Annexon, Inc.

Good morning, everyone, and welcome to the Annexon Business Update Call. At this time, all attendees are in a listen-only mode, and a question-and-answer session will follow the formal remarks. As a reminder, this call is being recorded, and a replay will be made available on the Annexon website following the conclusion of the event. I'd now like to turn the call over to Doug Love, President and Chief Executive Officer of Annexon. Please go ahead, Doug.

Thank you, operator. Good morning and welcome, everyone. Earlier this morning, Nexon issued a press release announcing that we have expanded our Archer II Phase III trial for bond improvement and geographic atrophy, and a press release announcing key business updates and second quarter financial results. Copies of these press releases are available on the company's website and through our SEC filings. On today's call, we will be making forward-looking statements, including statements relating to the existing clinical data and the therapeutic and commercial potential of our investigational drug candidates. Joining me today are Dr. Jamie Dannenberg, our EVP and Chief Medical Officer, and Dr. Lloyd Clark, SVBP of Ophthalmology Strategy and Innovation, who will discuss our GBS and GA programs, respectively. I will then close before we open the call for questions. We will be joined by Dr. Chet Yednock, EVP and Chief Innovation Officer, and Jin Liu, our Chief Financial Officer. Before we turn to the updates, I'd like to briefly frame Annexon's broader opportunity and our excitement about building a leading, fully integrated biotech company driven by our mission to help millions of people live their best lives. Annexon was founded on discoveries from Stanford University to create a new class of targeted immunotherapies that stop C1Q-mediated neuroinflammation at its source, with the goal of rapidly and meaningfully preserving and potentially improving function for patients with serious neuroinflammatory diseases of the body, the brain, and the eye. Built on more than two decades of foundational C1Q biology and a highly translational approach in the clinic, we have generated robust, compelling evidence supporting the potential of C1Q inhibition across multiple diseases. Indeed, leveraging our pioneering science and our warrior spirit culture to tackle some of the most pressing diseases in our industry, Nexon is the first and only company to successfully conduct fully randomized placebo-controlled trials in GBS, a life-threatening and debilitating disease that is sudden and completely indiscriminate in who it strikes, robbing otherwise healthy people of their normal lives. Nexon is also the first and only company to demonstrate significant vision preservation in a fully randomized sham-controlled study in geographic atrophy, a mass population disease of irreversible blindness that robs millions of people of their independence. Lastly, Nexon is the first and only company to develop and clinically study an oral small molecule designed to selectively inhibit the classical pathway, with the potential to offer those with serious complement-mediated autoimmune conditions a convenient and flexible oral dosing option. While disruptive science is not always quickly recognized, we are more energized than ever by the opportunity to create significant value with not just one, but with multiple potential blockbuster paradigm shifting programs designed to bring hope and better outcomes to millions of people worldwide. Turning to our GBS program update, this program reflects the foundation of an Exxon and our determination to take on challenges others have not. We are pleased to have generated the first positive placebo-controlled pivotal data in the 110 years since GBS was discovered. Tam Rupert Bart is now under regulatory review in Europe, and we are on track to submit the USBLA in the fourth quarter of this year. Last week, we reported clinical outcomes from the first cohort of patients enrolled in our FORGE study across the United States and Europe, marking an important milestone for Nexon and for the GBS community. Tam Rupert Bart flat out works, and these data are more than the next step in our development program. They provide compelling evidence that the rapid, meaningful clinical improvements seen in our phase three study, where approximately 90% of treated patients responded by week one, are reproducible in Western patients. All 10 patients treated to date in Ford improved rapidly, with many showing outsized gains. These unprecedented outcomes, together with a well-tolerated safety profile, support a highly differentiated benefit-risk profile for the roughly 150,000 people worldwide diagnosed with GBS each year. We plan to include these data in our BLA submission in the fourth quarter. Turning next to our GA program, our second drug candidate, Vaughn Improvement, is advancing in the pivotal ARCHER II Phase III trial for patients at risk of irreversible vision loss. Today, we announced a strategic expansion of the program by adding an independent month 24 dual primary endpoint alongside the existing month 15 primary endpoint. To be clear, we remain excited and confident about the month 15 readout expected in the fourth quarter of this year, supported by a powerful mechanism of action, robust preclinical package, compelling dose-dependent proof-of-concept data, and a well-powered, well-executed phase three study designed to replicate those results. With mask events tracking on plan, month 15 remains our base case for success. At the same time, adding the month 24 endpoint meaningfully strengthens the program and a potential $100 billion-plus franchise. The endpoint is willpower, requires no change to the conduct of the already masked 24-month trial, and gives VonApprovement additional time to demonstrate the growing treatment effect observed in the proof of concept trial. Lloyd will discuss this shortly, but in short, the ARCHER program is stronger with this enhancement. Related to the GA program, we were also pleased to announce initiation of the ARCHER II Open Label Extension, or OLE, study. This allows all patients to enter the OLE after month 24 to receive VON improvement while enabling us to assess its longer-term safety and benefit profile. Shifting to corporate matters, as both the Town Rupert Barr GBS and Vaughn Improvement GA programs advanced toward registration, we also in the second quarter took a strategic step to further strengthen our financial position. During the quarter, we entered a credit facility with Oxford Finance that provides access up to $200 million in non-dilutive capital extending our cash runway into 2028. This facility enhances our financial and operational flexibility as we prepare for global commercialization, while further diversifying our capital structure, strengthening our balance sheet, and supporting both near and longer-term growth strategies. With that overview, I will now turn the call over to Jamie to review the recent data for our GBS program. Following that, Lloyd will then discuss our vine improvement program updates in more detail. Jamie, over to you.

Thanks, Doug. Before reviewing the forward data, I'd like to briefly highlight the significant unmet need in GBS. As Doug mentioned, GBS is an indiscriminate, life-threatening neuromuscular emergency with a rapid, devastating onset compounded by long-term, life-altering consequences. GBS can strike anyone, anywhere, causing paralysis, respiratory failure, and even death. Without immediate intervention, patients face continued neuroinflammation and peripheral nerve damage caused by GBS that leads to muscle weakness and paralysis, with lifelong residual deficits impacting their health and quality of life. Approximately 22,000 patients each year across the U.S. and Europe are afflicted with GBS, and it carries an estimated annual health care burden of more than $20 billion in the U.S. alone. Despite more than 110 years since GBS was first described, there are still no approved targeted therapies that meaningfully alter the course of the disease. Current standard of care, intravenous immunoglobulin, or IVIG, is not FDA approved for GBS and provides incomplete benefit for many patients. Despite treatment, one-year mortality remains as high as 10% overall and approaches 25% of patients over the age of 65. Many patients continue to deteriorate during or shortly after five-day IVIG treatment. requiring mechanical ventilation, prolonged ICU stays, and experiencing months or even years of disability and persistent physical limitations. These challenges underscore the urgent need for therapies that can rapidly stop the underlying disease process and improve patient outcomes. Turning now to the forward study, We are very encouraged by the initial results from the first cohort of 10 patients treated with a single 30 milligram per kilogram infusion of 10 Rupabart. Across this initial cohort, every patient demonstrated rapid, clinically meaningful improvement in muscle strength within four days of treatment. Importantly, four patients who were bed-bound early in the course of their disease regained the ability to walk with or without assistance between days two and eight. We also observed outsized improvements in some of the most severely effective patients. The one patient who required mechanical ventilation early in the disease course was successfully weaned from the ventilator within four days. Five additional patients experienced marked functional improvement within 48 hours of treatment. Bear in mind that these outcomes with tenrupapart occurred well short of the five-day span that is typically required to deliver a full course of IVIG. From a safety perspective, tenrupapart was generally well tolerated. The most significant adverse events were related to GBS itself and expected complications of the disease and were consistent with the safety profile observed in our Phase III study. It's also worth noting that this initial cohort represented a broad cross-section of GBS patients, including both males and females, ranging from 12 to 78 years of age and spanning moderate to severe disease. Importantly, these findings are consistent with the outcomes we observed in our phase 3 study, where approximately 90% of patients demonstrated rapid, clinically meaningful improvement by day 8. Taken together, we believe these results provide further evidence that targeted inhibition of C1q with tanrubabart has the potential to fundamentally change the treatment paradigm for patients with GBS by delivering rapid and meaningful clinical benefit after a single infusion. Finally, I'd like to briefly touch on where we are from a regulatory and clinical development perspective. Our marketing authorization application is currently on track and under review by the European Medicines Agency and is supported by a comprehensive data package. This includes robust placebo-controlled studies demonstrating rapid improvement in function and disability, as well as real-world evidence showing favorable outcomes compared with current standard of care, including IVIG and plasma exchange. At the same time, we continue to advance the FORWARD study across the U.S. and Europe. This study is designed to expand our experience with tanroopobard in Western patients, including pediatric patients, while further characterizing its pharmacokinetic and pharmacodynamic profile, early effects on function and biomarkers, and overall safety. Importantly, the forward data are expected to support our planned biologics license application, or BLA, submission to the FDA in the fourth quarter of this year. Together with our ongoing EMA review, these data are intended to further support the generalizability of tenrupaBART's rapid clinical benefit across diverse populations and geographies and reinforce the broad treatment label we are seeking for patients with GBS. With that overview, I'll turn it over to Lloyd to discuss the GA Archer II Phase III program.

Thanks, Jamie. Lloyd? Thanks, Jamie. Before reviewing the Bon Apprimant Phase III program, I'd like to briefly highlight the significant unmet need in geographic atrophy, or GA. As Doug mentioned, GA is a neurodegenerative disease that leads to gradual loss of central vision, difficulty seeing in low light, and blurry or distorted vision. The GA patient, whose average age is nearly 80 years old, suffers most from the loss of their independence when everyday activities like reading, driving, and recognizing the faces of loved ones becomes more challenging as their disease advances over time. GA meaningfully impacts the lives of approximately 8 million patients worldwide, including 1.5 million patients in the U.S. alone, and the incidence is projected to increase due to the aging population. A vision-preserving treatment in GA is the greatest unmet need in the retina space today. Current approved treatments have not shown to preserve visual acuity, and new innovations are needed. Now turning to our Vaughan Improvement Program, which has the potential to be the first vision-sparing therapy for patients with GA. Notably, our Phase III ARCHER II trial enrolled 659 patients, 30 more than our original target to slightly enhance powering. Powering has been further enhanced with strong trial execution, where the patient discontinuation rate has been less than 10%, and dosing compliance has been more than 95%, both which exceeded our targets. All eligible patients have now received at least 12 months of treatment in the trial, and the mass event accruals continue to track in line with our projections. This all gives us further confidence in Archer 2. The strong power and execution of our Phase III ARCHER II trial provide a clear opportunity to seamlessly incorporate a month 24 dual primary endpoint while maintaining the month 15 primary endpoint. The overall study is highly powered at more than 90% for both time points. Importantly, as ARCHER2 was already designed to remain masked through month 24, this strategic addition allows us to evaluate the longer-term profile of VaN improvement for inclusion into the label without change to the study operation. Here's how the timeline works from here. An independent data monitoring committee, or DMC, will assess the study's month 15 primary endpoint, and we expect to report that assessment on schedule in the fourth quarter of this year. At that point, the DMC may find that we've met the month 15 primary endpoint, which would allow us to move into the separate and additional planned analysis of the trial's two substudies with results expected in the first quarter of 2027. or the DMC may recommend the study continue through the month 24 analysis. The ARCHER II study, including month 24 analyses, is expected to be completed in the third quarter of 2027. On the regulatory side, recall that Vaughn Improvement has fast-track designation from the FDA. It is also the only geographic atrophy program with prime designation from the EMA and has been selected for the EMA's Product Development Coordinator pilot, which provides enhanced regulatory support, including expedited scientific advice and MAA submission readiness. Together, these designations facilitate more frequent engagement with regulators as we advance this program towards potential registration. We at Inexxon, along with retina specialists in the broader GA community, are highly enthusiastic about our Vaughn Improvement Program and its potential to help the 8 million patients globally with geographic atrophy. With that, I'll turn the call back to Doug.

Thanks, Lori. Thanks, Jamie. Nice job. After more than a decade building the scientific and clinical foundation of our platform, we are now entering a pivotal period where the work can translate into new medicines for patients and significant value for shareholders. The time is now. Imagine a world where GBS can be halted within a week, and people at risk of GA-related blindness have a real choice to preserve their vision. Simply put, we're playing to win for patients, stakeholders, and each other. To support that goal, over the course of this year, we have strengthened the balance sheet with non-diluted debt capital, bolstered our ophthalmic capabilities at the board of directors level with the recent appointment of renowned retina specialists, and biotech leader, Dr. Mark Blumenkrantz, and the addition of key internal talent across the organization. We've established the most comprehensive and compelling GBS data package ever generated, including the first US-EU trial in over 40 years, where all patients treated to date rapidly improved. We've also effectively executed and are executing the GA Phase III program, have now expanded the program to enhance its probability for overall success, and we're continuing the steadfast work to deliver on the first and only oral therapy targeting the complement classical pathway. Each element is significant on its own. Together, they create the potential to drive substantial asymmetric value for an exon and for others. So in closing, I want to thank the patients, medical teams, supporters, employees, and advisors who have joined us on this journey. We look forward to continuing to partner with you as we fully leverage the foundation we've laid over the next six to 18 months. And I want to thank all of you who joined us this morning on today's call. With that, I will now ask the operator to begin our Q&A session. Operator?

Great. Thank you, Doug. Yeah, so at this time, we will be conducting a live Q&A session. To our covering analysts, please use the raise hand feature to be added to the queue. Kindly hold for a brief moment while we pull for questions. So our first question comes from Anupam Rama at JPMorgan. Please go ahead, Anupam.

Hey, guys. Thanks so much for taking the question, and congrats on all the progress. I just want to confirm that you guys have shared the for Archer 2 with regulators both in the U.S. and globally and what feedback you may have gotten on the strategy from regulators. Thanks so much.

Yeah, thanks Anupam and appreciate you joining us this morning. Yeah, the short answer is Yeah, both regulators on both sides of the pond have been very clear that if we want to include month 24 in the label, we would need to apply alpha to month 24. As you know, month 24 was already the design of the study for safety purposes. This addition that we've made here this morning allows it to be counted in the label from an efficacy perspective. And I don't know, Lloyd, is there anything you'd like to add on to that?

No, I think that's very clear. I mean, we have full alignment at month 15, and we've had several discussions with both regulatory bodies about the importance of putting alpha at month 24 if we want to include efficacy data from that time point.

Thanks, Anupam. Thanks so much for taking our question. Absolutely.

Thanks, Anupam. Our next question comes from Derek Garcia at Wells Fargo. Please go ahead, Derek.

Hey, good morning and thanks for the question, taking the questions and congrats on the progress here. So I guess maybe the first one is just, you know, kind of bring us back, like what kind of really drove the decision for the 24 month endpoint? Obviously it's something that you can do, but I guess the main thing that I feel like people are gonna be asking us is what did you see in the blinded data? Is there worry around the 15 month endpoint? So maybe, you know, give us a sense of like the decision process, but also, you know, your confidence in that 15 month endpoint.

Yeah, good morning, Derek. Really good question. I'll start and then invite the others to join in. So first and foremost, super confident in month 15. It is our base case and maybe just a little bit of history on how we got here today. We passed the 12-month point for all patients receiving their dose. So we have a really strong handle at this particular point in time on how the study is faring. We're very confident in our targets for mass event rates. As we've said, it's continued to track over the last several months and it continues to do so today. So we're very pleased by that. You know, to be completely candid, we fielded questions from various investors and strategics. on the idea of adding a month 24 endpoint. It absolutely creates a stronger overall profile for voniprune in this disease and, in effect, builds a moat around this franchise in a way that it will be very difficult with the wind for others to come in and usurp us in a reasonable period of time. And so the notion of being able to run a really effective study that gave us additional power, and I'm sure Lauren and or Jamie will talk more about that, And applying that to month 24 just became increasingly attractive. But really, it was not until we crossed the 12-month hurdle on this study, which is, in effect, the Archer 1 study, that we began to really consider whether or not it can be opportunistic, if you will, in playing a bit of offense here. So, Lloyd, maybe I'll turn it over to you to see if you want to add anything to that.

Yeah, Derek, thanks for the question. I mean, I think I'm going to borrow from Doug. Doug likes to use sports analogies, and this is how it's made a lot of sense to me. We effectively went to the locker room at halftime as we were assessing the month 12 progress of the trial, and we came to three important conclusions about the study. The first was that we went to month 15, which gave us additional powering over our initial 12-month calculations. The second was that we over enrolled the study by 30 patients. If you remember, we had such brisk enrollment at the end that we ended up over enrolling by 30 patients. So we had additional power there to spend. And then finally, we've had really, really encouraging patient retention in this study over single-digit percentages of dropouts, which is significantly lower than we anticipated. So sort of at this halftime evaluation of the study, we found ourselves with increased power. And so we made the strategic decision to apply that power to a second time point. So we have not weakened the study at month 15 by any way. We're still extremely confident for where we stand at the month 15 time point. But we've given ourselves the flexibility through execution to look at a second time point.

Very helpful. Thank you.

Thank you.

Great. Thanks for the questions, Derek. Our next question comes from Andrew Sy at Jefferies. Please go ahead.

Hey, congrats on the updates. This is Matt Barkis dialing in for Andrew Tai. We wanted to know, would you expect lesion growth to hit STAT-SIG2 by month 24 as a secondary?

Yeah, I mean, look, we've talked about this before. I have two thoughts on this, and one is maybe not the most popular. On some level, we care about lesion growth. On another level, we don't as it relates to vision. And that's not because we don't think it's important to protect our PE cells. It is. They provide trophic support under your neurons that are responsible for vision. But it's not important to protect lesion growth for the purposes of protecting vision. And that's been borne out not only by our data, but clearly the first generation approved therapies to have four or five years worth of data of protecting lesion growth, but no impact on vision. And it's a bit of a curious circumstance for me in this particular therapeutic area that we continue to get that question because It's just not the biology for what we're seeking in this disease, right? And I think that's very well elucidated. That being said, we were encouraged that by protecting photoreceptor cells over time, we're showing a healthier overall neuronal unit, which is showing greater protection to the lesion over time. And so when you look in the second six months of the study, we have a 10% protection over just a six-month period of time in RPE growth. growth in the second six months of the Archer study. So we expect that will continue. Whether that will be stats, they get 15 months, 24 months, a little bit TBD, but we do expect we will get there in time. So Lloyd, I don't know what you want to add on to that.

Yeah, Doug, I totally agree with that discussion. We recognize that RPE lesion growth is still important for us to discuss. We recognize that that's where the community is today. The community will not be there tomorrow, though. The community is going to be more interested in protecting photoreceptors and neuronal cells as measured by ellipsoid zone. We do anticipate seeing protection of RPE lesion at the later time points based on our Phase II data, and we recognize that we'll continue to have to discuss this from a historical perspective, but I would encourage you to continue to pay close attention to ellipsoid zone as a primary biomarker for this neurodegenerative disease.

Great. Thanks for the question, Matt. Our next question comes from Salvine Richter at Goldman Sachs. Please go ahead, Salvine. Salvine, you might be on mute.

Sorry about that. Good morning. Thanks for taking my question. What would be the commercial outlook if there, you know, when you think about what you plan to see for separation at month 15, but more of a stat-sig outlook at 24 months, and how would a delayed time to response be perceived despite vision preservation here?

Thanks for your question. I guess maybe a couple things. We expect to be positive at month 15. So month 15 is not kind of just kind of a speed bump look, but we expect stats to get month 24. We are the base case is still winning at month 15. And I guess what I would say, but invite others to weigh in on this. Whether that positive outcome occurs at month 15 or month 24, the word delay certainly cannot be associated with it. No drug has ever done it. The approved drugs have four or five years worth of data, and they haven't done it. So doing it more than half the time quicker than anybody has ever done it would be certainly not a delay. But I don't know, Floyd, if there's anything you'd like to add on this.

Yeah, our work with the retina community suggests that this is a transformative therapy with rapid adoption over the currently available therapies, regardless of when it's available commercially. Again, we have tremendous confidence in the month 15 time point. But we also have tremendous confidence that this drug will make a big benefit to patients. And so our goal, our primary goal is success of this program. This change by adding the month 24 time point increases our probability of success for the entire program, which would deliver a transformative therapy to the market.

One other quick point, Salveen, this is Jamie. Just bear in mind, we have full confidence in month 15 with month 24 gets us is the ability to put efficacy data in the label at two years, which just adds to the overall story of vision protection for patients, not just at 15 months, but onward.

Got it. Thank you.

Thanks for the question, Salveen. Our next question comes from Joey Stringer at Needham. Please go ahead, Joey.

Thanks for taking our questions in the morning. I had a question just on that alpha allocation. So with the month 15 and month 24 now independent kind of registrational time points here where you can hit success at either time point, does the month 15 still carry the full alpha or has the statistical threshold there tightened?

Yeah, good morning, Joey. Good question. Lloyd, I'll turn it over to you and Jamie to talk about the alpha.

Yeah, right. Good morning, Joey. Obviously, yes, we are splitting alpha between month 15 and month 24. But as I stated earlier, our base assumptions at the initiation of this study have been exceeded due to strong trial execution. And so really what we're looking at in terms of overall powering based on where we stand today is a negligible difference at month 15 compared to where we thought we would be at the initiation of the study. And so essentially what we're doing here is we're using found money in terms of strong trial execution to add a secondary time point. So we are not in any substantive way reducing the likelihood of the month 15 win, but rather we're using the additional powering that we've achieved through execution to add a second time point.

Great, thank you. Thanks, Joey.

Yes, thanks, Joey. Our next question comes from Ananda Ghosh at HC Wainwright. Please go ahead, Ananda.

Yeah, hi. Thanks, and comrades on the quarter. Maybe, you know, the first question I have is like, if you can briefly talk about how the powering is designed for the sub-studies. And the second thing is, if the blinded pooled event, you know, that you see in line with the projections, is that track with what you have seen in your phase one, phase two, like the POC trial? Thank you.

Yeah, good question. Good morning. Actually, Lloyd, I'll just turn it over to you.

Sure. The first question about powering, yes, we are splitting alpha. We haven't disclosed specifically what that alpha split's going to be. But again, what I would tell you is that this change, based on our execution updates allows us to split this off and retain phase three powering at the sub study level and continue to be well overpowered for the phase three at the combined study. So we feel really confident about where we are in terms of powering, not substantially different with the second time point than where we would have been at the beginning of the study. In terms of mass event rates, again, that really is our really our best metric in terms of understanding how trial execution is going. We follow that on a regular basis. We have multiple models to predict where we're going to be. We continue to be on track, and that gives us this strong confidence that Doug talks about in the month 15 time point. It gives us confidence two ways. It gives us confidence that we understand the disease process well. because otherwise we'd be off in terms of event rates. And secondly, it gives us confidence in what we observed in terms of a treatment effect in the phase two. So on target with massed event rates, and that leads to confidence with the month 15 primary endpoint.

Thanks. Thanks so much.

Thanks, Ananda. Our next question comes from Phil Nadeau at TD Cowen. Please go ahead, Phil.

Good morning. Thanks for taking our questions. Three from us. First, in terms of the Q4 disclosure, I guess, what exactly will we learn? It sounds like you might be able to disclose whether you hit the primary endpoint, but the data won't come out to Q1 2027. Is that correct? Or I guess, what are the scenarios for that release? Is it possible that futility could be triggered and the trial will be stopped? That's first. Second question, follow-up to the last one. We're curious if you're willing to disclose what actually the powering is today at month 15 and month 24. Then third, just a question on GBS. With the Q4 filing, have you had further discussions with the FDA on the number of patients and follow-up necessary from forward, or are you just going with your prior understanding? Thank you.

Yeah, thanks, Phil. Thanks for joining us this morning. Maybe we'll start with GBS. I'll quickly answer that by Jamie, and then we'll turn it over to Lloyd and others for the GA questions. On the GBS front, we are in ongoing discussions with the FDA. So I will say that we're really encouraged with the posture of the FDA, both at the macro level and then at the micro level and a program-specific level. Those are ongoing discussions, and we feel quite confident that with the addition of the four data, we will be filing for BLA in Q4 of this year. So we're encouraged all around on that. This program is moving. And of course, the discussions and interactions with the EU are going really, really well as well. And things have advanced on multiple fronts there. So GBS is coming. And we're excited by that because patients obviously need this therapy. With regard to GA and the disclosure in Q4, as Lloyd spoke to, the DMC will take a look at this and make a determination. They always have the opportunity to declare the study futile. And they have been and will continue to look at that over the course of the study. And thus far, it's been continue on, continue on. At Q4, they'll have an opportunity to disclose whether the study is positive at month 15 on the overall study. or to continue on to month 24? And I'll just open it up to you, Lloyd, see if you want to add anything in addition to that.

Oh, yeah, no, that's absolutely. So we'll find out in Q4 if the study is positive or, as Doug said, if we continue on to month 24. If the study is positive in Q4, then that would trigger the initiation of the two-sub study analysis, of which would be available in the first quarter of 2027. But you will get... results on the overall study in Q4 as promised. Oh, and then the other question about powering. Yes, we have not shared specifically what the powering is, but again, I want to reiterate that both time points remain well powered at a conventional phase three level, both month 15 as well as month 24.

That's perfect. Thanks for taking our questions.

Thank you.

Thanks for the questions, Phil. Our final question comes from John Wallaban at Citizens. Please go ahead, John.

Hey, good morning. Thanks for the question. A couple follow-ups from me. I'm wondering if in 4Q, the decision is to continue in month 24, if you'll be seeing the data from the DMC and providing that publicly as well. And then just a question. You mentioned your masked event rate is in line with projections. Can you tell us what that looks like? And then how do you think about month 24 projections without that data from Archer? Thanks, guys.

Yeah, thanks, John. Thanks for joining us. Yeah. First and foremost, John, could you repeat your first question? I forgot. I actually lost track. Oh, I'm sorry. Yeah, whether we'd be seeing. Let me just start on that quickly. I just want to make a quick point on that. No, the short answer is no. It will be masked all the way through month 24. Which is the pre-designed setup for that. Bear in mind, there's precedent for this. This has been done before. So if you look at the Appellus Phase 3 program and the Derby study in particular, it was a 12-month study primary endpoint, but to read out and with following patients out to month 24 and amassed They did not hit stat sig at month 12 and ultimately looked again at month 18. We wanted to make sure if we were in that circumstance, we did this prospectively. So we're doing this with the full light of day and with alignment with the regulators with regard to that. But to do so, you do need to remain masked. at the time you take your first look at your data. So Lloyd, I'll turn it over to you, see if you wanna add on to that.

Yeah, no, absolutely. So there will be no patient level data released in the Q4 of 2026. Now, we'll then initiate the sub-study analysis. And if both sub-studies are positive, then likely we'll have a different conversation about data in the first quarter of 2027. But again, you will have the results of the full analysis in line with the Q4 2026 guidance. Your question about event rates was a great question about essentially how do we model event rates out to 24 months, given that our phase two study was only one year. Well, keep in mind, as we've discussed publicly, we did an extensive review of event rates, and we planned a two-year study from the start. And so we've used a number of data points, including our phase two data, which is very, very valuable to us, but a number of other data points, including trials that lasted much longer than 12 months, to arrive at models for events. And in general, events in geographic atrophy continue to progress for several years. So We have a good handle on what the events should look like in the second year based on our review of multiple different protocols. So we have that modeled and we anticipate a similar behavior of that model in year two compared to year one.

Great. Thanks for the questions, John. So I'll now turn it back over to Doug to close out the call.

All right. Well, thank you all for joining us on the call today. We really appreciate your time and attention and for the good questions. We look forward to continuing to communicate as we advance over the remainder of the year, and we wish you all a good day. Thanks again.