Apellis Pharmaceuticals Inc (APLS) 2024 Q1 法說會逐字稿

Good morning, ladies and gentlemen. Thank you for standing by, and welcome to the Apellis Pharmaceuticals First Quarter 2024 Earnings Conference Call. (Operator Instructions)

各位女士、先生，早安。感謝各位在線等候，歡迎參加 Apellis Pharmaceuticals 2024 年第一季財報電話會議。（接線員指示）

Please be advised today's call is being recorded. I will now turn the call over to your speaker host, Meredith Kaya, Senior Vice President, Investor Relations & Strategic Finance. Please go ahead.

提醒各位，今天的電話會議將被錄音。現在我將把電話交給本次會議的主持人——投資人關係與策略財務資深副總裁 Meredith Kaya。請開始。

Good morning, and thank you for joining us to discuss Apellis' First Quarter 2024 financial results. With me on the call are: Co-Founder and Chief Executive Officer, Dr. Cedric Francois; Chief Operating Officer, Adam Townsend; Chief Medical Officer, Dr. Caroline Baumal and Chief Financial Officer, Tim Sullivan.

各位早安，感謝各位加入我們，一同討論 Apellis 2024 年第一季財務結果。與我一同出席電話會議的有：共同創辦人兼執行長 Cedric Francois 博士；營運長 Adam Townsend；醫務長 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 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，我先提醒各位，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。此類陳述受若干風險與不確定性影響，實際結果可能出現重大差異。我鼓勵各位參閱我們向美國證券交易委員會（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 this morning. 2024 is off to a strong start. SYFOVRE continues to deliver robust growth in the first quarter driven by an acceleration in demand, resulting in $137 million in net sales, up 20% compared to Q4. EMPAVELI also making a difference for patients with PNH generating $26 million in revenue for the quarter, and we have a number of exciting opportunities to potentially expand EMPAVELI into new indications.

謝謝你，Meredith，也謝謝各位今天早上加入我們。2024 年開局強勁。SYFOVRE 第一季在需求加速帶動下持續展現強勁成長，淨銷售額達 1.37 億美元，較第四季成長 20%。EMPAVELI 也持續為 PNH 病患帶來改變，本季創造 2,600 萬美元營收；此外，我們也有多項令人振奮的機會，可能將 EMPAVELI 擴展至新的適應症。

We are one of the rare companies in our industry to have 2 drugs approved in just 3 years, a testament to the strength of our science and our incredible team. As a result, Apellis is now well positioned strategically, operationally and financially to deliver significant long-term value to our shareholders. SYFOVRE is key to delivering this long-term value and the growth in Q1 underscores the strong demand we continue to see from both physicians and patients.

在本產業中，我們是少數能在短短 3 年內就有 2 款藥物獲批的公司之一，這證明了我們科學實力的堅強，以及團隊的卓越。也因此，Apellis 如今在策略、營運與財務面都具備良好定位，可望為股東創造可觀的長期價值。SYFOVRE 是實現此長期價值的關鍵，而第一季的成長也凸顯我們持續從醫師與病患端看到的強勁需求。

Through March, eye care professionals administered 250,000 SYFOVRE injections. And in the first 12 months of launch, SYFOVRE generated over $400 million in sales, substantially exceeding both our and Wall Street's expectations. This is extraordinary performance for any new product launch. SYFOVRE's leadership in the market is driven by 3 important factors: first, treatment with SYFOVRE results in increasing effects over time with up to 42% slowing of GA progression in year 3 of GALE, building on the meaningful effect demonstrated in DERBY and OAKS. Second, SYFOVRE has a well-documented safety profile based on extensive experience, both clinically and in the real world. And third, SYFOVRE offers flexible dosing as described in our label which means that patients can benefit from SYFOVRE's impressive clinical profile in as few as 6 doses per year.

截至 3 月，眼科照護專業人員已施打 25 萬針 SYFOVRE。且在上市後前 12 個月，SYFOVRE 的銷售額超過 4 億美元，顯著超出我們以及華爾街的預期。對任何新產品上市而言，這都是非凡的表現。SYFOVRE 在市場上的領先地位由三項重要因素驅動：第一，SYFOVRE 的治療效果會隨時間增加，在 GALE 試驗的第 3 年，GA 進展減緩幅度最高可達 42%，並建立在 DERBY 與 OAKS 中已證實的具意義效果之上。第二，SYFOVRE 具有完善且有充分文件支持的安全性概況，來自大量臨床與真實世界的使用經驗。第三，SYFOVRE 依照核准標籤提供彈性給藥，意味著病患每年最少僅需 6 次給藥，即可受益於 SYFOVRE 令人印象深刻的臨床特性。

As the market leader, we are only getting started. Our performance to date reaffirms our belief that SYFOVRE has the potential to become a multibillion dollar product in the U.S. alone. We are also working to bring SYFOVRE patients worldwide. We recently announced that the European Medicines Agency reset the review of the SYFOVRE application back to day 180 of our initial assessment, which is the last phase of that procedure. This decision follows a judgment made by the Court of Justice in the EU regarding the competing interests of experts. The decision for SYFOVRE is strictly procedural and not related to the SYFOVRE application. The remainder of our review is expected to be led by the original reporters. We are working closely with the CHMP and EMEA on next steps with the upcoming CHMP opinion anticipated no later than July.

作為市場領導者，我們才正要開始。我們迄今的表現再次印證我們的信念：僅在美國市場，SYFOVRE 就有潛力成為數十億美元級的產品。我們也正努力讓全球病患都能使用 SYFOVRE。我們近期宣布，歐洲藥品管理局（EMA）已將 SYFOVRE 申請案的審查程序重置回初始評估的第 180 天，這是該程序的最後階段。此決定係因歐盟法院就專家競合利益所作出的判決而起。針對 SYFOVRE 的此項決定純屬程序性，與 SYFOVRE 申請案內容無關。後續審查預期仍由原始報告人主導。我們正與 CHMP 與 EMEA 密切合作推進下一步，預期最晚於 7 月取得即將出爐的 CHMP 意見。

Shifting to EMPAVELI. Since its launch in 2021, EMPAVELI has transformed the standard of care for patients with PNH. EMPAVELI was the first available treatment proven to effectively control both intravascular and extravascular hemolysis, 2 hallmarks of PNH while also significantly improving anemia and protecting the majority of patients from transfusions over the long term. We continue to serve PNH patients who may benefit from EMPAVELI and we believe it has the potential to become a best-in-class treatment option for additional high unmet need areas.

接著談 EMPAVELI。自 2021 年上市以來，EMPAVELI 已改變 PNH 病患的照護標準。EMPAVELI 是第一個被證實能有效同時控制血管內與血管外溶血的可用治療，而這兩者是 PNH 的兩大特徵；同時也能顯著改善貧血，並在長期上保護多數病患免於輸血。我們將持續服務可能受益於 EMPAVELI 的 PNH 病患，並相信它有潛力成為其他高度未被滿足需求領域中的同級最佳（best-in-class）治療選項。

Our biggest near-term opportunity is in C3G and IC-MPGN, 2 rare and devastating kidney diseases that often start in adolescents. There are currently no approved treatments for these diseases, which often leads to kidney failure or lifelong dialysis. Our Phase II NOBLE data showed unprecedented effects on disease activity, including complete clearing of disease activity in 40% of the treated patients at week 12 and reductions by one or more magnitude of intensity in 80% of treated patients. We plan to share the 52-week data from the NOBLE study at the European Renal Association meeting later this month and we look forward to sharing the top line data from our Phase III VALIANT study in mid-2024.

我們近期最大的機會在 C3G 與 IC-MPGN——兩種罕見且具毀滅性的腎臟疾病，往往在青少年時期發病。目前這些疾病尚無核准治療，且常導致腎衰竭或終身洗腎。我們的第二期 NOBLE 數據顯示對疾病活動度具有前所未見的效果，包括在第 12 週時，40% 受治療病患的疾病活動度完全清除，且 80% 受治療病患的強度降低一個或以上的量級。我們計畫在本月稍晚的歐洲腎臟協會（European Renal Association）年會分享 NOBLE 研究的 52 週數據，並期待在 2024 年年中分享第三期 VALIANT 研究的主要結果（top-line data）。

Separately, I'm sure many of you saw the recent news out of New York University regarding the first ever combined mechanical heart pump and big kidney transplant. This was a historic event and we are thrilled that EMPAVELI played a role in making this xenotransplant surgery a success by helping to protect the kidney from potential rejection. EMPAVELI was also involved in the xenotransplant surgery performed at Mass General Hospital in March by helping to stabilize the transplanted kidney when it showed signs of early rejection. And while the research is early and we have a lot to learn still, we are encouraged by the potential of EMPAVELI in xeno-transplantation.

另外，我相信許多人都看到了紐約大學近期發布的消息：史上首次結合機械心臟幫浦與豬腎移植的手術。這是一項歷史性事件，我們也很高興 EMPAVELI 在其中扮演角色，透過協助保護腎臟免於潛在排斥反應，讓這次異種移植手術得以成功。EMPAVELI 也參與了麻省總醫院於 3 月進行的異種移植手術，當移植腎出現早期排斥跡象時，EMPAVELI 協助穩定移植腎。雖然研究仍在早期、我們仍有許多需要學習之處，但我們對 EMPAVELI 在異種移植領域的潛力感到鼓舞。

Overall, I am thrilled with the progress we have made so far in 2024. With 2 commercial products and an emerging pipeline, which we are excited to share more about later this year, we remain steadfast in our vision to develop life-changing medicines for people living with some of the most challenging diseases. And with that, I will now turn it over to Adam to discuss our commercial activities.

整體而言，我對我們在 2024 年迄今取得的進展感到非常振奮。憑藉 2 項商業化產品與逐步成形的研發管線——我們也期待在今年稍晚分享更多內容——我們仍堅定秉持願景：為罹患一些最具挑戰性疾病的人們開發能改變生命的藥物。接下來，我把電話交給 Adam，請他說明我們的商業活動。

Thanks, Cedric, and good morning, everyone. I will jump right in with SYFOVRE. As Cedric shared, SYFOVRE sales over the past 12 months have been strong. Initially, our success was largely driven by fast uptake from early adopters. More recently, we've seen both new patient demand and an increasing prescriber base driving sales. While we continue to focus our marketing efforts on retina specialists, we are also educating the referring eye care provider network on the importance of patients with GA getting the treatment they need.

謝謝你，Cedric，各位早安。我先從 SYFOVRE 談起。如 Cedric 所分享，SYFOVRE 過去 12 個月的銷售表現強勁。起初，我們的成功主要由早期採用者的快速導入所驅動。近期，我們看到新病患需求與處方醫師基礎擴大共同推動銷售成長。雖然我們仍將行銷重點放在視網膜專科醫師，我們也在教育轉介端的眼科照護提供者網絡，強調 GA 病患獲得所需治療的重要性。

Further, we are investing in direct-to-consumer marketing initiatives to increase patient awareness and education about SYFOVRE and GA. Suffice to say that our efforts are paying off. In the first quarter, we distributed 72,000 commercial doses and 5,000 samples. The first 3 months of this year were the 3 largest volume months since launched through Q1. Growth rates varied monthly with a slight decline in February as compared to January and then a reacceleration in March, resulting in some of the largest demand weeks to date and our biggest month of the quarter.

此外，我們也投資於直接面向消費者（DTC）的行銷計畫，以提升病患對 SYFOVRE 與 GA 的認知與教育。可以說，我們的努力正在奏效。第一季我們出貨 72,000 劑商業用藥量與 5,000 份樣品。今年前 3 個月是自上市以來截至第一季的三個最高出貨量月份。各月成長率有所不同：2 月相較 1 月略有下滑，3 月則再度加速，帶來迄今部分需求最高的週次，並使 3 月成為本季出貨量最高的月份。

Additionally, in Q1, we continue to see a double-digit number of new sites come on board each week. With over 2,000 sites of care now using SYFOVRE across a broad range of practice types. We are thrilled by the continued growth we have seen in the second quarter so far across both new and existing patients. It has been an incredible launch. And now that we are in its second year, we will be going back to sharing key metrics with you as of quarter end. Regarding vasculitis, the rate remains rare at approximately 1 in 10,000 injections. What we have learned is that this appears to be our first injection phenomenon with the rate following a first injection estimated at about 1 in 4,000. Given the extensive real-world experience with SYFOVRE to date, retina specialists are more confident that these rates are rare and stable, and we are seeing many physicians who had either paused or decreased their use now start to use SYFOVRE again or use it in more of their patients.

另外，在第一季，我們持續看到每週都有雙位數的新據點加入。目前已有超過 2,000 個照護據點在各類型的醫療機構中使用 SYFOVRE。我們對第二季迄今在新病患與既有病患兩方面所見的持續成長感到非常振奮。這是一個令人驚嘆的上市表現。現在進入第二年，我們將恢復在每季季末與各位分享關鍵指標。關於血管炎，其發生率仍屬罕見，約為每 10,000 次注射 1 例。我們所了解到的是，這似乎是首次注射現象；在首次注射後的發生率估計約為每 4,000 次 1 例。鑑於迄今 SYFOVRE 大量的真實世界使用經驗，視網膜專科醫師對這些發生率屬罕見且穩定更具信心；我們也看到許多先前曾暫停或降低使用的醫師，現在開始再次使用 SYFOVRE，或將其用於更多病患。

Shifting gears to longer-term dynamics. SYFOVRE remains the #1 chosen treatment for GA with approximately 85% of the treated market. We are confident that it will remain the market leader due to its strong efficacy, well-documented safety profile, flexible dosing and the robustness of our overall data set. Even more, we are only in the early stages of a large and growing market. The estimated prevalence of GA patients is up to 1.5 million in the United States. Today, based on a recent clients analysis, patients treated are estimated to make up 12% of the market has defined only by those patients who have been diagnosed and are managed by an ECP. However, many GA patients are not yet diagnosed or have not been referred to a specialist. In fact, only a small portion of newly diagnosed patients currently being treated with SYFOVRE are referrals. This means there continues to be a huge opportunity for SYFOVRE as the vast majority of GA patients have not yet been treated.

接著談較長期的動態。SYFOVRE 仍是 GA 治療中被選用的第 1 名，約占已治療市場的 85%。我們有信心，憑藉其強勁療效、完善且有充分文件支持的安全性概況、彈性的給藥方式，以及我們整體資料集的穩健性，SYFOVRE 將持續保持市場領導地位。更重要的是，我們仍處於一個龐大且持續成長市場的早期階段。美國 GA 患者的估計盛行人數高達 150 萬。根據近期一份客戶分析，目前接受治療的患者估計約占市場的 12%，而此市場的定義僅限於已被診斷且由 ECP 管理的患者。然而，許多 GA 患者尚未被診斷，或尚未被轉介至專科醫師。事實上，目前新診斷且正在接受 SYFOVRE 治療的患者中，轉介個案僅占一小部分。這表示 SYFOVRE 仍有巨大的機會，因為絕大多數 GA 患者尚未接受治療。

Now that we are in year 2, we are executing the next stage of our commercial strategy. Remember, we are launching a transformative medicine for a disease that has never had a treatment available. So we have learned a lot about what drives both physicians and patients. Let me start with physicians. We plan to further increase our reach within existing physician targets as well as expand our use amongst those who have not used SYFOVRE yet. We are refining our messaging as we better understand what is resonating. At launch, our messaging initially focused on efficacy, then shifted to safety last summer. Now we have pivoted back to leading with efficacy, highlighting the positive results from our 3-year GALE extension study in addition to our OAKS and DERBY data and the multiple post hoc analyses that demonstrate functional benefits following SYFOVRE treatment. We are also broadening our reach to provide disease state education to other referring eye care providers who see tens of thousands of GA patients.

現在我們進入第 2 年，正執行商業策略的下一階段。請記得，我們推出的是一款具變革性的藥物，用於一種過去從未有治療可用的疾病。因此，我們對於驅動醫師與患者行為的因素學到了很多。我先從醫師端談起。我們計畫在既有目標醫師中進一步提升觸及率，同時也擴大在尚未使用過 SYFOVRE 的醫師中的使用。我們正隨著更了解哪些訊息最能引起共鳴而精煉溝通內容。上市初期，我們的訊息一開始聚焦於療效，之後在去年夏天轉向安全性。現在我們已再度轉回以療效作為主軸，除了 OAKS 與 DERBY 的資料外，也強調我們 3 年期 GALE 延伸研究的正面結果，以及多項事後分析（post hoc analyses）所顯示的 SYFOVRE 治療後功能性獲益。我們也正在擴大觸及範圍，向其他轉介來源的眼科照護提供者提供疾病教育，這些提供者每年會接觸到數以萬計的 GA 患者。

As the market leader, we are educating those doctors on the importance of GA treatment, so that patients see a specialist who can then decide the right treatment approach.

作為市場領導者，我們正在教育這些醫師了解 GA 治療的重要性，讓患者能夠就診於專科醫師，進而由專科醫師決定合適的治療方式。

Moving to patients. Another key learning over the past year is how motivated and actively engaged patients are in their treatment decisions. As you may have seen in our unbranded DTC campaign, our initial message was focused on increasing awareness of GA and encouraging patients to see their eye care professional. These efforts have netted very positive results, including thousands of new GA diagnosis and a significant number of patients starting SYFOVRE treatment. We recently launched a branded DTC campaign with the focus now on encouraging patients to talk to their physicians about GA treatment with SYFOVRE. Our goal for this campaign is to increase awareness, access many more patients and accelerate the speed to diagnosis and treatment of GA.

接著談患者端。過去一年另一項重要的學習是，患者在治療決策上非常有動機且積極參與。如同各位可能在我們的非品牌（unbranded）DTC 活動中所見，我們最初的訊息聚焦於提升對 GA 的認知，並鼓勵患者就診其眼科照護專業人員。這些努力帶來非常正面的成果，包括數千例新的 GA 診斷，以及相當數量的患者開始接受 SYFOVRE 治療。我們近期推出了品牌（branded）DTC 活動，現在的重點是鼓勵患者與其醫師討論使用 SYFOVRE 進行 GA 治療。本活動的目標是提升認知、觸及更多患者，並加速 GA 的診斷與治療進程。

Now let me shift to EMPAVELI for PNH. Revenues in the quarter were $26 million. Compliance rates remain incredibly high at 97%, and the product also continues to have a compelling safety profile. With over 1,600 patient years of systemic pegcetacoplan exposure, there have still been zero cases of meningococcal infection and very low rates of thrombosis. But obviously, we are now seeing heightened competition. With the new entrant in the market, we anticipate pressure on EMPAVELI sales at least for the next 6 to 12 months. Although we have a strong foothold, I want to be realistic that demand is expected to be flat in the medium term. We still expect to see new patients starting on treatment but we also expect to see some patients switching to an oral. The EMPAVELI team is laser focused on emphasizing the real-world profile of EMPAVELI with physicians including its 3-year efficacy data and strong safety profile. We are confident that this profile will drive some physicians and patients to return to EMPAVELI over time. While still very early, we've already seen a few instances of this.

現在我轉到 EMPAVELI 用於 PNH。該季度營收為 2,600 萬美元。依從率仍然非常高，達 97%，而產品也持續展現具吸引力的安全性概況。累計超過 1,600 個患者年（patient years）的全身性 pegcetacoplan 暴露後，仍然沒有出現任何腦膜炎雙球菌感染病例，且血栓發生率非常低。但顯然，我們現在正面臨更激烈的競爭。隨著新進入者加入市場，我們預期 EMPAVELI 的銷售在未來至少 6 到 12 個月將承受壓力。雖然我們已建立穩固基礎，但我也希望務實地指出，中期需求預期將持平。我們仍預期會有新患者開始治療，但也預期部分患者會轉換至口服藥。EMPAVELI 團隊高度聚焦於向醫師強調 EMPAVELI 的真實世界（real-world）表現，包括其 3 年療效資料與強勁的安全性概況。我們有信心，這樣的概況將隨時間推動部分醫師與患者回到 EMPAVELI。雖然仍非常早期，我們已經看到少數此類案例。

Finally, we are particularly excited about the opportunity to potentially expand EMPAVELI into C3G and primary IC-MPGN. These are 2 devastating diseases with tremendous unmet need and a patient population that is 3x bigger than PNH. If approved, we will be able to leverage much of our existing infrastructure such as utilization of our field-based teams to reach nephrologists and deliver EMPAVELI to patients and physicians. Caroline will give more detail on the opportunity we have for these diseases. Caroline?

最後，我們對於 EMPAVELI 可能擴展至 C3G 與原發性 IC-MPGN 的機會特別感到振奮。這兩種疾病都極具破壞性，未被滿足的醫療需求非常高，且患者族群規模是 PNH 的 3 倍。若獲核准，我們將能運用既有的多數基礎建設，例如運用我們的外勤團隊觸及腎臟科醫師，並將 EMPAVELI 提供給患者與醫師。Caroline 會就我們在這些疾病上的機會提供更多細節。Caroline？

Thanks, Adam, and good morning, everyone. Yes, we are really looking forward to the top line data from our Phase III VALIANT study in C3G and IC-MPGN, which we expect mid-2024. I'm going to focus my remarks today on this upcoming development milestone, providing some background on the patient population as well as on the study.

謝謝你，Adam，各位早安。是的，我們非常期待 C3G 與 IC-MPGN 的第三期 VALIANT 研究主要結果（top line data），預計在 2024 年年中公布。今天我將把重點放在這個即將到來的研發里程碑，並提供一些患者族群與研究設計的背景。

C3G and IC-MPGN are debilitating kidney diseases caused by uncontrolled complement activation and breakdown of C3. Symptoms include protein and blood in the urine, swelling, fatigue and high blood pressure. These diseases are estimated to affect 5,000 people in the United States and up to 8,000 in Europe, with the first diagnosis typically occurring in adolescence. Within 5 to 10 years of diagnosis, approximately 50% of people living with C3G and IC-MPGN ultimately suffer from kidney failure, resulting in either a kidney transplant or lifelong dialysis, both of which are highly burdensome and life-threatening to the patient.

C3G 與 IC-MPGN 是由補體活化失控以及 C3 分解所引起的致殘性腎臟疾病。症狀包括尿中蛋白與血液、水腫、疲勞以及高血壓。據估計，這些疾病在美國影響約 5,000 人，在歐洲最多可達 8,000 人，且首次診斷通常發生於青少年時期。在確診後 5 到 10 年內，約有 50% 的 C3G 與 IC-MPGN 患者最終會出現腎衰竭，導致需要腎臟移植或終身透析；兩者對患者而言都負擔沉重且危及生命。

However, neither are curative and there are no approved therapies for these diseases. The incidence of disease recurrence is high and up to 50% of patients lose their kidney transplant due to the disease recurrence. Some patients may have multiple transplants in their lifetime, depending on their age at the first diagnosis. The VALIANT study enrolled 124 patients with either C3G or primary IC-MPGN in a randomized, placebo-controlled, double-blinded multicenter study designed to evaluate pegcetacoplan efficacy and safety. It is the only Phase III study to include a broad population, inclusive of adolescent and adult patients with native and post-transplant forms of both diseases.

然而，這些方式都無法根治，而且目前沒有任何核准的治療可用於這些疾病。疾病復發的發生率很高，且多達 50% 的患者會因疾病復發而失去移植腎。部分患者一生中可能需要多次移植，取決於首次診斷時的年齡。VALIANT 研究在一項隨機、安慰劑對照、雙盲、多中心研究中，納入 124 名 C3G 或原發性 IC-MPGN 患者，用以評估 pegcetacoplan 的療效與安全性。這是唯一一項第三期研究，納入廣泛族群，包含青少年與成人患者，以及兩種疾病的原生腎與移植後型態。

Study participants were randomized 1:1 to receive pegcetacoplan or placebo twice weekly for 26 weeks. Following this 26-week period, patients move to a 26-week open-label phase in which all patients received pegcetacoplan. The primary endpoint is a log-transformed ratio of urine protein to creatinine ratio, or uPCR, a key marker of disease progression in all patients at week 26 compared to baseline. Physicians consider a statistically significant response to the primary endpoint as clinically meaningful in this disease. Key secondary endpoints include additional measures on both uPCR and on eGFR. We are very excited about the potential opportunity that pegcetacoplan may have on patients with C3G and IC-MPGN.

研究受試者以 1:1 隨機分派，每週兩次接受 pegcetacoplan 或安慰劑治療，共 26 週。完成這 26 週後，患者進入為期 26 週的開放標籤期（open-label phase），在此期間所有患者皆接受 pegcetacoplan。主要終點為第 26 週相較於基線的尿蛋白/肌酸酐比（urine protein to creatinine ratio, uPCR）之對數轉換比值（log-transformed ratio），uPCR 是所有患者疾病進展的重要指標。醫師認為，主要終點達到統計上顯著的反應，在此疾病中具有臨床意義。關鍵次要終點包括 uPCR 與 eGFR 的其他衡量指標。我們對 pegcetacoplan 在 C3G 與 IC-MPGN 患者上的潛在機會感到非常振奮。

Turning to SYFOVRE briefly. We participated in several global medical meetings over the past few months. The retina community has been highly engaged with the Apellis team especially regarding our latest data from the GALE study, which demonstrated up to 42% slowing of GA growth in year 3 in non-subfoveal patients compared to projected sham. These increasing effects have never been shown before in any GA study.

簡要回到 SYFOVRE。過去幾個月我們參與了多場全球醫學會議。視網膜社群與 Apellis 團隊互動非常熱絡，特別是針對我們 GALE 研究的最新資料；該研究顯示，在非中心凹下（non-subfoveal）患者中，第 3 年相較於推估的假治療（projected sham），GA 生長可減緩最高達 42%。這種隨時間增加的效果，過去在任何 GA 研究中都未曾被證實。

Finally, before I hand it over to Tim, I want to extend a warm welcome to Dr. Phil Ferrone, who joins us as our Chief Medical Retina Advisor. I have known Phil for a long time, having worked on multiple clinical trials and other programs together throughout our careers. Phil is a leading figure within the medical community with deep expertise in patient care and retina research. He is also a past President of the ASRS and has been on its Board for 18 years. Given Phil's in-depth experience with SYFOVRE and overall retina experience, he is uniquely positioned to help us continue to bring SYFOVRE to GA patients and develop our retina pipeline. I know I speak for all of us at Apellis when I say we are thrilled to have him on board. Now I will turn the call over to Tim for a review of the financials. Tim?

最後，在我把時間交給 Tim 之前，我想熱烈歡迎 Phil Ferrone 醫師加入我們，擔任首席醫學視網膜顧問（Chief Medical Retina Advisor）。我與 Phil 相識已久，在我們的職涯中曾一起合作多項臨床試驗與其他計畫。Phil 是醫學界的領導人物，在患者照護與視網膜研究方面具備深厚專業。他也曾擔任 ASRS 主席，並在其董事會任職 18 年。憑藉 Phil 對 SYFOVRE 的深入經驗以及整體視網膜領域的經驗，他具備獨特優勢，能協助我們持續將 SYFOVRE 帶給 GA 患者，並推進我們的視網膜產品線。我想我代表 Apellis 全體同仁表示，我們非常高興他加入團隊。現在我把電話會議交給 Tim，請他回顧財務表現。Tim？

Thank you, Caroline. I will provide a brief overview of our financials, and you can find additional details in the press release that we issued earlier this morning. Total revenue for the first quarter of 2024 was $172.3 million, including $137.5 million in SYFOVRE and $25.6 million in EMPAVELI U.S. net product revenue. This compares with $44.8 million in total revenue in the first quarter of 2023.

謝謝你，Caroline。我將簡要概述我們的財務狀況；更多細節可參閱我們今天稍早發布的新聞稿。2024 年第一季總營收為 1.723 億美元，其中包括 SYFOVRE 1.375 億美元，以及 EMPAVELI 美國淨產品營收 2,560 萬美元。相較之下，2023 年第一季總營收為 4,480 萬美元。

Turning to the rest of the P&L. For the first quarter, cost of sales was $20.2 million. R&D expenses were $84.7 million. The reason R&D expenses are slightly higher in Q1 versus Q4 is because there was a $15 million onetime noncash expense in Q1 related to the discontinuation of CAD. SG&A expenses were $129.5 million, and we reported a net loss of $66.4 million. While R&D and SG&A may fluctuate on a quarterly basis, we continue to expect our total operating expenses for the full year 2024 to be less than our total expenses in 2023.

接著談損益表（P&L）的其餘部分。第一季銷貨成本為2,020萬美元。研發（R&D）費用為8,470萬美元。第一季研發費用較第四季略高的原因，是第一季因停止CAD而產生一次性、非現金費用1,500萬美元。銷售、一般及行政（SG&A）費用為1億2,950萬美元，我們報告的淨損為6,640萬美元。雖然研發與SG&A可能會按季波動，我們仍預期2024年全年總營運費用將低於2023年的總費用。

Turning to our balance sheet. As of March 31, 2024, we had $326 million in cash and cash equivalents. As Cedric mentioned, we are in a strong position financially. With our existing cash, combined with projected revenues, we continue to believe that we have sufficient cash to fund our operations for the foreseeable future. I will now hand the call back over to Cedric for closing remarks. Cedric?

接著談資產負債表。截至2024年3月31日，我們持有3億2,600萬美元的現金及約當現金。如Cedric所提到，我們的財務狀況相當穩健。以現有現金結合預估營收，我們仍相信我們擁有足夠的現金可在可預見的未來支應營運。我現在把電話交回給Cedric做結語。Cedric？

Thanks, Tim. We are highly encouraged by the start of 2024 and excited for the value-driving milestones on the horizon. I want to emphasize our determination to be the leader in complement medicine. The progress across our pipeline exemplified by, but not limited to SYFOVRE and EMPAVELI is presenting us with opportunities to create meaningful therapies and substantial value for shareholders. We appreciate your continued support. We truly believe that the best is yet to come. Let us now open the call for questions. Operator?

謝謝，Tim。我們對2024年的良好開局深受鼓舞，也對即將到來、可驅動價值的里程碑感到振奮。我想強調我們致力成為補體醫學領導者的決心。我們在產品線上的進展——包括但不限於SYFOVRE與EMPAVELI——正為我們帶來機會，創造具意義的療法並為股東創造可觀價值。感謝各位持續支持。我們真心相信最好的尚未到來。現在讓我們開放提問。接線員？

(Operator Instructions) Our first question comes from Umer Raffat with Evercore ISI.

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

It's actually Jon Miller on for Umer here. I would love to start with the competitive dynamics in GA. Obviously, we heard recently from your recently launched competitor that they expect to see 25% market share already and going to 40% by the end of the year, that doesn't jive with what you just told us saying you have 85% market share. So maybe you could put into context some of the differences, how we square that circle with the market share that they reported versus your reported? And maybe a little bit about how you expect competitive dynamics in GA to evolve over the course of the year as a new competitor launches?

其實我是代Umer提問的Jon Miller。我想先從GA的競爭態勢談起。顯然，我們最近聽到你們剛上市的競爭對手表示，他們預期已經拿到25%的市占率，並在年底達到40%，這與你們剛才所說你們有85%市占率並不一致。能否請你們說明一下差異的背景，我們該如何理解他們所報告的市占率與你們所報告的市占率之間的落差？另外，也請談談隨著新競爭者上市，你們預期今年GA的競爭態勢將如何演變？

Thank you, Jon. Great to hear you. Adam?

謝謝你，Jon。很高興聽到你的聲音。Adam？

Thanks, Jon. It's Adam. So yes, firstly, we are thrilled with the 20% growth we saw in Q1 versus Q4. So obviously, there are many ways to estimate market share. And what we do here is that we look at market share as patients treated with GA. We think it's the most robust way of measuring market share. You then know that the drug is actually being used within a patient. Astellas calculates market share based off of vials distributed. So again, patients is the #1 choice for us when it comes to market share. It means you can roll out things like vials stacked wholesalers, vials stacked in hospital fridges and doctors fridges. And also, it accounts for frequency of administration, right? We are -- tend to be a very much strong every other month drug. And by looking at patients, you can be much more specific than that. So we're the #1 chosen GA therapy. I continue to see that progressing as we progress through the year. This is a massive market. We've chosen first across new patients and continued physician choice. We have the potential to be a multibillion dollar product in the U.S., and I expect that to continue as we push to execute our plans for the rest of the year.

謝謝，Jon。我是Adam。是的，首先，我們對第一季相較第四季看到的20%成長感到非常振奮。顯然，估算市占率有很多方法。我們在這裡看待市占率的方式，是以接受GA治療的病患數來衡量。我們認為這是衡量市占率最穩健的方法，因為你知道藥物確實被用在病患身上。Astellas則是以分發的藥瓶數（vials distributed）來計算市占率。因此，就市占率而言，對我們來說「病患數」是第一選擇。這樣可以排除例如批發商囤積的藥瓶、醫院冰箱或醫師冰箱裡堆放的藥瓶等因素。同時，它也會反映給藥頻率，對吧？我們——通常是一個非常強勢的隔月給藥（every other month）用藥。透過看病患數，你可以比其他方式更精準。因此，我們是GA治療的首選。我預期這個趨勢會在今年持續推進。這是一個非常龐大的市場。我們在新病患上是首選，同時也持續是醫師的選擇。我們在美國有潛力成為數十億美元的產品，我也預期在我們推動並落實今年剩餘時間的計畫時，這一點會持續。

That makes a ton of sense. And I guess as we think about moving beyond that U.S. market, which, as you say, is very robust. I have a question about the EU process that now seems to have been restarted or set back or gone back to the original reporters. Can you just bottom line for us is that good news or bad news? Does this increase the likelihood or decrease the likelihood of EU actually getting approved at some point?

這非常合理。我想，當我們把視野從你所說非常強勁的美國市場延伸出去時，我有一個關於歐盟流程的問題：現在看起來似乎已經重新啟動、或被延後、或回到原始報告人。你能否直接告訴我們，這是好消息還是壞消息？這會提高還是降低歐盟最終在某個時間點獲得核准的可能性？

Thank you, Jon. In terms of the answer of approval, quite frankly, we think nothing has changed. This is a procedural delay that was caused by a loss that had nothing to do with us between the EU and another company. So we're going to have to wait a little bit longer, but we think that the other approvability stay the same.

謝謝你，Jon。就核准與否的答案而言，坦白說，我們認為沒有任何改變。這是一個程序性的延遲，原因是歐盟與另一家公司之間的一場訴訟失利，且與我們無關。因此我們需要再多等一段時間，但我們認為其他可核准性的判斷仍然相同。

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

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

I just wanted to get a sense about how you're seeing the rate of growth we saw in 1Q? We know that you had impact several insurances needing to be reset. But now that that's largely or completely behind you. Can you talk about the general rate of growth and whether or not the rate of growth is starting to flatline or 1Q is going to be a seasonal effect going forward.

我想了解一下你們如何看待第一季所見的成長速度？我們知道有幾家保險需要重新設定而造成影響。但現在這些大致上或完全已經過去了。你們能否談談整體成長速度，以及成長速度是否開始趨於持平，或第一季是否會是未來的季節性影響？

Thank you so much, Tazeen. You were breaking up a little bit. I think your question was whether the rate of growth continues to be in line with what it was before for SYFOVRE, right?

非常謝謝你，Tazeen。你的聲音有點斷斷續續。我想你的問題是，SYFOVRE的成長速度是否會持續與之前一致，對嗎？

Yes. With the exception of 1Q being impacted with the insurance reset.

是的，除了第一季受到保險重新設定的影響之外。

Okay. Yes. Excellent. Thank you. Adam?

好的。是的。非常好，謝謝。Adam？

Thanks, Tazeen. So yes, for us to see 20% quarterly growth 1 year into the launch, I think it's an incredible indicator for long-term success. Also remember that last year, October to December, we had a better understanding of our efficacy profile with the 3-year GALE data in November. And we're going to continue to push that for the remainder of the year. This large market, we believe, is driven by efficacy. We are incredibly well positioned for strong future growth, both in the near term and the long term. And we continue to see that strong growth into Q2, and we're excited for our next earnings call where we can share a lot more details about that.

謝謝，Tazeen。是的，對我們而言，在上市滿一年之際仍能看到20%的季度成長，我認為這是長期成功的一個極佳指標。也請記得，去年10月至12月期間，我們在11月取得3年期GALE數據後，對我們的療效特徵有了更好的理解。我們將在今年剩餘時間持續推動這點。我們相信這個龐大市場是由療效所驅動。我們在短期與長期的強勁未來成長方面都具備非常有利的定位。我們也持續看到這股強勁成長延續到第二季，並期待下一次財報電話會議，屆時我們可以分享更多相關細節。

Our next question comes from Anupam Rama with JPMorgan.

我們的下一個問題來自摩根大通（JPMorgan）的Anupam Rama。

This is Priyanka on for Anupam. And just building up a little bit on the first question, how are you thinking about the dynamics around the November regulatory action for IZERVAY? And what various scenarios could do to market share?

我是代Anupam提問的Priyanka。延續第一個問題再深入一點，你們如何看待11月針對IZERVAY的監管行動所帶來的動態？不同情境可能會如何影響市占率？

Thank you so much for that question. We do not want to comment on our competitor. You would have to ask them about that. But of course, these are all elements that will factor into where ultimately the landscape ends. I think what really stands out here is that this market is absolutely enormous, unfortunately, because there are so many patients, and we have only begun to scratch the surface.

非常謝謝你的問題。我們不想評論競爭對手；你需要向他們詢問。不過，當然，這些都是最終市場版圖走向時會納入考量的因素。我認為這裡真正突出的重點是，這個市場絕對非常龐大——不幸的是，因為病患數量非常多——而我們才剛開始觸及表面而已。

Our next question comes from Salveen Richter with Goldman Sachs.

我們的下一個問題來自高盛（Goldman Sachs）的Salveen Richter。

Could you just speak to the magnitude of seasonality impact in the first quarter? And then regarding your launch here, maybe help us understand in the first quarter, what new prescribers and new patients look like in terms of uptake here and as well as follow-up doses.

你能否談談第一季季節性影響的幅度？另外，關於你們的上市推進，能否協助我們了解第一季新開立處方的醫師與新病患的採用情況，以及後續追加劑量（follow-up doses）的情況？

Thank you, Salveen. Great to hear you. Adam?

謝謝你，Salveen。很高興聽到你的聲音。Adam？

Thanks, Salveen. So yes, March was the strongest month for our first quarter. So February dipped a little bit. And as you know, right, this is the first time we learn about seasonality with SYFOVRE with all of the work that we did for insurance recertifications plus the impact of storms. Agnostic to that, et cetera, and that seasonality, we still saw great strong growth. So -- and we're seeing that growth continue into Q2. As Cedric has said earlier in the previous question, this is an incredibly big market, of which we think the profile of our drug with its strong efficacy, well-documented safety, flexible dosing and the unmatched data that back all of that up is going to be incredibly strong for us moving forward. Q2, the team is laser-focused on executing our plan, and we are the #1 picked GA treatment.

謝謝，Salveen。是的，3月是我們第一季最強的月份，因此2月稍微下滑了一點。而且如你所知，這是我們第一次在SYFOVRE上學習季節性因素，因為我們為保險重新認證所做的所有工作，再加上暴風雨的影響。撇開這些因素等等，以及季節性影響，我們仍然看到非常強勁的成長。而且我們也看到這股成長延續到第二季。正如Cedric在前一個問題中所說，這是一個極其龐大的市場；我們認為我們藥物的特徵——強勁的療效、充分記錄的安全性、彈性的給藥方式，以及支撐這一切的無可匹敵數據——將使我們在未來前進時具備非常強的優勢。第二季，團隊高度聚焦於執行我們的計畫，而我們是GA治療的第一選擇。

Our next question comes from Yigal Nochomovitz with Citigroup.

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

I had a few, Adam, on some of the commercial dynamics. Could you comment at all on switching rates either from IZERVAY or SYFOVRE or vice versa? And then you mentioned there are about 2,000 sites of care that you've already seen uptake. Could you comment what percent of those are exclusively stocking SYFOVRE? Or is there a fraction of stocking both drugs? And is there a fraction that's just stocking IZERVAY. And then you mentioned that the rate following the first injection on ROV is 1 out of 4,000. I'm not sure if I misheard that. Can you just comment, was it 1 out of 4,000 or a different number? I would have thought it would have been lower if it was the first injection phenomenon with the rate 0.01%.

我有幾個問題，Adam，關於一些商業動態。你能否評論一下從 IZERVAY 轉換到 SYFOVRE 或反之亦然的轉換率？另外你提到你們已經看到約 2,000 個照護據點（sites of care）開始採用。你能否說明其中有多少百分比是只備貨 SYFOVRE？或是有一部分同時備貨兩種藥？以及是否也有一部分只備貨 IZERVAY？最後你提到 ROV 在第一次注射後的發生率是每 4,000 人中 1 人。我不確定我是否聽錯。你能否確認一下，是每 4,000 人中 1 人，還是不同的數字？如果這是第一次注射現象且發生率為 0.01%，我原本以為應該會更低。

Yes, Yigal. So switching. So again, we have the strong majority of new patient starts. They choose SYFOVRE. No surprise, right? By the way, J-code is now into action. We'll see some fluctuations on new starts as we did with our J-code. But the strong majority of new starts choose SYFOVRE. I think that's a very positive metric moving forward. Yes, we have over 2,000 sites of care and my very nerdy metric continues that we get double-digit new sites starting SYFOVRE every week, and that has been the same since the beginning of the launch. That's a very strong indicator of demand. Some sites share both drugs. There are certain sites that are SYFOVRE-only sites, predominantly SYFOVRE, they tend to choose SYFOVRE for the efficacy of the drug and the data set that supports that efficacy. There are 1 or 2 sites that during vasculitis did switch to IZERVAY but we've also started to see those sites come back. And we started to see physicians who did pause during last year's vasculitis conversations have started to come back to. So the trends are very positive for what is going to be a very large opportunity in GA. You also had a question on first injection rate.

是的，Yigal。關於轉換。再說一次，我們絕大多數的新病人起始治療都選擇 SYFOVRE。這不意外，對吧？順帶一提，J-code 現在已經開始啟用。我們會像當初我們的 J-code 一樣，看到新起始治療有一些波動。但絕大多數的新起始治療選擇 SYFOVRE。我認為這是未來非常正面的指標。是的，我們有超過 2,000 個照護據點，而我那個很「宅」的指標仍然是：每週都有雙位數的新據點開始使用 SYFOVRE，而且自上市以來一直如此。這是需求強勁的非常有力指標。有些據點同時使用兩種藥。有些據點是僅 SYFOVRE 的據點，或以 SYFOVRE 為主；他們傾向選擇 SYFOVRE，因為藥物的療效以及支持該療效的資料集。有 1 到 2 個據點在血管炎事件期間曾轉換到 IZERVAY，但我們也開始看到那些據點回流。我們也開始看到一些醫師在去年血管炎討論期間暫停後，現在也開始回來。因此，對於 GA 這個將會非常巨大的機會而言，趨勢非常正面。你也問到第一次注射的發生率。

Sorry, this is Cedric. So the rate has been stable since the very beginning at about 1 in 10,000, and this is predominantly a first injection phenomenon where the odds are about 1 in 4,000, which is in the same range of what you would find, for example, infectious endophthalmitis but it is really that first injection. So if you are a physician with a patient that is the conversation that you can have. After that, we believe that the very low vasculitis rate is in line with what it was defined for anti-VEGF.

抱歉，我是 Cedric。這個發生率自一開始以來一直很穩定，大約是每 10,000 人中 1 人；而這主要是第一次注射現象，機率大約是每 4,000 人中 1 人，這與例如感染性眼內炎（infectious endophthalmitis）所見的範圍相近，但確實主要集中在第一次注射。所以如果你是醫師、面對病人時，這就是你可以進行的對話。之後，我們相信非常低的血管炎發生率與先前對抗 VEGF（anti-VEGF）所界定的水準一致。

I understand what you're saying. I thought you said the 1 in 4,000 was for the second and third -- and subsequent, but it's for the first. I get you.

我理解你的意思。我以為你說每 4,000 人中 1 人是針對第二、第三——以及之後的注射，但其實是第一次。我明白了。

Only the first injection. Correct.

只有第一次注射。沒錯。

Our next question comes from Steve Seedhouse with Raymond James.

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

This is Nick on for Steve. We just wanted to clarify if you're able to submit new data whether it's long-term GALE data, functional analyses or real-world safety data as part of the updated review process in Europe?

我是代替 Steve 的 Nick。我們想確認一下，在歐洲更新審查流程中，你們是否能提交新的資料，例如長期 GALE 資料、功能性分析或真實世界安全性資料？

Thank you so much, Steve. So we are allowed to make changes and submit new data as part of the first review. It is in the appeals process that, that is not allowed.

非常感謝你，Steve。我們在第一次審查期間是被允許進行變更並提交新資料的；但在申訴（appeals）程序中，則不允許。

And one quick follow-up. Are you able to comment on how many patients have been treated with SYFOVRE to date?

再追問一個。你們能否評論一下，截至目前為止有多少病人接受過 SYFOVRE 治療？

That is not a number that we provide.

這不是我們會提供的數字。

Our next question comes from Colleen Kusy with Baird.

下一個問題來自 Baird 的 Colleen Kusy。

Great. Adam, you commented on a slight dip in February. Is that a factor of every 8-week dosing? Or kind of what do you think was driving that slight dip? And then can you just comment on inventory in the quarter? I think our math is showing as a slight draw down in the quarter, but could you just comment, please?

很好。Adam，你提到 2 月有小幅下滑。那是因為每 8 週給藥的因素嗎？或你認為是什麼在驅動那個小幅下滑？另外你能否評論一下本季的庫存？我想我們的計算顯示本季庫存似乎有小幅下降，但能否請你說明一下？

Colleen, yes, I mean, obviously, February was a shorter month and I think there's always a little bit of seasonality in January, February and March that we've seen. But we pick straight back up in March and continue to see growth into Q2. Now we previously announced mid-February, 40,000 doses and just add a little bit of context to your question. That was within the first 7 weeks of the 13-week quarter. We then saw an additional 37,000 doses distributed across the remaining 6 weeks. So that just shows you a little bit about the timing of those type of announcements and the seasonality within. What was the second part of your question? Just I didn't catch it.

Colleen，是的，我的意思是，很明顯 2 月是較短的月份，而且我認為我們一直看到 1 月、2 月、3 月都有一些季節性因素。但我們在 3 月就直接回升，並且持續看到成長延續到 Q2。我們先前在 2 月中旬公布過 40,000 劑量，我再補充一些脈絡來回應你的問題：那是在 13 週季度中的前 7 週。接著我們在剩下的 6 週又額外配送了 37,000 劑量。這就讓你看到這類公告的時間點，以及其中的季節性。你問題的第二部分是什麼？我剛剛沒聽清楚。

Draw down in inventories.

庫存下降。

Draw down of inventory, we did see certain wholesalers draw down inventory, and we -- that's, again, normal as part of the seasonality of the month.

庫存下降方面，我們確實看到某些批發商降低了庫存，而我們——這同樣是月份季節性的一部分，屬於正常情況。

Our next question comes from Phil Nadeau with TD Cowen.

下一個問題來自 TD Cowen 的 Phil Nadeau。

One from us and a follow-up. On the future trends, there seems to be a lot of focus among investors on what IZERVAY is going to do to your growth in future quarters. I know you've expressed confidence that you'll continue to grow given the size of the market. I think people are debating whether current consensus is achievable. It looks like for Q2 and Q3 consensus calls for 11% to 12% growth quarter-over-quarter in both those quarters, it seems like a meaningful deceleration compared to what you showed here in Q1. So is that reasonable? Is that conservative? Is that aggressive based on your expectations and what you've seen thus far in Q2?

我們這邊一個問題再加一個追問。關於未來趨勢，投資人似乎非常關注 IZERVAY 在未來幾季會如何影響你們的成長。我知道你們對於在市場規模之下仍能持續成長表達過信心。我想大家在辯論目前市場共識是否可達成。看起來對 Q2 與 Q3 的共識預期是兩季都季增 11% 到 12%，相較你們在 Q1 展示的成長，似乎是明顯放緩。所以這樣合理嗎？以你們的預期以及目前在 Q2 看到的情況來看，這是保守、合理，還是偏積極？

Thank you so much, Phil. Adam?

非常感謝你，Phil。Adam？

Yes. Thanks, Phil. So 20% growth Q1 versus Q4, I think is a very positive thing and we continue to seeing growth into Q2, strong growth. We don't comment on what that growth will look like for the fourth quarter. We're excited to be able to represent that at our next earnings call.

是的，謝謝，Phil。Q1 相較 Q4 成長 20%，我認為是非常正面的事情，而我們也持續看到成長延續到 Q2，且是強勁成長。我們不評論第四季的成長會是什麼樣子。我們很期待在下一次財報電話會上呈現。

That's fair enough. And then just one follow-up on the EU. Should you get a negative CHMP opinion in July, do you still now have the Apellis process available to you? Could you go down the same road that you thought you were going to go down back in January once this review is over?

可以理解。那再追問一個關於歐盟的問題。如果你們在 7 月收到 CHMP 的負面意見，你們現在是否仍可使用 Apellis 的流程？也就是在這次審查結束後，是否可以走回你們在 1 月時原本打算走的同一條路？

Thank you, Phil. Yes, we can. So as I mentioned before, the process will be longer, but we believe that the other approvability stay the same.

謝謝你，Phil。是的，我們可以。如我先前提到的，流程會更長，但我們相信其他可核准性（approvability）仍然相同。

And our next question comes from Akash Tewari with Jefferies.

下一個問題來自 Jefferies 的 Akash Tewari。

This is Ivy on for Akash. We have a couple of quick ones on SYFOVRE. The first is on safety. What's your current hypothesis on the causes behind the cases? Have you done any testing on PEG antibodies? And then on the competitive landscape, if there's no more retinal vasculitis cases for either way over the next 2 quarters, how would your internal market share projections shift? And finally is for your branded DTC campaign. What's the ROI you're targeting at? And also like what's the spend associated with this campaign for this year?

我是代替 Akash 的 Ivy。我們有幾個關於 SYFOVRE 的快速問題。第一個是安全性：你們目前對於這些案例背後原因的假說是什麼？你們是否做過 PEG 抗體的任何檢測？另外在競爭態勢方面，如果未來兩個季度不再出現任何一方的視網膜血管炎案例，你們內部的市占率預測會如何調整？最後是關於你們的品牌 DTC（直接面向消費者）活動：你們目標的 ROI 是多少？以及今年這個活動相關的支出大概是多少？

Thank you so much and wonderful to hear you. So first of all, on the hypothesis, again, as we've discussed before, it is pretty remarkable that there is this first injection phenomenon, right, from an immunological perspective. Our leading hypothesis, as you correctly mentioned, is indeed around polyethylene glycol. That is the work that we will continue to do to further explore.

非常感謝，也很高興聽到你的聲音。首先，關於假說，如同我們之前討論過的，從免疫學角度來看，出現這種第一次注射現象確實相當引人注目，對吧？我們目前的主要假說，如你正確提到的，確實與聚乙二醇（polyethylene glycol）有關。我們會持續進行這方面的工作，以進一步探索。

Now for our competitor, we will see where things land. I think what is really important for us is that the rates of vasculitis is extremely low and stays extremely low is a first injection phenomenon. And the efficacy is something that, of course, really stands out for SYFOVRE versus our competitor, which at the end of the day, we think will be the most important. All of this stands in the background, of course, of this enormous market that geographic atrophy represents because of the enormous amount of patients that are unfortunately affected by this disease. So as it relates to the DTC campaign, let me hand it over to Adam.

至於競品，我們會觀察最終情況如何。我認為對我們真正重要的是：血管炎的發生率極低並且維持極低，而且它是第一次注射現象。當然，療效是 SYFOVRE 相較競品非常突出的地方，而我們認為到最後這會是最重要的。當然，所有這些都發生在一個巨大的背景之下：地圖樣萎縮（geographic atrophy）所代表的是一個龐大的市場，因為不幸受此疾病影響的病人數量非常可觀。至於 DTC 活動，我把問題交給 Adam。

Yes, Ivy, and I'll just add on to what Cedric said, right? Our market leadership is driven by our strong efficacy, well-documented safety, flexible dosing and the unmatched data set that holds all of that up. So that's, I think, incredibly important for the rest of the year. And I think people choose GA drugs for their incredibly strong efficacy.

是的，Ivy，我再補充 Cedric 剛才說的，對吧？我們的市場領導地位來自於我們強勁的療效、充分記錄的安全性、彈性的給藥方案，以及支撐上述各點的無可匹敵的資料集。所以我認為，這對今年剩餘時間而言極其重要。而且我認為，人們選擇 GA 藥物是因為其非常強的療效。

As to DTC, so our DTC campaign is actually live now on TV. So our new campaigns are streaming. We're investing in this campaign because we think it has an incredibly strong positive return on investment. It will drive more patients into retina specialist offices and those patients will see our ad and ask for SYFOVRE. And then the 4 pillars of what we think builds up a great GA drug come into play there where the physician will have that conversation with those patients and hopefully put those patients on. So as Cedric said, this is a large market, and all of our DTC activities will push more SYFOVRE patients into the market.

至於 DTC，我們的 DTC 行銷活動其實現在已經在電視上線了。所以我們的新活動正在串流播放。我們投資這個活動，是因為我們認為它具有非常強的正向投資報酬率。它將帶動更多病患走進視網膜專科醫師的診間，而這些病患會看到我們的廣告並主動詢問 SYFOVRE。接著，我們認為構成優秀 GA 藥物的 4 大支柱就會在那裡發揮作用，醫師會與這些病患進行對話，並希望讓這些病患開始用藥。正如 Cedric 所說，這是一個龐大的市場，而我們所有的 DTC 活動都會把更多 SYFOVRE 病患推進市場。

Our next question comes from Ellie Merle with UBS.

下一個問題來自 UBS 的 Ellie Merle。

Just one quickly on expenses and profitability. Just given you expect expenses to be less in '24 versus '23? And with SYFOVRE growing, how are you thinking about when you might reach profitability? And what are the potential swing factors there? And then just a second one on your pricing strategy. Just what are your expectations for gross to net in the second quarter? And do you expect any uptick in gross to net or your use of sampling in the second quarter? And just walk us through how you're thinking about your pricing and contracting strategy.

先快速問一個關於費用與獲利能力的問題。鑑於你們預期 2024 年的費用會低於 2023 年？而隨著 SYFOVRE 成長，你們如何看待何時可能達到獲利？以及可能的變動因素有哪些？第二個問題是關於你們的定價策略。你們對第二季的 gross-to-net 有何預期？以及你們是否預期第二季 gross-to-net 或你們的試用（sampling）使用會有所上升？也請帶我們了解你們如何思考定價與合約（contracting）策略。

Thank you, Ellie. Great to hear you. Tim?

謝謝你，Ellie。很高興聽到你的聲音。Tim？

Sure. Thanks, Ellie. So the good news is we're in a very strong financial position, and we've previously said that our cash and our projected revenues are sufficient to fund our operations for the foreseeable future. From an expense perspective, on a quarterly basis, our Q4 2023 expenses were lower than our Q3 2023 expenses by about 7% and then taking into account the onetime charge for cold agglutinin disease. This quarter, they would have been down a further 5 or so percent. So we have seen that decrease in operating expenses, and we continue to believe that our expenses will be lower in 2024 than in 2023. On the topline, you can see that we're also growing nicely. And that combination, we've said, will obviously allow us to fund our operations, but we don't actually guide on when we would become profit...

好的。謝謝，Ellie。好消息是我們的財務狀況非常強健，我們先前也說過，我們的現金與預期營收足以在可預見的未來支應營運。從費用角度來看，以季度為基礎，我們 2023 年第四季的費用比 2023 年第三季低了約 7%，並且在考量冷凝集素疾病的一次性費用後；若看本季，費用還會再下降約 5% 左右。所以我們確實看到營運費用的下降，我們也持續相信 2024 年的費用會低於 2023 年。在營收端，你也可以看到我們成長得不錯。而這樣的組合，我們也說過，顯然能讓我們支應營運，但我們並不會指引何時會達到獲利……

Our next question comes from Annabel Samimy with Stifel.

下一個問題來自 Stifel 的 Annabel Samimy。

I want to ask about the referrals from ophthalmologists. Has that just started or retinal specialists will working with their own patients? And with this DTC campaign, can the retinal specialists handle the number of -- the volume of referrals that are going to be coming in, if the referrals have just started. And on the competitive landscape, obviously, IZERVAY has been out for a little bit now. Now they have a J-code. But I mean, instead of thinking about it as a competitive headwind, do you actually think that having a competitor out there is creating more of a tailwind for the whole entire space? And maybe you can speak to that and what dynamics you're seeing there?

我想問關於眼科醫師轉介的情況。這是才剛開始嗎？還是視網膜專科醫師主要在治療他們自己的病患？另外，配合這個 DTC 活動，如果轉介才剛開始，視網膜專科醫師是否能夠承接即將湧入的轉介量／病患量？再談競爭態勢，顯然 IZERVAY 已經上市一段時間了，現在也有 J-code。但與其把它視為競爭逆風，你們是否反而認為有競品在市場上，會為整個領域帶來更多順風？也請談談你們看到的相關動態。

Thank you so much, Annabel. I'll leave it over to Adam.

非常謝謝你，Annabel。我把問題交給 Adam。

Yes. Thanks, Annabel. So at the moment, referrals are quite low. And as you said, right, this is a very large market. So the vast majority of retina physicians are treating patients that they already had a relationship with or what on their books, so to speak. And we believe the DTC campaign will start to push those patients that they don't have and those referrals from ophthalmologists and optometrists in to get treatment. So that's the core aspects of our DTC. The feedback we hear from retinal physicians is that they have the capability of accepting many, many more patients. And I don't think it's remotely a problem for them to treat those new additional patients. And that's been consistent feedback we've got as we progress through the launch.

是的。謝謝，Annabel。目前轉介量相當低。而如你所說，這是一個非常大的市場。所以絕大多數視網膜醫師是在治療他們原本就有關係、或說在他們名單上的病患。我們相信 DTC 活動將開始推動那些他們原本沒有接觸到的病患，以及來自眼科醫師與驗光師的轉介進來接受治療。這就是我們 DTC 的核心面向。我們從視網膜醫師那裡聽到的回饋是，他們有能力接收更多、更多的病患。我不認為他們在治療這些新增病患方面會有任何問題。這也是我們在上市推進過程中持續收到的一致回饋。

Now competition is healthy and competition does grow in incredibly large market. And I think the team that we have in the field is laser focused on executing because we believe that we have the strongest product profile out there in this large and growing market. So I do think market growth driven by competition is a great tailwind for us. And I think we're primed and have the best drug to be able to capitalize upon.

另外，競爭是健康的，而競爭確實會推動一個非常大的市場成長。我認為我們的前線團隊非常專注於執行，因為我們相信在這個龐大且成長中的市場裡，我們擁有最強的產品特性（product profile）。所以我確實認為由競爭帶動的市場成長，對我們而言是很好的順風。而且我認為我們已經準備就緒，並擁有最好的藥物來把握這個機會。

Our next question comes from François Brisebois with Oppenheimer.

下一個問題來自 Oppenheimer 的 François Brisebois。

Just quickly 2 here. So in terms of the 2,000 sites that you're now in, do you discuss -- you discussed some that are only IZERVAY, some that are only SYFOVRE, but can you discuss how many sites you will ultimately like to get into? What's your market penetration in terms of sites that make sense?

快速兩個問題。關於你們現在進入的 2,000 個據點（sites），你們提到有些據點只用 IZERVAY、有些只用 SYFOVRE，但你們能否談談最終希望進入多少據點？就合理的據點而言，你們的據點滲透率大概是多少？

Thank you, François. Adam?

謝謝你，François。Adam？

Thanks, François. So yes, we're in over 2,000 sites that have chosen to use SYFOVRE. And as I said before, some of those sites are very SYFOVRE dominant. We believe that there are over 3,000 sites initially that we want to target. So we still have an opportunity for growth when it comes to sites. And as I said, my very nerdy metric of more than double-digit new accounts using SYFOVRE for the first time every week since launch continues. So that shows you that we're making impact. It's a big market with a large prescriber base.

謝謝，François。是的，目前有超過 2,000 個據點選擇使用 SYFOVRE。正如我之前說的，其中一些據點非常以 SYFOVRE 為主。我們相信一開始我們想要鎖定的據點超過 3,000 個。所以在據點拓展方面，我們仍有成長空間。而且如我所說，我那個很「宅」的指標——自上市以來，每週都有超過雙位數的新帳戶首次使用 SYFOVRE——仍在持續。這顯示我們正在產生影響。這是一個大市場，處方醫師基礎也很龐大。

And then just quickly, in terms of the readout here, midyear VALIANT readout, can you just help remind us what would you consider a successful readout here?

另外快速問一下，關於年中 VALIANT 的讀出（readout），你能否幫我們回顧一下，你們會把什麼樣的讀出視為成功？

Thank you so much for that question as well. We are very excited about the VALIANT readout. We believe that in C3G and IC-MPGN, there is a very high and unmet medical need that will be associated with an important new market for EMPAVELI. In the VALIANT trial, we have enrolled 124 subjects, a very large trial across both IC-MPGN and C3G pre-transplant as well as post-transplant. And the primary endpoint is a local transformation in proteinuria reduction powered to show approximately 13%, but a significant reduction in proteinuria is what we are looking for and will be placed in the context with some of the secondary endpoints.

也非常謝謝這個問題。我們對 VALIANT 的讀出感到非常興奮。我們相信在 C3G 與 IC-MPGN 領域存在非常高且未被滿足的醫療需求，這將對 EMPAVELI 帶來一個重要的新市場。在 VALIANT 試驗中，我們已納入 124 位受試者，這是一項非常大型的試驗，涵蓋 IC-MPGN 與 C3G 的腎移植前以及腎移植後。主要終點是蛋白尿降低的 log 轉換（local transformation），其統計力設計可顯示約 13% 的差異；但我們所尋求的是蛋白尿的顯著降低，並會結合一些次要終點來一併解讀。

Our next question comes from Adam Vogel with Wells Fargo.

下一個問題來自 Wells Fargo 的 Adam Vogel。

I'm on for Derek today. Maybe just a little bit more on the VALIANT's readout. How granular will you report this data out across each indication and setting? And then within those, is there like one that's clearly the largest opportunity for you? Or are they fairly similar across indication and settings?

我今天代替 Derek 提問。想再多問一點關於 VALIANT 的讀出。你們會把各適應症與各情境的資料拆得多細來報告？另外，在這些之中，是否有某一個明顯是你們最大的機會？還是各適應症與情境之間其實相當類似？

Thank you so much, Adam. So this is, again, a very large market opportunity and something that we're really looking forward to reading out. I didn't exactly hear your question because it was breaking up little bit. Could you repeat that, please?

非常謝謝你，Adam。這同樣是一個非常大的市場機會，也是我們非常期待讀出的項目。剛才你的聲音有點斷斷續續，我沒有完全聽清楚你的問題。可以請你再重複一次嗎？

Sorry. Yes. So just across indications, how granular are you going to be reporting out like each indication across like pre- and post-kidney transplant and is there a market opportunity among these that is kind of like the largest opportunity for you guys? Or is it fairly similar across each indication and setting?

抱歉。好的。就是跨不同適應症，你們會把資料報告得多細，例如各適應症在腎移植前與腎移植後各自的結果？另外，在這些之中，是否有一個市場機會是你們最大的？還是各適應症與情境之間其實差不多？

Yes. Thank you so much. So the C3G is the larger markets and the larger opportunity in terms of patients compared to IC-MPGN. But I think it's important here to point out as well that correctly differentiating between those 2 indications is also not straightforward. You have to look at the scope at and make the determination there. I think for us, the purpose was to really go very broad, again, not just between the 2 indications, but also in the pre- and the post-transplant setting and especially in the post-transplant setting, we think we have a really unique opportunity to stand out as a best-in-class opportunity.

是的，謝謝你。C3G 相較於 IC-MPGN，在病患數上是更大的市場、也有更大的機會。但我也認為在這裡要指出，正確區分這兩個適應症並不容易。你必須檢視檢體（scope）並在那裡做出判定。對我們而言，目的就是要做得非常廣泛——不僅涵蓋兩個適應症，也涵蓋移植前與移植後的情境；尤其在移植後情境中，我們認為我們有一個非常獨特的機會，能以同類最佳（best-in-class）的定位脫穎而出。

Got you. And then maybe just one follow-up. On the SFJ Loan repayment. Is there any new color you can provide us on loan repayment strategies?

了解。接著可能再追問一題，關於 SFJ 貸款的償還。你們能否就貸款償還策略提供任何新的補充說明？

Thank you. Tim?

謝謝。Tim？

Sure. Thank you. And so look, one of the things we look at carefully is our cash management. So ultimately, when you look at our SFJ payments, they amount to approximately $200 million over the next, call it, 20 months. And that, along with our increase in the receivables that we extend, so the credit we extend to the channel. That represents a fairly large cash use for us. So obviously, we spent a good amount of time thinking about the best way to perform balance sheet management, and we have a number of options available to us. Tactical options, non-dilutive options are -- there are several of those. So we evaluate those all the time. We'll update you if we plan to do anything there.

當然。謝謝。所以你看，我們會非常仔細地檢視的一件事是我們的現金管理。最終來看，若看我們的 SFJ 付款，未來大約 20 個月內合計約為 2 億美元。再加上我們所延伸的應收帳款增加，也就是我們提供給通路的信用額度，這對我們而言代表相當大的現金使用。因此，我們顯然花了不少時間思考最佳的資產負債表管理方式，而我們也有多種可用選項。戰術性選項、非稀釋性選項——有好幾種。我們一直都在評估這些選項。如果我們計畫在這方面採取任何行動，會再向各位更新。

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

下一題來自 Needham & Company 的 Joseph Stringer。

Just to follow-up on a prior question on the switching between SYFOVRE and IZERVAY. I understand you haven't provided quantitative metrics on this, but maybe I'll ask a different way. Could you give us any color into perhaps the most common reasons why patients would switch between the 2 drugs?

我想延續先前關於在 SYFOVRE 與 IZERVAY 之間切換的問題。我了解你們尚未提供量化指標，但我換個方式問：你們能否就病患在這兩種藥物之間切換最常見的原因提供一些補充說明？

Thank you so much for the question. So look, I think the switchers, quite frankly, is not something that I think is an easy conversation between physicians and patients. When you are on either of the 2 drugs, and you want to switch that patient over, you're going to have a conversation around that. Again, we are mostly focused on the new patients and as they come on board. And as we've mentioned, we have, of course, our differentiated efficacy profile to work from. And again, it's an enormous market and it's an enormous number of patients who are in dire need. Adam, Caroline, do you want to add something?

非常感謝這個問題。你看，坦白說，我認為「切換用藥」並不是醫師與病患之間一個容易的對話。當病患正在使用這兩種藥物之一，而你想把病患轉換到另一個藥物時，勢必需要就此進行溝通。再次強調，我們主要聚焦在新病患以及他們開始治療的情況。如同我們提到的，我們當然有差異化的療效特徵可作為基礎。而且這是一個非常龐大的市場，也有大量迫切需要治療的病患。Adam、Caroline，你們要補充嗎？

I think it's uncommon for our physicians to be switching now. The majority of physicians are really very happy with our transparency, with our messaging and with our efficacy. And in the long term, this is an elderly patient population. They want to have this true every other month dosing, which shows enormous efficacy for us into year 3 and beyond. And I think that really speaks to the doctors. And they sort of understand the safety messaging and which has also been associated with intravitreal injections as a whole, understand that are able to inform their patients and have moved on from that.

我認為目前我們的醫師很少在做切換。大多數醫師對我們的透明度、訊息傳達以及療效都非常滿意。從長期來看，這是一個高齡病患族群；他們希望能真正做到每兩個月一次的給藥，而我們的數據顯示在第 3 年及之後仍有非常顯著的療效。我認為這點確實打動醫師。他們也理解安全性訊息——而這也與玻璃體內注射整體相關——並且能夠向病患說明，且已經不再被那部分所困擾。

And Joey, just to add, it's Adam. Yes. So I think the switching dynamic did occur during the late summer months of last year. We have also seen some patients anecdotally switched back to SYFOVRE. As Caroline said, our assumption there is that this is an efficacy driven market, and these are incredibly well educated patients and physicians. So we continue to see the strong majority of new starts start on SYFOVRE and I think that's a very positive indicator.

Joey，我再補充一下，我是 Adam。是的，我認為切換的動態確實在去年夏末期間發生過。我們也零星聽到有些病患又切換回 SYFOVRE。正如 Caroline 所說，我們的假設是這是一個以療效驅動的市場，而病患與醫師都受過非常良好的教育。因此，我們持續看到絕大多數的新開始治療者會選擇從 SYFOVRE 開始，我認為這是一個非常正面的指標。

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

下一題來自 H.C. Wainwright 的 Douglas Tsao。

Congrats on the progress. Just you've noted that this -- the (inaudible) seems to be a first injection phenomenon. I'm just curious, is there anything that you can do to lower the rate from the 1 in 4,000, which is already rare, but to minimize it even further, and I guess I'd just be curious if there are efforts both in the near term or perhaps longer-term work that could be done.

恭喜你們的進展。你們提到這個——（聽不清）——似乎是首次注射的現象。我想請教，有沒有任何方法可以把發生率從每 4,000 例 1 例（已經很罕見）再進一步降低？也想了解是否有近期或較長期可以進行的努力。

Thank you so much, Doug. Look, we are looking into ways to potentially predict the at-risk patients that are there. But again, kind of placing things into context here, right? I mean the rate that we have here is similar to what you have with -- for infectious endophthalmitis, which is a risk that happens at every single injection that is done, right? So most importantly, last year when we went into this, the question was, is this a problem that is just the beginning of much more, and it is not. So right now, we are in a period of stabilization, physicians understand the risk. We've been incredibly, I think, good and transparent at communicating it. And now the dialogue is shifting towards efficacy.

非常感謝你，Doug。你看，我們正在研究是否有方法可以預測哪些病患屬於高風險族群。不過，再把事情放回脈絡來看，對吧？我們目前的發生率其實與感染性眼內炎的風險相近，而感染性眼內炎是每一次注射都可能發生的風險，對吧？最重要的是，去年當我們面對這件事時，大家的問題是：這是否只是更大問題的開端？而答案是否定的。所以目前我們處於穩定期，醫師理解這個風險；我認為我們在溝通上也非常到位且透明。現在對話正逐步轉向療效。

And I'm just curious, as a follow-up, to the extent that there are practices using both SYFOVRE as well as IZERVAY. Do you get a sense whether the physician is sort of how has ultimately decided which drug a patient will get? Is it being left up to the patient, do you get the sense? Or is it sort of physicians choosing patients by any number of different reasons?

我再追問一下：在同時使用 SYFOVRE 與 IZERVAY 的診所中，你們是否感覺醫師最終是如何決定病患會使用哪一種藥？是否交由病患決定？或你們覺得是醫師基於各種不同原因來為病患做選擇？

Yes. Thank you. Caroline, do you want to add?

是的，謝謝。Caroline，你要補充嗎？

Well, I think some of these practices are so large. There's a benefit to offering across all of the therapeutic options. For example, a patient might come in who was treated in a different state and wants to continue on while they're vacationing with their treatment and then they'll go back. So there's a whole host of reasons that speak to physician choices. But I think the main thing that physicians like is efficacy. And that is really where we're strong efficacy and flexibility while being transparent with our safety dosing. So I can only say that in my practice, we offer every therapeutic option that's available. But the discussion is often based on the statistics with the patients and making that (inaudible) with them together.

我想有些診所規模非常大，提供所有治療選項是有其好處的。舉例來說，有些病患可能在其他州接受治療，度假期間來這裡希望能延續治療，之後再回去。所以醫師做選擇的原因有很多。但我認為醫師最在意的核心仍是療效。而這正是我們的強項：強勁的療效與彈性，同時在安全性與給藥方面保持透明。我只能說，在我的診所，我們會提供所有可用的治療選項；但討論通常是基於統計數據，並與病患一起做出那個（聽不清）決定。

Our next question comes from Graig Suvannavejh with Mizuho Securities.

下一題來自 Mizuho Securities 的 Graig Suvannavejh。

Congrats on the nice SYFOVRE number. I was wondering if you could either qualify or quantify what you're expecting the recent implementation of the CMS J-code for IZERVAY to have or has it already had if there has been any? And maybe a second question as a follow-up. I believe a question was asked earlier about expectations around gross to net, what we could expect them for perhaps the second quarter and how that might evolve throughout the year?

恭喜 SYFOVRE 的數字表現不錯。我想請教，你們能否定性或定量說明，近期 CMS 為 IZERVAY 實施 J-code 預期會帶來什麼影響？或如果已經有影響，是否能分享？第二個追問：我記得先前有人問到對 gross-to-net 的預期，你們能否談談第二季可能的水準，以及全年可能如何演變？

Thank you, Graig. Adam, on CMS and then Tim on gross-to-net.

謝謝你，Graig。Adam 先談 CMS，接著 Tim 談 gross-to-net。

Yes. So I think J-code unlocks prescribers. And so just like it was for us, I think the J-code will unlock some prescribers for IZERVAY. But just as a reminder, right, being the #1 chosen GA therapy across new starts and continuing patients, I think that we win when those conversations take place based on the strong efficacy and the well-documented safety. So J-code has an impact just like it did for us. We're laser-focused on executing our plan in this massive market. And I'm going to hand to Tim on gross-to-net.

是的。我認為 J-code 會讓更多開立處方的醫師得以採用。因此就像對我們一樣，我認為 J-code 也會為 IZERVAY 解鎖一些處方醫師。不過提醒一下，作為在新開始治療與持續治療病患中被選擇的 #1 GA 治療，我認為當這些對話發生時，我們會憑藉強勁的療效與充分記錄的安全性而勝出。J-code 會帶來影響，就像它對我們所帶來的一樣。我們會高度聚焦在這個龐大市場中執行我們的計畫。接下來我把時間交給 Tim 談 gross-to-net。

Thank you for the question, Graig. Yes. So for gross-to-net, it has been relatively stable. And really, we don't comment generally other than to say we've had a pretty wide range of 10% to 20% that we've said. I think it's a wide range, but you can get somewhere in the middle where we can understand our gross-to-net has been consistent.

謝謝你的問題，Graig。是的，關於 gross-to-net，它一直相對穩定。一般而言我們不會多做評論，只會說我們先前提過大約 10% 到 20% 的相當寬的區間。我知道這個區間很寬，但你可以抓中間某個水準來理解：我們的 gross-to-net 一直維持一致。

I'm showing no further questions at this time. I would now like to turn it back to Cedric Francois for closing remarks.

目前顯示沒有其他問題。我現在想把時間交回 Cedric Francois 作結語。

Thank you so much, everyone, for joining. If you have any follow-up questions, please feel free to reach out to Meredith, and we look forward to hearing and speaking with many of you today and the next week. Thank you.

非常感謝各位參與。如果你們有任何後續問題，請隨時聯繫 Meredith；我們也期待在今天以及接下來一週與各位中的許多人交流與對話。謝謝。

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

今天的電話會議到此結束。感謝各位參與。您現在可以掛線。