Annexon Q2 2026 Earnings Report

Annexon EPS Results

• Actual EPS: -$0.28
• Consensus EPS: -$0.24
• Beat/Miss: Missed by -$0.04
• One Year Ago EPS: N/A

Annexon Revenue Results

• Actual Revenue: N/A
• Expected Revenue: $6.50 million
• Beat/Miss: N/A
• YoY Revenue Growth: N/A

Annexon Announcement Details

• Quarter: Q2 2026
• Date: 8/12/2026
• Time: Before Market Opens
• Conference Call Date: Wednesday, August 12, 2026
• Conference Call Time: 8:00AM ET

Annexon (NASDAQ:ANNX) Inc. is a clinical-stage biotechnology company focused on the discovery and development of complement-targeted therapies for patients with neurodegenerative and neuroimmune diseases. The company’s research platform centers on the inhibition of the C1 complex, a key initiator of the classical complement pathway implicated in several rare and life-threatening disorders. By selectively targeting upstream complement activation, Annexon aims to prevent the aberrant immune-mediated damage that characterizes conditions such as Guillain-Barré syndrome (GBS) and autoimmune neuropathies.

At the core of Annexon’s pipeline is ANX005, a humanized monoclonal antibody directed against the C1q subcomponent, currently in Phase 2 clinical trials for acute GBS and chronic neurodegenerative indications. Complementing this program is ANX007, which targets C1s and is being evaluated in ophthalmic disorders such as geographic atrophy secondary to age-related macular degeneration. Preclinical studies and early human data have demonstrated the potential of these antibodies to modulate complement activity with favorable safety profiles, supporting further development in both inpatient and outpatient settings.

Founded in 2015 on the strength of foundational research from the University of Pennsylvania, Annexon is headquartered in San Francisco, California. The company was established by a team of scientists and industry veterans with deep expertise in the complement system and translational neuroscience. William B. Wetsel Jr., Ph.D., serves as President and Chief Executive Officer, guiding Annexon’s strategic initiatives and collaborations with academic partners, patient advocacy groups, and regulatory authorities.

Annexon’s clinical development programs span multiple geographies, with active sites in North America, Europe and Asia. By focusing on rare diseases with significant unmet medical need, the company seeks to deliver first-in-class therapies that can modify disease progression and improve patient outcomes. As a NASDAQ-listed entity (ANNX), Annexon continues to advance its portfolio toward pivotal milestones and potential regulatory approvals.

Annexon Q2 2026 Earnings Call Transcript

Key Takeaways

• Positive Sentiment: Tanruprubart showed rapid improvement in GBS patients: all 10 patients in the initial FORWARD cohort improved within four days, including recovery of walking ability in four bed-bound patients and ventilator weaning in one patient. Annexon plans to include the data in its U.S. BLA submission, still targeted for the fourth quarter of 2026.
• Positive Sentiment: Annexon expanded the ARCHER II geographic atrophy trial to include an independent month-24 dual primary endpoint while maintaining the month-15 endpoint. Management said strong enrollment, patient retention, dosing compliance, and trial execution provide sufficient power for both time points.
• Neutral Sentiment: The month-15 ARCHER II assessment remains expected in the fourth quarter of 2026, but patient-level data will remain masked if the trial continues to month 24. A month-15 success could lead to sub-study results in the first quarter of 2027, while completion of the full month-24 analysis is expected in the third quarter of 2027.
• Positive Sentiment: Annexon secured an Oxford Finance credit facility providing access to up to $200 million in non-dilutive capital, which management said extends its cash runway into 2028 and supports regulatory preparation and potential global commercialization.

Presentation

[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.

[Doug Love, President and CEO at Annexon]

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 III trial for vonaprument in 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 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.

[Doug Love, President and CEO at Annexon]

I will then close before we open the call for questions, where we will be joined by Dr. Chad Jednák, EVP and Chief Innovation Officer, and Yajing 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.

[Doug Love, President and CEO at Annexon]

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, 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.

[Doug Love, President and CEO at Annexon]

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.

[Doug Love, President and CEO at Annexon]

tanruprubart is now under regulatory review in Europe, and we are on track to submit the U.S. BLA in the fourth quarter 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 one, 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.

[Doug Love, President and CEO at Annexon]

We plan to include these data in our BLA submission in the fourth quarter. 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 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 III study designed to replicate those results. With masked 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 franchise.

[Doug Love, President and CEO at Annexon]

The endpoint is well-powered, requires no change to the conduct of the already masked 24-month trial, and gives vonaprument additional time to demonstrate the growing treatment effect observed in the proof of concept trial. Lloyd Clark 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 the second quarter took a strategic step to further strengthen our financial position.

[Doug Love, President and CEO at Annexon]

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.

[Jamie Dananberg, EVP and Chief Medical Officer at Annexon]

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 healthcare 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.

[Jamie Dananberg, EVP and Chief Medical Officer at Annexon]

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

[Jamie Dananberg, EVP and Chief Medical Officer at Annexon]

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 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.

[Jamie Dananberg, EVP and Chief Medical Officer at Annexon]

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.

[Jamie Dananberg, EVP and Chief Medical Officer at Annexon]

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 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 the fourth quarter 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.

[Doug Love, President and CEO at Annexon]

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

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

Thanks, Jamie.

[Doug Love, President and CEO at Annexon]

Lloyd.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

Thanks, Jamie. Before reviewing the vonaprument 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.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

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.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

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'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.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

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. 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 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.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

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.

[Doug Love, President and CEO at Annexon]

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. 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.

[Doug Love, President and CEO at Annexon]

We have established the most comprehensive and compelling GBS data package ever generated, including the first U.S.-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.

[Doug Love, President and CEO at Annexon]

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?

[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.

[Anupam Rama, Analyst at JPMorgan]

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 regulators both in the U.S. and globally, and what feedback you may have gotten on the strategy from regulators.

[Doug Love, President and CEO at Annexon]

Yeah.

[Anupam Rama, Analyst at JPMorgan]

Thanks so much.

[Doug Love, President and CEO at Annexon]

Yeah. Thanks, Anupam, and appreciate you joining us this morning. 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 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?

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

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 alpha at month 24 if we want to include efficacy data from that time point.

[Doug Love, President and CEO at Annexon]

Thanks. Thanks, Anupam.

[Anupam Rama, Analyst at JPMorgan]

Thanks so much for taking our question.

[Doug Love, President and CEO at Annexon]

Absolutely.

[Operator]

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

[Derek Archila, Analyst at Wells Fargo]

Hey, good morning, and thanks for taking the questions and congrats on the progress here. I guess maybe the first one is just, kind of bring us back, like what 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? 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.

[Doug Love, President and CEO at Annexon]

Yeah. Good morning, Derek. Really good question. I'll 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're very confident in our targets for masked 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. To be completely candid, we fielded questions from various investors and strategics on the idea of adding a month-24 endpoint.

[Doug Love, President and CEO at Annexon]

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'm 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 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.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

Yeah. Derek, thanks for the question. I think that 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. 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.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

So at this halftime evaluation of the study, we found ourselves with increased power, and 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.

[Derek Archila, Analyst at Wells Fargo]

Very helpful. Thank you.

[Doug Love, President and CEO at Annexon]

Thank you.

[Operator]

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

[Matt Bruso, Analyst at Jefferies]

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

[Doug Love, President and CEO at Annexon]

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 would 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?

[Doug Love, President and CEO at Annexon]

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 statistical significance at 15 months, 24 months, a little bit TBD, but we do expect we will get there in time. Lloyd, I don't know what you want to add on to that.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

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.

[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.

[Salveen Richter, Analyst at Goldman Sachs]

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 statistical significance outlook at 24 months, and how would a delayed time to response be perceived despite vision preservation here?

[Doug Love, President and CEO at Annexon]

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 statistical significance 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 do not know, Lloyd, if there's anything you'd like to add on this.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

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. 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.

[Jamie Dananberg, EVP and Chief Medical Officer at Annexon]

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.

[Salveen Richter, Analyst at Goldman Sachs]

Got it. Thank you.

[Operator]

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

[Joey Stringer, Analyst at Needham]

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?

[Doug Love, President and CEO at Annexon]

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

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

Yeah. Right. Good morning, Joey. Obviously, yes, we are splitting alpha between month 15 and month 24. 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.

[Joey Stringer, Analyst at Needham]

Great. Thank you.

[Doug Love, President and CEO at Annexon]

Thanks, Joey.

[Operator]

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

[Ananda Ghosh, Analyst at H.C. Wainwright]

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, does that track with what you have seen in your phase I, phase II, like the POC trial? Thank you.

[Doug Love, President and CEO at Annexon]

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

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

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.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

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 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.

[Ananda Ghosh, Analyst at H.C. Wainwright]

Thanks. Thanks so much.

[Operator]

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

[Phil Nadeau, Analyst at TD Cowen]

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 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.

[Doug Love, President and CEO at Annexon]

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 and 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, at a program-specific level. Those are ongoing discussions, and we feel quite confident that with the addition of the FORWARD 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, really well, as well, and things have advanced on multiple fronts there.

[Doug Love, President and CEO at Annexon]

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, and they have been and will continue to look at that over the course of the study. Thus far, it has been continue on, 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 in addition to that.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

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. 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 III level, both month 15 as well as month 24.

[Phil Nadeau, Analyst at TD Cowen]

That is perfect. Thanks for taking our questions.

[Doug Love, President and CEO at Annexon]

Thank you.

[Operator]

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

[Jon Wolleben, Analyst at Citizens]

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, President and CEO at Annexon]

Yeah. Thanks, Jon. Thanks for joining us. Yeah. First and foremost, Jon, could you repeat your first question? I forgot. I actually lost track. Oh, I am sorry. Whether we do month 24- Yeah, whether we would 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 is precedent for this. This has been done before. So 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.

[Doug Love, President and CEO at Annexon]

We wanted to make sure if we were in that circumstance, we did this prospectively. 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. Lloyd, I'll turn it over to you, see if you want to add on to that.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

Yeah, no, absolutely. So there will be no patient-level data released in the Q4 of 2026. We'll then initiate the sub-study analysis, and if both sub-studies are positive, then we'll likely 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 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 two-year study from the start. And so we've used a number of data points, including our phase II data, which is very, very valuable to us.

[Lloyd Clark, SVP of Ophthalmology Strategy and Innovation at Annexon]

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 continued 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.

[Operator]

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

[Doug Love, President and CEO at Annexon]

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.

Participants

Executives

• Doug Love, President and CEO
• Jamie Dananberg, EVP and Chief Medical Officer
• Lloyd Clark, SVP of Ophthalmology Strategy and Innovation

Analysts

• Anupam Rama, Analyst at JPMorgan
• Derek Archila, Analyst at Wells Fargo
• Matt Bruso, Analyst at Jefferies
• Salveen Richter, Analyst at Goldman Sachs
• Joey Stringer, Analyst at Needham
• Ananda Ghosh, Analyst at H.C. Wainwright
• Phil Nadeau, Analyst at TD Cowen
• Jon Wolleben, Analyst at Citizens