Q2 2026 Annexon Inc Earnings Call

August 12, 2026

Speaker #1: Good morning, everyone, and welcome to the Anexon 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.

Speaker #1: As a reminder, this call is being recorded and a replay will be made available on the Anexon website following the conclusion of the event.

Speaker #1: I'd now like to turn the call over to Doug Love, President and Chief Executive Officer of Anexon. Please go ahead, Doug.

Speaker #2: Thank you, operator. Good morning and welcome, everyone. Earlier this morning, Anexon issued a press release announcing that we have expanded our Archer 2 Phase 3 trial for Vonapruma in geographic atrophy and a press release announcing key business updates in Q2 financial results.

Speaker #2: 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.

Speaker #2: Joining me today are Dr. Jamie Dannenberg, our EVP and Chief Medical Officer, and Dr. Lloyd Clark, SVVP of Ophthalmology Strategy and Innovation, who will discuss our GVS and GA programs respectively.

Speaker #2: I will then close, before we open the call for questions, where we will be joined by Dr. Chad Yetnock, EVP and Chief Innovation Officer, and Jin Liu, our Chief Financial Officer.

Speaker #2: Before we turn to the updates, I'd like to briefly frame Anexon'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.

Speaker #2: Anexon was founded on discoveries from Stanford University to create a new class of targeted immunotherapies that stops 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.

Speaker #2: Built on more than 2 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.

Speaker #2: Indeed, leveraging our pioneering science and our Warrior Spirit culture to tackle some of the most pressing diseases in our industry, Anexon is the first and only company to successfully conduct fully randomized placebo-controlled trials in GVS, a life-threatening and debilitating disease that is sudden and completely indiscriminate in who it strikes, robbing otherwise healthy people of their normal lives.

Speaker #2: Anexon 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.

Speaker #2: Lastly, Anexon 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.

Speaker #2: 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.

Speaker #2: Turning to our GVS program update, this program reflects the foundation of Anexon 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 GVS was discovered.

Speaker #2: Tan 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.

Speaker #2: Last week, we reported clinical outcomes from the first cohort of patients enrolled in our forward study across the United States and Europe, marking an important milestone for Anexon and for the GVS community.

Speaker #2: Tan 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 3 study where approximately 90% of treated patients responded by week 1 are reproducible in Western patients, all 10 patients treated to date in forward-improved rapidly, with many showing outsized gains.

Operator: 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.

Speaker #2: 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 GVS each year.

Speaker #2: We plan to include these data in our BLA submission in the fourth quarter. Turning next to our GA program, our second drug candidate, Vonapruma, is advancing in the pivotal Archer 2 Phase 3 trial for patients at risk of irreversible vision loss.

Doug Love: Thank you, operator. Good morning and welcome, everyone. Earlier this morning, Annexon issued a press release announcing that we have expanded our ARCHER II Phase 3 trial for vonaprument in geographic atrophy in a press release announcing key business updates and Q2 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 Dananberg, our EVP and Chief Medical Officer, and Dr. Lloyd Clark, SVP of Ophthalmology Strategy and Innovation, who will discuss our GBS and GA programs respectively.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: Robust preclinical package, compelling dose-dependent proof-of-concept data, and a well-powered, well-executed Phase 3 study designed to replicate those results. With mass events tracking on plan, month 15 remains our base case for success.

Speaker #2: At the same time, adding the month 24 endpoint meaningfully strengthens the program in a potential 100 billion dollar plus franchise. The endpoint is well-powered, requires no change to the conduct of the already mass 24-month trial, and gives Vonapruma additional time to demonstrate the growing treatment effect observed in the proof-of-concept trial.

Doug Love: I will then close before we open the call for questions, where we will be joined by Dr. Chad Gednacht, 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.

Speaker #2: 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 2 open label extension, or OLE, study.

Speaker #2: This allows all patients to enter the OLE after month 24 to receive Vonapruma while enabling us to assess its longer-term safety and benefit profile.

Doug Love: Built on more than 2 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, Annexon 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. Annexon 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.

Speaker #2: Shifting to corporate matters, as both the Tan Rupert-Bart GVS and Vonapruma GA programs advance toward registration, we also in the second quarter took a strategic step to further strengthen our financial position.

Speaker #2: During the quarter, we entered a credit facility with Oxford Finance that provides access up to 200 million dollars in non-dilutive capital extending our cash runway into 2028.

Speaker #2: 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.

Speaker #2: With that overview, I will now turn the call over to Jamie to review the recent data for our GVS program. Following that, Lloyd will then discuss our Vonapruma program updates in more detail.

Speaker #2: Jamie, over to you.

Doug Love: Lastly, Annexon 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 Annexon 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.

Speaker #3: Thanks, Doug. Before reviewing the forward data, I'd like to briefly highlight the significant unmet need in GVS. As Doug mentioned, GVS is an indiscriminate life-threatening neuromuscular emergency with a rapid devastating onset compounded by long-term life-altering consequences.

Speaker #3: GVS can strike anyone anywhere, causing paralysis, respiratory failure, and even death. Without immediate intervention, patients face continued neuroinflammation and peripheral nerve damage caused by GVS that leads to muscle weakness and paralysis, with lifelong residual deficits impacting their health and quality of life.

Speaker #3: Approximately 22,000 patients each year across the US and Europe are afflicted with GVS, and it carries an estimated annual healthcare burden of more than 20 billion dollars in the US alone.

Doug Love: tanruprubart is now under regulatory review in Europe, and we are on track to submit to US BLA in Q4 of this year. Last week, we reported clinical outcomes from the first cohort of patients enrolled in our FORWARD study across the United States and Europe, marking an important milestone for Annexon and for the GBS community. tanruprubart 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 III study, where approximately 90% of treated patients responded by week 1, are reproducible in Western patients. All 10 patients treated to date in FORWARD 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.

Speaker #3: Despite more than 110 years since GVS was first described, there is still no approved targeted therapies that meaningfully alter the course of the disease.

Speaker #3: Current standard of care—intravenous immunoglobulin, or IVIG—is not FDA approved for GVS, 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.

Speaker #3: 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.

Speaker #3: 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 Tan Rupert-Bart.

Doug Love: We plan to include these data in our BLA submission in Q4. Turning next to our GA program, our second drug candidate, vonaprument, 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 Q4 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 III study designed to replicate those results. With mass 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 in a potential $100 billion-plus franchise.

Speaker #3: Across this initial cohort, every patient demonstrated rapid clinically meaningful improvement in muscle strength within four days of treatment. Importantly, four patients who were bedbound early in the course of their disease regained the ability to walk, with or without assistance, between days two and eight.

Speaker #3: We also observed outsized improvements in some of the most severely affected patients, the one patient who required mechanical ventilation early in the disease course was successfully weaned from the ventilator within four days.

Speaker #3: Five additional patients experienced marked fluctuational improvement within 48 hours of treatment. Bear in mind that these outcomes with Tan Rupert-Bart occurred well short of the five-day span that is typically required to deliver a full course of IVIG.

Speaker #3: From a safety perspective, Tan Rupert-Bart was generally well tolerated. The most significant adverse events were related to GVS itself and expected complications of the disease, and were consistent with the safety profile observed in our phase three study.

Doug Love: The endpoint is well-powered, requires no change to the conduct of the already mass 24-month trial, and gives vonaprument 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 vonaprument while enabling us to assess its longer-term safety and benefit profile. Shifting to corporate matters, as both the tanruprubart GBS and vonaprument GA programs advance toward registration, we also in Q2 took a strategic step to further strengthen our financial position.

Speaker #3: It's also worth noting that this initial cohort represented a broad cross-section of GVS patients, including both males and females, ranging from 12 to 78 years of age, and spanning moderate to severe disease.

Speaker #3: Importantly, these findings are consistent with the outcomes we observed in our phase three study, where approximately 90% of patients demonstrated rapid clinically meaningful improvement by day eight.

Speaker #3: Taken together, we believe these results provide further evidence that targeted inhibition of C1Q with Tan Rupert-Bart has the potential to fundamentally change the treatment paradigm for patients with GVS by delivering rapid and meaningful clinical benefit after a single infusion.

Speaker #3: 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.

Doug Love: 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 vonaprument program updates in more detail. Jamie, over to you.

Speaker #3: 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.

Speaker #3: At the same time, we continue to advance the forward study across the US and Europe. This study is designed to expand our experience with Tan Rupert-Bart in Western patients, including pediatric patients, while further characterizing its pharmacokinetic and pharmacodynamic profile early effects on function and biomarkers and overall safety.

Jamie Dananberg: Thanks, Doug. Before reviewing the FORWARD data, I would 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 of paralysis with lifelong residual deficits impacting their health and quality of life. Approximately 22,000 patients each year across the US and Europe are afflicted with GBS, and it carries an estimated annual healthcare burden of more than $20 billion in the US 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.

Speaker #3: Importantly, the forward data are expected to support our plan biologics license application, or BLA, submission to the FDA in the fourth quarter of this year.

Speaker #3: Together with our ongoing EMA review, these data are intended to further support the generalizability of Tan Rupert-Bart's rapid clinical benefit across diverse populations and geographies, and enforce reinforce the broad treatment label we are seeking for patients with GVS.

Speaker #3: With that overview, I'll turn it over to Lloyd to discuss the GA Archer 2 phase three program.

Speaker #4: Thanks, Jamie.

Speaker #3: Lloyd?

Speaker #4: Thanks, Jamie. Before reviewing the Vonapremant phase three 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.

Jamie Dananberg: 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% in 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 outcome. 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 tanruprubart. Across this initial cohort, every patient demonstrated rapid, clinically meaningful improvement in muscle strength within four days of treatment.

Speaker #4: 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 become more challenging, as their disease advances over time.

Speaker #4: GA meaningfully impacts the lives of approximately 8 million patients worldwide, including 1.5 million patients in the US alone, and the incidence is projected to increase due to the aging population.

Speaker #4: A vision-preserving treatment in GA is the greatest unmet need in the retina space today. Currently, current approved treatments have not shown to preserve visual acuity and new innovations are needed.

Speaker #4: Now turning to our Vonapremant program, which has the potential to be the first vision-sparing therapy for patients with GA. Notably, our phase three Archer 2 trial enrolled 659 patients, 30 more than our original target to slightly enhance powering.

Jamie Dananberg: 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 2 and 8. We also observed outsized improvements in some of the most severely affected 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 tanruprubart occurred well short of the five-day span that is typically required to deliver a full course of IVIG. From a safety perspective, tanruprubart 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.

Speaker #4: 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.

Speaker #4: All eligible patients have now received at least 12 months of treatment in the trial, and the masked event accruals continue to track in line with our projections.

Speaker #4: This all gives us further confidence in Archer 2. The strong power and execution of our phase three Archer 2 trial provide a clear opportunity to seamlessly incorporate a month 24 dual primary endpoint while maintaining the month 15 primary endpoint.

Speaker #4: The overall study is highly powered at more than 90% for both time points. Importantly, as Archer 2 was already designed to remain masked through month 24, this strategic addition allows us to evaluate the longer-term profile of Vonapremant for inclusion into the label without change to the study operation.

Jamie Dananberg: 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 III 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 tanruprubart 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 Authorisation Application is currently on track and under review by the European Medicines Agency and is supported by a comprehensive data package.

Speaker #4: 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.

Speaker #4: 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 sub-studies, with results expected in the first quarter of 2027.

Speaker #4: Or the DMC may recommend the study continue through the month 24 analysis. The Archer 2 study including month 24 analyses is expected to be completed in the third quarter of 2027.

Jamie Dananberg: 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 US and Europe. This study is designed to expand our experience with tanruprubart 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 Q4 of this year. Together with our ongoing EMA review, these data are intended to further support the generalizability of tanruprubart's rapid clinical benefit across diverse populations and geographies and reinforce the broad treatment label we are seeking for patients with GBS.

Speaker #4: On the regulatory side, recall that Vonapremant 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.

Speaker #4: Together, these designations facilitate more frequent engagement with regulators as we advance this program towards potential registration. We at Anexon, along with Retina Specialists and the broader GA community, are highly enthusiastic about our Vonapremant program and its potential to help the 8 million patients globally with geographic atrophy.

Speaker #4: With that, I'll turn the call back to Doug.

Speaker #2: Thanks, Lloyd. 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.

Jamie Dananberg: With that overview, I'll turn it over to Lloyd to discuss the GA ARCHER II phase III program.

Lloyd Clark: Thanks, Jamie.

Jamie Dananberg: Lloyd.

Lloyd Clark: Thanks, Jamie. Before reviewing the vonaprument Phase III program, I would 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 US 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.

Speaker #2: The time is now. Imagine a world where GVS can be halted within a week. And people at risk of GA-related blindness have a real choice to preserve their vision.

Speaker #2: 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 stripped in 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.

Speaker #2: We've established the most comprehensive and compelling GVS data package ever generated, including the first US-EU trial in over 40 years, where all patients treated to date rapidly improved.

Speaker #2: We've also effectively executed and are executing the GA phase three program, have now expanded the program to enhance its probability for overall success, and we're continuing to steadfast work to deliver on the first and only oral therapy targeting the complement classical pathway.

Lloyd Clark: Current approved treatments have not shown to preserve visual acuity, and new innovations are needed. Now turning to our vonaprument 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 masked event accruals continue to track in line with our projections. This all gives us further confidence in ARCHER II.

Speaker #2: Each element is significant on its own. Together, they create the potential to drive substantial asymmetric value for Anexon and for others. So in closing, I want to thank the patients, medical team, supporters, employees, and advisors who have joined us on this journey.

Speaker #2: 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.

Speaker #2: With that, I will now ask the operator to begin our Q&A session. Operator?

Speaker #1: Great. Thank you, Doug. Yes. So at this time, we'll be conducting a live Q&A session. To our covering analysts, please use the raise hand feature to be added to the queue.

Speaker #1: 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.

Lloyd Clark: 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 ARCHER II was already designed to remain masked through month 24, this strategic addition allows us to evaluate the longer-term profile of vonaprument for inclusion into the label without change to the study operation. Here is 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 Q4 of this year.

Speaker #5: 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 dual primary endpoint strategy for Archer 2 with regulators both in the US and globally, and what feedback you may have gotten on the strategy from regulators.

Speaker #2: Yes. 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.

Lloyd Clark: At that point, the DMC may find that we have met the month 15 primary endpoint, which would allow us to move into the separate and additional planned analysis of the trial's two sub-studies, with results expected in Q1 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 Q3 of 2027. On the regulatory side, recall that vonaprument 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.

Speaker #2: 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.

Speaker #2: And I know Lloyd, is there anything you'd like to add on to that?

Speaker #4: 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.

Speaker #2: Thanks. Thanks, Anupam.

Speaker #5: Thanks so much for taking our question.

Speaker #2: Absolutely.

Speaker #1: Thanks, Anupam. Our next question comes from Derek Arcia at Wells Fargo. Please go ahead, Derek.

Speaker #4: Hey, good morning. And thanks for the question. I'm taking the questions and congrats on the progress here. So I guess maybe the first one is just kind of bring us back.

Speaker #4: 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 going to be asking us is, what did you see in the blinded data?

Lloyd Clark: We at Annexon, along with retina specialists and the broader GA community, are highly enthusiastic about our vonaprument program and its potential to help the 8 million patients globally with geographic atrophy. With that, I will turn the call back to Doug.

Speaker #4: Is there worry around the 15-month endpoint? So maybe give us a sense of the decision process, but also your confidence in that 15-month endpoint.

Speaker #2: Yeah. Good morning, Derek. Really good question. I'll start, and then invite the others to join in. So the first and foremost, super confident in month 15.

Doug Love: 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 are 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 specialist and biotech leader Dr. Mark Blumenkranz, and the addition of key internal talent across the organization.

Speaker #2: We are, 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.

Speaker #2: 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 masked event rates as we've said.

Speaker #2: It's continued to track over the last several months, and it continues to do so. Today, so we're very pleased by that. To be completely candid, we feel the questions from various investors and strategics on the idea of adding a month 24 endpoint.

Speaker #2: It absolutely creates a stronger overall profile for vonapremant 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.

Doug Love: We have 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 have 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 are 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 Annexon and for others. In closing, I want to thank the patients, medical team, 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 have laid over the next 6 to 18 months.

Speaker #2: And so the notion that being able to run a really effective study that gave us additional power and I'm sure Lloyd and/or Jamie will talk more about that, and applying that to month 24, just became increasingly attractive.

Speaker #2: But really, it was not until we crossed the month 20 the 12-month hurdle on this study, which is in effect the Archer 1 study that we began to really consider whether or not we can be opportunistic, if you will, in playing a bit of offense here.

Speaker #2: So Lloyd, maybe I'll turn it over to you to see if you want to add anything to that.

Speaker #4: Yeah. Derek, thanks for the question. I mean, I think I'm going to bar from Doug. Doug likes to use sports analogies, and this is how it's made a lot of sense to me.

Speaker #4: 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.

Doug Love: I want to thank all of you for joining us this morning on today's call. With that, I will now ask the operator to begin our Q&A session. Operator?

Speaker #4: 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.

Operator: Great. Thank you, Doug. 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. Our first question comes from Anupam Rama at JPMorgan. Please go ahead, Anupam.

Speaker #4: 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.

Speaker #4: And then finally, we've had really, really encouraging patient retention in the study over single-digit percentages of dropouts, which is significantly lower than we anticipated.

Speaker #4: 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.

Anupam Rama: 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 dual primary endpoint strategy for ARCHER II with the regulators, both in the US and globally, and what feedback you may have gotten on the strategy from regulators.

Speaker #4: 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.

Doug Love: Yeah.

Anupam Rama: Thanks so much.

Speaker #4: Very helpful. Thank you.

Doug Love: Yeah. Thanks, Anupam, and appreciate you joining us this morning. The short answer is 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 have made here this morning allows it to be counted in the label from an efficacy perspective. I do not know, Lloyd, is there anything you would like to add on to that?

Speaker #2: Thank you.

Speaker #1: Great. Thanks for the questions, Derek. Our next question comes from Andrew Sy at Jefferies. Please go ahead.

Speaker #6: Hey, congrats on the updates. This is Matt Barkus, dialing in for Andrew Tsai. We've wanted to know with the well, would you expect lesion growth to hit stat sig 2 by month 24 as a secondary?

Speaker #2: Yeah. I mean, look, we've talked about this before. I have two thoughts on this, and they're maybe not one is maybe not the most popular.

Speaker #2: 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.

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

Speaker #2: They provide trophic support under their neurons that are responsible for vision. But it's not important to protect lesion growth for the purposes of protecting vision.

Speaker #2: And that's been borne out not only by our data, but clearly the first-generation approved therapies we have four or five years' worth of data of protecting lesion growth, but no impact on vision.

Doug Love: Thanks.

Lloyd Clark: Thanks, Anupam.

Lloyd Clark: Thanks so much for taking our question.

Anupam Rama: Thanks so much for taking our question.

Lloyd Clark: Absolutely.

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

Speaker #2: 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?

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

Speaker #2: 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.

Speaker #2: 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 in the second six months of the Archer study.

Doug Love: Yeah. Good morning, Derek. Really good question. I will start and then invite the others to join in. The 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 are very confident in our targets for masked event rates, as we have said. It has continued to track over the last several months, and it continues to do so today. So we are very pleased by that. To be completely candid, we fielded questions from various investors and strategics on the idea of adding a month 24 endpoint.

Speaker #2: So we expect that will continue. Whether that will be stat sig at 15 months, 24 months, a little bit TBD, but we do expect we will get there in time.

Speaker #2: So Lloyd, I don't know what you want to add on to that.

Speaker #4: Yeah. No, 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.

Speaker #4: 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.

Speaker #4: We do anticipate seeing protection of RPE lesion at the later time points based on our phase 2 data. And we recognize that we'll continue to have to discuss this from a historical perspective.

Doug Love: It absolutely creates a stronger overall profile for vonaprument 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. The notion of being able to run a really effective study that gave us additional power, and I am sure Lloyd 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 study, that we began to really consider whether or not we can be opportunistic, if you will, in playing a bit of offense here. So, Lloyd, maybe I will turn it over to you to see if you want to add anything to that.

Speaker #4: But I would encourage you to continue to play close attention to ellipsoid zone as a primary biomarker for this neurodegenerative disease.

Speaker #1: 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.

Speaker #5: Sorry about that. Good morning. Thanks for taking my question. What would be the commercial outlook if there when you think about what you plan to see for separation at month 15, but more of a stat sig outlook at 24 months?

Lloyd Clark: Yeah. Derek, thanks for the question. I am going to borrow from Doug. Doug likes to use sports analogies, and this is how it has 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 have had really encouraging patient retention in this study over single-digit percentages of dropouts, which is significantly lower than we anticipated.

Speaker #5: And how would a delayed time to response be perceived despite vision preservation here?

Speaker #2: Good morning, Salvine. Thanks for your question. I guess maybe a couple of 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 stat sig at month 24.

Speaker #2: 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.

Speaker #2: 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.

Lloyd Clark: So, sort of 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. We have not weakened the study at month 15 by any way. We are still extremely confident for where we stand at the month 15 time point. But we have given ourselves the flexibility through execution to look at a second time point.

Speaker #2: But I don't know, Floyd, if there's anything you'd like to add on this.

Speaker #4: 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 phase in the month 15 time point.

Speaker #4: 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.

Derek Archila: Very helpful. Thank you.

Doug Love: Thank you.

Operator: Great. Thanks for the questions, Derek Archila. Our next question comes from Andrew Tsai at Jefferies. Please go ahead.

Speaker #4: 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.

Matt Vargas: Hey. Congrats on the updates. This is Matt Vargas dialing in for Andrew Tsai. We wanted to know, would you expect lesion growth to hit stat sig too by month 24 as a secondary?

Speaker #3: One other quick point, Salvine. 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.

Doug Love: Yeah. 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. That's not because we don't think it's important to protect RPE cells. It is. They provide trophic support under the neurons that are responsible for vision. But it's not important to protect lesion growth for the purposes of protecting vision. That's been borne out not only by our data, but clearly the first-generation approved therapies that have four or five years' worth of data of protecting lesion growth, but no impact on vision. 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?

Speaker #1: Got it. Thank you. Thanks for the question, Salvine. Our next question comes from Joey Stringer at Needham. Please go ahead, Joey.

Speaker #2: Thanks for taking our questions and warning. I had a question just on the 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?

Speaker #2: Or has the statistical threshold there tightened?

Doug Love: 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. 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 in the second six months of the ARCHER study. So we expect that will continue. Whether that will be stat sig at 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.

Speaker #6: Yeah. Good morning, Joey. Good question. Lloyd, I'll turn it over to you and Jamie to talk about the alpha.

Speaker #4: Yeah. 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 the study have been exceeded due to strong trial execution.

Speaker #4: 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.

Lloyd Clark: Yeah. No, 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 play close attention to ellipsoid zone as a primary biomarker for this neurodegenerative disease.

Speaker #4: 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.

Speaker #2: Great. Thank you.

Speaker #6: Thanks, Joey.

Speaker #1: Yes. Thanks, Joey. Our next question comes from Ananda Ghosh at AC Wainright. Please go ahead, Ananda.

Speaker #6: Yeah. Hi. Thanks, and congrats on the quarter. Maybe the first question I have is, 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 that you see in line with the projections, is that track with what you have seen in your phase 1, phase 2, like the POC trial?

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

Speaker #6: Thank you.

Speaker #2: Yeah. Good question. Good morning, Ananda. Yeah. So both actually, Lloyd, I'll just turn it over to you.

Salveen Richter: Sorry about that. Good morning. Thanks for taking my question. What would be the commercial outlook 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?

Speaker #4: Sure. The first question about powering, yes, we are splitting alpha. We haven't disclosed specifically what that alpha split is going to be. But again, what I would tell you is that this change based on our execution updates allows us to split this alpha and retain phase 3 powering at the sub-study level and continue to be well overpowered for the phase 3 at the combined study.

Doug Love: Good morning, Salveen. Thanks for your question. I guess maybe a couple things. We expect to be positive at month 15. Month 15 is not just a speed bump look, but we expect stat sig at month 24. The base case is still winning at month 15. 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 4 or 5 years worth of data, and they haven't done it. So doing it more than half the time quicker than anybody's ever done it would be certainly not a delay. I don't know, Lloyd, if there's anything you'd like to add on this.

Doug Love: Good morning, Salveen. Thanks for your question. I guess maybe a couple things. We expect to be positive at month 15. Month 15 is not just a speed bump look, but we expect stat sig at month 24. The base case is still winning at month 15. 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's ever done it would be certainly not a delay. I don't know, Lloyd, if there's anything you'd like to add on this.

Speaker #4: 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.

Speaker #4: In terms of mass event rates, again, that really is our best metric in terms of understanding how trial execution is going. We follow that on a regular basis.

Speaker #4: 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.

Speaker #4: 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.

Lloyd Clark: 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 phase, in the month 15 time point, but we also have tremendous confidence that this drug will make a big benefit to patients. 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.

Speaker #4: And secondly, it gives us confidence in what we observed in terms of a treatment effect in the phase 2. So on target with mass event rates, and that leads to confidence with the month 15 primary endpoint.

Speaker #6: Thanks. Thanks so much.

Speaker #1: Thanks, Ananda. Our next question comes from Phil Nadeau at TD Cowan. Please go ahead, Phil.

Speaker #2: 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.

Jamie Dananberg: One other quick point, Salveen. This is Jamie. Just bear in mind, we have full confidence in month 15. What month 24 gets us is the ability to put efficacy data in the label at 2 years, which just adds to the overall story of vision protection for patients, not just at 15 months, but onward.

Jamie Dananberg: One other quick point, Salveen. This is Jamie. Just bear in mind, we have full confidence in month 15. What 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.

Speaker #2: Is that correct? Or I guess what are the scenarios for that data? Is a or for that release, is it possible that futility could be triggered in the trial will be stopped?

Speaker #2: 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.

Salveen Richter: Got it. Thank you.

Speaker #2: Then third, just a question on GBS. With the Q4 filing, have you had just 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?

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

Joseph Stringer: Thanks for taking our questions, and morning. I had a question just on the alpha allocation. With the month 15 and month 24 now independent 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?

Joey Stringer: Thanks for taking our questions, and morning. I had a question just on the alpha allocation. With the month 15 and month 24 now independent 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?

Speaker #2: Thank you.

Speaker #6: Yeah. Thanks, Phil. Thanks for joining us this morning. Maybe we'll start with GBS. I'll quickly answer that. Invite Jamie, and then we'll turn it over to Lloyd and others for the GA questions.

Speaker #6: 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 our program specific level.

Doug Love: Yeah. Good morning, Joey. Good question. Lloyd, I will turn it over to you and Jamie to talk about the alpha.

Speaker #6: 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.

Lloyd Clark: 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. Really, what we are 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. Essentially, what we are doing here is we are using found money in terms of strong trial execution to add a secondary time point. We are not in any substantive way reducing the likelihood of the month 15 win, but rather we are using the additional powering that we have achieved through execution to add a second time point.

Speaker #6: So we're encouraged all around on that. This program is moving in, of course, the discussions and interactions with the EU are going really, really well as well on things of advanced on multiple fronts.

Speaker #6: So GBS is coming. And we're excited by that because patients obviously need this therapy. With regard to GEA and the disclosure in Q4, as Jamie or as Lloyd spoke to, the DMC will take a look at this, and make a determination.

Speaker #6: 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 continued on, continued on.

Speaker #6: 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.

Speaker #6: And I'll just open it up to you, Lloyd, see if you want to add anything in addition to that.

Joseph Stringer: Great. Thank you.

Joey Stringer: Great. Thank you.

Doug Love: Thanks, Joey.

Operator: Yes. Thanks, Joey. Our next question comes from Ananda Ghosh at H.C. Wainwright & Co. Please go ahead, Ananda.

Speaker #4: 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.

Ananda Ghosh: Yeah. Hi. Thanks, and congrats on the quarter. Maybe the first question I have is if you can briefly talk about how the powering is designed for the sub-studies. The second thing is, if the blinded pooled event that you see in line with the projections, is that track with what you have seen in your phase I, phase II, like the POC trial? Thank you.

Speaker #4: 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.

Speaker #4: 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 3 level, both month 15 as well as month 24.

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

Lloyd Clark: 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 alpha and retain phase III powering at the sub-study level and continue to be well overpowered for the phase III 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've been at the beginning of the study. In terms of masked event rates, again, that really is 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.

Speaker #2: That's perfect. Thanks for taking our questions.

Speaker #6: Thank you.

Speaker #1: Thanks for the questions, Phil. Our final question comes from John Wallaban at Citizens. Please go ahead, John.

Speaker #5: Hey. Good morning. Thanks for the updated question. A couple of follow-ups for me. I'm wondering if in 4Q the decision is to continue the month 24 if you'll be seeing the data from the DMC and providing that publicly as well.

Speaker #5: And then just a question you mentioned your mass 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?

Speaker #5: Thanks, guys.

Speaker #6: Yeah. Thanks, John. Thanks for joining us. Yeah. First and foremost, John, could you repeat your first question? I actually lost her. Oh, I'm sorry.

Lloyd Clark: We continue to be on track, and that gives us this strong confidence that Doug talked 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 would be off in terms of event rates. Secondly, it gives us confidence in what we observed in terms of a treatment effect in the phase II. So on target with masked event rates, and that leads to confidence with the month 15 primary endpoint.

Speaker #6: Whether we can do month 24. Yeah. Whether we'd be seeing let me just start on that quickly, Lloyd. I just want to make a quick point on that.

Speaker #6: No, the short answer is no. It will be massed all the way through month 24, which is the pre-designed setup for that. Bear in mind, there's precedent for this.

Speaker #6: This has been done before. So if you look at the appellates phase 3 program and the Derby study in particular, it was a 12-month study.

Speaker #6: Primary endpoint, but to read out and with following patients out to month 24 and a massed fashion, they did not hit stat sig at month 12 and ultimately looked again at month 18.

Doug Love: Thanks. Thanks so much.

Ananda Ghosh: Thanks. Thanks so much.

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

Speaker #6: 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.

Phil Nadeau: Good morning. Thanks for taking our questions. Three from us. First, in terms of the Q4 disclosure, just what exactly will we learn? It sounds like you might be able to disclose whether you hit the primary endpoint, but the data will not come out until Q1 2027. Is that correct? Or, I guess, what are the scenarios for that data, or for that release? Is it possible that futility could be triggered and the trial will be stopped? That is first. Second question, follow-up to the last one, we are curious if you are 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.

Speaker #6: But to do so, you do need to remain massed at the time you take your first look at your data. So Lloyd, I'll turn it over to you to see if you want to add on to that.

Speaker #4: Yeah. No. Absolutely. So there will be no patient-level data released in the Q4 of 2026. Now, will then initiate the sub-study analysis and if both sub-studies are positive, then we'll have we're likely we'll have a different conversation about data in the first quarter of 2027.

Speaker #4: But again, you will have the results of the full analysis in line with the Q2026 Q4 2026 guidance. In terms your question about event rates was a great question about how do we essentially how do we model event rates out to 24 months given that our phase 2 study was only one year.

Doug Love: Yeah. Thanks, Phil. Thanks for joining us this morning. Maybe we will start with GBS. I will quickly answer that by Jamie, and then we will turn it over to Lloyd others for the GA questions. On the GBS front, we are in ongoing discussions with the FDA. I will say that we are 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. We are encouraged all around on that. This program is moving, and of course, the discussions and interactions with the EU are going really well as well, and things have advanced on multiple fronts there.

Speaker #4: 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.

Speaker #4: And so we've used a number of data points including our phase 2 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.

Speaker #4: 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.

Speaker #4: So we have that model, then we anticipate a similar behavior of that model in year two compared to year one.

Doug Love: GBS is coming, and we are 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. They have been and will continue to look at that over the course of the study, and thus far it has been continue on. At Q4, they will have an opportunity to disclose whether the study is positive at month 15 on the overall study or to continue on to month 24. I will just open it up to you, Lloyd, see if you want to add anything additional to that.

Speaker #1: Great. Thanks for the questions, John. So I'll now turn it back over to Doug to close out the call.

Speaker #6: 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.

Lloyd Clark: Oh, yeah. No, absolutely. We will 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. 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 III level, both month 15 as well as month 24.

Lloyd Clark: Oh, yeah. No, absolutely. We will 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 Q1 of 2027. But you will get results on the overall study in Q4 as promised. 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 III level, both month 15 as well as month 24.

Phil Nadeau: That is perfect. Thanks for taking our questions.

Lloyd Clark: Thank you.

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

John Woloshin: Hey, good morning. Thanks for taking the question. A couple follows from me. Wondering if in Q4, the decision is to continue to month 24, if you will be seeing the data from the DMC and providing that publicly as well. Then just a question, you mentioned your masked event rate is in line with projections. Can you tell us what that looks like? Then how do you think about month 24 projections without that data from ARCHER? Thanks, guys.

Doug Love: Yeah. Thanks, John. Thanks for joining us. Yeah. First and foremost, John, could you repeat your first question? I forgot. I actually lost it. Oh, I am sorry.

Lloyd Clark: It's about

Lloyd Clark: It's about whether you'll be seeing the data.

Lloyd Clark: Whether you'll be seeing the data

Doug Love: Whether we'd be seeing. Let me just start on that quickly, Lloyd. 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. If you look at the Apellis phase III 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 in a masked fashion. 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. We are doing this with the full light of day and with alignment with the regulators with regard to that.

Doug Love: To do so, you do need to remain masked at the time you take your first look at your data. Lloyd, I will turn it over to you if you want to add on to that.

Lloyd Clark: Yeah. No, absolutely. There will be no patient-level data released in Q4 2026. We'll then initiate the sub-study analysis, and if both sub-studies are positive, then we likely will have a different conversation about data in Q1 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 II 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 2-year study from the start.

Lloyd Clark: We've used a number of data points, including our phase II data, which is 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. 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 2 compared to year 1.

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

Doug Love: 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.

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Q2 2026 Annexon Inc Earnings Call

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