Apellis Pharmaceuticals Inc (APLS) 2023 Q2 法說會逐字稿

Good day, and thank you for standing by. Welcome to Apellis Pharmaceuticals Second Quarter 2023 Earnings Conference Call. (Operator Instructions) Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Meredith Kaya. Please go ahead.

各位好，感謝您稍候。歡迎參加 Apellis Pharmaceuticals 2023 年第二季財報電話會議。（接線員指示）請注意，今天的會議將被錄音。現在我想把會議交給今天的發言人 Meredith Kaya。請開始。

Good morning, and thank you for joining us today. Earlier this morning, we reported our second quarter 2023 financial results. We will be happy to take questions from you on these results in the Q&A session. However, we will be focusing our prepared remarks today on SYFOVRE, including feedback from the recent ASRS Annual Meeting and an update on our comprehensive review of the rare safety events. With me on the call are Co-Founder and Chief Executive Officer, Dr. Cedric Francois; Chief Commercial Officer, Adam Townsend; Chief Medical Officer, Dr. Caroline Baumal; and Chief Financial Officer, Tim Sullivan.

各位早安，感謝今天加入我們。今天稍早，我們已公布 2023 年第二季財務業績。我們很樂意在問答環節就這些結果回答各位的問題。不過，我們今天的事先準備發言將聚焦於 SYFOVRE，包括近期 ASRS 年會的回饋，以及我們對罕見安全性事件之全面性檢視的最新進展。與我一同參與電話會議的有共同創辦人暨執行長 Cedric Francois 博士；首席商務長 Adam Townsend；首席醫療長 Caroline Baumal 博士；以及財務長 Tim Sullivan。

Before we begin, let me point out that we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties and that actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail. Now I'll turn the call over to Cedric.

在開始之前，我要指出我們將發表以前瞻性陳述為主的內容，這些陳述係基於我們目前的預期與信念。這些陳述受到特定風險與不確定性影響，實際結果可能出現重大差異。我建議各位參閱我們向 SEC 提交文件中所討論的風險因素，以取得更多細節。現在我把電話交給 Cedric。

Thank you, Meredith, and thank you all for joining us today. As Meredith said, we are going to take a different approach on today's call and focus the discussion on the rare events of escalators we have seen with SYFOVRE. We know you have questions, and we will do our best to answer as many of them as we can. But before we do, let me provide some overarching comments.

謝謝你，Meredith，也謝謝各位今天加入我們。如 Meredith 所說，我們今天的電話會議將採取不同方式，聚焦討論我們在 SYFOVRE 上所見到的罕見視網膜血管炎事件。我們知道各位有問題，我們會盡力回答盡可能多的問題。不過在此之前，先讓我提出一些總體性的說明。

First, I have never been prouder to be part of the Apellis team. The past few weeks have been challenging and once again, the team has shown incredible dedication and resilience. Second, we had a strong second quarter. We reported approximately $90 million in total product sales, including $67 million for SYFOVRE, demonstrating the early strength of this launch. With more than 68,000 vials of SYFOVRE now distributed to physicians, SYFOVRE is having a positive impact on the lives of tens of thousands of patients across the United States.

第一，我從未像現在這樣以身為 Apellis 團隊的一員而感到自豪。過去幾週充滿挑戰，而團隊再次展現了驚人的投入與韌性。第二，我們第二季表現強勁。我們報告的產品總銷售額約 9,000 萬美元，其中 SYFOVRE 為 6,700 萬美元，展現了這次上市初期的強勁動能。目前已有超過 68,000 瓶 SYFOVRE 配送至醫師端，SYFOVRE 正在對全美數以萬計患者的生活帶來正面影響。

And third, SYFOVRE continues to demonstrate increasing effects over time. Data from our GALE long-term extension study showed a reduction in non-subfoveal GA lesion growth of up to 45% between months 24 and 30 as compared to projected sham. These are incredible findings further strengthening our understanding of SYFOVRE as an important treatment for patients with GA.

第三，SYFOVRE 持續展現隨時間增加的療效。我們的 GALE 長期延伸研究數據顯示，與推估的安慰劑組相比，在第 24 至 30 個月期間，非中央凹（non-subfoveal）GA 病灶生長可降低最高達 45%。這些令人振奮的發現，進一步強化我們對 SYFOVRE 作為 GA 患者重要治療選項的理解。

With that, let's get into the discussion. Patient safety is our top priority, and we care deeply for the physicians who rely on us. We are conducting a comprehensive investigation into the potential causes of the events of vasculitis working closely within the retina community. We do not know the cause yet. And realistically, we may never identify a singular cause. What we do know, however, is that these events have been very rare and sporadic and that 0 events were reported in our clinical studies. SYFOVRE is a newly launched drug in a new disease with a new mechanism of action. It is not unexpected that events may emerge when bringing a drug into the real world, but it is expected that we take them very seriously.

接下來進入討論。病人安全是我們的首要優先事項，我們也非常重視仰賴我們的醫師。我們正與視網膜醫療社群密切合作，針對血管炎事件的可能原因進行全面性調查。我們目前尚不清楚原因。實際上，我們也可能永遠無法找出單一原因。然而，我們確知的是，這些事件非常罕見且零星，而且在我們的臨床研究中未報告任何事件。SYFOVRE 是一款新上市藥物，用於一個新疾病領域，且具新的作用機轉。當藥物進入真實世界使用時出現事件並非完全出乎意料，但我們必須非常嚴肅地看待。

Now let's get into some of your questions. First, what do we know so far about these events? And what are the visual outcomes for these patients? I will hand it over to Caroline to speak about this. Caroline?

現在來回答各位的一些問題。首先，關於這些事件，我們目前已知哪些資訊？這些患者的視覺結局如何？我把時間交給 Caroline 來說明。Caroline？

Thank you, Cedric. As we get into the details, I want to recognize the patients and physicians who have been impacted by these rare but serious events. I will reiterate what Cedric said, patient safety is and has always been our top priority, along with providing physicians with the information they need to make the best decisions for their patients. Let me share what we know today. Overall, these events have been rare. We have confirmed 7 events since our launch in March and 1 additional reported event is being evaluated by Apellis. More than 68,000 vials of SYFOVRE have been distributed to physician practices. And based on our research, we estimate over 60,000 of those have been administered to patients.

謝謝你，Cedric。在進入細節之前，我想先向受到這些罕見但嚴重事件影響的患者與醫師致意。我再次重申 Cedric 所說，病人安全一直且永遠是我們的首要優先事項，同時也會向醫師提供其為患者做出最佳決策所需的資訊。以下分享我們目前所知。整體而言，這些事件相當罕見。自 3 月上市以來，我們已確認 7 起事件，另有 1 起通報事件正在由 Apellis 評估中。已有超過 68,000 瓶 SYFOVRE 配送至醫師診所。根據我們的研究估算，其中超過 60,000 瓶已施打給患者。

These events occurred sporadically. There were 2 events following injections in April, 2 in May and 3 in June. This is important because as the number of injections increased each month, there was not a corresponding increase in the number of vasculitis events. Each event happened between 7 and 13 days following drug administration and all cases reported to Apellis occurred after the first injection.

這些事件呈零星發生。4 月注射後有 2 起事件、5 月 2 起、6 月 3 起。這點很重要，因為隨著每月注射次數增加，血管炎事件數並未相應增加。每起事件皆發生於給藥後 7 至 13 天之間，且所有通報給 Apellis 的病例皆發生在首次注射之後。

We recognize that the numbers we reported on Saturday are slightly different than the numbers presented by ASRS. This is because we make determinations based on the information that we received directly from the treating physician and following review by external retina and uveitis specialists. Given physician confidentiality, we must be careful in what we share regarding detailed patient information. Additionally, these are highly complex cases and are sometimes difficult to interpret. However, we are working closely with ASRS to make sure we are better aligned in how we evaluate each of these events going forward.

我們注意到，我們在週六公布的數字與 ASRS 所呈現的數字略有不同。這是因為我們的判定係根據治療醫師直接提供給我們的資訊，並經外部視網膜與葡萄膜炎專家審閱後做出。基於醫師與患者的保密性，我們在分享詳細患者資訊時必須謹慎。此外，這些病例高度複雜，有時也不易解讀。不過，我們正與 ASRS 密切合作，以確保未來在評估每一事件時能更一致、更對齊。

It is still too early to know the outcomes for each of these patients. Retina vasculitis by definition is a severe inflammatory event that can potentially lead to significant vision loss. With standard of care treatment, we hope patients will recover, but this can take up to a few months. Of the 7 confirmed patients reported to us to date, 2 have recovered vision nearly back to baseline, 2 have severe vision impairment and are unlikely to be resolved and 3 are still evolving. For the 1 suspected case, the patient's vision has already returned to baseline. Working with the physicians, we are monitoring each of these patients very closely.

目前仍言之過早，尚無法得知每位患者的最終結局。依定義，視網膜血管炎是一種嚴重的發炎事件，可能導致顯著視力喪失。透過標準治療，我們希望患者能恢復，但可能需要長達數個月。就目前通報給我們且已確認的 7 位患者而言，其中 2 位視力幾乎恢復至基線，2 位有嚴重視力損害且不太可能改善，另有 3 位仍在演變中。至於 1 起疑似病例，該患者視力已回到基線。我們正與醫師合作，密切監測每位患者的狀況。

Thank you, Caroline. The next question is why these events are happening. What are we doing to find the cause? And what do we know so far?

謝謝你，Caroline。下一個問題是：為什麼會發生這些事件？我們正在做什麼來找出原因？以及目前我們已知哪些資訊？

These are really important question and we have been collaborating with the retina community to better understand the potential factors contributing to these events. One of the first questions we asked ourselves was why we did not see this in the clinical trials. There is a robust process for evaluating safety in a clinical study. Patients are assessed by the trial investigator and all imaging from the study is reviewed by a mass independent reading center. Following more than 23,000 SYFOVRE injections administered in our studies to date, 0 events of vasculitis have been reported. To confirm these findings, one of the first things we did upon receiving these case reports is go back to our Phase III data to make sure that nothing was missed.

這些都是非常重要的問題，我們一直與視網膜醫療社群合作，以更深入了解可能促成這些事件的因素。我們最先問自己的問題之一是：為什麼在臨床試驗中沒有看到這種情況？臨床研究中有一套嚴謹的安全性評估流程。患者由試驗研究者評估，且研究中的所有影像皆由大型獨立判讀中心審閱。截至目前，在我們研究中已施打超過 23,000 次 SYFOVRE 注射，未報告任何血管炎事件。為確認這些發現，在收到這些病例報告後，我們做的第一件事之一就是回頭檢視第三期數據，以確保沒有遺漏任何情況。

We rereviewed all cases of intraocular inflammation and retina vascular occlusion and confirmed no vasculitis event. Additionally, we asked the panel of retina and uveitis specialists to rereview all severe intraocular inflammation events as well as 2 leading neuro-ophthalmologists to rereview our ischemic optic neuropathy event, both of whom further confirmed that there were no vasculitis events. We also know from our clinical trials that there was no indication of drug-related immunogenicity. Data showed no correlation between IOI events and any antidrug antibodies, providing evidence that these events were unlikely to be caused by an immune response to either the peptide or to polyethylene glycol. These findings are important to our investigation as there were no changes in the formulation of the product between clinical and commercial supply.

我們重新審閱所有眼內發炎（IOI）與視網膜血管阻塞的病例，並確認沒有血管炎事件。此外，我們請視網膜與葡萄膜炎專家小組重新審閱所有嚴重眼內發炎事件，並請兩位頂尖神經眼科醫師重新審閱我們的缺血性視神經病變事件；兩方皆進一步確認並無血管炎事件。我們也從臨床試驗得知，沒有任何藥物相關免疫原性的跡象。數據顯示 IOI 事件與任何抗藥物抗體之間沒有相關性，提供證據顯示這些事件不太可能是對胜肽或聚乙二醇（polyethylene glycol）的免疫反應所致。這些發現對我們的調查很重要，因為臨床與商業供應之間的產品配方並無任何變更。

Thank you, Caroline. So if we did not see anything in the clinical trials, then what else are we looking into as a potential cause?

謝謝你，Caroline。所以如果在臨床試驗中沒有看到任何訊號，那麼我們還在把哪些方向納入可能原因的調查？

The next important area we look into was manufacturing processes and drug quality and there is no indication that these contributed to the vasculitis events. No single manufacturing lot was implicated. No manufacturing issues were identified related to intraocular inflammation and no quality issues or contamination such as endotoxins were found. There has been some confusion around SYFOVRE being a biologic and that these events may have been due to endotoxin. To clarify, SYFOVRE is not a biologic. It is a synthetic peptide that binds specifically to C3 and C3b. Levels of drug products endotoxin in all clinical and commercial batches of SYFOVRE are significantly lower than the reporting threshold and the FDA's expectation for ophthalmic dosage forms for injection. As for what else, we are continuing to investigate potential contributing factors. This includes looking into patient characteristics as well as evaluating any variations from the clinical trials to real world. We don't have any answers on these today.

我們接下來調查的另一個重要面向是製造流程與藥品質量，目前沒有任何跡象顯示這些因素導致血管炎事件。沒有任何單一製造批次被指涉。未發現與眼內發炎相關的製造問題，也未發現任何品質問題或污染（例如內毒素）。外界對 SYFOVRE 是否為生物製劑，以及這些事件是否可能由內毒素造成，存在一些混淆。為釐清，SYFOVRE 並非生物製劑；它是一種可特異性結合 C3 與 C3b 的合成胜肽。所有臨床與商業批次 SYFOVRE 的藥品內毒素水準，均顯著低於通報門檻以及 FDA 對眼科注射劑型的預期。至於其他可能性，我們仍在持續調查潛在的促成因素，包括檢視患者特徵，以及評估臨床試驗與真實世界使用之間的任何差異。我們今天尚無答案。

Thanks again, Caroline. Okay. Now that we've talked about the investigation, let's turn to how the conversations have been with physicians over the past few weeks, and of course, specifically here at SRS. Caroline, why don't you start and then turn it over to Adam to share what you're both hearing from the retina community, and what this might mean for treatment going forward?

再次感謝你，Caroline。好的。既然我們已經談過調查，接下來讓我們把焦點轉向過去幾週與醫師之間的對話情況，當然也特別是在這裡的 SRS。Caroline，你先開始，然後再交給 Adam，分享你們兩位從視網膜社群聽到的回饋，以及這對未來治療可能意味著什麼？

Sure. Thanks, Cedric. Over the past 2 weeks, we have been deeply engaged with the physician community. And as Adam will share also conducted some early market research to better understand perception and impact. Upon hearing of these events, the first thing I did was reach out to multiple physician practices to better understand their experiences with SYFOVRE so far. These are physicians who in total have administered thousands of SYFOVRE injections to date, and they have not seen any cases of vasculitis. Since then, we have continued to talk with dozens of leading experts in our field and just spent the past 4 days with hundreds of retina specialists at the ASRS meeting in Seattle.

好的。謝謝你，Cedric。過去兩週，我們一直與醫師社群密切互動。而且如 Adam 也會分享的，我們也進行了一些早期市場研究，以更好地了解外界的觀感與影響。得知這些事件後，我做的第一件事就是聯繫多家醫師診所，以更深入了解他們迄今為止使用 SYFOVRE 的經驗。這些醫師合計至今已施打了數千針 SYFOVRE 注射，但他們並未看到任何血管炎病例。此後，我們持續與本領域數十位頂尖專家交流，並在西雅圖的 ASRS 會議上與數百位視網膜專科醫師共度了過去 4 天。

Overall, physicians are eager for more information, and this will take time and more data. These are serious safety events and physicians need to understand how to think about treatment. As a retina physician, I can attest that my colleagues are experts when it comes to treating their patients, especially with intravitreal injections. They are thoughtful in the decisions that they make, understand the risks associated with these therapies and can effectively communicate the benefit risk profile to their patients.

整體而言，醫師們渴望獲得更多資訊，而這需要時間與更多數據。這些是嚴重的安全性事件，醫師需要了解該如何看待治療。作為一名視網膜醫師，我可以證明我的同儕在治療病患方面是專家，尤其是在玻璃體內注射方面。他們在所做的決策上很審慎，了解這些療法相關的風險，並能有效地向病患溝通其效益—風險概況。

I'll turn it over to Adam to share a bit of what he and his team are also hearing.

我把時間交給 Adam，請他分享一下他和他的團隊也聽到了什麼。

Thanks, Caroline, and good morning, everyone. The commercial team has also spent an enormous amount of time engaging with retina doctors over the past few weeks. And then in person this weekend at ASRS. Our #1 priority is to make sure that physicians know that we are sharing information with them as quickly as we can and that we are available to answer any questions they have. Following the member communication from ASRS, we have sent 2 communications to physicians sharing additional color and context about these events and held numerous calls with our physicians and our speakers.

謝謝你，Caroline，各位早安。商業團隊在過去幾週也投入了大量時間與視網膜醫師互動，並在本週末於 ASRS 現場面對面交流。我們的首要任務是確保醫師知道：我們會盡可能快速地與他們分享資訊，並且我們隨時可用以回答他們的任何問題。在 ASRS 的會員溝通之後，我們已向醫師發出兩次溝通，提供關於這些事件的更多細節與背景，並與我們的醫師及講者進行了多次通話。

The feedback we are getting from the field is very consistent with what Caroline spoke to earlier. Additionally, and prior to the ASRS meeting, we conducted some early market research with U.S. retina specialists, most of whom had previous experience treating patients with SYFOVRE. The key takeaways of this survey were that 1/3 of the survey doctors said they plan to continue using SYFOVRE as they had been prior to the vasculitis events in both new and existing patients. The next 1/3 said they plan to continue using SYFOVRE in their existing patients but may pause use in new patients. And the remaining 1/3 of doctors said they plan to pause treatment until they have more information or until their patients request treatment. Based on this, we do anticipate some sale bumpiness in the near term as many seek to gain more information.

我們從第一線收到的回饋，與 Caroline 先前提到的非常一致。此外，在 ASRS 會議之前，我們也對美國視網膜專科醫師進行了一些早期市場研究，其中多數人先前有使用 SYFOVRE 治療病患的經驗。這份調查的重點結論是：三分之一的受訪醫師表示，他們計畫在新病患與既有病患上，仍將如同血管炎事件發生前一樣繼續使用 SYFOVRE。接下來三分之一表示，他們計畫在既有病患上繼續使用 SYFOVRE，但可能會暫停在新病患上的使用。其餘三分之一的醫師表示，他們計畫暫停治療，直到獲得更多資訊，或直到病患主動要求治療。基於此，我們確實預期短期內銷售可能會出現一些波動，因為許多人希望先獲得更多資訊。

Our job is to be a thoughtful, transparent partner over these next few months. We believe it is important to continue to bring this treatment to the millions of people suffering from GA in the U.S. and to be ready to bring this to patients worldwide very soon. A quick update on the latter. Our marketing applications are under review in multiple territories worldwide, including the EU, and we expect approval decisions starting in early 2024. With that, Cedric, I'll hand it back to you.

我們的工作是在接下來幾個月成為一個審慎且透明的合作夥伴。我們相信，持續將此治療帶給美國數以百萬計受 GA 影響的人非常重要，並且也要準備好在不久的將來把它帶給全球病患。關於後者快速更新一下：我們的上市申請正在全球多個地區審查中，包括歐盟，我們預期自 2024 年初開始陸續收到核准決定。Cedric，我把時間交回給你。

Thank you, Adam. Okay. Another question on everyone's mind is how we think these rare events will impact SYFOVRE sales and ultimately, of course, our cash runway. And how are we thinking about financing at this point? Tim, can you comment on this?

謝謝你，Adam。好的。大家心中另一個問題是：我們認為這些罕見事件將如何影響 SYFOVRE 的銷售，並最終影響我們的現金可支撐期間（cash runway）。以及我們目前如何看待融資？Tim，你可以評論一下嗎？

Of course. Thanks, Cedric. As of the second quarter, we had $1,616 million (sic) [$616 million] in cash. based on our current assumptions, this provides us with a runway into the first quarter of 2025. However, these safety events may impact the sales trajectory in the near term, but because it is all very new, we don't know the magnitude. We are monitoring demand very closely and in parallel, looking at our overall spend to ensure we are being disciplined and thoughtful going forward. We will be transparent with you, but we don't have all of the details for you today. As for financing, we are not under any immediate pressure to raise money. As we always do, we will evaluate multiple ways in which to finance the company at the right time and with our shareholders in mind.

當然。謝謝你，Cedric。截至第二季，我們有 1,616 百萬美元（原文如此）[6.16 億美元] 的現金。根據我們目前的假設，這可提供我們的資金支撐至 2025 年第一季。不過，這些安全性事件可能會在短期內影響銷售軌跡，但由於一切都還很新，我們尚不清楚影響幅度。我們正非常密切地監測需求，同時也在檢視整體支出，以確保未來我們保持紀律並審慎行事。我們會對各位保持透明，但今天我們還沒有所有細節可提供。至於融資，我們目前沒有任何立即募資的壓力。如同一貫作法，我們會在適當時點、並以股東利益為念，評估多種為公司籌資的方式。

Thank you, Tim. On to the last question then because the ASRS was not just about safety for us this weekend. We also presented some exciting new data from our GALE long-term extension study. Caroline, can you please give us an overview about some of the new data that was shared.

謝謝你，Tim。那麼進入最後一個問題，因為這個週末的 ASRS 對我們而言不僅僅是安全性議題。我們也發表了來自 GALE 長期延伸研究的一些令人振奮的新數據。Caroline，你能否為我們概述一下所分享的新數據？

Yes. Absolutely. Thanks, Cedric. We had a strong presence at ASRS this weekend with 7 podium presentations. Notably, we shared for the first time data from our GALE extension study, reinforcing the long-term efficacy and safety of SYFOVRE. These data demonstrated that SYFOVRE reduced GA lesion growth by up to 39% in the monthly arm between months 24 and 30 as compared to the projected sham arm. What we were most excited about were the effects seen in nonsubfoveal GA patients, as Cedric mentioned earlier. Between months 24 and 30, SYFOVRE reduced nonsubfoveal GA lesion growth by 45% in the monthly arm. This means that within 3 years, patients with nonsubfoveal lesions are seeing the rate of GA progression slow by nearly half.

可以，當然。謝謝你，Cedric。我們這個週末在 ASRS 有很強的能見度，共有 7 場口頭報告。值得注意的是，我們首次分享了 GALE 延伸研究的數據，進一步強化 SYFOVRE 的長期療效與安全性。這些數據顯示，在第 24 至第 30 個月期間，相較於推估的假治療（sham）組，SYFOVRE 在每月給藥組可將 GA 病灶生長降低最多達 39%。如 Cedric 先前提到，我們最興奮的是在非中心凹下（nonsubfoveal）GA 病患中觀察到的效果。在第 24 至第 30 個月期間，SYFOVRE 在每月給藥組可將非中心凹下 GA 病灶生長降低 45%。這意味著在 3 年內，具有非中心凹下病灶的病患，其 GA 進展速度幾乎減緩一半。

This is the first time we have seen slowing of GA lesion growth at this level in a large, well-controlled study. The safety profile in GALE was consistent with previously reported Phase III data. In addition to the GALE data, we also shared data using AI technology, demonstrating the effect of SYFOVRE in protecting photoreceptor cell degeneration. Photoreceptor cells are responsible for visual acuity and the degradation of these photoreceptor cells are significantly reduced upon initiation of SYFOVRE treatment. Both the GALE and the photoreceptor data along with additional analysis presented over these past few days contribute to the most robust data set against GA and reinforce the importance of treatment with SYFOVRE to help to protect against this irreversible disease. I'll turn it back over to Cedric for closing remarks.

這是我們首次在一項大型、良好對照的研究中，看到 GA 病灶生長能以這樣的幅度被減緩。GALE 的安全性概況與先前報告的第三期數據一致。除了 GALE 數據之外，我們也分享了運用 AI 技術的數據，顯示 SYFOVRE 在保護感光受器細胞退化方面的效果。感光受器細胞負責視力（視覺敏銳度），而在開始 SYFOVRE 治療後，這些感光受器細胞的退化會顯著降低。GALE 與感光受器數據，加上過去幾天所呈現的額外分析，共同構成了針對 GA 最為扎實的數據集，並再次強調使用 SYFOVRE 治療以協助對抗這種不可逆疾病的重要性。我把時間交回給 Cedric 做結語。

Thank you, Caroline. We are very excited about the data presented at ASRS. Although it has been a turbulent few weeks, we believe that we have a strong future ahead of us. We are closely monitoring the safety of SYFOVRE in the real world and will formally update on the rate of events on our quarterly calls. We will not be commenting on future individual cases. We intend to handle the situation with the utmost integrity and transparency and do what is right for our patients, physicians and investors.

謝謝你，Caroline。我們對於在 ASRS 發表的數據感到非常振奮。雖然過去幾週相當動盪，但我們相信未來仍然前景強勁。我們正密切監測 SYFOVRE 在真實世界中的安全性，並將在每季電話會議上正式更新事件發生率。我們不會就未來個別案例發表評論。我們打算以最高的誠信與透明度處理此情況，並做出對病患、醫師與投資人最正確的事。

Blazing a new trail in geographic atrophy is not easy, but I am confident in the Apellis team, and we look forward to bringing SYFOVRE with good patients in need worldwide. We are also proud of the impact that EMPAVELI is having on patients with PNH. Additionally, we continue to advance a robust clinical and preclinical pipeline to achieve our goal of improving the lives of people living with debilitating diseases by bringing new and innovative complement therapies to market.

在地理性萎縮（GA）領域開創新道路並不容易，但我對 Apellis 團隊充滿信心，我們也期待能將 SYFOVRE 帶給全球有需要的病患。我們也為 EMPAVELI 對 PNH 病患所帶來的影響感到自豪。此外，我們持續推進一個強健的臨床與臨床前研發管線，以達成我們的目標：透過將全新且創新的補體療法推向市場，改善罹患致殘性疾病人們的生活。

Let us now open the call for questions. Operator?

現在讓我們開放提問。接線員？

(Operator Instructions) Our first question comes from the line of Umer Raffat with Evercore.

（接線員指示）我們的第一個問題來自 Evercore 的 Umer Raffat。

It's John on for Umar. I would love a little bit more clarity on the inventory in that 68,000 vials shipped as of this past weekend. Can you confirm how much inventory and average stock keeps on stock and how much inventory would be in the channel at any given time. Then furthermore, one bit of feedback that we were hearing out of ASRS is that there may have been a change from trial to commercial in the device. Was there a supplier for the trials that had automatic draw up of the SYFOVRE solution? Commercial docs have been complaining that drop from the vial obviously, is challenging, and that's a little bit different for this product. So is that something that could be driving this or something you've looked into?

我是 John，代替 Umar 發問。我希望能更清楚了解截至上週末已出貨的 68,000 瓶（vials）中，庫存的情況。你能否確認：平均而言會保留多少庫存與平均安全庫存（stock）水位，以及在任何時間點通路中大約會有多少庫存？另外，我們從 ASRS 聽到的一點回饋是，裝置可能從臨床試驗到商業化之間有所變更。臨床試驗是否有供應商提供可自動抽取（automatic draw up）SYFOVRE 溶液的裝置？商業端的醫師一直在抱怨從小瓶滴取（drop from the vial）顯然很具挑戰性，而這對這個產品來說有點不同。所以這是否可能是驅動因素之一，或是你們已經針對此點進行過調查？

Thank you, John. I will hand the first question over to Adam and then take the second one.

謝謝你，John。我會先把第一個問題交給 Adam，然後再回答第二個。

John, it's Adam. So yes, of the 68,000 vials, those have been distributed to physician practices. And we contacted our top prescribers. And on average, we -- after those discussions, our top prescribers tell us they held approximately a week's worth of inventory within their fridges. So the vast majority of those 68,000 vials are likely not sitting in fridges, they're probably being used with patients. So on average, about a week held in a refrigerator. Hopefully, that answers the first part, and then I'll hand back to Cedric.

John，我是 Adam。是的，在 68,000 支小瓶中，這些已經分發到醫師診所。我們也聯繫了我們的主要開立處方者。平均而言，在那些討論之後，我們的主要開立處方者告訴我們，他們在冰箱裡大約保有約一週的庫存。因此，這 68,000 支小瓶中的絕大多數很可能不是放在冰箱裡，而是正在用於病人。所以平均大約在冰箱中存放一週。希望這回答了第一部分，接著我把問題交回給 Cedric。

Thank you, Adam. So I think, John, we had an important objective this week and coming to ASRS. And that was first of all, to work closely with ASRS and get a very good sense of what is happening nationwide, i.e., how large is this problem? Is there something that we have missed. And secondly, is this rate changing over time, right? And so what's very important here and the key objective of this weekend and the research that we did in the past couple of weeks is that we can conclude that these events are very rare. And as Caroline mentioned earlier, that they don't increase over time, right? They're sporadic in nature. I think that is really, really important. Then, of course, comes the question, what is the potential etiology behind this.

謝謝你，Adam。所以我想，John，我們本週以及來到 ASRS 有一個重要目標。首先，是與 ASRS 緊密合作，並非常清楚地掌握全國正在發生什麼，也就是說，這個問題有多大？是否有我們遺漏的事情。其次，這個發生率是否會隨時間改變，對吧？因此，這裡非常重要、也是本週末以及我們過去幾週所做研究的關鍵目標是：我們可以得出結論，這些事件非常罕見。而且如 Caroline 先前提到的，它們不會隨時間增加，對吧？它們本質上是零星發生的。我認為這真的非常、非常重要。接著，當然就會出現問題：其背後可能的病因是什麼。

And as you can imagine, of course, and as you mentioned, the best starting point is what was different in the clinical trials versus the real world. We are going to be very methodical and we are not going to engage in hypothesizing until we have data. And I think that is really important. That is something that we owe to physicians and to patients. In that investigation, the first step was to find out is the direct product that we are delivering to physicians today, the same as the drug product that we used in the clinical trials. And the answer is, yes. We are now going to take next steps to evaluate other factors that could have [stayed] role, but we will indicate on those when we have more clarity.

而如你所想，當然也如你所提到的，最好的起點是：臨床試驗與真實世界之間有什麼不同。我們會非常有系統地進行，在有數據之前不會進行假設。我認為這非常重要。這是我們對醫師與病人應盡的責任。在這項調查中，第一步是確認：我們今天交付給醫師的實際產品，是否與我們在臨床試驗中使用的藥品相同。答案是：是的。接下來我們將採取下一步來評估其他可能扮演[stayed]角色的因素，但在我們更清楚時才會對外說明。

So when you see the product is the same, you're specifically not talking necessarily about any of the additional materials that may have come along with the vial of drug like syringes, drop, existing devices, things like that.

所以當你說產品相同時，你並不是特別在談那些可能隨藥品小瓶一起提供的額外材料，例如注射器、滴管、既有裝置之類的東西，對嗎？

All of this will be part of our investigation.

這些都會納入我們的調查範圍。

Our next question comes from the line of Tazeen Ahmad with Bank of America.

我們的下一個問題來自美國銀行（Bank of America）的 Tazeen Ahmad。

Also, I wanted to clarify upon some of your prepared remarks. So Cedric, how are you thinking about on a go-forward basis, the risk mitigation plan? Maybe this is appropriate for Adam, because Adam, you've talked about what you've done so far, but I think docs probably would benefit from guidance from the company going forward. And so where are you in trying to plan that out. Secondly, I wanted to clarify, were all of the cases of escalators that were reported to ASRS, were they injected by retina specialists or were any of them done by general ophthalmologists. And then I have a follow-up.

另外，我想釐清你們部分事先準備的發言。Cedric，往後你們如何思考風險緩解計畫？也許這題更適合 Adam，因為 Adam 你談到目前為止做了什麼，但我認為醫師可能會受益於公司往後提供的指引。所以你們在規劃上進展到哪一步？第二，我想確認，所有向 ASRS 回報的血管炎病例，是否都是由視網膜專科醫師注射的？還是其中有些是由一般眼科醫師施作？然後我還有一個追問。

Thank you so much, Tazeen. So first of all, briefly on the risk mitigation and docs guidance. I think it is really important here that we have a label that we have a way of -- that we have thoroughly evaluated in clinical trials of distributing this products and using this product, and that is something that we, of course, want to stick to as closely as possible. We have communicated with physicians through letters to update them, and we will continue to do so to make sure that the route of communication are thorough. We will continue to work with the ASRS. As far as it relates to practice mitigation steps, et cetera.

非常謝謝你，Tazeen。首先，簡要談風險緩解與醫師指引。我認為這裡非常重要的是：我們有標籤（label），也有一套在臨床試驗中已徹底評估過的產品分發與使用方式，而這是我們當然希望盡可能嚴格遵循的。我們已透過信函與醫師溝通以更新資訊，並且會持續這麼做，確保溝通管道完整。我們也會持續與 ASRS 合作。至於與實務上的緩解步驟等相關的部分。

We are going to be working with the retina community, but the retina community is better positioned than anyone, right, to talk about how this should be handle. I think, again, the most important fact that we wanted to get our hands on this weekend was to understand the rate and the sporadic nature and to communicate that with ASRS to the community. So I think that is really important. The vasculitis cases that were all reported, I will look to Caroline, but I believe we're all done by retina doctors. That is correct, yes.

我們將與視網膜社群合作，但視網膜社群比任何人都更適合來討論這應該如何處理，對吧？我想再次強調，我們本週末最重要想掌握的事實，是了解發生率與其零星特性，並與 ASRS 一起把這點傳達給社群。我認為這非常重要。至於所有回報的血管炎病例，我會請 Caroline 補充，但我相信都是由視網膜醫師施作。是的，沒錯。

Okay. And then lastly, I think ASRS said that there's been a suspected case that maybe hasn't been confirmed that occurred after the second SYFOVRE injection. I think this was not reported to you. But over the past weekend, have you had the opportunity to learn a little bit more about that particular patient's characteristics.

好的。最後，我想 ASRS 表示有一個疑似病例，可能尚未確認，是在第二次 SYFOVRE 注射後發生。我想這個沒有回報給你們。但在過去這個週末，你們是否有機會更了解那位病人的特徵？

Yes. I think it's important to point out here that suspected cases are suspected for a reason, right, in the sense that we -- there are many [confirming] factors that come into this. This is not an exact science, right? But the key thing is that after kind of a really thorough search nationwide, right, that we ended up realizing that we are very close to where we were a few weeks ago, right? There was not like a hidden Tsunami that all of a sudden came our way. So there will, in all likelihood, be new cases. We will take those and evaluate those. We will continue to work with ASRS, but with the knowledge that the rates and the sporadic nature of these events create a risk-benefit profile that physicians can then openly communicate about with their patients.

是的。我認為這裡重要的是要指出：疑似病例之所以是疑似，是有原因的，對吧？因為我們——有許多[confirming]因素會影響判定。這不是一門精確科學，對吧？但關鍵是，在全國範圍內做了相當徹底的搜尋之後，我們最後意識到，我們的情況非常接近幾週前的狀態，對吧？並沒有什麼突然出現、朝我們而來的隱藏海嘯。因此，很可能仍會出現新病例。我們會接收並評估這些病例。我們會持續與 ASRS 合作，同時也理解：這些事件的發生率與零星特性，形成了一個風險—效益概況，使醫師能夠與病人開誠布公地溝通。

Our next question comes from the line of Anupam Rama with JPMorgan.

我們的下一個問題來自摩根大通（JPMorgan）的 Anupam Rama。

Maybe a question on how you segmented the physicians. So the -- maybe the 1/3 of physicians who you've talked to that are remaining -- going to continue to prescribe -- can you give us a sense of where these physicians fall into sort of what you've seen amongst your top prescribers to date?

也許問一下你們如何對醫師做分群。你們訪談中——可能那剩下的三分之一醫師——將會繼續開立處方；你能否讓我們了解，這些醫師在你們目前所見的主要開立處方者中大概屬於哪一類？

Adam?

Adam？

Yes, absolutely. So yes, the 1/3 of our market research, so they tend to be actually a mix. So they're a mix of our top prescribers, large accounts, but they're also slightly smaller accounts. So the SYFOVRE users within our market research had between 1 and 250 patients. So you can tell there that there's a broad bolus of SYFOVRE use within that snapshot market research we did prior to ASRS. So we tend to get usage across the large PE-backed accounts and smaller accounts as well. So in our market research, that was consistent within that 1/3.

是的，當然。所以是的，我們市調中的那三分之一，其實是混合組成。他們包含我們的主要開立處方者、大型客戶，但也包含一些規模稍小的客戶。我們市調中的 SYFOVRE 使用者，其病人數介於 1 到 250 位之間。你可以從中看出，在我們 ASRS 之前所做的那次市調快照中，SYFOVRE 的使用分布相當廣泛。因此，我們在大型 PE 支持的帳戶與較小帳戶中都看到使用。在我們的市調中，那三分之一的情況也是一致的。

Our next question comes from the line of Colleen Kusy with Baird.

我們的下一個問題來自 Baird 的 Colleen Kusy。

So we've heard similar feedback on the needle in the commercial kit. Are there any progress -- is there any progress made on potentially developing a prefilled syringe for SYFOVRE and how long would that take to bring to market?

我們聽到對商業套組中針頭的類似回饋。針對可能為 SYFOVRE 開發預充式注射器（prefilled syringe），目前是否有任何進展？以及要多久才能推向市場？

So again, as mentioned earlier, our investigation around the ancillaries as part of the overall investigation. And of course, a prefilled syringe is an important objective for us. It was before these events occurred as well. That is unfortunately something that takes several years of development as was the case for Lucentis and Eylea as well. We are working very hard towards that, but that is not something that you should expect in the near future.

所以再次如先前所提，我們對輔助器材（ancillaries）的調查是整體調查的一部分。當然，預充式注射器對我們而言是一個重要目標，在這些事件發生之前也是如此。不幸的是，這需要數年的開發時間，Lucentis 和 Eylea 當時也是如此。我們正非常努力推進，但這不是你們在短期內應該期待會看到的。

That's helpful. And a follow-up. So at least one of the patient's vision did recover encouragingly. Anything notable about that case that you think can be applied if future cases come up? Any guidance on how you think the best treatment for these cases would be in the future?

這很有幫助。接著追問：至少有一位病人的視力令人鼓舞地恢復了。那個案例有什麼值得注意之處，可能可在未來若出現病例時加以應用嗎？對於未來這些病例的最佳治療方式，你們有任何指引嗎？

Caroline?

Caroline？

As I presented earlier in this talk that 2 of the patients have recovered vision nearly back to baseline and 3 cases are still in evolution. What I would say is that these cases are so rare and complex, it's difficult to make any interpretation about treatment guidelines at the present, but we will continue to communicate with the retina community and update them when we have some guidance.

如我先前在這次談話中所呈現的，有 2 位病人的視力幾乎恢復到基線，另有 3 例仍在演變中。我想說的是，這些病例非常罕見且複雜，目前很難對治療指引做任何解讀，但我們會持續與視網膜社群溝通，並在有一些指引時更新他們。

And last one from us. Just in Europe, have you submitted these vasculitis cases to European regulators? And do you expect that to be part of the review?

我們最後一題：在歐洲方面，你們是否已將這些血管炎病例提交給歐洲監管機構？你們預期這會成為審查的一部分嗎？

Of course, we communicate all safety events to all the regulatory authorities.

當然，我們會將所有安全性事件通報給所有監管機關。

Our next question comes from the line of Yigal Nochomovitz with Citigroup.

我們的下一個問題來自花旗集團（Citigroup）的 Yigal Nochomovitz。

On the survey you conducted, you mentioned that the market research was conducted before ASRS. So just when you presented the survey to the physicians, was that just based on the content of the ASRS letter from mid-July? Or were there any further details that they were given with respect to either the retinal images or detailed aspects of the case studies presented on Saturday?

關於你們所做的調查，你提到市場研究是在 ASRS 之前進行的。所以你們把調查呈現給醫師時，是否只是以 7 月中旬的 ASRS 信函內容為基礎？還是他們另外也收到任何進一步的細節，例如視網膜影像，或是週六所呈現病例研究的更詳細面向？

Adam?

Adam？

Yes. So what we did was with the survey, we only used the letter from ASRS as the basis for that.

是的。所以我們在做這份調查時，只是以 ASRS 的那封信作為基礎。

Okay. And then just being very specific with respect to the statement around drug product or manufacturing. I mean, are you saying that, that excludes the potential of the underlying mechanism of action of SYFOVRE on C3 inhibition? Or does the drug product in manufacturing just apply to the way the excipients were produced or any other aspects of the manufacturing process, but not necessarily the motive action itself.

好的。接著我想非常具體地問一下關於藥品成品或製造的說法。我的意思是，你是在說這排除了 SYFOVRE 透過抑制 C3 的潛在作用機轉嗎？還是說你所指的藥品成品與製造，只是適用於賦形劑的製備方式或製造流程的其他面向，但不一定包含作用機轉本身？

Yes. So the mode of action is going to be part of the broader investigation. But again, the mode of action was the same in the clinical trials, of course, as it was in the real world. So again, no answers there yet. All we can say is that the product that was manufactured and used in the clinical trials, is the same product as the product that we are distributing to physicians to date, all within the same specs and the same manufacturing process.

是的。作用機轉會是更廣泛調查的一部分。但再次強調，作用機轉在臨床試驗中當然與真實世界是一樣的。所以目前也還沒有答案。我們目前能說的是：臨床試驗中製造並使用的產品，與我們迄今分發給醫師的產品是同一個產品，全部都在相同規格內，且採用相同的製造流程。

Okay. And then I know, Caroline mentioned a few times these are highly complex cases. And I don't think I saw in the ASRS slide any demographics on the -- other than [GA] -- is there anything you can say, any potential commonality in terms of comorbidities or other conditions or disease conditions that may be at least a hypothesis that you're going to pursue? Or are these all just highly divergent, highly complex and no clear way to pursue hypothesis other than, obviously, the commonality of all having GA.

好的。然後我知道 Caroline 多次提到這些都是高度複雜的病例。我想我在 ASRS 的投影片裡除了 [GA] 之外，沒有看到其他人口統計資料——你能否談談是否有任何可能的共同點，例如共病或其他狀況或疾病狀態，至少作為你們將要追查的假設？還是說這些病例都高度分歧、非常複雜，除了大家都有 GA 這個共同點之外，沒有明確方向可用來提出假設？

These cases are so rare that, as you can imagine, kind of trying to find commonalities between patients require something that would require a much larger denominator or numerator. So -- and we continue to track it and continue to investigate. But right now, all we have done is be able to exclude manufacturing. The rest will be subject to further research.

這些病例非常罕見，所以如你所想，要在病人之間找出共同點，需要更大的分母或分子才能做到。因此——我們會持續追蹤並持續調查。但目前我們所做的只是能夠排除製造因素。其餘部分將需要進一步研究。

Our next question comes from the line of Steven Seedhouse with Raymond James.

下一個問題來自 Raymond James 的 Steven Seedhouse。

I have a commercial one and then a follow-up for Caroline, if I could. Some of the numbers that we now have in hand of 42,000 vials distributed to offices in the second quarter. 60,000 per the ASRS letter as of July 15. That implies, if we back out 1Q as well, it implies like 8,000 or 9,000, let's say, in the first 2 weeks of July that were distributed, and then we have the 65,000 number on July 21 and 68,000 on July 29 that you're updating today as well, which would imply like 8,000 vials distributed in the second half of July. So can you just collaborate that math? I mean, I appreciate you said that you expect some sales impact, and certainly, the survey work suggests that. But it really does look like the first half and the second half of July had about the same number of vials distributed.

我有一個商業面的問題，然後如果可以的話再追問 Caroline。一些我們現在掌握的數字：第二季向診所配送了 42,000 瓶；截至 7 月 15 日，ASRS 信函提到 60,000 瓶。這表示如果我們也把第一季扣回去推算，7 月前兩週大概配送了 8,000 或 9,000 瓶；然後你們今天也更新了 7 月 21 日的 65,000 以及 7 月 29 日的 68,000，這又意味著 7 月下半月大概配送了 8,000 瓶。所以你能否確認一下這個推算？我的意思是，我理解你說你預期會有一些銷售影響，調查結果也確實顯示如此。但看起來 7 月上半月與下半月配送的瓶數其實差不多。

Thank you, Steve. Adam?

謝謝你，Steve。Adam？

Steve, yes, I think your math is right. But one thing to think about is this week and -- sorry, the week just gone. And this current week is obviously the ASRS weekend. So a lot of physicians are actually here or were here in Seattle. So we always calendarize some bumpiness for this week as physicians tend to attend these conferences. But the orders for vials are continuing and have continued throughout the last couple of weeks as your math explained.

Steve，是的，我想你的數學推算是對的。但有一點要考量的是本週以及——抱歉，是剛過去的那一週——以及本週，顯然是 ASRS 週末。因此很多醫師其實在西雅圖這裡，或是剛在這裡。我們一向會把這一週可能出現的波動納入行事曆考量，因為醫師通常會參加這些會議。不過，如你推算所示，瓶裝訂單在過去幾週仍持續進來，也一直在延續。

Okay. And for Caroline, just there seem to be some discussion during the ASRS panel presentation on Saturday that Tapan and Jack, for instance, especially vancomycin is not necessarily an optimal approach for management of retinal vasculitis if that is suspected, which it wasn't because it hadn't been observed in the clinical study. And based on the Beovu experience, I think something like intraocular steroids, especially early on, might be a better approach and could maybe mitigate some of the worst outcomes now that this is a known possibility. So is that characterization accurate? And do you think visual outcomes could be improved just on that basis alone going forward if this happens in the future.

好的。那對 Caroline 的問題是：週六 ASRS 的專家座談中似乎有一些討論，例如 Tapan 和 Jack 提到，特別是萬古黴素（vancomycin）未必是處理疑似視網膜血管炎的最佳方式——而之所以會這樣說，是因為在臨床研究中並未觀察到這種情況。根據 Beovu 的經驗，我認為像是眼內類固醇，尤其是早期使用，可能是更好的做法，並且在現在已知這是一種可能性之後，或許能減輕一些最糟的結果。所以這樣的描述是否正確？而且你是否認為，如果未來再發生這種情況，僅僅基於這一點，視力結局就可能改善？

Well, as I said before, and thank you for that question. These cases are complex, and they're not all bound by commonality. I think we have more to learn with our retina colleagues on management of these cases.

嗯，正如我先前所說，謝謝你的問題。這些病例很複雜，而且並非都具有共同性。我想我們需要與視網膜領域的同儕一起，在這些病例的處置上學到更多。

Our next question comes from the line of Phil Nadeau with TD Cowen.

下一個問題來自 TD Cowen 的 Phil Nadeau。

A couple from us. First, on the conclusion that manufacturing was involved, can you discuss a bit more of the basis for that conclusion, what assays were performed and generally, what analysis did you do to conclude manufacturing is that an issue?

我們有幾個問題。第一個，關於你們得出「製造並非因素」的結論，你能否更進一步說明這個結論的依據、做了哪些檢測（assays），以及你們大致做了哪些分析來判定製造不是問題？

Yes. Thank you, Phil. So as you know, the way these investigations start by looking into manufacturing are actually quite well standardized, right? So our CMC group has a process to go through where a lot specifically -- a lot specifically get investigated to find out that all of these cases were not related to one specific lot. We then look whether all the drug product that was shipped was within the specs that are predefined in our registrational batches and through the NDA. And then much more work around testing and evaluating whether the possibility of the introduction of a manufacturing problem was involved in these cases. And the answer to that was no.

是的，謝謝你，Phil。如你所知，這類調查一開始從製造端著手，其實有相當標準化的流程，對吧？因此我們的 CMC 團隊有一套流程會逐步檢視，其中很具體地——會針對批次（lot）進行調查，以確認這些病例並非都與某一特定批次相關。接著我們會檢視所有出貨的藥品成品是否都在我們於註冊批次以及 NDA 中預先定義的規格範圍內。然後還會做更多工作，測試並評估這些病例是否可能涉及製造問題的引入。而答案是否定的。

You may recall the EPREX situation about 20 years ago where EPREX was associated with red cell aplasia and I think it turned out to be the change like the supplier, the rubber stoppers something that seemed totally inoculus. If that same situation had been the case here, would the analysis you did to look at manufacturing and supply have picked up that as a potential cause. Are they that detail?

你可能還記得大約 20 年前的 EPREX 事件，EPREX 與紅血球再生不良（red cell aplasia）有關，我想最後發現原因是像更換供應商、橡膠塞之類看似完全無害的變更。如果這裡也是同樣的情況，你們針對製造與供應所做的分析，是否能把那種潛在原因抓出來？你們的檢視有到那麼細嗎？

If there was a change between what we did in the clinical trials in terms of how we manufacture the product and what we do now in the real world, we would have told you. So this is all within the same specs and the same use and the same manufacturing process that we used in our clinical trials as well.

如果在我們臨床試驗時的製造方式，與我們現在真實世界中的製造方式之間有任何變更，我們就會告訴你。因此這一切都在相同規格內、相同用途，且採用與臨床試驗相同的製造流程。

Perfect. And then second question, ASRS, there were some questions from physicians on the per patient incidents. Since it seems to happen after the first dose physicians were wondering what would be the risk of a naive patient of going on therapy. Do you have any estimates as to how many patients are on therapy. And so what is the per patient incidence of a naive patient getting the vasculitis.

很好。第二個問題，ASRS 那邊有一些醫師在問以「每位病人」計算的發生率。由於看起來是在第一劑後發生，醫師想知道對於初次用藥（naive）的病人開始治療的風險會是多少。你們是否能估計目前有多少病人正在接受治療？因此，初次用藥病人發生血管炎的每位病人發生率是多少？

Yes. Thank you so much for that question, Phil. It's very early, of course, to look into something like that. Of course, the majority of these estimated 60,000 injections in the real world are probably going to -- will probably have been first-time injections in first-time patients. So that, of course, provides a huge denominator from which to work. And now we're going to find out, right? I mean, whether this is the first injection phenomenon, subsequent injections. We just don't know a lot yet other than the fact that it's an extremely rare event and that it is an event that is sporadic in nature, right?

是的，非常謝謝你的問題，Phil。當然現在要看這種指標還太早。當然，在真實世界估計的 60,000 次注射中，多數很可能——應該會是首次病人的首次注射。因此這當然提供了一個非常大的分母可供分析。接下來我們就會找出答案，對吧？也就是這是否是第一針現象、是否與後續注射相關。我們目前還不知道太多，只知道這是極其罕見的事件，而且它本質上是零星、散發性的事件，對吧？

And I think that's really important to bear in mind is that the retina community ran through kind of a very traumatizing event a couple of years ago, where a product was introduced, where an increased incidence over time was taking place where this product was sensitizing patients and more patients came on the wood works and physicians, that is absolutely not what is happening here. So I think it's important to state that categorically.

我認為非常重要的一點是：視網膜社群在幾年前經歷過一個相當令人創傷的事件——當時有一個產品上市後，發生率隨時間增加，該產品使病人逐漸致敏，更多病人陸續浮現；而醫師們——這絕對不是我們這裡正在發生的情況。所以我認為有必要明確、斷然地說清楚這一點。

Then last question for us. In terms of the path going forward, do you have any information on when ASRS could provide an update on its analysis of cases? Or does Apellis have any time lines to providing an ex disclosure on either your root cause analysis or the incidence of vasculitis?

那我們最後一個問題：就後續路徑而言，你們是否知道 ASRS 何時可能就其病例分析提供更新？或者 Apellis 是否有任何時間表，會就你們的根本原因分析或血管炎發生率提供對外揭露（disclosure）？

Yes. So as we mentioned, we will provide a quarterly update as it relates to the rates and we are going to provide updates on the investigation when we have things to tell, right? So we're not going to make an update unless we have real clarity around understanding this. And we are going to continue to work with ASRS. We're very grateful for the partnership that we have with them.

是的。如我們提到的，我們會就發生率提供每季更新；而在調查方面，我們會在有內容可說時提供更新，對吧？因此除非我們對此有真正清楚的理解，否則不會發布更新。我們也會持續與 ASRS 合作。我們非常感謝與他們之間的夥伴關係。

Our next question comes from the line of Justin Kim with Oppenheimer & Company.

我們的下一個問題來自 Oppenheimer & Company 的 Justin Kim。

Maybe shifting gears a little bit towards GALE. Just in the context of the safety events and given that GALE is really delivering on [doing] those increasing effects over time, just wondering how you've heard the feedback in terms of patient participation in the U.S. for the clinical study and whether sort of those subgroups are continuing on, especially given that these events aren't being observed in clinical study.

或許稍微把焦點轉到 GALE。就安全性事件的背景來看，且鑑於 GALE 確實隨時間推移呈現出那些遞增的效果，想請教您目前聽到的回饋是：在美國臨床研究中病患參與度如何？以及這些亞族群是否仍持續留在研究中，特別是考量到在臨床研究裡並未觀察到這些事件。

Yes. Thank you so much for that question, Justin. So first of all, as you may recall, the number of patients that went from DERBY and OAKS to GALE was very high, right approximately 80% of the patients in the trial decided to go into this 3-year extension study. We are actually I think, months away from having the first patient who has been on treatment for 5 years with SYFOVRE already in the GALE study. So an incredibly rich and important data base for us to understand not just the safety but also, as you mentioned, the efficacy.

是的。非常感謝你的問題，Justin。首先，如你可能記得，從 DERBY 和 OAKS 進入 GALE 的病患比例非常高，大約有 80% 的試驗病患決定進入這項為期 3 年的延伸研究。我們其實我想已經距離第一位在 GALE 研究中使用 SYFOVRE 治療滿 5 年的病患只剩幾個月了。因此，這對我們而言是一個極其豐富且重要的資料庫，不僅能理解安全性，也能如你所提到的，理解療效。

As Caroline mentioned earlier, if you have a patient with extra foveal lesions and as a reminder for those that are not familiar with this, these are patients who have GA in the periphery of their vision. So still with typically a good ability to read and recognize objects with their central vision. In other words, patients that can really benefit, being able to slow down the progression of the disease by something that looks like it's close to 50% is, of course, incredibly important. And with all of these things, of course, we have these safety events which we take very seriously, which we will investigate on the flip side the efficacy profile is also evolving and something very exciting, I think, for patients to look forward to.

如 Caroline 先前提到，如果病患有黃斑中心凹外（extra foveal）的病灶，提醒一下不熟悉的人：這些病患的地圖狀萎縮（GA）位於視野周邊，因此通常仍保有良好的中央視力，能閱讀並辨識物體。換言之，對於確實能受益的病患而言，若能將疾病進展減緩到看起來接近 50%，當然極其重要。當然，伴隨這一切，我們也有這些安全性事件，我們非常嚴肅看待並會加以調查；另一方面，療效輪廓也在演進，我認為對病患而言是非常令人期待的。

Our next question comes from the line of Derek Archila with Wells Fargo.

我們的下一個問題來自 Wells Fargo 的 Derek Archila。

Just 2 from us. I guess first off, can you just remind us how many patients present with bilateral disease. And I just -- do you think the ASRS notification may deter docs from doing injections in both eyes and then also, I know you haven't said you're still working on the investigation, but no similarities or commonalities between these patients experiencing retinal vasculitis has been determined, but if there is, would you expect future label language that could direct patients or -- sorry direct docs to the patients who are best suited for therapy? Is that something that would ultimately end up happening?

我們有兩個問題。首先，能否提醒我們有多少病患是雙眼（bilateral）疾病？另外，我想問 ASRS 的通知是否可能讓醫師不願意在雙眼都進行注射？再者，我知道你們仍在進行調查、尚未定論，目前也尚未找出這些發生視網膜血管炎的病患之間有任何相似性或共通點；但如果未來真的找到共通點，你們是否預期未來標籤文字可能會加入內容，以便引導病患或——抱歉，是引導醫師辨識哪些病患最適合接受治療？這是否最終可能會發生？

Let me start with the second question. It is way too early to talk about that. We are obviously in very close communication with the FDA on all of these things. That is something that we will evaluate and potentially do when more information is available. As it relates to bilateral patients, Caroline, maybe you could speak to that.

我先回答第二個問題。現在談這個還太早。我們顯然正就所有這些事項與 FDA 保持非常密切的溝通。當有更多資訊可用時，我們會評估並可能採取相應作法。至於雙眼病患的部分，Caroline，也許你可以說明一下。

Thank you, Cedric. As the ASRS did present -- they did present that one bilateral case. And I think that -- that is -- retina physicians who are very thoughtful in what they do. And we typically do include bilateral injections in our treatment paradigm. And however, that case does highlight that when we have a new product, it may be prudent to consider unilateral injection first time with use.

謝謝你，Cedric。ASRS 確實提出——他們確實呈報了那一例雙眼病例。我認為——視網膜專科醫師在臨床決策上都非常審慎。我們的治療模式通常也會納入雙眼注射。不過，那個案例確實凸顯：當我們面對一個新產品時，首次使用時先考慮單眼注射可能是較為審慎的作法。

Our next question comes from the line of Eliana Merle with UBS.

我們的下一個問題來自 UBS 的 Eliana Merle。

What's your understanding in the cases if all of those were given using the provided administration materials? Or did any of the physicians choose to use, say, a different syringe for the injection or maybe deviate in any way from the proper administration procedures. And then just also, you alluded to -- you submitted the safety findings to the EMEA. Just any color on that so far from those interactions.

就這些病例而言，你們的理解是是否全部都使用了隨附提供的給藥器材？還是有任何醫師選擇使用例如不同的注射器，或在任何方面偏離了正確的給藥程序？另外，你們提到——你們已將安全性發現提交給 EMEA。能否就目前與他們互動的情況提供一些補充說明？

So again, I think it's important to note here that we are very fortunate that the retina community is so professional and experienced with intravitreal injections, right? I mean this is the heart and the bread and butter of these practices for the last 15 years or so. So that is something that needs to be remembered here. Syringes, ancillaries, as mentioned before, will be part of our broader investigation, and we will comment on that when we have more information. As it relates to the EMEA, we communicate, as I mentioned, everything, of course, to these agencies it becomes part of the evaluation that evaluation with EMEA so far has been going well. So for now, we don't see any changes.

我想再次強調，我們非常幸運，因為視網膜醫界在玻璃體內注射方面非常專業且經驗豐富。畢竟這是這些診所過去大約 15 年來的核心與主要業務。因此，這點需要被記住。至於注射器與相關輔助器材，如先前提到的，將會是我們更廣泛調查的一部分；待我們有更多資訊時會再評論。至於 EMEA，我們如我所說，當然會把所有資訊與這些主管機關溝通，並納入其評估流程。到目前為止，與 EMEA 的評估進展良好，因此目前我們不認為會有任何變更。

Great. And just a quick follow-up. In the patients that had IOI, who didn't have retinal vasculitis. I guess, did they have any vision impact? And any color on if those cases fully recovered?

很好。再快速追問一下：在那些發生 IOI、但沒有視網膜血管炎的病患中，他們的視力是否受到任何影響？以及這些案例是否已完全恢復，有沒有任何補充說明？

Yes. I think that is a very important question, Eli, because there is a bit of a misconception with the way the slide was presented that IOI cases and vasculitis are confusable with each other. Intraocular inflammation is very normal with intravitreal injections and the rates of intraocular inflammation that we have seen in our trials and in the real world are in line with what we saw in the clinical trials and with what we saw or what you would see with anti-VEGF injections in general. So on that end, we have no concerns. It's of course, these cases of vasculitis, which do look like they are kind of a severe complication of severe inflammation that draw our special attention. So I think that's an important difference there. IOI cases without vasculitis, typically having a much better recovery. I don't know, Caroline, if you would like to add something?

是的。我認為這是個非常重要的問題，Eli，因為投影片呈現方式可能造成一種誤解，好像 IOI 病例與血管炎可以相互混淆。眼內發炎（intraocular inflammation）在玻璃體內注射後其實相當常見，而我們在試驗與真實世界中觀察到的眼內發炎發生率，與臨床試驗所見一致，也與一般抗 VEGF 注射所見相符。因此在這方面我們沒有疑慮。當然，真正需要我們特別關注的是這些血管炎病例，它們看起來像是嚴重發炎的一種嚴重併發症。我認為這是重要的差異。沒有合併血管炎的 IOI 病例，通常恢復情況會好得多。我不知道，Caroline，你是否想補充？

We looked into -- we're looking into every single case that is reported to us and the rates of IOI that we've seen in the real world are consistent with the clinical study.

我們已經在檢視——我們正在檢視每一個向我們通報的個案，而我們在真實世界看到的 IOI 發生率與臨床研究一致。

Our next question comes from the line of Annabel Samimy with Stifel.

我們的下一個問題來自 Stifel 的 Annabel Samimy。

I just wanted to go back to the methods that were used in clinical trials versus the methods that are to be real world, is there anything that you can sense from the way physicians are assessing a patient right now in the real world for treatment versus what was done in clinical trials where you obviously didn't see any of these the cases of retinal vasculitis and anything that you can gather from that to, I guess, develop some kind of risk mitigation plan or some kind of protocols that they can even better assess the patients going forward?

我想回到臨床試驗中使用的方法與真實世界方法之間的差異：你們是否能從目前醫師在真實世界評估病患是否適合治療的方式，與臨床試驗中所做的方式之間，感受到任何差異？畢竟在臨床試驗中你們並未看到任何這些視網膜血管炎病例。你們能否從中整理出一些線索，以便制定某種風險緩解計畫，或一些流程／規範，讓醫師未來能更好地評估病患？

Yes. Thank you, Annabel. So look, as mentioned before, we have as strong a desire as anyone, more probability than anyone to try to understand this, but it is very important to be methodical in that process, which is something that we are very much dedicated to. So we don't want to comment about what could be. We are going to look into everything. And when we have more information, we will share it. Of course, as a general comment, and that is how it works, right? Clinical trials are different from the real world where there is much more variability on every front and being able to understand these signals, which again, it's unfortunate, but it is not at all unique, right? Many drugs when they go into the real world will run into unexpected findings. At that point in time, it is on the company on us as a sponsor to be diligent to take these cases seriously and to evaluate them and communicate them properly.

是的。謝謝你，Annabel。你看，如先前所提，我們和任何人一樣——甚至可能比任何人都更希望理解這件事；但在這個過程中保持有條不紊、按部就班非常重要，而我們也非常致力於此。因此我們不想評論可能的原因。我們會把所有面向都納入調查，當有更多資訊時會與大家分享。當然，作為一般性評論——這也是常態：臨床試驗與真實世界不同，真實世界在各方面的變異性都更大。要理解這些訊號——再次強調，雖然很不幸，但也並非獨一無二；許多藥物進入真實世界後都會遇到意料之外的發現。在那個時點，作為公司、作為贊助者，我們有責任保持嚴謹，認真看待這些病例，進行評估並適當溝通。

Okay, great. And then as far as the differences between what was reported to Apellis versus what ASRS reported on. Are you going to be getting these cases and reviewing them? Or -- and -- to what extent is your independent panel overlapping at all with the ASRS panel? Is there any (inaudible) are they completely different sets of physicians?

好的，很好。那關於回報給 Apellis 的內容與 ASRS 所報告內容之間的差異：你們會取得這些病例並加以審查嗎？或者——以及——你們的獨立專家小組與 ASRS 小組在成員上是否有任何重疊？是否有任何（聽不清）還是他們完全是不同的一組醫師？

Yes. Thank you so much for that question. So the wonderful news here from my vantage point is that this partnership that we had with the rest committee ASRS was a very thorough process and a collaborative process, where many of these cases were shared overlap, as you could see from that slide. And Importantly, we set in stone that the rate is extremely rare and that it is sporadic in nature, right? Being up or down 1 case, we ended up remarkably close to each other, right? So now about the exact nature of these cases, exclusive, nonexclusive, depending on which experts you show this to, you're going to get different answers, right? But the most important thing here is you cannot count these cases as to 1 up or 1 down or even to their nature, but we are very much in the same ballpark, right? So this is a very rare event, unfortunately, and one, again that is sporadic in its distribution over time.

是的。非常感謝你的問題。從我的角度來看，這裡的好消息是：我們與 ASRS 的這個合作——與其委員會——是一個非常徹底且協作的流程，許多病例都有分享並且有重疊，如你從那張投影片所見。更重要的是，我們已明確確認其發生率極其罕見，且本質上是零星散發的，對吧？就算多或少 1 例，我們彼此的結果也非常接近。至於這些病例的確切性質——是否互斥、是否非互斥——取決於你給哪位專家看，可能會得到不同答案。但最重要的是，你不能用多 1 例或少 1 例、甚至用其性質來計數；我們的結論非常一致，仍在同一個範圍內。也就是說，這是一個非常罕見的不良事件，且再次強調，它在時間上的分布是零星的。

Okay. Great. And if I could just follow up with one more. I know that a lot of people have been making a Beovu comparison. And maybe just to repeat in context for us one more time why this is not going the way of Beovu maybe in terms of onset in the rarity. Can you maybe just speak to that again so we can sort of put that in context.

好的。很好。如果我可以再追問一個問題。我知道很多人一直在拿 Beovu 來做比較。也許能否再為我們重申一次、放在脈絡裡說明，為什麼這件事不會走上 Beovu 的路徑——例如在發生時間點以及罕見程度方面。你能否再談一次，讓我們把它放在正確的脈絡中。

Yes. Thank you, Annabel. So we're very fortunate because Caroline was actually the lead author on the lead paper on the Beovu investigation and the work that was done there. So she is uniquely positioned to comment on this.

是的。謝謝你，Annabel。我們非常幸運，因為 Caroline 其實是 Beovu 調查以及相關工作的主要論文的第一作者。因此她在評論這件事上有獨特的立場。

Thank you, Cedric. I think that what we have seen with SYFOVRE is very rare. In contrast, the rate of vasculitis with brolucizumab was 3.3% in patients who are in the HAWK and HARRIER studies, and we did not see this at all in our clinical studies. Also, as you alluded to, the onset and the clinical features differ from what was seen with brolucizumab.

謝謝你，Cedric。我認為我們在 SYFOVRE 上看到的情況非常罕見。相較之下，在 HAWK 與 HARRIER 研究中的 brolucizumab 患者，血管炎的發生率為 3.3%，而我們在臨床研究中完全沒有看到這種情況。此外，如你所提到的，發生時間點與臨床特徵也不同於 brolucizumab 所見。

Different in terms of when was the onset.

不同之處在於發生時間點是什麼時候。

Well, so with brolucizumab, the onset was typically after 3 to 4 weeks, and of note, having the events were more common with multiple injections with a shorter time interval between injections and this played a role in the discontinuation of some of the brolucizumab clinical studies. As well, brolucizumab caused an arteritis and different sorts of features on clinical exams.

嗯，brolucizumab 的發生通常是在 3 到 4 週之後；而且值得注意的是，在多次注射、且注射間隔較短時，事件更常見，這也在部分 brolucizumab 臨床研究的中止上扮演了角色。另外，brolucizumab 造成的是動脈炎，並且在臨床檢查上呈現不同類型的特徵。

Our next question comes from the line of Joseph Stringer with Needham & Company.

下一個問題來自 Needham & Company 的 Joseph Stringer。

Just curious, can you comment on the return to vials and what visibility you have into this? More specifically, how many vials have been returned and/or how many practices have returned SYFOVRE vials.

我只是好奇，你能否評論一下退回藥瓶（vials）的情況，以及你們對此有多少能見度？更具體地說，有多少藥瓶被退回，和／或有多少診所退回了 SYFOVRE 的藥瓶？

Adam?

Adam？

So yes, we have seen some vial returns, but the number is actually very small.

是的，我們確實看到有一些藥瓶退回，但數量其實非常少。

Our next question comes from the line of Douglas Tsao with H.C. Wainwright.

下一個問題來自 H.C. Wainwright 的 Douglas Tsao。

Just first, I'm just curious, Adam, in terms of the market research for the physicians who said that they are either pausing altogether or the third who are stopping with new patient start, I'm just curious if you got a sense from -- and maybe this is more anecdotal, but just what would they sort of does it -- do they need to see to restart?

首先我只是好奇，Adam，就市場調查而言，那些表示要完全暫停、或有三分之一表示停止新病人起始用藥的醫師，我想知道你是否從——也許比較偏軼事，但他們大概需要看到什麼才會重新開始？

Yes. Thanks for the question. So within the [read section] with our conversations at ASRS this weekend, I think a lot of physicians are the ones that have said they would pause, they want to just see what happens over the next couple of weeks, right? This has all happened relatively quickly over the last few weeks, and they want to see that stability. They want to see if any more information comes out. They have found having conversations with their patients about a rate would be important, and they want to hear updates from Apellis in a very transparent way. That tends to be the theme for those physicians that are either pausing new starts or have decided to pause for enough time to get more information. That was a consistent theme at ASRS as also within our research. Caroline, I don't know if you want to add anything to that based on your positions. Caroline says the same thing. So that's where we are.

是的，謝謝你的問題。就我們在 ASRS 這個週末的對話來看，我認為很多表示會暫停的醫師，是想先看看接下來幾週會發生什麼，對吧？過去幾週這些事情發生得相對很快，他們想看到穩定性。他們想看看是否會有更多資訊出來。他們也認為與病人討論發生率會很重要，並且希望以非常透明的方式聽到 Apellis 的更新。這往往是那些暫停新起始或決定暫停一段時間以取得更多資訊的醫師的共同主題。這在 ASRS 上以及我們的研究中都是一致的主題。Caroline，我不知道你是否想基於你的立場補充什麼。Caroline 也說同樣的事情。所以我們目前就是這樣。

So just to be clear, so Adam, so it's not as if they're waiting for some definitive sort of conclusion on this issue. There just seems like they're waiting more to see some stability for lack of a better word, to sort of get a sense of now that it's come to life that more cases are coming out of the wood work, et cetera?

所以只是要確認一下，Adam，並不是說他們在等待對這個議題有某種明確的定論。看起來更像是他們在等待某種穩定性——如果沒有更好的說法——想要感受一下，現在事情浮上檯面後，更多案例陸續被揭露等等？

Correct.

正確。

Great. And then just as a follow-up, I think somebody asked and I'm not sure maybe I missed the answer, but just do you know of the 68,000, how many were first injections right now?

很好。然後再追問一下，我想有人問過但我不確定是否錯過答案：在 68,000 次當中，目前有多少是第一次注射？

We don't know but our assumption is that the vast majority are first injections.

我們不知道，但我們的假設是絕大多數都是第一次注射。

Okay. Great. And then just one final quick one. Are you continuing with DTC work or I know you had just started the Henry Winkler campaign? Or is that on pause right now?

好的。很好。最後再快速問一個：你們是否仍在進行 DTC（直接面向消費者）推廣？我知道你們才剛開始 Henry Winkler 的宣傳活動。還是目前先暫停？

Yes, it's a great question. So DTC has had a really good impact and has driven patients to have conversations about losing vision. I think we'll be very thoughtful moving forward how we use that. Now is the time for us to have really transparent open conversations with physicians. But the DTC impact and getting patients to go and check their vision, I think, is a good thing for all. All patients who are of a certain age. So I'm very proud of that work, but we'll be thoughtful in how we use that moving forward.

是的，這是個很好的問題。DTC 的確帶來了很好的影響，並促使病人去談論視力流失。我想我們接下來會非常審慎地思考如何運用它。現在對我們而言，是與醫師進行非常透明、開放對話的時候。但 DTC 的影響、以及讓病人去檢查視力，我認為對所有人都是好事——所有達到一定年齡的病人。我對這項工作感到非常自豪，但我們會審慎思考未來如何運用。

Our next question comes from the line of Laura Chico with Wedbush.

下一個問題來自 Wedbush 的 Laura Chico。

I had just one clarification question. I apologize if I missed this. But I think rest noted there was one incident that occurred after a second injection. So I just wanted to clarify if I have that correct, but also how Apellis came to kind of a different conclusion there? And then I have a follow-up.

我只有一個釐清問題。如果我漏聽了我先道歉。但我想 Rest 提到有一個事件是在第二次注射後發生。我只是想確認我理解是否正確；另外，Apellis 是如何得出不同結論的？然後我還有一個追問。

So that was a suspected case. We need to look into that based on our findings also for our first injections.

那是一個疑似案例。我們需要根據我們的發現再去深入了解，這也同樣適用於我們的第一次注射相關發現。

Okay. And then just kind of going back, Adam, thank you for the market research color. I guess I realize it's premature, but what is your expectation around how the dosing interval frequency might evolve over time here now that we've kind of encountered these safety events. How do you think physicians are going to lean one way or another in terms of the dosing interval with SYFOVRE.

好的。然後回到剛才，Adam，謝謝你提供市場調查的補充說明。我知道現在可能還太早，但你對於在我們遇到這些安全性事件之後，未來給藥間隔頻率可能會如何隨時間演變，有什麼預期？你認為醫師在 SYFOVRE 的給藥間隔上會如何傾向於某一種做法？

Yes, absolutely. So our assumption and my assumption was prior to these vasculitis -- rare vasculitis events, the vast majority of physicians were using every other month type dosing. And I think this just confirms that, again, every other month dosing will be used by the vast, vast majority moving forward. And I expect that to be consistent for the future. And I think as we progress through this and people look at the GALE data and the increasing effects over time and once the physician segment that needs to get comfortable with these safety events gets comfortable, I think you'll start to see a little bit of fluctuation as monthly dosing moves, but every other month will be the vast majority. Caroline, from your perspective, anything you want to add?

是的，當然。我們的假設——而且在這些血管炎（罕見血管炎）事件之前，我的假設是——絕大多數醫師都在採用隔月一次的給藥方式。我認為這件事再次確認了：未來絕大、絕大多數仍會使用隔月一次的給藥。我預期未來也會維持一致。並且我認為，隨著我們持續推進、大家檢視 GALE 數據以及隨時間增加的效果，且當需要對這些安全性事件感到安心的那一群醫師逐漸安心後，你可能會看到每月給藥的採用有些微波動，但隔月一次仍會是大宗。Caroline，從你的角度，有什麼想補充的嗎？

I think that physicians are very, very thoughtful and very experienced with this type of medication and the vast majority of physicians appreciate having a label that's so flexible. I've heard all different sorts of things, but I think between every 6 to 8 weeks with every other month dosing is the preferred paradigm.

我認為醫師非常、非常審慎，而且對這類藥物非常有經驗。絕大多數醫師也很欣賞標籤具有高度彈性。我聽到各種不同的做法，但我認為以隔月一次給藥為主、每 6 到 8 週一次，是偏好的模式。

Thank you. I would now like to hand the conference back over to Cedric Francois for closing remarks.

謝謝。我現在想把電話會議交回給 Cedric Francois 做結語。

Thank you very much. Well, in closing, thank you all for joining us today. It's been, of course, an intense couple of weeks for us. But we are very happy with how we come out of ASRS because we believe that we have gained significant clarity. We are ready to take on the next couple of weeks. We will continue the investigation and promise to continue to be as transparent as we have been. We are around later today and tomorrow. If you have any additional questions, feel free to reach out to Meredith. Thank you.

非常感謝。最後，謝謝各位今天加入我們。對我們而言，過去幾週當然是非常緊湊的一段時間。但我們對 ASRS 之後的結果感到非常滿意，因為我們相信已獲得相當程度的釐清。我們已準備好面對接下來幾週。我們將持續調查，並承諾會一如既往保持透明。我們今天晚些時候以及明天都在。如果你有任何其他問題，歡迎聯絡 Meredith。謝謝。

This concludes today's conference call. Thank you for your participation. You may now disconnect.

今天的電話會議到此結束。感謝各位的參與。您現在可以掛線。