this kind of spans both sides of the pond, that there is a lot of enthusiasm and excitement for a new standard of care here for our patients with geographic atrophy. With that, let me pass it over to Lloyd to walk through the program. Roger, thanks so much for your clinical insights. Very astute, and it really helps ground us in terms of the importance of treatment for geographic atrophy, really an unmet medical need today, and really the largest unmet medical need in the retina space as we treat patients in the clinic. I am going to go through today some important data from the phase II study and then put that in perspective of as to how it has shaped the planning for the phase III. Let me call out some key topics from my presentation today. First, our vonaprument program is the only GA program to demonstrate vision protection across a wide range of functional measures. Today, first, we will review the mechanistic rationale for that functional protection. We will review key anatomic data demonstrating protection of photoreceptors, particularly those in the central retina critical for visual acuity. Finally, we will review some exciting directional dose-dependent vision protection data across multiple measures. Next slide. Annexon was founded based on the discoveries of our scientific co-founder, Dr. Ben Barres, the chair of neurobiology at Stanford. He described the key role C1q has in neurodegeneration. C1q binds to neurons and tags them for elimination in normal development as well as disease. C1q has been implicated in a number of neuroinflammatory and neurodegenerative diseases, many of which are listed on this slide. Important to remember that the initial clinical studies inhibiting C1q were performed in the eye on glaucoma patients 10 years ago. As Douglas described earlier, we have a robust pipeline targeting C1q in the brain, body, and eye. But today's discussion will focus on vonaprument, our geographic atrophy asset. Next slide. Let's look at the mechanism of disease in geographic atrophy. This is a cross-section histology of the retina in a patient with GA. We have three regions here. First, on your right, an area of geographic atrophy. Most notably is the complete loss of the green band, the retinal pigment epithelium. On your far left is basically normal retinal anatomy with intact RPE, healthy photoreceptors in blue, and synapses in red. The area in the middle is that of reduced function, and that is critically important here. The RPE is still present, but working left to right, we see decreasing numbers of photoreceptors in blue and synapses in red. This is where photoreceptor function and vision loss occurs. Here, we demonstrate that GA is a neurodegenerative disease where photoreceptors are lost first. Photoreceptor loss equals vision loss. In contrast, RPE atrophy is a lagging indicator of disease progression. Over top the area of atrophy, the synapses are gone. We must intervene in the area of declining photoreceptor function with a neuroprotective drug to make an impact in this neurodegenerative disease. Next slide. In the ARCHER phase II study, we saw strong photoreceptor protection with vonaprument. Ellipsoid zone, or EZ, as measured by OCT, is a reliable objective measure of photoreceptor health. It is the most appropriate anatomic endpoint when considering the drug effect on visual function. Across the entire macula, we saw a 27% reduction in EZ loss in the vonaprument group compared to sham, demonstrating a strong biologic effect of the drug on key retinal anatomy. Importantly, as we look at smaller central regions of the macula, those critical for reading and visual acuity, we saw increased photoreceptor protection. It follows that a drug that protects central photoreceptors is also one that protects central visual acuity, since that's where vision lies. This objective measure builds confidence in the ability to replicate visual acuity results in the phase III ARCHER II study. Next slide. A number of pre-specified functional endpoints were evaluated in ARCHER. Let's look at two of the most important. First, on your left, you see the proportion of confirmed 15-letter loss events in the phase II treatment groups. We saw strong dose-dependent vision protection with vonaprument. Comparing the sham and monthly treatment groups, this translated to a 73% risk reduction of clinically significant vision loss in patients receiving vonaprument. In addition to these important data points, we saw directional, dose-dependent vision protection across a wide array of functional measures. This highly consistent clinical effect builds confidence as well as we move towards the phase III readout. We know that geographic atrophy is a heterogeneous disease. We are encouraged that vonaprument demonstrates vision protection across the entire spectrum of disease. In the next two slides, we're going to look at heterogeneity a couple of different ways, both structural and functional. In terms of structure first, the natural history of GA tells us that eyes with foveal RPE atrophy have the highest rates of vision loss. We defined foveal in the phase II as eyes where RPE atrophy touched the geometric center of the fovea. Meeting that definition, 25% of foveal eyes in the sham group had confirmed 15-letter loss events, compared to 5.9% in the monthly group, a nearly 20% delta. In the non-foveal group, events, as expected, were less, but we still saw a strong treatment effect. This data underscores the importance of including eyes with foveal disease in our development program, one based on protection of visual function in a population at risk for vision loss. Now, let's look at heterogeneity a different way, from a functional perspective. Low luminance visual deficit is a composite functional measure defined as the difference between BCVA, best corrected vision, and low luminance visual acuity. Eyes with LLVD less than 30 generally have healthier photoreceptors. When looking at eyes with more severe photoreceptor dysfunction, or LLVD greater than 30, we again see high rates of vision loss in these eyes with more severe disease, but a robust treatment delta of nearly 15% in these sick eyes. In contrast, in eyes with healthier photoreceptors, the treatment effect was dramatic, with no vision loss events in the vonaprument group during the phase II. Pay attention to these subgroups, foveal disease and LLVD less than 30, as we look at baseline characteristics in a few minutes. Next slide. Finally, this is what we refer to as our off-treatment slide. The percentage of 15-letter loss visits was plotted against time here from the phase II. What did we see? We see clear separation of the active treatment groups in blue and red, beginning most notably around month six. By month 12, the separation is quite prominent. As a reminder, in the final six months of the phase II, all patients were followed off treatment. During this final six months, vision loss resumed in all three groups at the same rate, without treated eyes catching up. This demonstrates a disease-modifying effect of vonaprument that we look to see as we extend treatment intervals to longer time points. Next slide. Let's go into some specific details about the phase III trial that increase our probability for success. We are really pleased with the design and execution of ARCHER II, our registration study for vonaprument. Enrollment was completed two months ahead of schedule and was over-enrolled by 30 subjects. Combined with very low attrition during the first 12 months of the study, we have found ourselves with a larger, longer study with greater statistical power. We have applied that additional statistical power to a second time point at month 24 in order to establish alpha control for regulatory flexibility and labeling strength of those efficacy endpoints. ARCHER II has a fully aligned global regulatory pathway. We have Fast Track status with the FDA in the U.S. as well as PRIME designation and selection for the important product development coordinator program in Europe. In the next few minutes, we'll review some data from both the phase II and phase III, which give us confidence going into the ARCHER II readout. Finally, as discussed earlier, GA is a heterogeneous disease, and we have controlled for that in the phase III by enrolling the right types of patients with very similar characteristics to the phase II cohort. Next slide. Here's the design of ARCHER II, the phase III registration program for vonaprument. We've enrolled a total of 659 patients, randomized 2:1 active treatment versus sham. The primary endpoints confirmed 15-letter loss at two consecutive visits are at month 15 and month 24. Our base case remains month 15, with the majority of alpha allocated there. We allocated excess statistical power accumulated during the course of the study at month 24 without disadvantaging month 15. We are the only GA program with a global regulatory path with Fast Track designation and PRIME designation, as discussed earlier. In addition to the gold standard endpoint, BCVA, we are also evaluating key secondary functional and structural endpoints. Next slide. We've recently released baseline characteristics for the phase II ARCHER study depicted on this slide. Overall, we've replicated clinical characteristics with the phase II, with one important difference. In the phase III, we excluded subjects with visual acuity below 20/100 because their vision is so poor, they don't have much to lose. As you review our treatment effects in the phase II, remember that roughly 20% of those subjects were below 20/100, diluting the treatment effect seen in patients with better vision. The net result for this change, and only change, is that the mean BCVA is slightly higher. Otherwise, the two studies are very similar, and I want to point your attention to the two subgroups we discussed earlier. First, we enrolled nearly identical numbers of patients with foveal disease, a group in which we saw a 20% treatment delta. In the less severe LLVD less than 30 group, again, virtually identical enrollment in a subgroup that experienced no vision loss with vonaprument therapy in the phase II. These baseline characteristics allow us to position the phase III ARCHER II study as a replication study to the robust vision protection benefits we saw in the phase II. We have recently updated ARCHER II to add a second primary endpoint at month 24 to capture efficacy under alpha control. Why do we like this change so much? First, we maintain full confidence in month 15. Month 15 remains our base case, and the majority of alpha is still allocated there. If we had lost confidence in month 15, we would have simply moved all alpha to month 24. The graph on your left depicts the power of the extended endpoints. We have plotted the phase II primary outcome data here in the dark lines out to month 12. Based on our understanding of numerous natural history studies, confirmed 15-letter loss occurs in a linear fashion with a similar slope out past two years. This allows for widening of the treatment delta as you move out to longer time points, allowing the ability to demonstrate a widening treatment effect over time. On your right, key features of ARCHER II designed for success. First, in the phase III program, we have a trial that is three times larger than the phase II. We have established detailed estimates of sham and treatment event rates at the outset of the study, and they have held true throughout, giving us confidence in our understanding of the disease. By allowing for linear progression over longer time points, the selection of month 15, and ultimately adding month 24, allows for expansion of the treatment delta over time. This is a critical feature of our current trial design that de-risks ARCHER II going into the data readout. I wanted to take a moment to review our regulatory pathway. We have separate, fully aligned strategies for the U.S. and for Europe. Let us start first with Europe, on your left. We plan to file on a single analysis of the total protocol of 659 patients. In order to satisfy the FDA's convention of two separate studies, the agency suggested that we split our single study into two sub-analyses with a pre-specified plan. We are randomizing at the site level and are using the number of patients, the number of events, and stratification factors to create two cohorts with very similar baseline characteristics. This strategy, fully aligned with the FDA, allows us to minimize the likelihood of a split result when performing these sub-analyses. Also note, we have greater than or equal to 90% powering of the sub-studies at both month 15 and month 24. Next slide. What is going to happen in the next few weeks in terms of data readouts and public announcements? Let me walk you through it. We will run the single analysis of 659 patients, and we will announce either a win or continue in the fourth quarter of 2026. With a win on the single analysis, this establishes a pathway for approval in Europe and demonstrates overall clinical utility of our drug, vonaprument. Then we will initiate the two sub-studies, and the process will begin again with the DMC first seeing the results, and then Annexon announcing either a win or continue. That will occur in the first quarter of 2027. With a win on all three analyses, we will unmask the study, release more detailed data, and prepare for regulatory filing. If any of these three analyses are not positive, we will continue the study completely masked until month 24 in order to protect data integrity and the regulatory value of the month 24 endpoint. Well, those are some of the key important updates as we move into the data readout of the phase III ARCHER II program. Wanted to review some of the baseline data from the phase II that informed our design and our strategy. We look forward to our data coming in the fourth quarter of 2026. With that, let me hand things back to Douglas. Thanks, Lloyd. Thanks, Roger. Really nice job. As many of you know, as Roger spoke to, GA affects more than eight million people worldwide, as you can see here on this slide. It is important to note that this just represents the numbers at a patient level and not the larger eyes opportunity due to patients with bilateral disease. That alone has the potential to increase the commercial opportunity by roughly 30%. Overall, we are energized by this unique opportunity to serve this large and growing patient population, and we anticipate positioning vonaprument as a replacement therapy for the currently approved therapies and a driver of market expansion. As Dr. Goldberg alluded to, none of the current therapies show a clear functional benefit, and greater than 80% of GA patients today remain untreated. Lastly, we are keenly aware of the moat that we are building around vonaprument upon positive data at launch and at launch, with the first-ever vision protection data in GA and a long IP tail into the 2040s. There are no other current drugs in development with BCVA 15-letter loss as a primary endpoint, which will have to be demonstrated at 24-month endpoint, and thus raises the bar further. Our vonaprument program, that started out as a big idea about a decade ago, is now at the doorsteps to becoming a very large program that helps millions of patients live their best lives, which motivates us daily. Next slide. Indeed, we are playing to win, is the short answer here. Among other things, we continue to add to our deep retina expertise with the addition of world-renowned and generational leader, Dr. Mark Blumenkranz, who has joined our board of directors, and retina and neuro expert, Dr. Nora Lad, who has joined our scientific advisory board. Both of these individuals have and continue to play and provide invaluable insights into the development of this program and other related ophthalmic programs. One of the things we have not talked much about with our portfolio is, we are not just a GA drug in ophthalmology. As Lloyd went through the mechanism of action and showed the impact of C1q in protecting synapses and neurons in the eye, that plays out in multiple diseases, including glaucoma, retinitis pigmentosa, et cetera. We are excited about really developing a dominant franchise. Also excited about the continued growth internally, where we have gotten stronger with some recent additions. Returning to the fold is Dr. Don Fong, who runs our ophthalmology clinical development program. Don was the clinical lead for the ARCHER phase II program, and we are delighted to have him back to close out the phase III program. Last, but certainly not least, we are thrilled to have brought on Jake Schumacher to lead the ophthalmology franchise. Jake joins us after a long and successful track record, having led VABYSMO to blockbuster status for the treatment of wet AMD, and more recently served as the commercial lead for IZERVAY in GA. Jake brings a wealth of strategic experience and success to the AMD space, and he has hit the ground running. Together with the talent already on board and more to come, our team is built for the transition from pivotal data to commercialization to mega blockbuster status, and we are fired up about getting after it. With that, we will bring this to a close, the prepared remarks, by just punctuating, this program has been intentionally designed and executed for success. We are leveraging a differentiated mechanism of action. The phase II demonstrated dose-dependent functional benefit on several measures, including impact on the key structural measures associated with visual acuity. We have learned from all the prior studies. Although they were structural studies, there were learnings from those that we have informed to this vision study, and we have intentionally designed a larger, longer, and well-powered phase III study to replicate the phase II outcomes. With eight million patients and growing in need of a vision-improving treatment, this program is positioned to achieve rapid and durable game-changing status, creating value for patients worldwide, as well as those who are participating with us. With that, we thank you for your attention, and we will now open the call up for Q&A. Operator, we will turn it back over to you. Thank you, Douglas, and to our speakers. at this time, we will be conducting a live Q&A session. To our covering analysts joining us live, please use the raise hand feature to be added to the queue, and kindly limit your participation to one question per analyst. Please hold for a brief moment while we poll for questions. Our first question comes from Joyce Zhu from JPMorgan. Please go ahead, Joyce. Great. Hey, guys. This is Joyce on for Anupam. Thanks for taking our question and for the presentation this morning. First, for the KOL, Dr. Goldberg, I was wondering if you could speak to, from a compliance perspective, how is compliance currently in your patients on one of the approved therapies? Then with the ARCHER II study appearing to have really strong compliance, how do you envision that will translate in the real world if approved? Then just one for the team. If you could clarify what dropout rate you are assuming at month 15 versus month 24 for powering purposes. I see on your projection slide at month 24, it seems like you are expecting sham to be in the 30%-35% range. Could you just speak to your confidence in those projections and in a growing treatment effect with vonaprument? Thanks. Yeah. Thanks, Joyce, for that question. Dr. Goldberg, you want to start with talking about compliance, just currently approved therapies, as well as with regard to vonaprument in the phase III study? Sure. So, great question. It is interesting. This is an area, I think, where my own clinical experience sometimes does not necessarily ring true with the kind of large real-world database studies, which show about 50% of patients with the current agents, SYFORVE and IZERVAY, stop treatment after a year or within a year of being on therapy. Remarkably, this is quite similar to the number of patients who drop out with wet AMD treatment. So, you would think in wet AMD, you would have better compliance, just due to the fact that you can actually kind of gain vision and the patients lose vision more quickly. Yet we see very similar numbers. I say it does not ring true in a sense because I am only seeing the patients who show up and who come in for their care. Sometimes I think clinicians are a little bit kind of almost blind to the patients who are missing all their visits and stop coming in for care. I think with SYFORVE and IZERVAY, again, because we do not have any best corrected visual acuity data to hang our hat on, it is really around just kind of like the lesion growth and showing them the lesions versus some actual kind of talking points around vision. "Hey, if we stay the course here, if we go through, whatever, 15 months or two years of treatment, we can significantly reduce the risk of you losing vision." I do think that will be an easier conversation to help keep patients on therapy. Douglas, I will hand it back to you or Lloyd to discuss the, I guess, what you are seeing in the phase III study. Yeah. Thanks, Roger. Yeah. Just quickly, I will tee it up, and Lloyd, I want to get you in on this, Joyce. We have not disclosed what our projected sham rates are at month 15 or month 24. We certainly have used month 12 as a benchmark for us, as well as looked at data from a host of other studies. As Lloyd alluded to, the way we have built our rates have really come from both the prior studies and assessments of RPE growth, et cetera, as well as the visual measurements in our phase II study. We are the only company who has been able to pull both of those together. A lot of folks have done their own independent work, but they do not have the phase II data we have. We think we have a more grounded understanding of what that rate could be. Maybe, Lloyd, I will just turn it over to you to see if you have got anything you want to add into this. Absolutely. Totally agree. I mean, in terms of specifics for this slide, I want to be clear that what we did here was we plotted the actual data from the phase II study as an example. This is not our sham event rate projections. We used a battery of data to establish a more conservative sham event rate to power our study into phase III. We did this purely for demonstration purposes, but it is also important to note that in a number of natural history studies, the progression of confirmed 15-letter loss event rates continues well past year two in a near linear fashion. This is really for demonstration purposes. Using the phase II data as an example, we have used more conservative estimates for phase III powering. Understand that this is not specifically what our estimates are. In terms of your discontinuation rates, important question. We have really been encouraged by the lower numbers of discontinuation rates in the ARCHER II study at 12 months, and that was an important review that we did in the summer. We see mid-single digits discontinuation rates in the phase III study, significantly lower than we saw in our phase II study of around 15%, significantly lower than the other registration programs. I think it speaks to the excitement of the ability to potentially offer vision protection. It also speaks to a lack of treatment options outside the U.S. So, we do not have a clear sense of what month 24 will look at, but we anticipate that it will be lower than historical norms. Thanks, Lloyd. Great. Thanks for taking our questions. Thank you, Joyce. Our next question comes from Derek Archila from Wells Fargo. Please go ahead, Derek. Hey, good morning, and thanks for taking the questions and putting together this event. Just a couple from us. Maybe just first off, can you discuss the level of alignment you have with the EMA under the PRIME designation around the amended ARCHER II design? Then the second question is, if month 15 doesn't hit stats in the overall trial, can you walk us through what happens to the alpha at month 24? Does the alpha carry forward, or is there a threshold that's already pre-specified? Thanks. Yeah, I'll start with the first one, and then Lloyd, to you for the alpha. With regard to EMA and alignment, full alignment on a single study approval with a good outcome in this study. Just with regard to the amendment, we had had prior discussions with EMA and the FDA. This study, as you know, was already a 24-month study, with safety being the primary reason for 24 months. We had asked could we add efficacy in at month 24, and it was told to us that we needed to add alpha to do so. That's why we added alpha, to ensure we could get 24 months into the label there. We've since sent the updated information to EMA, and we have alignment with regard to that as well. What has been important, both for EMA and the FDA's perspective, is that we maintain the data integrity of the study, and that is why we are releasing the data in the fashion in which Lloyd alluded to previously, where we are masked at the company until we have full outcomes of success on the overall study and the two sub-studies. But with regard to how we are doing it and ultimately getting it into the month 24 label, we have alignment there. And then Lloyd- Yeah, Derek- it's open to you. Yeah, sorry. Yeah, Derek, thanks for your question about the alpha split. In order to satisfy a dual primary endpoint strategy, we have to pre-specify alpha at both time points. We have allocated a majority at month 15. We do have significant alpha at month 24 for the single analysis. We are really relying on that treatment delta from slide 27 that we talked about earlier, really to drive power. This really is incredibly and there is a lot of power here in terms of time. Time is incredibly important in a study like this where you accumulate sham event rates. We really are leaning heavily on the increased treatment delta that we anticipate seeing at a longer time point to drive power at month 24. Got it. Thanks, guys. Thank you, Derek. Our next question comes from Andrew Tsai with Jefferies. Please go ahead, Andrew. Thank you so much. Maybe a few more questions around this upcoming analysis. In the positive scenario, to be clear, you will PR when the single study hits in Q4, PR when two sub-studies hit in Q1. To be clear, the question is, when exactly would we have, in this scenario, positive scenario, detailed top-line data on the overall study as well as the two sub-studies? Secondly, assuming month 15 is also positive again, you hit stat sig, the study will continue to month 24 still. In this scenario, will you have thus become unblinded such that month 24 can be nominally stat sig, or can it still be fundamentally stat sig? Thank you. Yeah, great question, Andrew. I'll start, and Lloyd, get you in on this as well. We anticipate having the full study data, as we said, in Q4 here on this slide, and the sub-study data in early Q1 on this slide as well. Assuming both of those studies are positive, we will unmask a segment of the organization to begin filing the BLA for review, as with both FDA and as well as with Europe, with the EMA. It won't be the entire organization that will be unmasked, but there will be a designated group unmasked to do that to maintain data integrity, which leads into your question with regard to month 24. Fully expect, with the way that we are maintaining data integrity, that with a win on month 24, that also will be deemed a positive outcome, which will go into the label not as a nominal positive outcome, but a full positive outcome. We anticipate, again, going back to this overall moat strategy of having data in the label that covers both month 15 and month 24 at the overall study level as well as at the sub-study level. Yeah, just a couple of details, Andrew. Thanks for the question. Remember that after we do these top-line announcements, first in Q4 and then in Q1 of 2027, we'll have to start the clock in terms of analysis of the TFL. We will get that data to you very shortly in a very timely fashion, but there will be some data analysis that will have to occur after this sort of top-line DMC announcement. But we'll get that to you in very rapid order. As Douglas alluded to in terms of the month 24, remember that the patients will still be masked to treatment out to month 24. The investigators will still be masked out to month 24, again, consistent with the initial design of the ARCHER II study. And this has been done in other programs. Actually, one of the reasons why we're doing this in a very detailed fashion was to avoid the need to potentially use unmasked clinical data later after the study was totally unmasked. The way Douglas laid out the strategy is very clear. We are going to protect data integrity out to month 24 in order to have it available for a regulatory tool as well as for labeling. Thank you. Thank you. Thank you, Andrew. Our next question comes from Tazeen Ahmad with Bank of America. Please go ahead, Tazeen. Hi, good morning. Thanks for hosting this event. A couple of questions from me. Can I ask about a scenario in which your data is statistically significant at month 15, but for whatever reason, not at month 24? How should we interpret that in terms of durability of response, and what would your interaction with FDA look like in that instance? Then I'll have a follow-up on commercial opportunity right after. Yeah, good question, Tazeen, and obviously, we'd factor that in, which has always been the case given that this was a 24-month study from a safety perspective, that the primary is at month 15. So the topic you're raising has always existed, and based on this slide in particular, as well as a bunch of other analyses that we've done, that's a highly unlikely scenario. As Lloyd alluded to, the sham group is going to continue to lose vision, and over time, vonaprument's treatment effect is going to continue to grow. So we think it's highly unlikely. That being said, if that were to occur, we would still and have had the discussion with the FDA on filing in Europe with month 15, with vision protection out to that time period. That in and of itself is a benefit, and so we would be encouraged by that. But I think ultimately, it will be a fact-based discussion looking at the totality of the data, what you have done on the primary endpoint, what you have done on some of the structural assessments, as well as some of the other secondary endpoints like low-luminance visual acuity. Lloyd, I do not know if you want to add anything to that. No, I think that is a great explanation. We, again, with positive data at month 15, we demonstrate the clinical utility of the drug and that it has a neuroprotective effect. Given the significant accumulation of vision loss in that remaining nine months, it is just very unlikely for that scenario to occur. Okay. The reason I ask is because IZERVAY did have an observation of a perceived benefit at month 12. Yeah That benefit gap closed by the time they revealed month 24 data. So wanted to get your thoughts on that. Obviously, different programs in the study. Yeah. Yeah, it's a little different scenario in the sense that they did demonstrate vision protection at a year that was lost at two years. It's important to note that their overall vision loss rate in the sham group was very, very low. We see that 12-month result in the IZERVAY programs as somewhat of a statistical anomaly. Their sham event rate was only 8%, so that really is not consistent with a wide spectrum of patients with GA. It is consistent with the patient population that they enrolled. The other point, just quickly on that, not to pile on, but that was a post hoc analysis. You actually don't know what was demonstrated, right? Versus a sham-controlled prospective analysis, which is what we did here. We take your point nonetheless. Okay. Thanks for the color. On commercial, for you guys as well as Dr. Goldberg, Regeneron does have a product that it hopes will be part of the mix for GA treatments, cemdisiran, which they want to deliver systemically within frequent dosing. To the doctor, how do you think about the commercial viability of that product, especially if this drug from Annexon is also available? Thanks. Maybe before you go, Dr. Goldberg, let me just quickly say, is the way I understand it, the primary endpoint for that study is a structural endpoint, i.e., protection against RPE loss. I think the same topics arise with the currently approved therapies in that- Right you're still not providing function or independence to patients. The fact that you're doing that with less frequent dosing doesn't overcome what is the primary concern for patients. Maybe Dr. Goldberg, you should weigh in on this. Yeah. First of all, I think I was going to make the same point, which is that program from Regeneron and pretty much all the other programs in earlier stage development are using structural endpoints, not a functional endpoint. I do think this program still stands alone in its ability to be able to show a functional benefit. Number two, I would add, which Douglas didn't mention, is retina specialists feel very comfortable delivering therapies to the eye. One of the advantages, although kind of in theory, patients kind of, quote unquote, "don't like getting a needle in the eye," is they have very little, as close to no systemic side effects as possible. Because although we deliver a large dose to the eye, we deliver a tiny dose to the rest of the body. I'll tell you that retina specialists don't feel very comfortable managing systemic side effects and systemic risks. I think when you introduce a systemic drug, like these subcutaneous interfering RNAs and other approaches, you're talking about a whole host of systemic risks that the retina doc won't feel comfortable with. I think if there's an option out there for local therapy, it slots much easier into our existing workflow, and sits kind of in our comfort zone. I don't know, Lloyd, do you have anything else to add on that? I know you wear both hats here, but Oh, yeah. No, I totally agree with you. The other issue is systemic therapy from the other side. Systemic therapy offers significant safety issues in this older population in terms of risk of infection, need for vaccines. There's a number of sort of practical issues that make systemic therapy in this space, I think, very challenging for these patients. Great. Thank you. Thank you, Tazeen. Our next question comes from Salveen Richter with Goldman Sachs. Please go ahead, Salveen. Thank you. Good morning. On the 15-letter loss over time, as we think about the separation from 12 - 24 months, perhaps just walk us through your views on what the separation of the curves could look like and expectations on variability. Then for Dr. Goldberg, on the commercial front, how do you view the lack of lesion growth slowing in the context of vision preservation for your patients? Yeah. Two good questions, Salveen. Thanks for joining us. Lloyd, first over to you, just how we think about kind of the variability around the sham rate and the treatment rate over time from 12- 24. Yeah. Salveen, thanks for your question. Let's start with, we'll talk about sham event rates, then we'll talk about event rates in the treated group. In terms of sham event rates, we know two things. The first thing we know is that based on numerous natural history studies, that these patients continue to have confirmed 15-letter loss, vision loss events at a near linear fashion past two years. That occurred in the lampalizumab studies. It occurred in other natural history studies as well. That is well understood in terms of the natural history of geographic atrophy. The other piece that we know from our work, looking at post hoc analyses in the ARCHER study, is that once a patient loses 15 letters at two confirmed visits, they don't come back. It's actually not. That's the whole point of the confirmed definition here, is to eliminate noise and variability of the endpoint in this patient population. We fully recognize that visual acuity at a single time point can be a very noisy measure. But this confirmed at two consecutive visits is really what filters out a good bit of the noise. Our experience in the phase II study is that almost 50% of first 15-letter loss visits are not confirmed at the second visit. So, those are the two factors related to the sham events, which I think are very important as you go into the phase III. In terms of the treatment effect, obviously, we've observed directional, dose-dependent functional benefit of vonaprument across a broad range of functional measures. We anticipate seeing a significant reduced rate of events in the treatment group compared to the sham group over time. We also have clearly demonstrated a disease-modifying effect of the drug. We do have confidence that the effect of vonaprument in this patient population is durable, is chronic, and will hold past 12 months. Lloyd, if I could just jump in and address the second part of your- Yeah Question, which was around the fact that the phase II ARCHER I study, the original primary endpoint was growth of GA lesion on fundus autofluorescence, which missed, even though it showed this profound vision protection effect. I will be honest, count me in as kind of an initial kind of skeptic of like, "Geez, how did they show this vision protection effect without slowing the lesion growth?" I think, to my mind, Annexon has done a phenomenal job going back and looking at the photoreceptor data, not the RPE data, because fundus autofluorescence measures RPE lesion growth. We actually know from even the SYFORVE and IZERVAY programs, it is not just Annexon saying this, that photoreceptor loss precedes RPE loss. Lloyd kind of went through the critical real estate, which is the central 1.5mm and 3 mm of photoreceptors, and it actually is showing a structural benefit in those patients that then is very consistent with, okay, that explains why we are seeing a functional benefit. So I think that is really supportive evidence to me that actually there is a structural explanation for why we see this. It often gets glossed over, but I actually love the slide that Lloyd showed, really like the first one where it is like the histology. Yes, this one. Thank you. Where you can actually see that the photoreceptors are getting lost first, and those photoreceptor synapses, and that is what C1q does, is it comes in and it strips out the photoreceptor synapses. You lose like the functional connection between the photoreceptors and then these amacrine and bipolar cells, this kind of intermediate layer of neurons. By blocking C1q, you actually protect those synapses and help maintain the photoreceptors. So I think they actually have gone and shown that. Obviously, if we can show that in phase III, both the functional with a structural explanation of why, I think that will be very well accepted and makes a lot of sense. Salveen, one last point on your question. It was a good question. We did not show statistically significant benefit on RPE lesion protection from baseline to month 12. It is important to remember, though, that during the final six months of the phase II, we demonstrated a 10.5% reduction in RPE lesion growth. We believe that that is consistent with our mechanism of action, where we protect photoreceptors first. By protecting photoreceptors, we protect this bidirectional cellular relationship between photoreceptors and the RPE. So think about it as a secondary protection of RPE atrophy. By protecting the photoreceptors, we secondarily protect the RPE. We anticipate seeing further RPE lesion protection in a longer study. But that second six months is very encouraging and consistent with the mechanism. Well said. Thanks, Clark. Thank you. Our next question comes from Philip Nadeau with TD Cowen. Please go ahead, Philip. Good afternoon, and thanks for hosting the session. Two from us also. First, for Annexon, would you be willing to share the ARCHER phase II data, the treatment effect for the patient population who had BCVA over 45? So, eliminating those patients who are being eliminated in the phase III trial, what does the treatment effect look like? Second, for Dr. Goldberg, again on the treatment effect, what is the minimum treatment effect you want to see to think that the drug has a clinically meaningful vision preservation? Is it any statistically significant benefit, or is there a certain magnitude that you think is necessary to drive adoption? Thank you. Yeah, maybe we start with the question to Dr. Goldberg first, and what you would think is a clinically meaningful outcome on BCVA 15-letter loss. Yeah, on the one hand, I'll tell you, just anything that's good enough to get it approved is going to be well received, because what that does is it puts a tool in our toolbox, and it allows us to have that conversation with patients about, "Hey, we now have an FDA-approved medicine. It can protect against vision loss." One of the nice things about a really large clinical program like this is, we're going to then do post-hoc and secondary analyses up the wazoo, frankly, to figure out who are the patients most likely to respond and get that vision benefit, or conversely, who are the patients most at risk of significant vision loss, and therefore, are the ones we want to make sure we're intervening in. So to some extent, I'll say, "Hey, anything that gets the drug approved is going to be well received." Then it's just about kind of the magnitude of the proportion of patients is the magnitude of the response, excuse me, is going to impact kind of the proportion of patients that we consider this a great treatment for. So, I'm kind of slightly avoiding the answer, but obviously, they showed what, 65% reduction in the risk of significant vision loss, and I think- 73. 73, sorry, Douglas. I don't think it has to be that high. Obviously, that's a tremendous difference, but here, the absolute risk is 16.9% down to 4.5% in the monthly group. So, I think that would certainly be plenty sufficient to be, again, kind of adopted. Then particularly, this kind of came up, I think, in one of the earlier questions. Particularly, as Lloyd said, if we see that effect size increasing over time, I think that's going to actually add to the, not just the statistical power of the study, but actually the power, the impact of the study that, hey, this is a really important drug over time to keep your patients on, and I think that'll actually help drive kind of compliance and adherence to therapy. Yeah, really good. Really good question, Phil. Your second question is just with regard to the analysis with patients who are 45 or lower, about 20% in the phase II. Post-hoc analysis, we've resisted releasing too much post-hoc data. In fact, we've released very little. Most all the data we've released has been pre-specified. But what we can say is, the data get a bit better. They're a bit stronger when you drop out that 20, 23% of patients who had no event, 15-letter loss, confirmed 15-letter loss. Now, recognize that those patients were both in the sham group and in the treatment arm. So the data are directionally better, but at this stage, we don't feel like there's much advantage in releasing another post-hoc analysis. Yeah, Philip, they were well-balanced across the three treatment groups. That is perfect. Thank you. Thank you, Philip. Our next question comes from Joseph Stringer with Needham. Please go ahead, Joseph. Hi, thanks for taking our questions. Just as a follow-up question to one of the earlier ones, just on the BCVA ≥15 primary endpoint, can you speak to the clinical and commercial importance of the relative risk reduction versus the absolute risk reduction? Also, is there a range for, say, the number needed to treat that you would consider commercially meaningful in this indication? Can you just quickly repeat the second part of that question, Joseph? I want to make sure I understood that. In terms of the number needed to treat, is there a range that could be commercially meaningful in this indication? I am not sure I understand that question, but let's take the first one first, and the relative risk versus actual risk here. Lloyd, do you want to- Sure, yeah. Well, Joseph, great question. The first way to look at this is that really, from a regulatory perspective, the simple proportional difference is really what makes the most sense to us from a regulatory perspective in terms of a clinical trial endpoint. But to your point, the hazard ratio and the risk reduction, I think, are incredibly important data when we talk to patients, when we talk to physicians, to understand the real clinical utility, to bring it down to a patient level. For me, when I talk to folks about this program, that 73% risk reduction is an incredibly important number, as you sort of bring it down into a more humanistic discussion about what this drug can do for individual patients. Your other question was about needed to treat, and that's an interesting question. And one of the things that we obviously, we want to get our drug approved, and our regulatory endpoint is confirmed 15-letter loss at two visits. However, going a step up, with positive data, we've demonstrated that this drug has a strong neuroprotective effect, which means that it's protecting photoreceptors throughout the retina. It's making the retina healthier. I don't know that necessarily a number needed to treat the endpoint, I don't know that we've come up with a number for that. We believe that any statistically significant difference in a clinically meaningful endpoint, and as Roger alluded to earlier, this endpoint is the gold standard in terms of clinically meaningful endpoint. Any statistically significant difference is clinically meaningful. But with positive data, we've got our first neuroprotective drug in the eye, and that's important globally across the entire retina. I think the number of patients to treat is an interesting conversation, but I think it can help large swaths of patients with dry AMD. Thank you, Joseph. Our next question comes from Pete Stavropoulos at Cantor Fitzgerald. Please go ahead, Pete. Hi, this is Samantha on the line for Pete. Thanks for taking our question. So, question for Dr. Goldberg. For foveal and non-foveal lesions, specifically what minimum percentage reduction in ellipsoid zone loss versus sham at month 15 or 24 would compel you to prescribe? If vonaprument demonstrates substantial slowing of disease progression and preservation of visual acuity, how would that impact which patients you would prescribe to, meaning the stage of disease? Thank you. Yeah, it's a difficult question to answer because in clinic, we don't sit there and measure ellipsoid zone loss. We don't actually have a way to do that. This is something that reading centers and perhaps when we have AI algorithms routinely incorporated into clinical practice, we could probably get some sort of ellipsoid zone measurements in real time as we're acquiring these images and then seeing the patient five minutes later after getting the image. It's a hard question to answer clinically, but I can tell you that the differentiation in the clinic between foveal and non-foveal is very different than the differentiation for these clinical trials, because Lloyd said, "Oh, the way it's defined and the way they defined it here in the ARCHER program and in all the prior studies is the foveal center point," which is to say zero microns from the very center of the fovea. If it was one micron away, it was considered non-foveal, and if it was zero, it was foveal. The way clinically we really define it is foveal is a little bit more based on vision, because a lot of the patients with foveal-involving GA, they have still good vision because they've got a little bit of eccentric fixation, and when they're sitting in the visual acuity lane, they can pick out a black letter on a white background in a dark room when they're trying to read one letter at a time, and that's how we measure visual acuity in the clinic. It turns out that actually, like other factors, and Lloyd didn't talk about this, but something, for example, called macular occupancy, which is how much of the central 1 mm or 1.5 mm or 3 mm of photoreceptors are lost, and when that number starts to it's actually very uncorrelated with vision until you hit high percentage of the central, particularly the central 1 mm being lost, then the patients kind of don't have any room to fixate and find the letters on the eye chart. I think clinically we use visual acuity more if it So they could be 20/40, maybe it's foveal, maybe it's not foveal, but we know that they've got a lot of functional vision there, and we want to do everything we can to protect it. I did not exactly answer the question in part because I do not have a way to assess really photoreceptor measurements in clinic. Thanks so much. The second part of the question was just if vonaprument demonstrates the slowing of disease progression and preservation of visual acuity, how would that impact which patients you would prescribe to? Yes, I think, look, I think if they have already lost, let us say it is very advanced GA and they have already wiped out their macula, like, okay, and they are worse than 20/200 vision, like, probably not a good patient to treat. If they have got some tiny little bit of RPE atrophy, far away from the foveal center point and do not have any symptoms, probably too early to treat. I do not know, maybe of the total population, there is 20%, 25% that are already very advanced. My gut feeling is, I do not know, maybe 20% might be too early to treat, and there is kind of a big bolus of patients in the middle, 50%, 60%, that are good candidates for treatment. I do not think this drug or any drug, frankly, is going to be appropriate for the entire landscape of GA patients. Yes, I guess the only thing I would add onto that, certainly agree, Dr. Goldberg, as you think about patients who are too far gone and they have already lost all their photoreceptors. I think as we see the advent of OCT and EZ imaging where you can assess impact on photoreceptors even before you start seeing demonstrable vision loss, given that this drug has shown a really pronounced treatment effect in patients earlier in the disease process, as measured by LLVD less than 30, we think we are going to have an opportunity to treat patients earlier in the disease when, for example, think about Alzheimer's, a neurodegenerative disease. The earlier in the disease process where you have healthier neurons to protect, the better your outcome. Initially, we certainly are going to be getting after the patients who are tried and true GA patients, but we think this drug has the opportunity to move upstream, particularly as OCT imaging becomes more readily available to give patients and physicians an understanding of their status with regard to photoreceptor health, even before they are having meaningful decline on BCVA 15 letter loss. We want to stop neurodegeneration as quickly as possible, and that is going to prolong the function and independence for patients there. But all of that is marketplace-type opportunities for us as we move forward with regard to that. I think we have one or two additional questions, and we will wrap up. Thank you. Our next question comes from Ananda Ghosh with H.C. Wainwright. Please go ahead, Ananda. Ananda, you may be on mute. Thank you. Thanks, guys, for hosting this. This has been very helpful. I have a couple of questions. I will just run through them quickly. You mentioned about event rate holding strong throughout. How have you been tracking those, and does it tell anything about the treatment arm? What natural history studies are you referring to when you alluded to your month 24 expectation? How have you de-risked the idea that both sub-studies need to hit stat sig? You mentioned about other studies using similar 15, 24-month analysis. What studies are you alluding to? Thank you. Yeah, maybe I will start, and Lloyd, jump in on it. First, just in terms of what we looked at for 15 and 24 months, multiple studies have followed patients out to 24 months, including natural history cohorts. I would say lampalizumab gives you the best sham trajectory. Not 100% apples to apples with our study in terms of patient populations, but close. We think that is a nice landmark in which to consider. I think one of the things that is important here is, Lloyd alluded to before, we put this up for illustration purposes to show what the phase II did during month 12 and how it is projected to go out to month 24. I think what is really important is the point that he made that this is not what is required to win. In fact, the outcomes for the phase III are meaningfully less than what we demonstrated in phase II, based on the size and the powering and the assumptions we took into this to still win in the phase III. This is what it looks like projected out on the phase II, but the phase III does not require this, and I think it's important for people to understand that. We have not said what the ultimate delta is between the sham group and the treatment group on which to win, but I would say, it's certainly much lower than the numbers we've been hearing from many who have done their analysis on this. We're really encouraged about where we are. The event rates are tracking. We are looking at those on an almost every other week basis, and we know exactly where we are with regard to month 15. Plus or minus, we are pretty much right on target, which is really gratifying for us, because what it tells us is that, excuse me, we understand the patient population. We've enrolled the right or desired types of patients, and they are progressing at the rates at which we would expect them to. Bear in mind that this study is a 2:1 randomization, so that's factored into what we would expect to see in the sham arm as well as on the treatment arm. All of that is going exactly as we hoped, which is why when we had the additional alpha, we moved it to month 24 and kept 15 wholly intact. Did not jeopardize month 15 at all, because we're really quite encouraged there. If we don't win at month 15, we're right around the corner from it. We're going to get there is the way we feel about that. Maybe, Lloyd, I'll bring you in to answer some of the other questions that Ananda had. No, that's absolutely correct. I mean, the event rate, the other piece about being right on top of the event rate estimates is that it gives us a sense of the type of strong work that the group did, the team did in terms of planning this study, really understand the disease well. There was a question about how did we de-risk the sub-studies. There's two ways to de-risk the sub-analyses. The first is this plan that actually was initiated by the FDA. They actually suggested to us that we take this large analysis and split it into two sub-analyses and do it using stratification factors, events, and the number of patients, so that essentially we end up with two identical groups. It gives us patient cohorts that are much more likely to be very, very similar than running two parallel studies. This is sort of a synthetic two-study analysis in the sense that it is patients coming out of a single analysis, but being split into two very, very similar populations. We think that it is very unlikely we will see a split decision in the sub-analyses, de-risking a split decision on the month 15. Of course, the other de-risking move clearly is extending the study to month 24 as a backstop. In the event that we do get a continue, we have nine months to grow the treatment delta in these sub-studies that are smaller than the single analysis. Those are really two key factors which de-risk the program going into readout. I guess the only other thing I would say is that, Ananda, while these sub-studies are smaller than the overall study, they are still meaningfully larger than the phase II study and much greater powering. As Lloyd alluded to, at the sub-study level, each sub-study is powered at 90% or better. With all of the other things that Lloyd alluded to, when you couple in how well it is powered, and the fact that we are tracking with our event rates, and that we do not need to do as well as we did in the phase II study to win, we are encouraged by the outlook for this at month 15. Great. Thank you. Very helpful. Thank you. Our final question comes from Jon Wolleben with Citizens. Please go ahead, Jon. Hey. Thanks for the day and taking the question. For Dr. Goldberg, wondering if you'd talk a little bit about why patients aren't seeking treatment today. Is it something I can worry about next year or two years from now, or is it injection burden? Is it safety risk? Is it efficacy of the approved agents and how vonaprument might change that? For the team, Lloyd, you just talked about this a little bit. Wondering if you'd give us the logistics of how you're splitting up the sub-studies and any of those stratification measures that you've mentioned a couple times here. Thanks. Jon, I'll start here. Please, Roger. Jon, great question. I think it's multifactorial, to be honest. My sense is that had the safety risks associated with SYFORVE that kind of became apparent after launch, I do think there would be more patients on therapy, whether that was driven by, frankly, patient demand or a change in the patient demand versus retina doctor comfortability. But I think what happened is when the safety We were so excited to have a treatment available to treat patients with GA, and that we started to prescribe it. I mean, that drug was on a kind of a rocket ship of a launch, and then the safety issues emerged. What the safety issues caused was a kind of a reconsideration of the data, and I think a lot of retina specialists out there felt like, "Hey, you know something? I'm not actually having a functional benefit for my patients, so why am I doing this and taking that safety risk associated with SYFORVE? That made them question even the IZERVAY data, which showed some anatomic benefit, but no functional benefit. I think the safety issue is what caused the doctors to reconsider kind of, is the juice worth the squeeze, so to speak. I think, obviously, I think vonaprument will offer a very different picture and story because then it's really all about the functional benefit for the patient. It gives us, as a community, the opportunity to kind of revisit GA and GA treatment and really expand it from whatever, 10% of the market to something much, much greater. I think there's just a huge There's, A, a huge unmet need, and there's a willingness to consider treatment in this population should we have something that's been proven to benefit the patient. Thanks, Roger. Lloyd, just quickly- Yeah, Jon. Yeah, Jon, it's a great question in terms of sort of the mechanics of how we're splitting. Think of this as sort of a synthetic two-study plan where we are splitting at the site level, first of all. Not at the patient level. If you were at a site in Chicago, all of those patients go into one study or the other. We're splitting at the site level, and then we are able to balance in a pre-specified manner the number of patients, the number of events, as well as our major stratification factors, which was a vision cutoff, which was basically the median from the phase II, foveal status, and the presence or absence of fellow eye choroidal neovascularization, which is an important predictor of vision loss. Those are the factors that we're using to create two basically identically sized cohorts with extremely similar clinical characteristics. That is why we anticipate that the outcomes of the sub-studies will be consistent. Yeah, I will just quickly add, Lloyd, we also included for the SAP some additional clinical characteristics to ensure. Ultimately, the question is, will you see a consistent sham rate between the two sub-studies and a consistent treatment effect with vonaprument in the two sub-studies? The way we've been able to design these two studies and stratify, we're very confident that you're going to see very consistent outcomes on both of those two assessments at the sub-study level. Great. Thank you for your questions, Jon, and to all of our analysts. I will now turn it back to Douglas to close out the call. Alrighty. Well, listen, thank you all again for your attention. We really appreciate it. We're excited about this program. I think you can hear that. We've been really intentional about how we've approached this program. We're not trying to get lucky. This is built on 20 years of biology and a really well, smartly designed clinical program that's been executed in a top-shelf way. So, we know we have the right patients. We know that we have a drug that has shown a dose effect in a wide range of patients. One of the risks always in neurodegenerative diseases is heterogeneity. In fact, I think that's always the largest risk. We know we have a drug that works in a multitude of different patient populations, and we've been able to enroll them in this study to very much mirror what we saw in the ARCHER phase II study. We're excited about turning over the cards in the not-too-distant future and then making this drug available to patients worldwide. We look forward to continuing to work with you all as we do all of that. Thanks again for your attention. Thanks, Lloyd. Thanks, Roger. Wish you all a good day.