아넥손(ANNX) 2026년 2분기 실적 발표회: ARCHER II 확장, BLA 제출 순항

핵심 요약

• 아넥손(NASDAQ: ANNX)은 보나프루멘트의 ARCHER II 임상 3상 시험에 기존 15개월 시점 평가변수와 함께 독립적인 24개월 시점의 이중 1차 평가변수를 추가하여 임상을 확대했다. 경영진은 여전히 15개월 시점을 성공의 기본 시나리오로 보고 있다.
• ARCHER II 임상시험에는 당초 목표보다 30명 많은 659명의 환자가 등록되었다. 환자 중도 탈락률은 10% 미만, 투약 순응도는 95%를 상회했으며, 회사 측은 두 1차 평가 시점 모두에서 통계적 검정력이 90% 이상을 유지하고 있다고 밝혔다.
• 독립 데이터 모니터링 위원회는 2026년 4분기에 15개월 시점 평가변수를 평가할 예정이다. 긍정적인 결과가 나올 경우 2027년 1분기로 예정된 2개의 하위 연구 분석이 진행되며, 그렇지 않을 경우 블라인드 임상시험은 2027년 3분기 24개월 시점 분석까지 계속될 수 있다.
• 아넥손에 따르면, 탄루프루바트 30mg/kg을 단회 투여받은 초기 FORWARD 코호트의 환자 10명 전원이 4일 이내에 신속하고 임상적으로 의미 있는 개선을 보였다.
• 아넥손은 2026년 4분기에 탄루프루바트에 대한 미국 품목허가 신청(BLA)을 차질 없이 진행하고 있다. 유럽 허가 신청서는 이미 유럽의약품청(EMA)의 심사를 받고 있다.
• 옥스포드 파이낸스와의 신용 공여 약정을 통해 최대 2억 달러의 비희석성 자금을 확보할 수 있게 되었으며, 경영진은 이를 통해 회사의 현금 소진 소요 기간이 2028년까지 연장되었다고 밝혔다.

사업 및 영업 실적

길랭-바레 증후군 치료제 탄루프루바트

아넥손은 미국 및 유럽에서 진행된 FORWARD 연구의 초기 환자 10명에 대한 데이터를 강조했다. 모든 환자가 탄루프루바트 투여 후 4일 이내에 신속하고 임상적으로 의미 있는 근력 개선을 나타냈다.

초기에 침상 생활만 가능했던 환자 4명은 2일에서 8일 사이에 보조 기구 유무와 관계없이 다시 걸을 수 있게 되었다. 인공호흡기가 필요했던 환자 1명은 4일 이내에 호흡기를 뗐으며, 추가 환자 5명은 48시간 이내에 현저한 기능적 개선을 보였다.

탄루프루바트는 전반적으로 우수한 내약성을 보였다. 가장 주요한 이상반응은 길랭-바레 증후군 및 예상되는 합병증과 관련된 것이었으며, 안전성 프로필은 회사의 임상 3상 연구와 일치했다.

해당 코호트에는 중등도에서 중증 질환을 앓고 있는 12세에서 78세 사이의 남성과 여성이 포함되었다. 아넥손은 이번 결과가 투여 환자의 약 90%가 8일까지 임상적으로 의미 있는 개선을 보였던 임상 3상 결과와 일치한다고 밝혔다.

소아 환자를 포함한 FORWARD 연구는 미국과 유럽 전역에서 계속 진행 중이다. 본 연구는 약동학, 약력학, 초기 기능 및 바이오마커 영향, 안전성을 평가하고 있다.

지도모양 위축증 치료제 보나프루멘트

주요 임상인 ARCHER II는 지도모양 위축증으로 인한 비가역적 시력 손실 위험이 있는 환자를 대상으로 보나프루멘트를 평가하고 있다. 모든 적격 참가자는 최소 12개월 동안 치료를 받았으며, 블라인드 상태의 이벤트 발생률은 회사의 예상치에 부합하고 있다.

해당 임상시험은 이미 24개월 동안 블라인드 상태를 유지하도록 설계되어 있었다. 따라서 아넥손은 24개월 차 효능 평가변수를 추가하더라도 연구 운영에는 변화가 없으며, 제품 라벨에 2년 효능 데이터를 포함하는 데 도움이 될 수 있다고 밝혔다.

보나프루멘트는 미국 식품의약국(FDA)의 패스트 트랙 지정을 받았다. 또한 유럽의약품청(EMA)의 프라임(PRIME) 지정을 받은 유일한 지도모양 위축증 파이프라인이며, EMA의 제품 개발 코디네이터 파일럿 프로그램에도 선정되었다.

아넥손은 또한 ARCHER II 공개 연장 연구를 시작했다. 24개월을 완료한 후, 모든 적격 환자는 보나프루멘트를 투여받을 수 있어 회사가 장기적인 안전성과 잠재적 이점을 평가할 수 있게 된다.

경영진 가이던스

• 탄루프루바트 미국 BLA: 추가적인 FORWARD 데이터와 진행 중인 FDA와의 논의를 바탕으로 2026년 4분기로 계획됨.
• ARCHER II 15개월 차 평가: 2026년 4분기로 예상됨. 아넥손은 전체 연구 결과가 긍정적인지 또는 24개월 차까지 계속 진행할지 여부를 공개할 예정임.
• ARCHER II 하위 연구 결과: 15개월 차 전체 분석이 긍정적일 경우 2027년 1분기로 예상됨.
• ARCHER II 24개월 차 완료: 연구가 이후 평가변수까지 진행될 경우 2027년 3분기로 예상됨.
• 현금 소진 소요 기간: 경영진에 따르면 옥스포드 파이낸스와의 신용 공여 약정에 따라 2028년까지 연장됨.

리스크 및 관전 포인트

• 유의수준(알파)은 15개월 및 24개월 평가변수 사이에 분할 적용된다. 아넥손은 구체적인 배분 방식이나 정확한 통계적 검정력을 공개하지 않았으나, 경영진은 두 평가변수 모두 통상적인 임상 3상 수준의 검정력을 유지하고 있다고 설명했다.
• ARCHER II가 15개월 차 평가변수를 충족하지 못할 경우, 연구는 24개월 차까지 블라인드 상태가 유지된다. 이러한 시나리오에서는 2026년 4분기 평가 시 환자 수준의 데이터가 공개되지 않는다.
• 데이터 모니터링 위원회는 연구 계속을 권고하거나, 15개월 차 분석을 긍정적으로 선언하거나, 무용성을 결정할 수 있다.
• 경영진은 망막색소상피 병변 확장에 대한 보호 효과가 시간이 지남에 따라 나타날 것으로 기대하고 있으나, 15개월 또는 24개월 시점에서의 통계적 유의성 확보 여부는 여전히 불확실하다고 밝혔다.
• 보나프루멘트의 임상 2상은 1년 동안 진행되었다. 아넥손은 임상 2상 결과와 타 장기 프로토콜의 데이터를 활용하여 2년 차 이벤트 발생률을 모델링했다.

애널리스트 Q&A 주요 내용

애널리스트들은 24개월 차 평가변수 추가가 15개월 차 결과에 대한 우려를 반영한 것인지에 집중적으로 질문했다. 경영진은 15개월 차가 여전히 기본 시나리오라며 이러한 해석을 일축했다. 또한 초과 등록, 낮은 탈락률, 높은 투약 순응도 및 계획보다 강화된 통계적 검정력이 평가변수 추가의 이유라고 설명했다.

아넥손은 미국 및 유럽 규제 당국과 협의를 진행했음을 확인했다. 규제 당국은 제품 라벨에 2년 효능 데이터를 포함하려면 24개월 차 평가변수에 유의수준(알파)을 배분해야 한다고 지적했다.

상업적 포지셔닝과 관련해 경영진은 망막 전문의들이 15개월 또는 24개월 차에 효능이 입증되는지 여부와 관계없이 시력 보존을 잠재적인 혁신으로 보고 있다고 전했다. 회사는 보나프루멘트의 핵심 목표가 병변 성장 감소보다는 광수용체 및 신경원 보호에 있다고 강조했다.

탄루프루바트와 관련해 아넥손은 FDA와의 논의가 계속 진행 중이라고 밝혔다. 경영진은 FORWARD 데이터가 계획된 2026년 4분기 BLA 신청을 뒷받침할 것이라고 자신감을 내비쳤으나, 필요한 환자 수나 추적 관찰 기간에 대한 구체적인 세부 정보는 제공하지 않았다.

실적 발표 전화회의 전문

전체 실적 발표 컨퍼런스 콜 녹취록

경영진 발표

Operator

Good morning, everyone, and welcome to the Annexon Business Update Call. [Operator Instructions] 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.

Douglas 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 III trial for vonaprument in geographic atrophy, in 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. I will then close before we open the call for questions, where we will be joined by Dr. Ted Yednock, EVP and Chief Innovation Officer; and Jen Lew, 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 of serious neuroinflammatory diseases of the body, the brain and the eye. 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 of 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, irreversible blindness that robs millions of people of their independence.

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. 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 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. 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 and a potential $100 billion-plus franchise. 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 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 the 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 advanced towards registration, we also, in the second quarter, took a strategic step to further strengthen our financial position.

During the quarter, we entered a credit facility with Oxford Finance that provides access up to $200 million in non-dilutive capital, extending our cash runway into 2028. This facility enhances our financial and operational flexibility as we prepare for global commercialization while further diversifying our capital structure, strengthening our balance sheet and supporting both near- and longer-term growth strategies.

With that overview, I will now turn the call over to Jamie to review the recent data for our GBS program, following that, Lloyd will then discuss our vonaprument program updates in more detail. Jamie, over to you.

Jamie Dananberg

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 or 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 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 is still no approved targeted therapies that meaningfully alter the course of the disease. Current standard of care, intravenous immunoglobulin, or IVIG, is not FDA approved for GBS and provide incomplete benefit for many patients.

Despite treatment, 1-year mortality remains as high as 10% overall and approaches 25% of patients over the age of 65, many patients continue to deteriorate during or shortly after 5-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 loss of strength within 4 days of treatment. Importantly, 4 patients who are bed-bound early in the course of their disease, regain 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 4 days. 5 additional patients experienced marked functional improvement within 48 hours of treatment. Bear in mind that these outcomes with tanruprubart occurred well short of the 5-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 disease, and were consistent with the safety profile observed in our Phase III study. It's also worth noting that this initial cohort represented a broad cross-section of GBS patients, including both males and females, ranging from 12 to 78 years of age and spanning moderate to severe disease.

Importantly, these findings are consistent with the outcomes we observed in our Phase III study, where approximately 90% of patients demonstrated rapid, clinically meaningful improvement by day 8. Taken together, we believe these results provide further evidence of targeted inhibition of C1q with tanruprubart as the potential to fundamentally change the treatment paradigm for patients with GBS, by delivering rapid and meaningful clinical benefit after a single infusion.

Finally, I'd like to briefly touch on where we are from a regulatory and clinical development perspective. Our marketing authorization application is currently on track and under review by the European Medicines Agency and is supported by a comprehensive data package. This includes robust placebo-controlled studies demonstrating rapid improvement in function and disability as well as real-world evidence showing favorable outcomes compared with current standard of care, including IVIG and plasma exchange.

At the same time, we continue to advance the FORWARD study across the U.S. and Europe. This study is designed to expand our experience with 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 FDA in the fourth quarter of this year.

Together with 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.

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

Lloyd Clark

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. Currently, 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.

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 priority 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. 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 2 substudies, with results expected in the first quarter of 2027, or the DMC may recommend the study continue through the month 24 analysis.

The ARCHER II study, including month 24 analysis 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. 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'll turn the call back to Doug.

Douglas Love

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're playing to win for patients, stakeholders and each other.

To support that goal, over the course of this year, we have strengthened the balance sheet with non-dilutive 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 Blumenkranz, and the addition of key internal talent across the organization.

We've established the most comprehensive and compelling GBS data package ever generated, including the first U.S./EU trial in over 40 years, where all patients treated to date rapidly improved. We've also effectively executed and are executing the GA Phase III program, have now expanded the program to enhance the probability for overall success and we're continuing the steadfast work to deliver on the first and only oral therapy targeting the complement classical pathway. Each element is significant on its own. Together, they create the potential to drive substantial asymmetric value for Annexon and for others.

So in closing, I want to thank the patients, medical teams, supporters, employees and advisers who have joined us on this journey. We look forward to continuing to partner with you as we fully leverage the foundation we've laid over the next 6 to 18 months. And I want to thank all of you who are joining us this morning on today's call.

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

Operator

[Operator Instructions] So our first question comes from Anupam Rama at JPMorgan.

질의응답

Anupam Rama

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 the regulators.

Douglas Love

Yes. Thanks, Anupam, and appreciate you joining us this morning. The short answer is, yes, 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 we've made here this morning allows it to be counted in the label from an efficacy perspective.

And I don't know, Lloyd, is there anything you'd like to add on to that?

Lloyd Clark

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

Operator

Our next question comes from Derek Archila at Wells Fargo.

Derek Archila

Congrats on the progress here. So I guess maybe the first one is just, kind of bring us back like what kind of really drove the decision for the 24-month endpoint? Obviously, it's something that you can do. But I guess the main thing that I feel like people are going to be asking us is, what did you see in the blinded data? Is there worry around the 15-month endpoint? So maybe give us a sense of like the decision process but also your confidence in that 15-month endpoint.

Douglas Love

Yes. Derek, really good question. I'll start, and then invite the others to join in. So first and foremost, super confident in month 15. 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. 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. 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 win for others to come in and usurp us in a reasonable period of time. And so the notion that being able to run a really effective study that gave us additional power, and sure, Lloyd or Jamie will talk more about that, 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 I study that we began to really consider, whether or not it can be opportunistic, if you will, and playing a bit of offense here.

So Lloyd, maybe I'll turn it over to you if you want to add anything to that.

Lloyd Clark

Yes. Derek, thanks for the question. I mean I think I'm going to borrow from Doug. Doug likes to use sports analogies, and this is how it's made a lot of sense to me. We effectively went to the locker room at halftime as we were assessing the month 12 progress of the trial. And we came to 3 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 overenrolled the study by 30 patients. If you remember, we had such brisk enrollment at the end that we ended up overenrolling by 30 patients. So we had additional power there to spend. 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.

So sort of at this halftime evaluation of the study, we found ourselves with increased power. And so we made the strategic decision to apply that power to a second time point. So we have not weakened the study at month 15 by any way. We're still extremely confident for where we stand at the month 15 time point. But we've given ourselves the flexibility through execution to look at a second time point.

Operator

Our next question comes from Andrew Tsai, Jefferies.

Matthew Barcus

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

Douglas Love

Yes. I mean, look, we've talked about this before. I have 2 thoughts on it, and maybe not -- 1 is maybe not the most popular. On some level, we care about lesion growth. On another level, we don't as it relates to vision, and that's not because we don't think it's important to protect 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. And that's been borne out not only by our data, but clearly, the first generation approved therapies, we have 4, 5 years' worth of the 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? And I think that's very well elucidated. That being said, we were encouraged that by protecting photoreceptor cells over time, we're showing a healthier overall neuronal unit, which is showing greater protection to the lesion over time. And so when you look in the second 6 months of the study, we have a 10% protection over just a 6-month period of time in RPE growth in the second 6 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.

Lloyd Clark

Yes. 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. 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 continue to have to discuss this from a historical perspective. But I would encourage you to continue to pay close attention to ellipsoid zone as a primary biomarker for this neurodegenerative disease.

Operator

Our next question comes from Salveen Richter of Goldman Sachs.

Salveen Richter

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 static outlook at 24 months? And how would a delayed time to response be perceived despite vision preservation here?

Douglas Love

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. We are -- the base case is still winning at month 15. And I guess what I would say, would 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 out 4, 5 years' worth of data, and they haven't done it. So doing it more than half the time quicker than anybody has ever done it would be certainly not a delay.

But I don't know, Lloyd, if there's anything you'd like to add on this.

Lloyd Clark

Yes. 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. And so our goal, our primary goal is success of this program. This change by adding the month 24 time point increases our probability of success for the entire program, which would deliver a transformative therapy to the market.

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.

Operator

Our next question comes from Joey Stringer at Needham.

Joseph Stringer

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? Or has the statistical threshold there tightened?

Douglas Love

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

Lloyd Clark

Yes, right. 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. So really what we're looking at in terms of overall powering based on where we stand today, is a negligible difference at month 15 compared to where we thought we would be at the initiation of the study. And so essentially, what we're doing here is we're using found money in terms of strong trial execution to add a secondary time point.

So we are not in any substantive way reducing the likelihood of the month 15 win, but rather we're using the additional powering that we've achieved through execution to add a second time point.

Operator

Our next question comes from Ananda Ghosh at H.C. Wainwright.

Ananda Ghosh

Congrats on the quarter. Maybe the first question I have is like, if you can briefly talk about how the powering is designed for the sub-studies. And the second thing is, if the blinded pooled event 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?

Douglas Love

Yes. Good question, Ananda. Yes, so both -- actually, Lloyd, I'll just turn it over to you.

Lloyd Clark

Sure. The first question about powering, yes, we are splitting alpha, and 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 out and retain Phase III powering at the substudy 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 have been at the beginning of the study.

In terms of masked event rates, again, that really is our -- really our best metric in terms of understanding how trial execution is going. We follow that on a regular basis. We have multiple models to predict where we're going to be. We continue to be on track and that gives us this strong confidence that Doug talked about in the month 15 time point. It gives us confidence 2 ways. It gives us confidence that we understand the disease process well, because otherwise, we'd be off in terms of event rates. And secondly, it gives us confidence in what we observed in terms of a treatment effect in the Phase II. So on target with masked event rates, and that leads to confidence with the month 15 primary endpoint.

Operator

Our next question comes from Phil Nadeau at TD Cowen.

Philip Nadeau

Three from us. First, in terms of the Q4 disclosure, I guess what exactly will we learn? It sounds like you might be able to disclose whether you hit the primary endpoint, but the data won't come out to Q1 2027. Is that correct? Or I guess, what are the scenarios for that data is a -- or for that release, is it possible that futility could be triggered, and the trial will be stopped? That's first.

Second question, a 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. And third, just a question on GBS. With the Q4 filing, have you had further discussions with the FDA and the number of patients and follow-up necessary from FORWARD? Or are you just going with your prior understanding.

Douglas Love

Yes. Thanks, Phil. Thanks for joining us this morning. Maybe we'll start with GBS. I'll quickly answer that by Jamie, and then we'll turn it over to Lloyd for the GA questions. On the GBS front, we are in ongoing discussions with the FDA. So I will say that we're really encouraged with the posture of the FDA, both at the macro level and then at the micro level and a program-specific level. Those are ongoing discussions, and we feel quite confident that with the addition of the FORWARD data, we will be filing for BLA in Q4 of this year.

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, and things have advanced on multiple fronts there. So GBS is coming, and we're excited by that because patients obviously need this therapy.

With regard to GA and disclosure, in Q4, as Jamie -- or 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 we'll continue to look at that over the course of the study. And thus far, it's been continue on, continue on. At Q4, they'll have an opportunity to disclose whether the study is positive at month 15 on the overall study or to continue on to month 24. And I'll just open it up to you, Lloyd, see if you want to add anything in addition to that.

Lloyd Clark

Yes. No, that's absolutely. So we'll find out in Q4, if the study is positive, or, as Doug said, if we continue on to month 24. If the study is positive in Q4, that will trigger the initiation of the 2 substudy 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.

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 in a conventional Phase III level, both month 15 as well as month 24.

Operator

Our final question comes from Jon Wolleben at Citizens.

Jonathan Wolleben

A couple follows from me. Wondering if in 4Q, the decision is to continue to month 24, if you will be seeing the data from the DMC and providing that publicly as well. And then just a question, you mentioned your masked event rate is in line with projections. Can you tell us what that looks like? And then how do you think about month 24 projections without that data from ARCHER?

Douglas Love

Yes. Thanks, Jon. Thanks for joining us. Yes, first and foremost, Jon, could you repeat your first question? I forgot. I actually lost -- I'm sorry. Whether we do month 24. Yes, whether we would be seeing. Let me just start on that quickly, Lloyd, I just want to make a quick point on that. Now the short answer is no. It will be masked all the way through month 24, which is the predesigned setup for that. Bear in mind, there's 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 primary endpoint, but to read out and with following patients out to month 24 and 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. So we're doing this with the full light of day and with alignment -- with the regulators with regard to that. But to do so, you do need to remain masked at the time you take your first look at your data. So Lloyd, I'll turn it over to you, see if you want to add on to that.

Lloyd Clark

Yes. No, absolutely. So we'll -- there will be no patient-level data released in the Q4 of 2026. We'll then initiate the substudy analysis. And if both substudies are positive, then we'll have -- likely we'll have a different conversation about data in the first quarter of 2027. But again, you'll have the results of the full analysis in line with the 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 II study was only 1 year. Well, keep in mind, as we've discussed publicly, we did an extensive review of event rates. We planned a 2-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, but a number of other data points, including trials that lasted much longer than 12 months, to arrive at models for events. And in general, events in geographic atrophy continue to progress for several years. So we have a good handle on what the events should look like in the second year based on our review of multiple different protocols. So we have that modeled, and we anticipate a similar behavior of that model year 2 compared to year 1.

Operator

So I'll now turn it back over to Doug to close out the call.

Douglas 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.