Alnylam Pharmaceuticals Inc (ALNY) 2024 Q4 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Alnylam Pharmaceuticals fourth-quarter full-year 2024 earnings conference call. (Operator Instructions)

女士們、先生們，早安，歡迎參加 Alnylam Pharmaceuticals 2024 年第四季全年財報電話會議。（操作員指令）

I would now like to turn the conference call over to the company. Please go ahead.

現在我想將電話會議轉給公司。請繼續。

Good morning. I'm Christine Lindenboom, Chief Corporate Communications Officer at Alnylam. With me today are Yvonne Greenstreet, Chief Executive Officer; Tolga Tanguler, Chief Commercial Officer; Pushkal Garg, Chief Medical Officer; and Jeff Poulton, Chief Financial Officer. For those of you who participate a conference call, the accompanying slides can be accessed by going to the Events section of the Investors page of our website, investors.alnylam.com/events.

早安.我是 Christine Lindenboom，Alnylam 首席企業傳播長。今天與我一起的是首席執行官 Yvonne Greenstreet； Tolga Tanguler，首席商務官； Pushkal Garg，首席醫療官；以及財務長 Jeff Poulton。對於參加電話會議的各位，可以透過造訪我們網站投資者頁面的活動部分（investors.alnylam.com/events）來存取隨附的幻燈片。

During today's call, as outlined on Slide 2, Yvonne will offer introductory remarks and provide general context. Tolga will provide an update on our global commercial progress. Pushkal will review pipeline updates and clinical progress, and Jeff will review our financials and guidance, followed by a summary of upcoming milestones before we open the call to your questions. I would like to remind you that this call will contain remarks concerning Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995.

在今天的電話會議中，正如幻燈片 2 中概述的那樣，Yvonne 將作介紹性發言並提供一般背景資訊。托爾加 (Tolga) 將提供有關我們全球商業進展的最新資訊。Pushkal 將審查管道更新和臨床進展，Jeff 將審查我們的財務狀況和指導，然後在我們開始回答您的問題之前總結即將到來的里程碑。我想提醒您，本次電話會議將包含有關 Alnylam 未來預期、計劃和前景的評論，這些評論構成《1995 年私人證券訴訟改革法》安全港條款規定的前瞻性陳述。

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent periodic reports on file with the SEC. In addition, any forward-looking statements represent our views only of the date of this recording and should not be relied upon representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements.

由於各種重要因素，包括我們向美國證券交易委員會提交的最新定期報告中所討論的因素，實際結果可能與這些前瞻性陳述所示的結果有重大差異。此外，任何前瞻性陳述僅代表我們對本記錄日期的觀點，不應被視為代表我們在任何後續日期的觀點。我們明確否認有更新此類聲明的義務。

With that, I'd like to turn the call over to Yvonne. Yvonne?

說到這裡，我想把電話轉給伊馮娜。伊馮？

Thanks, Christine, and thank you, everyone, for joining the call today. 2024 was a fantastic year for Alnylam with strong research, program development and commercial execution and significant progress across the business. This includes the highly positive results from the HELIOS-B Phase III study leading to submission of global regulatory filings for vutrisiran in ATTR cardiomyopathy. We also continue to advance and expand our robust and high-value pipeline of clinical programs, and we continue to demonstrate strong commercial and financial performance achieving combined net product revenues of over $1.6 billion at the upper end of our revised guidance range and we delivered $95 million in non-GAAP operating income for the full year, marking a significant milestone for the company.

謝謝，克里斯汀，也謝謝大家今天參加電話會議。 2024 年對 Alnylam 來說是豐收的一年，我們在研究、專案開發和商業執行方面表現出色，業務取得了重大進展。這包括 HELIOS-B 第三階段研究的高度正面結果，該研究促成了對 ATTR 心肌病變患者提交 vutrisiran 的全球監管備案。我們還將繼續推進和擴大我們強大且高價值的臨床項目管道，並繼續展示強勁的商業和財務業績，實現合併淨產品收入超過 16 億美元，達到我們修訂後的指導範圍的上限，全年實現非公認會計準則營業收入 9,500 萬美元，這對公司而言是一個重要的里程碑。

Furthermore, we maintained our award-winning culture, which has been a critical enabler of our success. As we look for year ahead, 2025 has the potential to be a landmark year for Alnylam. We believe that there are three core elements of our business that will drive sustainable growth and value creation, not just in 2025, but for years to come and will take Alnylam into its next exciting chapter. The first is ATTR leadership where vutrisiran, if approved, has the potential to become a new standard of care in ATTR cardiomyopathy and established a flagship franchise for our company with the advancement of our next-generation TTR assets, necrisiran, following along. Next is growth through innovation, including a pipeline with numerous multibillion dollar opportunities and an R&D engine set up to deliver sustainable innovation and value creation.

此外，我們保持了屢獲殊榮的文化，這是我們成功的關鍵推動因素。展望未來，2025 年有可能成為 Alnylam 具有里程碑意義的一年。我們相信，我們的業務有三個核心要素，它們將推動永續成長和價值創造，不僅在 2025 年，而且在未來幾年，並將帶領 Alnylam 進入下一個令人興奮的篇章。首先是 ATTR 的領導地位，如果獲得批准，vutrisiran 有可能成為 ATTR 心肌病變的新型治療標準，並隨著我們下一代 TTR 資產 necrisiran 的進步為我們公司建立旗艦特許經營權。接下來是透過創新實現成長，其中包括擁有數十億美元商機的管道和為實現永續創新和價值創造而設立的研發引擎。

The third pillar is strong financial performance, where we project that our robust commercial delivery and disciplined approach to capital allocation will enable us to sustain profitability going forward. All of this is underpinned by a best-in-class team and our award-winning culture. All of this represents tremendous progress against Alnylam -- fit by 25 goals, launched back in 2021. We are now on the cusp of turning the goals into reality and believe and in doing so, we're on track to become a top-tier biotech. Furthermore, the progress we make in 2025 will set us up for the second half of the decade, and our next era of significant growth. We are entering a new and exciting chapter in our Alnylam's history and truly believe the best has yet come.

第三個支柱是強勁的財務業績，我們預期強勁的商業交付和嚴謹的資本配置方法將使我們能夠在未來保持獲利能力。所有這一切都由一流的團隊和我們屢獲殊榮的文化所支撐。所有這些都代表著對陣 Alnylam 隊的巨大進步——比 2021 年推出的 Alnylam 隊多進了 25 球。我們目前正處於將目標變為現實的邊緣，我們相信，透過這樣做，我們正走在成為頂級生物技術公司的道路上。此外，我們在 2025 年取得的進步將為我們未來五年以及下一個顯著成長時代奠定基礎。我們正在進入 Alnylam 歷史的嶄新且激動人心的篇章，並堅信最好的時刻即將到來。

With that, let me now turn the call over to Tolga for a review of our commercial performance. Tolga.

說完這些，現在我將把電話轉給托爾加 (Tolga)，讓他審查我們的商業表現。托爾加。

Thanks, Yvonne, and good morning, everyone. Q4 was another strong quarter for our commercial portfolio with our combined TTR and rare franchises delivering 30% growth compared with the fourth quarter of 2023. On a full year basis, we delivered $1.646 billion in combined net product revenue at the very upper end of our 2024 product revenue guidance range. which translates to a 33% growth compared to 2023 as we continue to consistently increase the number of patients on therapy in both our TTR and rare franchises.

謝謝，伊馮娜，大家早安。第四季是我們商業投資組合的又一個強勁季度，與 2023 年第四季相比，我們的 TTR 和稀有特許經營權合計成長了 30%。從全年來看，我們實現了 16.46 億美元的綜合淨產品收入，達到 2024 年產品收入預期範圍的最高值。隨著我們繼續穩定增加 TTR 和罕見疾病特許經營中接受治療的患者數量，與 2023 年相比增加了 33%。

Let me now turn to a summary of our fourth quarter TTR performance. Our TTR franchise achieved $343 million in global net product revenues during the quarter representing a 35% increase compared with the fourth quarter of 2023 as we continue to increase the number of hATTR-PN patients on our therapies. In the US during our first full year of competent in hATTR-PN, combined sales of ONPATTRO and AMVUTTRA in the fourth quarter increased by 10% compared with the third quarter and finished the year with a robust 42% year-over-year increase, driving strong growth momentum.

現在讓我來總結一下我們第四季的 TTR 表現。隨著我們繼續增加接受我們治療的 hATTR-PN 患者數量，我們的 TTR 特許經營權在本季度實現了 3.43 億美元的全球淨產品收入，與 2023 年第四季度相比增長了 35%。在美國，在我們全面開展 hATTR-PN 業務的第一年，第四季度 ONPATTRO 和 AMVUTTRA 的綜合銷售額比第三季度增長了 10%，並以 42% 的強勁同比增長結束了這一年，推動了強勁的增長勢頭。

The 42% year-over-year growth was primarily driven by the following: a 34% increase in demand driven by the strength of ongoing AMVUTTRA patient uptake as well as continued switches from ONPATTRA. We are pleased with the growth in demand which was consistent throughout the year despite new competition entering the market at the end of 2023. The remaining growth in the quarter related to favorable adjustments in gross to net deductions, which were offset modestly by stocking dynamics as inventory in the distribution channel decreased in Q4.

42% 的同比增長主要得益於以下因素：由於 AMVUTTRA 患者接受度持續強勁以及 ONPATTRA 患者持續轉換，需求增長了 34%。儘管 2023 年底出現了新的競爭對手，但全年需求仍保持穩定成長，這讓我們感到滿意。本季剩餘的成長與總扣除額與淨扣除額的有利調整有關，但由於第四季度分銷管道的庫存減少，庫存動態略微抵消了這一增長。

I'd like to take a moment to reflect on our full year HATTR performance in the US where we generated $705 million in full year revenue, representing 39% growth compared with 2023 and almost $200 million in dollar growth. The dollar growth in 2024 and represents an increase relative to the dollar growth we generated in 2023 of $180 million despite the new competition that entered the market at the beginning of the year. We believe this is reflective of the leadership position we have established in the PN market over the last six years, the strength of AMVUTTRA safety and efficacy profile which is underpinned by rapid knockdown of TTR and solid commercial execution.

我想花點時間來回顧我們在美國全年的 HATTR 表現，我們全年創造了 7.05 億美元的收入，與 2023 年相比增長了 39%，增長了近 2 億美元。2024 年的美元成長相對於我們在 2023 年實現的 1.8 億美元的美元成長而言有所增加，儘管年初有新的競爭對手進入市場。我們相信，這反映了我們過去六年在 PN 市場確立的領導地位，以及 AMVUTTRA 安全性和有效性的實力，而這又得益於 TTR 的快速擊倒和穩健的商業執行。

Now let me turn to our international markets, where the TTR franchise grew 12% in the fourth quarter compared to the third quarter of 2024 and increased by 25% year-over-year compared with the fourth quarter of 2023. Similar to the U.S. The year-over-year growth was primarily driven by increased demand for AMVUTTRA as patient uptake remained robust. Before we discuss our rare diseases, I'd like to take a few minutes to review our readiness for our upcoming PDUFA target action date and the potential expanded label and launching TTR-CM in late March.

現在讓我來談談我們的國際市場，TTR 特許經營權在第四季度與 2024 年第三季度相比增長了 12%，與 2023 年第四季度相比同比增長了 25%。與美國類似。在我們討論罕見疾病之前，我想花幾分鐘回顧我們對即將到來的 PDUFA 目標行動日期以及潛在的擴展標籤和在 3 月底推出 TTR-CM 的準備情況。

We're excited about the potential of bringing in RNAi therapeutics to a patient population that is desperately in need of a product with a new mechanism of action. We've been preparing for this opportunity, which may now be only weeks away pending successful completion of the ongoing US regulatory review. We recently announced full year 2025 product revenue guidance at JPMorgan. Our guidance of over $0.5 billion in absolute growth versus 2024 is driven by mainly by our TTR franchise that includes our anticipated label accession into ATTR-CM and reflects our confidence and excitement about the launch.

我們很高興能夠將 RNAi 療法帶給急需具有新作用機制的產品的患者群體。我們一直在為這個機會做準備，現在距離成功完成正在進行的美國監管審查可能只有幾週的時間了。我們最近公佈了摩根大通 2025 年全年產品收入指引。我們預計 2024 年絕對成長將超過 5 億美元，這主要歸功於我們的 TTR 特許經營權，其中包括我們預期的 ATTR-CM 標籤加入，這反映了我們對此次發布的信心和興奮。

For 2025, we've guided for TTR product sales of between $1.6 billion and $1.725 billion. This would represent a 36% increase in an annual revenue compared with 2024 at the midpoint of our guidance, reflecting an acceleration from the 34% growth, our TTR business achieved in 2024. Now let me share with you a few reasons for our optimism and a sense of what's to come.

到 2025 年，我們預計 TTR 產品銷售額將在 16 億美元至 17.25 億美元之間。這意味著與我們預期的 2024 年中點相比，年收入將成長 36%，反映出我們的 TTR 業務在 2024 年實現的 34% 的成長加速。現在讓我與大家分享一些我們感到樂觀的理由以及對未來的展望。

As we said before, ATTR is an orphan disease. The category is rapidly growing and is still largely underserved. This will be a market growth story. An opportunity to help more patients in need, whether they are newly diagnosed or currently on a stabilizer therapy and experiencing disease progression. It is a category right for an entirely new treatment option.

正如我們之前所說，ATTR 是一種孤兒病。該類別正在快速增長，但服務仍然嚴重不足。這將是一個市場成長的故事。這是一個幫助更多有需要的患者的機會，無論他們是新診斷的還是目前正在接受穩定劑治療並經歷病情進展。這是適合全新治療選擇的類別。

In this context, we have the potential to introduce a disruptive treatment. Assuming approval, AMVUTTRA will be the first and only RNAi silence approved for both TTR-CM and CTRP, one that delivers rapid knockdown of TTR, working upstream at the source of disease, demonstrated profound impacts on CV outcomes in HELIOS-B, including a 36% reduction in all-cause mortality versus placebo in a study population representative of today's patient with 40% on a stabilizer and a significant number on other background therapies like diuretics and SGLT2 inhibitors. Early and consistent preservation of functional capacity and quality of life impacts that are critically important to patients and that they can feel.

在這種背景下，我們有可能引入一種顛覆性的治療方法。如果獲得批准，AMVUTTRA 將成為第一個也是唯一一個獲準用於 TTR-CM 和 CTRP 的 RNAi 沉默藥物，該藥物可快速敲低 TTR，在疾病源頭上游起作用，在 HELIOS-B 中顯示出對心血管結果的深遠影響，包括在代表當今患者的研究人群中，與安慰劑相比，全因死亡率降低了 36% 。早期並持續地保存功能能力和生活品質的影響對患者至關重要並且他們能夠感受到。

All of this achieved with just four doses per year and uniquely positioned for seamless access for patients. And while there is still much work still in front of us, we are building on a strong foundation in hATTR-PN and a demonstrated track record of consistent commercial execution, as you have seen from our Q4 and full year results. As we approach this important launch, we are building for durable long-term success of our TTR franchise and building on our experience and success over the past six years in this category.

所有這些只需每年四劑即可實現，並且具有獨特的優勢，可以為患者提供無縫銜接的服務。儘管我們面前還有許多工作要做，但我們正在 hATTR-PN 的堅實基礎上繼續發展，並且擁有持續的商業執行記錄，這一點您從我們的第四季度和全年業績中已經看到。隨著我們接近這項重要產品的發布，我們正在為 TTR 系列的長期成功而努力，並在過去六年中在這一類別中積累的經驗和成功的基礎上再接再厲。

This means taking the time to enable smooth access and to create a seamless experience for patients and providers alike. Toward that end, we have already been at work optimizing the access and patient onboarding experience. This means optimizing access pathways and health systems, where patients are actively managed today. given 80% of the population is being treated at 170 health systems, we are focusing on optimizing access pathways at these health systems so that health care professionals can easily prescribe AMVUTTRA with the knowledge that the patient will receive it at an optimal location, be it an office at an infusion center or at home.

這意味著要花時間確保順暢的訪問並為患者和提供者創造無縫的體驗。為此，我們已開始致力於優化訪問和患者入職體驗。這意味著優化就醫途徑和醫療系統，以便患者能夠得到積極的管理。鑑於 80% 的人口正在 170 個醫療系統中接受治療，我們正致力於優化這些醫療系統的獲取途徑，以便醫療保健專業人員可以輕鬆開出 AMVUTTRA 處方，並且知道患者將在最佳地點接受治療，無論是在輸液中心的辦公室還是在家裡。

We made good progress, laying the groundwork in this regard, and it is important to note that following FDA approval for the expanded indication, it can take several months for the product to be added to the system's formulary and for the access pathway to be fully optimized, which will result in a ramp-up in demand as the year progresses. In parallel, we've also been building a broad ecosystem of alternative sites of care to expand optionality for how patients can initiate therapy in a seamless way and adhere to it.

我們取得了良好的進展，在這方面奠定了基礎，值得注意的是，在 FDA 批准擴大適應症後，可能需要幾個月的時間才能將產品添加到系統的處方集中，並完全優化獲取途徑，這將導致隨著時間的推移需求增加。同時，我們也正在建立廣泛的替代照護場所生態系統，以擴大患者如何以無縫方式開始治療並堅持治療的選擇性。

As we previously shared at our 2024 TTR Investor Day, there currently are over 1,000 alternative sites of care available for patients. This is in addition to health systems group practices and clinics and at home administration. Now our goal is to expand these provider sites and ultimately for greater than 90% of patients to be within 10 miles of a treatment side. With regard to our field readiness, we've already scaled up all our customer teams cross-functionally that includes world-class sales, field reimbursement, key account management and medical and award-winning patient services teams.

正如我們之前在 2024 年 TTR 投資者日所分享的那樣，目前有超過 1,000 個可供患者選擇的替代護理地點。這是對醫療系統團體實踐、診所和家庭管理的補充。現在我們的目標是擴大這些提供者站點，最終使超過 90% 的患者能夠在距離治療點 10 英里以內的地方接受治療。關於我們的現場準備，我們已經跨職能擴大了所有客戶團隊，其中包括世界一流的銷售、現場報銷、大客戶管理以及醫療和屢獲殊榮的患者服務團隊。

Looking ahead to post approval, we will pivot our focus to securing health systems formulary approval via their pharmacy and therapeutics committee reviews and finalizing access pathway optimization, which again, could also take several months once we have an approved label. Expanding our value-based agreement in ATTR-CM, we've been an industry pioneer in establishing VBAs across our portfolio to deliver value and enable broad patient access.

展望批准後，我們將把重點轉向通過藥房和治療委員會的審查來確保獲得衛生系統處方集的批准，並最終確定獲取途徑的優化，這也可能需要幾個月的時間才能獲得批准的標籤。透過擴大我們在 ATTR-CM 中的基於價值的協議，我們已成為在整個產品組合中建立 VBA 的行業先驅，以提供價值並使廣泛的患者能夠使用。

We are focused on expanding these existing ATTR VBA partnerships to cover our expanded label. Finally, driving disciplined and compliant execution across our teams following approval. In short, we see tremendous opportunity in this category. We are on the cusp of a regulatory decision for what has the potential to become a transformational product for patients in need. And we have an -- commercial organization deeply engaged and experienced in the ATTR market.

我們專注於擴大這些現有的 ATTR VBA 合作夥伴關係，以涵蓋我們擴展的標籤。最後，在獲得批准後，推動我們的團隊進行紀律嚴明、合規的執行。簡而言之，我們在這個類別中看到了巨大的機會。我們即將做出監管決策，決定什麼產品有可能成為有需要的病患的轉型產品。我們有一個深入參與 ATTR 市場並經驗豐富的商業組織。

We plan to share relevant operational details over the course of the year to provide clarity on the progress of our launch, as we aim to achieve or exceed our full year revenue guidance. Now turning to our rare franchise and the performance of GIVLAARI and OXLUMO which delivered $108 million in combined product sales in the fourth quarter, representing a 3% decline compared with the third quarter of 2024, driven by purchase patterns and 18% growth compared with the fourth quarter of 2023.

我們計劃在今年內分享相關的營運細節，以明確我們發布的進展，因為我們的目標是實現或超過全年收入預期。現在談談我們稀有的特許經營權以及 GIVLAARI 和 OXLUMO 的表現，這兩款產品在第四季度的綜合產品銷售額為 1.08 億美元，與 2024 年第三季度相比下降 3%，這主要是由於購買模式的影響，與 2023 年第四季度相比增長了 18%。

For GIVLAARI, Q4 product sales decreased by 9% compared with the third quarter of 2024, primarily due to the timing of a large orders in the partner market in Q3, which did not recur in Q4. On a year-over-year basis, GIVLAARI sales increased by 9% compared with the fourth quarter of 23 with the following regional highlights. A 14% increase in the US, primarily driven by growth in new patients on therapy with additional growth driven by inventory stocking dynamics, a 1% increase in our international market where demand growth in our European markets was offset by gross adjustments in our partner markets.

對於 GIVLAARI 而言，第四季度的產品銷售額與 2024 年第三季相比下降了 9%，這主要是由於第三季合作夥伴市場出現了大量訂單，而這種情況在第四季度並未重現。與去年同期相比，GIVLAARI 的銷售額與 23 年第四季相比成長了 9%，具體地區亮點如下。美國市場成長了 14%，主要得益於接受治療的新患者的成長，另外庫存備貨動態也推動了成長；國際市場成長了 1%，其中歐洲市場的需求成長被我們合作夥伴市場的總調整所抵消。

For OXLUMO, Q4 product sales increased by 8% compared with the third quarter of '24 primarily due to continued demand growth and increased by a solid 33% compared with the fourth quarter of 2023 with the following year-over-year regional dynamics. Despite emerging competition, a 77% increase in the US, primarily driven by strong demand growth with additional growth driven by favorable gross to net pricing adjustments and inventory stocking dynamics, a 12% growth from rest of world markets, primarily driven by strong growth in patient demand. In conclusion, we delivered strong results in the fourth quarter with both our TTR and rare franchises, driven by continued robust growth in patients on therapy, which enabled us to close the year at the upper end of our '24 product revenue guidance range.

對於 OXLUMO 而言，第四季度產品銷售額與 24 年第三季度相比增長了 8%，這主要歸因於需求持續增長，並且與 2023 年第四季度相比穩步增長了 33%，這與以下同比區域動態有關。儘管競爭日益激烈，但美國市場仍成長了 77%，主要得益於強勁的需求成長，另外還得益於有利的毛利對淨利價格調整和庫存備貨動態；世界其他市場增長了 12%，主要得益於患者需求的強勁增長。總而言之，在接受治療的患者數量持續強勁增長的推動下，我們在第四季度憑藉 TTR 和罕見疾病特許經營權取得了強勁的業績，這使我們能夠在年底達到 24 種產品收入指導範圍的上限。

With that, I will now turn it over to Pushkal to review our recent R&D and pipeline progress. Pushkal?

現在，我將把主題轉到 Pushkal 身上，來回顧我們最近的研發和管道進度。普什卡爾？

Thanks, Tolga, and good morning, everyone. As you all know, 2024 was a very exciting year for our TTR franchise. We shared the landmark results from HELIOS-B at several conferences throughout the second half of the year. Together, these data presentations highlighted vutrisiran's potentially transformational profile in today's population of patients with ATTR-CM with benefits across a comprehensive series of assessments.

謝謝，托爾加，大家早安。眾所周知，2024 年對於我們的 TTR 特許經營來說是一個非常令人興奮的一年。我們在下半年的幾次會議上分享了 HELIOS-B 的里程碑式成果。總體而言，這些數據顯示強調了 vutrisiran 在當今 ATTR-CM 患者群體中的潛在變革特性，並透過一系列全面的評估帶來益處。

Based on these compelling data, we've completed several regulatory submissions that are now under review. In the United States, we have a PDUFA date of March 23, and parallel filings were achieved in all major regions, including Europe and Japan. Our goal is to bring this new and important therapeutic option to patients around the world as quickly as possible. We also continue to look ahead and innovate in TTR beyond vutrisiran with Nucresiran, formerly known as ALN-TTRsc 04. At AHA in November, we presented updated Phase I results, showing rapid knockdown of serum TTR that was robust and highly durable greater than 90% at six months, supporting the potential for an annual or biannual subcutaneous dosing regimen and an encouraging safety profile, which in addition to offering convenience for patients, could enable broad payer coverage.

基於這些令人信服的數據，我們完成了幾個項目前正在審查的監管提交。在美國，我們的 PDUFA 日期是 3 月 23 日，包括歐洲和日本在內的所有主要地區都已同時提交了申請。我們的目標是盡快為世界各地的患者帶來這種新的、重要的治療選擇。我們也將繼續展望未來，並透過 Nucresiran（以前稱為 ALN-TTRsc 04）在 TTR 領域進行創新，超越 vutrisiran。在 11 月的 AHA 大會上，我們展示了更新後的 I 期研究結果，結果顯示血清 TTR 迅速降低，並且在六個月內保持穩定且高度持久，降低幅度超過 90%，支持每年或每兩年進行一次皮下注射的潛力，且安全性令人鼓舞，除了為患者提供便利外，還可以實現廣泛的付款人覆蓋。

Together, we believe these data support a potential best-in-class profile. I'm also happy to announce today that the FDA has granted Nucresiran orphan drug designation for ATTR amyloidosis, encompassing both polyneuropathy and cardiomyopathy. As Yvonne announced at JPMorgan, we plan to quickly advance Nucresiran to a Phase III study in ATTR amyloidosis with cardiomyopathy that is expected to start in the first half of 2025. Additional details regarding the study design will be shared at our R&D Day on February 25. Beyond TTR, our R&D efforts have enabled us to build one of the most robust pipelines in the biotech industry today positioned to deliver strong growth and innovation across a broad range of disease areas and indications at all stages of development.

總之，我們相信這些數據可以支持潛在的最佳配置。今天我還很高興地宣布，FDA 已授予 Nucresiran 用於治療 ATTR 澱粉樣變性（包括多發性神經病變和心肌病變）的孤兒藥資格。正如 Yvonne 在摩根大通宣布的那樣，我們計劃迅速推進 Nucresiran 對 ATTR 澱粉樣變性伴有心肌病變的 III 期研究，該研究預計將於 2025 年上半年開始。有關研究設計的更多細節將於 2 月 25 日的研發日分享。除了 TTR 之外，我們的研發努力還使我們能夠建立當今生物技術產業最強大的管道之一，從而能夠在各個發展階段的廣泛疾病領域和適應症中實現強勁的成長和創新。

In the fourth quarter, we continued to make great progress in advancing our pipeline. Let me highlight a few key milestones. We continue to advance ZILEBESIRAN investigational therapeutic for the treatment of hypertension through Phase II and towards initiation of a Phase III cardiovascular outcomes trial expected to start in the second half of 2025. In fact, as announced this morning, we have recently completed enrollment in the CARDIO 3 Phase II study. ELEBSIRAN, our investigational therapeutic for the treatment of cerebral amyloid angiopathy in Alzheimer's disease continues to proceed as well.

第四季度，我們在推動產品線方面持續取得重大進展。讓我強調幾個關鍵的里程碑。我們將繼續推進 ZILEBESIRAN 治療高血壓的試驗性療法，直至 II 期，並啟動預計於 2025 年下半年開始的 III 期心血管結果試驗。事實上，正如今天上午宣布的那樣，我們最近已經完成了 CARDIO 3 第二階段研究的招募。我們用於治療阿茲海默症中的腦澱粉樣血管病變的試驗性療法ELEBSIRAN也在繼續進行中。

We presented multi-dose data showing high levels of knockdown with single and multiple doses, along with good safety and tolerability. We have an ongoing Phase II study in cerebral amyloid angiopathy and plan to start a Phase II study in Alzheimer's disease in the second half of the year. And we started four new Phase I programs last year. The first was for Huntington's disease, where we have a unique exon 1 targeting approach that nonhuman primates has shown deep and sustained knockdown with encouraging safety and tolerability. The Phase I trial is ongoing in the United States, Canada and the U.K.

我們提供的多劑量數據顯示單劑量和多劑量的擊倒率很高，並且具有良好的安全性和耐受性。我們目前正在進行腦澱粉樣血管病變的 II 期研究，並計劃在今年下半年啟動阿茲海默症的 II 期研究。去年我們啟動了四個新的第一階段計畫。第一個是針對亨廷頓氏症的，我們有一種獨特的外顯子 1 靶向方法，非人類靈長類動物已表現出深度和持續的敲除，具有令人鼓舞的安全性和耐受性。第一階段試驗目前正在美國、加拿大和英國進行。

The other programs initiated in Q4 include ZILEBESIRAN, plus Reversir for hypertension, TLN 6400 for bleeding disorder and ALN4324 for type 2 diabetes mellitus. This remarkable and unique pace of innovation puts us in a great position to have a strong self-sustainable pipeline that can deliver meaningful impact to patients for many years to come. I encourage you to join or to tune in to the webcast of our R&D Day that we will host on February 25, where we will provide more comprehensive reviews of the programs I've described and also highlight continued RNAi platform innovation that will drive the next era of Alnylam's growth.

第四季度啟動的其他項目包括 ZILEBESIRAN、用於治療高血壓的 Reversir、用於治療出血性疾病的 TLN 6400 和用於治療 2 型糖尿病的 ALN4324。這種非凡而獨特的創新步伐使我們處於有利地位，擁有強大的可自我維持的管道，可在未來許多年為患者帶來有意義的影響。我鼓勵您加入或收聽我們將於 2 月 25 日舉辦的研發日網絡直播，我們將在會上對我所描述的計劃進行更全面的回顧，並重點介紹將推動 Alnylam 下一個發展時代的持續 RNAi 平台創新。

With that, let me now turn it over to Jeff to review our financial results and upcoming milestones. Jeff?

現在，讓我將話題轉交給傑夫回顧我們的財務表現和即將到來的里程碑。傑夫？

Thanks, Pushkal, and good morning, everyone. I'm pleased to be presenting Alnylam's full year 2024 financial results and providing our complete financial guidance for 2025. Starting with a summary of our P&L results for the full year. Total global net product revenues for 2024 were $1.646 billion, representing 33% growth versus 2023 with both ATTR and rare franchises reporting strong growth of 34% and 29%, respectively. These results came in at the top end of our 2024 product revenue guidance which we had raised more than 10% at midyear from our original 2024 guidance.

謝謝，普什卡爾，大家早安。我很高興能夠介紹 Alnylam 2024 年全年財務表現並提供我們 2025 年的完整財務指導。從我們全年損益結果的總結開始。2024 年全球淨產品總收入為 16.46 億美元，較 2023 年增長 33%，其中 ATTR 和稀有特許經營權分別報告 34% 和 29% 的強勁增長。這些結果達到了我們 2024 年產品收入預期的最高水平，我們在年中將該預期從最初的 2024 年預期上調了 10% 以上。

For the full year, net revenue from collaborations was $510 million, including a $60 million sales milestone in Q4 from Novartis due to Leqvio exceeding $600 million in annual sales. Compared with 2023, collaboration revenues decreased 7%, primarily attributed to differences in certain revenue items between 2023 and 2024. During 2023, we recognized $310 million of revenue from the upfront payment received from Roche in connection with execution of our ZILEBESIRAN, collaboration. In comparison, during 2024 we recognized $185 million in revenues associated with the modification to our Regeneron collaboration driven by providing Regeneron an exclusive license to develop, manufacture and commercialize ZILEBESIRAN, as a monotherapy. Royalty revenue for the full year was $92 million or more than double what was recognized in 2023, driven by higher royalties from Novartis on sales of.

全年合作淨收入為 5.1 億美元，其中諾華在第四季度實現了 6,000 萬美元的銷售里程碑，原因是 Leqvio 的年銷售額超過 6 億美元。與 2023 年相比，合作收入減少了 7%，主要歸因於 2023 年和 2024 年之間某些收入項目的差異。2023 年，我們確認了與羅氏公司就 ZILEBESIRAN 合作實施而收到的預付款項 3.1 億美元的收入。相較之下，2024 年我們確認了 1.85 億美元的收入，這與我們與 Regeneron 合作的修改有關，該修改通過向 Regeneron 提供開發、製造和商業化 ZILEBESIRAN 作為單一療法的獨家許可來實現。全年特許權使用費收入為 9,200 萬美元，是 2023 年確認收入的兩倍多，這得益於諾華公司對銷售額的特許權使用費增加。

Gross margin on product sales was 81% for the full year, representing a 3% increase compared with 2023. The improvement in margin was primarily due to nonrecurring prior year expenses associated with canceled manufacturing commitments for ONPATTRO and other adjustments to inventory. These decreases were partially offset by an increased rate of royalties payable on net sales of AMVUTTRA. For 2025, we expect a decrease in gross margin on product sales as the average royalty rate payable Sanofi on AMVUTTRA is expected to be higher as sales of AMVUTTRA continue to increase.

全年產品銷售毛利率為81%，較2023年成長3%。利潤率的提高主要歸因於與取消 ONPATTRO 製造承諾和其他庫存調整相關的前一年非經常性費用。這些減少部分被 AMVUTTRA 淨銷售額應付特許權使用費稅率的提高所抵銷。到 2025 年，我們預計產品銷售毛利率將下降，因為隨著 AMVUTTRA 銷售額的持續成長，賽諾菲應付給 AMVUTTRA 的平均特許權使用費率將會更高。

Our non-GAAP R&D expenses increased 10% for the full year compared with prior year primarily due to increased costs associated with our preclinical activities as we develop our clinical pipeline of RNAi therapeutics targeting multiple tissues increased clinical trial expenses associated with the ZILEBESIRAN cardio Phase II study and increased employee compensation expenses. Our non-GAAP SG&A expenses increased 24% for the full year compared with 2023 primarily driven by increased investments in support of our TTR polyneuropathy business and in preparation for the potential launch of AMVUTTRA for cardiomyopathy along with increased personnel costs.

我們全年的非公認會計準則研發費用與上年相比增加了 10%，這主要是由於我們在開發針對多種組織的 RNAi 療法臨床管線時與臨床前活動相關的成本增加、與 ZILEBESIRAN 心臟 II 期研究相關的臨床試驗費用增加以及員工薪酬費用增加。與 2023 年相比，我們全年的非 GAAP 銷售、一般及行政費用增長了 24%，這主要是由於對支持 TTR 多發性神經病業務的投資增加以及為潛在推出用於治療心肌病的 AMVUTTRA 做準備以及人員成本增加。

For the first time, we full year non-GAAP operating profit of $95 million, representing a $156 million improvement compared with 2023, primarily driven by strong growth in product sales. This is a significant milestone for the company as achieving non-GAAP profitability has been a key goal associated with our P5x25 growth strategy. This achievement will enable further investment in our R&D pipeline as we strive to deliver sustainable long-term top and bottom line growth.

我們全年非公認會計準則營業利潤首次達到 9,500 萬美元，較 2023 年成長 1.56 億美元，主要得益於產品銷售的強勁成長。這對公司來說是一個重要的里程碑，因為實現非 GAAP 獲利一直是我們 P5x25 成長策略的關鍵目標。這項成就將促使我們進一步投資於研發領域，努力實現可持續的長期營收和利潤成長。

Finally, we ended the year with cash, cash equivalents and marketable securities of $2.7 billion compared to $2.4 billion at the end of 2023, with the increase primarily driven by improved operating performance and net proceeds received from the issuance of common stock in connection with employee stock option exercises. Now I'd like to turn to our 2025 financial guidance. Starting with net product revenues, we are reiterating our combined net product revenue guidance from ONPATTRO and AMVUTTRA, GIVLAARI and OXLUMO that was communicated in our JPMorgan press release dated January 12, 2025.

最後，我們截至今年底的現金、現金等價物和有價證券為 27 億美元，而 2023 年底為 24 億美元，成長主要得益於經營業績的改善以及與員工股票期權行使相關發行普通股所獲得的淨收益。現在我想談談我們的 2025 年財務指引。從淨產品收入開始，我們重申摩根大通 2025 年 1 月 12 日新聞稿中發布的 ONPATTRO 和 AMVUTTRA、GIVLAARI 和 OXLUMO 的綜合淨產品收入指引。

We anticipate combined net product sales for our four commercial products will be within a range of $2.05 billion to $2.25 billion, representing combined full year growth compared to 2024 of 31% at the midpoint of the guidance range or more than $500 million in growth. On a franchise level, the guidance is broken down as follows: total TTR, $1.6 billion to $1.725 billion, representing full year growth compared to 2024 of 36% at the midpoint of the guidance range. Importantly, this guidance assumes approval and launch of AMVUTTRA for ATTR cardiomyopathy in the US by the PDUFA date of March 23.

我們預計，我們四種商業產品的總淨銷售額將在 20.5 億美元至 22.5 億美元之間，與 2024 年相比，全年總成長率將達到 31%（指導範圍的中位數），或成長超過 5 億美元。在特許經營層面，指導意見細分如下：總 TTR 為 16 億美元至 17.25 億美元，與指導範圍中點的 2024 年相比，全年增長率為 36%。重要的是，該指南假定 AMVUTTRA 將於 3 月 23 日 PDUFA 日期之前在美國獲得批准並上市用於治療 ATTR 心肌病變。

Additionally, we assume launches for AMVUTTRA an ATTR CM in Germany and Japan in the second half of 2025. Total rare, $450million to $525 million representing full year growth compared to 2024 of 15% at the midpoint of the guidance range. Our guidance assumes foreign exchange rates as of December 31, 2024, which are noted in the footnote of our guidance slide. We are also providing constant exchange rate growth guidance for our net product revenues with a projected range of 26% to 39%.

此外，我們預計 AMVUTTRA 將於 2025 年下半年在德國和日本推出 ATTR CM。總額為 4.5 億美元至 5.25 億美元，與指導範圍中點的 2024 年相比，全年成長率為 15%。我們的指導假設外匯匯率截至 2024 年 12 月 31 日，這在我們的指導幻燈片的腳註中註明。我們也為我們的淨產品收入提供了恆定匯率成長指導，預計範圍為 26% 至 39%。

Collaboration and royalty revenue guidance range is $650 million to $750 million representing 16% growth compared to 2024 at the midpoint of the guidance range. Our guidance assumes achievement of a $300 million milestone payment from Roche associated with the initiation of our Phase III study for ZILEBESIRAN which we anticipate will occur in the second half of the year. We also expect the collaboration revenue associated with our partnerships with Roche and Regeneron as well as let deal royalties from Novartis will drive the majority of our collaboration and royalty revenue in 2025.

合作和特許權使用費收入指引範圍為 6.5 億美元至 7.5 億美元，與指導範圍中點的 2024 年相比成長 16%。我們的指導假設是，羅氏將支付 3 億美元的里程碑款項，用於啟動 ZILEBESIRAN 的第三階段研究，我們預計該付款將在今年下半年完成。我們也預計，與羅氏和再生元的合作收入以及來自諾華的交易特許權使用費將在 2025 年佔據我們合作和特許權使用費收入的大部分。

Our guidance for combined non-GAAP R&D and SG&A expenses is a range between $2.1 billion and $2.2 billion, with the midpoint of the range representing 17% growth compared with 2024. Growth drivers for R&D expense in 2025 include increased clinical investment across our early mid- and late-stage programs including the initiation of pivotal Phase III studies for ZILEBESIRAN and Nucresiran. Growth in SG&A will primarily be driven by the launch of AMVUTTRA for ATTR cardiomyopathy in the US, Germany and Japan assuming regulatory approvals.

我們對非公認會計準則研發和銷售、一般及行政開支總額的預期範圍在 21 億美元至 22 億美元之間，該範圍的中點與 2024 年相比增長 17%。2025 年研發費用的成長動力包括對我們早期、中期和後期計畫的臨床投資增加，包括啟動 ZILEBESIRAN 和 Nucresiran 的關鍵 III 期研究。銷售、一般及行政開支的成長將主要受益於美國、德國和日本監管部門批准後推出用於治療 ATTR 心肌病變的 AMVUTTRA。

Finally, as discussed last month at JPMorgan, we anticipate delivering non-GAAP operating income profitability in 2025. Let me now turn from financials and discuss some key goals and upcoming milestones for early 2025. As Pushkal mentioned, we will host an R&D Day on February 25 in New York City. The PDUFA target action date for the sNDA for vutrisiran is March 23, 2025. Please note that given the materiality of this decision, we will be entering a quiet period beginning on March 1.

最後，正如摩根大通上個月討論的那樣，我們預計 2025 年將實現非 GAAP 營業收入獲利。現在，讓我從財務角度轉而討論 2025 年初的一些關鍵目標和即將到來的里程碑。正如 Pushkal 所提到的，我們將於 2 月 25 日在紐約舉辦研發日。vutrisiran 的 sNDA 的 PDUFA 目標行動日期為 2025 年 3 月 23 日。請注意，鑑於該決定的重要性，我們將從 3 月 1 日開始進入靜默期。

We intend to initiate the Phase III study of Nucresiran in patients with ATTR amyloidosis cardiomyopathy in the first half of 2025. And our partners at Sanofi have a PDUFA target action date for fitusiran of March 28, 2025. Let me now turn it back to Christine to coordinate our Q&A session. Christine?

我們打算在 2025 年上半年啟動 Nucresiran 對 ATTR 澱粉樣變性心肌病變患者的 III 期研究。我們的合作夥伴賽諾菲為 fitusiran 設定的 PDUFA 目標行動日期為 2025 年 3 月 28 日。現在讓我把話題轉回給克莉絲汀，來協調我們的問答環節。克里斯汀？

Thank you, Jeff. Operator, we will now open the call for questions. Those dialed in, we would like to ask you to limit yourself to one question each and then get back in the queue if you have any additional questions.

謝謝你，傑夫。接線員，我們現在開始問答環節。對於那些撥打電話的人，我們希望你們將自己限制在每個問題上，然後如果你們還有其他問題，請回到隊列中。

(Operator Instructions) Tazeen Ahmad, Bank of America.

(操作員指示) Tazeen Ahmad，美國銀行。

I wanted to get a sense from your team about how long you think it's going to take to establish payer policies after the approval of -- and how do you think that could impact the initial trajectory of the launch?

我想從您的團隊那裡了解一下，您認為在批准後需要多長時間才能建立付款人政策——以及您認為這會對發布的初始軌跡產生什麼影響？

Thanks, Tazeen. That's a great question. I mean clearly, we're in a strong position, having already a TTR franchise supporting patients with polyneuropathy. And this really gives us a strong foundation on which to build. Tolga, perhaps you could ask a specific question around time to plan approvals.

謝謝，Tazeen。這是一個很好的問題。我的意思是，很明顯，我們處於有利地位，已經擁有支持多發性神經病變患者的 TTR 特許經營權。這確實為我們未來的發展奠定了堅實的基礎。托爾加，也許你可以問一個有關計劃審批時間的具體問題。

Look, obviously, we're really excited about the upcoming potential launch and our -- frankly, excitement is confirmed by the guidance that we've already provided. Now when it comes to the payer policies and formulary uptake, I think as you can see from my prepared remarks, this is really going to be a second half story. We're very much committed to the growth that we've already committed to. And we have value-based agreements that we know is going to be extended with some of these payer policies that considerate. But the formulary piece takes a little bit time. So I would expect the uptake really to be meaningful in the second half of the year. Thanks.

看，顯然，我們對即將推出的潛在產品感到非常興奮，而且我們的興奮感已經得到了我們已經提供的指導的證實。現在談到付款人政策和處方集的採用，我想正如您從我準備好的演講中看到的那樣，這實際上將是一個後半部分的故事。我們非常致力於我們已經承諾的成長。我們有基於價值的協議，我們知道這些協議將會隨著一些經過深思熟慮的付款人政策而延伸。但處方部分需要一點時間。因此我預計今年下半年的漲幅將非常顯著。謝謝。

Konstantinos Biliouris, BMO Capital Markets.

Konstantinos Biliouris，BMO 資本市場。

A quick one on AMVUTTRA from us. If we assume premium pricing for Ambutra compared to silence, which are approved already -- what are your thoughts around step edits for commercial insured patients who represent about 20% of the ATTR cardiomyopathy population. Thank you.

我們對 AMVUTTRA 做一個簡短介紹。如果我們假設 Ambutra 的定價高於已經核准的 Silence 的定價，那麼您對於佔 ATTR 心肌病變患者約 20% 的商業保險患者的分步編輯有何看法。謝謝。

Tolga, that's a question for you.

托爾加，這是一個問題。

Yes. Great question. Look, I mean, first and foremost, we really appreciate and like the product profile that Amitras still offer which is underpinned now by the HELIOS-B results. And in our engagements with payers at the prepricing discussions, we're also encouraged that they see, one, obviously, the value of this product can bring to the market. Second of all, the predictability of how we are actually being positioned as a Part B product.

是的。好問題。看，我的意思是，首先，我們非常欣賞和喜歡 Amitras 仍然提供的產品特性，而這一特性現在得到了 HELIOS-B 成果的支持。在我們與付款人的定價討論中，我們也很高興看到他們看到了該產品顯然可以為市場帶來的價值。其次，我們實際上如何被定位為 B 部分產品是可預測的。

So all these combined, we actually expect our uptake to be very consistent with what we have seen in the past with PN in terms of how payers will cover the product. And as we've already shared, very much committed to the guidance that we provided, which again underpins how we really see the growth, which is going to be accelerated in 2025.

因此，綜合所有這些因素，我們實際上預計，就付款人如何承保產品而言，我們的接受度將與我們過去在 PN 中看到的非常一致。正如我們已經分享的那樣，我們非常致力於我們提供的指導，這再次鞏固了我們如何真正看到成長，即成長將在 2025 年加速。

Huidong, Barclays.

惠東，巴克萊。

I know you cannot comment on the actual price for vital into the approval day, but wondering if you can share the key factors that impact your decision on pricing adjustment for AMVUTTRA. And related question, I know a few already asked, can you show with us what percentage of the current sites already have a coating place that you can use for AMVUTTRA in ATTR cutting ops?

我知道您無法對批准日的實際價格發表評論，但想知道您是否可以分享影響 AMVUTTRA 價格調整決定的關鍵因素。與此相關的問題是，我知道已經有幾個人問過了，您能否向我們展示一下，目前有多少比例的站點已經設有塗層場所，可以在 ATTR 切割操作中用於 AMVUTTRA？

Thanks, Gena, for the question and recognizing that it's too early to be specific about price. And as you know, we have our patient access principles. And when we think about price, we obviously consider the value that our product is bringing to patients and the ecosystem as well as assuring optimal access. And I think we've done a great job in PN along those dimensions, and we continue to plan to do an equally good job for CM. Don't we Tolga, do you want to add.

謝謝 Gena 提出這個問題，我承認現在具體討論價格還為時過早。如您所知，我們有患者訪問原則。當我們考慮價格時，我們顯然會考慮我們的產品為患者和生態系統帶來的價值以及如何確保最佳的訪問。我認為我們在 PN 的這些方面做得很好，我們繼續計劃在 CM 上做得同樣出色。我們不是托爾加嗎，你想添加嗎。

Yes, I mean one maybe answer to your last point, itch. We already have a J code for AMVUTTRA, which is going to be used Therefore, we don't expect any changes or any disruption on that. And in respect to our coverage, look, as we shared earlier on our TTR Day and other forums, the current makeup of our business from a Medicare perspective as well as commercial, we expect that to remain the same. And therefore, which we believe is going to result in rather smooth coverage for our product.

是的，我的意思可能是針對你的最後一點「癢」的回答。我們已經有了 AMVUTTRA 的 J 程式碼，並將投入使用，因此，我們預計不會發生任何變更或中斷。關於我們的報導，正如我們之前在 TTR 日和其他論壇上所分享的那樣，從醫療保險角度和商業角度來看，我們目前的業務組成將保持不變。因此，我們相信這將使我們的產品覆蓋範圍更加廣泛。

As Yvonne indicated, we're really excited about the Otago mechanism and how that's going to actually bring additional value and alternative, the disruptive treatment for payers as well as patients. And then actually, frankly, most importantly, the affordability for the patient. As you know, 70% of our patients currently pay 0 co-pay, and we expect that dynamic to remain the same, which we believe is going to be an important driver for our patient uptake.

正如伊馮所說，我們對奧塔哥機制感到非常興奮，以及它將如何為付款人和患者帶來額外的價值和替代方案以及顛覆性的治療。然後實際上，坦白說，最重要的是患者能否負擔得起。如您所知，我們 70％ 的患者目前支付 0 自付費用，我們預計這種動態將保持不變，我們相信這將成為我們吸引患者的重要驅動力。

Lori Raycroft, Jefferies.

傑富瑞的洛里‧雷克羅夫特 (Lori Raycroft)。

Congrats on the progress. Just wondering if there's any perspective you can provide on label discussion progress. And in addition to reduction of mortality and hospitalizations, are you advocating to have anything unique on the front page of the label and the indication and usage section such as wording related to preservation and quality of life and functional capacity.

祝賀你取得進展。只是想知道您是否能對標籤討論進度提供一些看法。除了減少死亡率和住院率之外，您是否主張在標籤首頁和適應症及用途部分添加一些獨特的內容，例如與保存和生活品質以及功能能力相關的措辭。

Yes. Thanks, Maurice. Look, first of all, we're really very enthusiastic about how the FDA review is going and we remain fully on track and for an approval date by the PDUFA. So we're excited about the progress that's been made on that front. In terms of the label, look, we believe that the study was designed and clearly demonstrated the benefit on mortality and hospitalization events.

是的。謝謝，莫里斯。首先，我們對於 FDA 的審查進展非常熱衷，我們仍然完全按照計劃進行，等待 PDUFA 的批准日期。因此，我們對這方面的進展感到非常興奮。就標籤而言，我們相信這項研究的設計和清楚地證明了其對死亡率和住院事件的益處。

And we expect that that will be reflected in the label as well as the ancillary benefits that we saw in terms of preservation of functional ability, quality of life and benefits across a series of endpoints there. So look, at the end of the day, we want a label that reflects the study that was designed and where we saw statistically significant results in predefined endpoints across a whole series of attributes that we think are a benefit and that we're able to actually then go and educate providers and patients on so we look forward to sharing that when an eventual approval occurs.

我們預計這將反映在標籤上，以及我們在保留功能能力、生活品質和一系列終點益處方面看到的附帶益處。所以，歸根結底，我們想要一個標籤來反映所設計的研究，我們在一系列我們認為有益的屬性的預定義端點中看到了具有統計意義的結果，並且我們能夠真正去教育提供者和患者，因此我們期待在最終獲得批准時分享這一點。

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

My question was actually a really good follow-up to Maurice on label language. To you think about the language in the label, specifically mortality but potentially having that mortality clinical data later in the label in the clinical data section. What sort of potential advantage could that give you or not, either detailing the product or with payers?

我的問題實際上是對莫里斯關於標籤語言問題的一個很好的跟進。您需要考慮標籤中的語言，特別是死亡率，但可能會在標籤的臨床數據部分中稍後顯示該死亡率臨床數據。無論是詳細介紹產品還是付款人，這能為你帶來什麼樣的潛在優勢？

Okay. Ritu, Look, we have a pretty clear view of the understanding of how we're going to be able to promote, communicate this. Mainly, obviously, what Pushkal indicated, we had reached significant results on all prespecified endpoints, 10 out of 10. And our ability to communicate that is going to be relatively smooth. We're pretty confident on how we can actually differentiate the product from a product profile perspective, given that this is an orthogonal mechanism of action that rapidly knocks down the disease-causing protein and has the ability to actually then demonstrate those clinical outcome benefits on both mortality as well as hospitalization coupled with the fact that we actually have four times a year subcutaneous injectable that really provides great adherence as we've seen on polyneuropathy as well as our relatively smooth access given that 70% of patients pay 0 co-pay.

好的。Ritu，你看，我們對如何促進和傳達這一點有一個非常清晰的認識。最主要的是，顯然正如 Pushkal 所指出的，我們在所有預先指定的終點上都取得了顯著的成果，10 個中 10 個。我們的溝通能力將會相對順暢。我們非常有信心從產品概況的角度對產品進行區分，因為這是一種正交作用機制，可以迅速抑制致病蛋白，並且能夠真正證明其對死亡率和住院率的臨床結果益處，再加上我們每年有四次皮下注射，這確實提供了很好的依從性，正如我們在多發性神經病上看到的那樣，而且考慮到 70% 的患者支付 0% 的自暢治療，我們支付順暢治療，相對暢用的患者支付相對暢用。

All those perspectives will be carrying through how we're going to actually communicate this exceptional medicine to the prescribers, which are very much in need of a disruptive treatment.

所有這些觀點都將貫穿我們如何將這種特殊的藥物傳達給非常需要顛覆性治療的處方醫生。

Do you still expect that to be in the actual labeling language though? Those data?

但是，您還期望這會出現在實際的標籤語言中嗎？那些數據？

Look, at the end of the day, we think that the label will reflect the things that we've shown in the clinical trial. That's traditionally what is done, and we would expect this, as we've said, Ritu, that we had a whole series of prespecified endpoints that show the impact of this drug on this disease. And so we would expect that to be generally reflected in the label. And again, consistent with labeling, Tolga's team, our medical teams will be able to speak about those attributes and the results of HELIOS B study to providers and patients and payers.

看，最終，我們認為標籤將反映我們在臨床試驗中所展示的內容。這就是傳統的做法，我們也期望，正如我們所說的，Ritu，我們有一整套預先指定的終點來顯示這種藥物對這種疾病的影響。因此我們希望這一點能夠普遍反映在標籤上。再次，與標籤一致，托爾加團隊，我們的醫療團隊將能夠向供應商、患者和付款人談論這些屬性以及 HELIOS B 研究的結果。

Greg Harrison, Scotia Bank.

加拿大豐業銀行的格雷格·哈里森。

This is Theresa Vitelle on for Greg Harrison. Congrats on all the updates. I was just curious to hear what your expectations are for nutrisiran's potential revenue mix among naive patients in the first-line setting and versus switches from...

這是 Theresa Vitelle 為 Greg Harrison 報道的。祝賀所有更新。我只是好奇，想聽聽您對 nutrisiran 在初治患者中以及從... 轉換而來的患者中的潛在收入組合有何期望？

Tolga, that question for you.

托爾加，這個問題問你。

To our best of our abilities, we were able to provide a pretty clear and ambitious guidance that really shows how we're going to actually accelerate this RTTR franchise and post 36%. Now how that mix is going to happen is, look, we believe this is a product well positioned to be a standard of care and to be cost the first line. But like any categories, we do also know that there is a need of another product with an -- mechanism of action beyond the stabilizers. So we certainly expect a good mix of patients so from naive patients that are coming in the door that are newly diagnosed and some perhaps eligible for switches or in a rare instances, some combination. So we do expect that, and obviously, as we built our guidance, all these elements were incorporated.

在我們能力範圍內，我們能夠提供非常清晰和雄心勃勃的指導，真正表明我們將如何加速這個 RTTR 特許經營並實現 36% 的成長。現在這種組合將如何發生，看，我們相信這是一種非常適合成為護理標準並成為成本第一的產品。但與任何類別一樣，我們也知道需要另一種具有穩定劑以外的作用機制的產品。因此，我們當然期望患者群體能夠很好地混合，既包括剛確診的初治患者，也包括可能適合轉換治療的患者，或者在極少數情況下，是某種組合。因此，我們確實期待這一點，而且顯然，在我們制定指導方針時，所有這些因素都已被納入其中。

Gary Nachman, Raymond James.

加里納赫曼、雷蒙詹姆斯。

Maybe you could talk about the competitive dynamics you're seeing with -- in polyneuropathy with both products growing at this point? And how is the difference between Part B and Part D playing out? And how you think that's going to translate over to cardiomyopathy with that approval.

也許您可以談談您所看到的多發性神經病變領域的競爭動態，目前兩種產品都在成長？B 部分和 D 部分的差異如何？您認為這項批准將如何轉化為治療心肌病變？

Thanks for the question. I mean, clearly, we're very pleased with our strong TTR performance in 2024, and that was with competition in the market. So I think we're doing a good job continuing to build the business. Tolga, perhaps you want to add some color to the specific dynamics.

謝謝你的提問。我的意思是，顯然，我們對 2024 年強勁的 TTR 表現感到非常滿意，這是在市場競爭的情況下實現的。因此我認為我們在繼續發展業務方面做得很好。托爾加，也許你想為具體的動態添加一些色彩。

Yes. So we just posted our full year results for '24, which happened to be the first year, actually, we faced competition. In this relatively narrow category where we always said this is going to be a growth category growth story. And I think what you can see, particularly in our US numbers, where US

是的。因此，我們剛剛發布了 24 年全年業績，實際上，這也是我們面臨競爭的第一年。在這個相對狹窄的類別中，我們總是說這將是一個成長類別的成長故事。我認為你可以看到，特別是在我們美國的數據中，

business from a pretty good healthy base, grew 42%, and year-over-year. And that was with the competition. And as far as I can tell, a New Year also getting their fair share of growth which is, again, very consistent with the growth story that we've been telling all along.

業務在相當健康的基礎上成長了 42%，並且比去年同期成長。這就是競爭。據我所知，新的一年也獲得了公平的成長，這與我們一直以來講述的成長故事非常一致。

We believe we have a highly differentiated product profile versus -- given that it's four times a year, and it's CP administered. And we had not seen any significant access headwinds. And we anticipate, frankly, this type of dynamic continue as we expand our expanded indication to cardiomyopathy.

我們相信，我們擁有高度差異化的產品組合——鑑於它每年四次，並由 CP 管理。我們並未看到任何重大的訪問阻力。坦白說，我們預計，隨著我們擴大對心肌病變的適應症，這種動態將會持續下去。

Jessica Fye, JPMorgan.

摩根大通的傑西卡·菲伊 (Jessica Fye)。

What do you think the early acoramadis scripts imply for the TTR cardiomyopathy market dynamics, market expansion and interest in agents beyond tafamidis as it relates to AMVUTTRA? And I think folks have been kind of trying to ask this in a few different ways, but maybe just to try one more time. What's the right way to think about the evolution of AMVUTTRA's net price as you move into this much larger patient population?

您認為早期的 acoramadis 腳本對於 TTR 心肌病變市場動態、市場擴張以及與 AMVUTTRA 相關的對 tafamidis 以外的藥物的興趣有何意義？我認為人們已經嘗試用幾種不同的方式來詢問這個問題，但也許只是再試一次。當您進入這個更大的患者群體時，如何正確思考 AMVUTTRA 淨價的演變？

Okay. I mean two questions there too. I mean, clearly, as Tolga said, I mean, we believe that this is a market growth opportunity, which makes a very exciting category to be playing and obviously becomes a cardiomyopathy with a strong track record in the TTR space. Tolga, perhaps that's the color to the first question and then the specific question around the evolution of net price.

好的。我也想問那裡兩個問題。我的意思是，顯然，正如托爾加所說，我們相信這是一個市場成長機會，這使得該類別非常令人興奮，並且顯然成為 TTR 領域擁有良好業績記錄的心肌病變。托爾加，也許這是第一個問題的重點，然後是有關淨價格演變的具體問題。

Yes. I mean, I think, look, the first sentiment that comes to mind is encouragement. Effectively seeing another stabilizer coming into the market, and they've shared some numbers on the prescription that are early innings obviously. We're very encouraged because if and other stabilizer that is four times a year with not really significant clinical data, obviously, they've actually shown that this is actually a growth category.

是的。我的意思是，我認為，看，首先想到的情感是鼓勵。實際上看到另一種穩定劑進入市場，並且他們分享了一些處方數字，顯然這是早期階段的數字。我們感到非常鼓舞，因為如果和其他穩定劑每年四次，雖然沒有真正重要的臨床數據，顯然，他們實際上已經表明這實際上是一個成長類別。

Now when I think about AMVUTTRA product profile that has really strong clinical profile as well as the fact that it's four times a year annual dosing, we're really well positioned to be in the access, we're very excited about what AMVUTTRA do given that the category is going to be -- continue to be growing, given the undiagnosed patient numbers.

現在，當我想到 AMVUTTRA 產品概況時，它具有非常強大的臨床特性，並且每年給藥四次，我們確實處於非常有利的位置，我們對 AMVUTTRA 的表現感到非常興奮，因為考慮到未確診患者的數量，該類別將繼續增長。

Paul Matteis, Stifel.

保羅·馬泰斯（Paul Matteis），Stifel。

On payer dynamics and how they evolve in this category, are you expecting the average insurer to cross manage between Part B and Part D? And I think, again, the underlying question that everyone is trying to get to on pricing is you're at a significant premium right now. Does it have to go down or not.

關於付款人動態以及他們在此類別中如何發展，您是否預計普通保險公司會在 B 部分和 D 部分之間進行交叉管理？我認為，在定價方面每個人都想弄清楚的根本問題是，現在的價格溢價相當高。它到底需不需要下降？

There's a lot of moving parts, right, like the payer liability on Part D is one of them. But just as it relates to how insurers are going to manage their formularies in this space, like could tafamidis or acoramidis actually be a step at it? Or is that just not something that's normal in practice at this point?

有很多活動的部分，對吧，例如 D 部分的付款人責任就是其中之一。但正如它與保險公司如何管理該領域的處方集有關一樣，tafamidis 或 acoramidis 實際上是否可以邁出這一步？或者這只是目前實務上不正常的事情？

Yes. Thank you for the question. Look, I mean there's a lot of noise around how the payers will be managing this. What we've seen is this is a rare condition, highly devastating condition and we expect the payers to cover the product and how the market is going to evolve. I think we have a pretty clear eye view given how we've been actually managing polyneuropathy as a Part D product.

是的。感謝您的提問。你看，我的意思是關於付款人將如何處理這個問題存在很多爭論。我們看到，這是一種罕見且極具破壞性的疾病，我們預計付款人將承擔該產品的費用，並關注市場將如何發展。我認為，考慮到我們實際上如何將多發性神經病變作為 D 部分產品進行管理，我們有一個非常清晰的看法。

And how -- has launched in the Part D product. We expect similar dynamics in terms of our payer mix. And we do anticipate that given the given the patient affordability is a key driver of how patients stay on therapy is to be very favorable for AMVUTTRA.

以及如何——已經推出了 D 部分產品。我們預計我們的付款人組合也會出現類似的動態。我們確實預計，鑑於患者的負擔能力是決定患者繼續接受治療的關鍵驅動因素，這對 AMVUTTRA 來說非常有利。

Salveen Richter, Goldman Sachs.

高盛的薩爾文·里希特（Salveen Richter）。

You plan to initiate a Phase III study for Nucresiran in in ATTR-CM in the first half. How are you thinking about the timing of enrollment and events, given the availability of new options? And how do you plan to conduct an interim here?

您計劃在上半年在 ATTR-CM 中啟動 Nucresiran 的 III 期研究。考慮到有新的選擇，您如何考慮招生和活動的時間表？您計劃如何在這裡進行臨時工作？

Yes. So thanks for the question. I mean, clearly, we'll be providing more detail around our acrisiran program at R&D Day at the end of this month. Pushkal, maybe you can share a little bit about how we're thinking about forward Nucresiran, which we're very excited about.

是的。感謝您的提問。我的意思是，顯然，我們將在本月底的研發日上提供有關我們的 acrisiran 計劃的更多細節。普什卡爾，也許你可以和我們分享我們對未來 Nucresiran 的看法，我們對此感到非常興奮。

Yes, Salveen, look, I think Nucresiran the profile that we've seen so far really sets it up, we think, to be a best-in-class therapy for patients with this disease, building on -- what we've seen with vutrisiran this now is a derisked asset. We think we can get deeper knockdown. We've already shown that over 90%, 95% knockdown, less frequent administration, and we think that's going to help patient outcomes.

是的，薩爾文，看，我認為 Nucresiran 迄今為止我們所看到的特徵確實使它成為這種疾病患者的最佳治療方法，基於我們在 vutrisiran 上所看到的，它現在是一種去風險資產。我們認為我們可以進行更深層的擊倒。我們已經證明，超過 90%、95% 的擊倒率，更少的給藥頻率，我們認為這將有助於改善患者的治療效果。

When we think about the development plan for it, I think there's a number of factors. A, we want to develop -- bring this to market as quickly as possible because of the value that it brings. Two, we want to think about how do we develop a clinical profile for that and a label that allows for broad uptake and a very durable franchise, right? And so you'll see those -- how we've kind of brought those factors together at R&D Day. We will talk more about the development program there in CM and PN and our overall approach to this disease.

當我們考慮它的開發計劃時，我認為有許多因素。答，我們希望開發它——盡快將其推向市場，因為它帶來了價值。二，我們要思考如何為此開發一個臨床概況和一個允許廣泛採用和非常持久的特許經營的標籤，對嗎？所以你會看到這些——我們如何在研發日將這些因素結合在一起。我們將進一步討論 CM 和 PN 的發展計劃以及我們對這種疾病的整體治療方法。

So stay tuned. It will just be a couple of weeks, and we'll be able to share more.

敬請關注。只需幾週時間，我們就能分享更多資訊。

Ellie Merle, UBS.

瑞銀的艾莉·梅爾（Ellie Merle）

Just a couple for me. So how would you characterize the mix of growth in the TTR guidance from polyneuropathy versus cardiomyopathy and then Tolga, you mentioned that post approval, you'll be finalizing value-based agreements in cardiomyopathy, can you elaborate a bit on how these could work and what this could look like for cardiomyopathy relative to polyneuropathy?

對我來說只有一對。那麼您如何描述 TTR 指導中多發性神經病變與心肌病變的增長組合？ 然後 Tolga，您提到批准後，您將最終確定心肌病變的基於價值的協議，您能否詳細說明一下這些協議如何發揮作用，以及對於心肌病變相對於多發性神經病變而言，這會是什麼樣子？

Tolga, two questions there. Polyneuropathy, cardiomyopathy and then a little bit more detail on how we're thinking about buying bill post approval?

托爾加，有兩個問題。多發性神經病變、心肌病變，然後能更詳細地介紹我們如何考慮購買批准後的法案嗎？

Look, unusual to our tradition, we actually at JPM broke down our guidance between TTR and rare -- but I think we'll stop there. We'll obviously continue to provide more color about how the launch is going in the -- particularly in the second half of the year where we do see -- where we do anticipate the growth to take place. Now can you remind me the second question.

你看，與我們的傳統不同，我們實際上在 JPM 將我們的指導分解為 TTR 和罕見兩種類型 - 但我想我們會就此止步。顯然，我們將繼續提供更多有關發布進展的資訊——特別是在今年下半年，我們確實看到——我們預計成長將會發生。現在你能提醒我第二個問題嗎？

First approval, how we're thinking about buy and bill.

首先批准，我們如何考慮購買和計費。

Value-based agreements, right? So look, we're very, very proud about the value-based agreements that we set out. Approximately, we have about of the lives that are currently covered on the PN is dependent on the value-based agreements. And the value-based agreements are actually essentially really provide our commitment to the clinical outcomes. So we have this experience already with PN, and we anticipate that to actually also carry over in most instances, for cardiomyopathy, which should actually provide a level of predictability for the payers about how the product is going to perform and the clinical outcomes that the payers expect us to achieve.

基於價值的協議，對嗎？所以，我們對我們制定的基於價值的協議感到非常非常自豪。大約有 % 的生命目前在 PN 上受到保障，而這些生命依賴於基於價值的協議。基於價值的協議實際上確實提供了我們對臨床結果的承諾。因此，我們在 PN 方面已經擁有了這方面的經驗，我們預計，在大多數情況下，這種經驗也適用於心肌病，這實際上應該為付款人提供一定程度的可預測性，讓他們了解產品的性能以及付款人期望我們實現的臨床結果。

So I think that's a great -- one of the great best practices that we've established over the years. and we anticipate that to carry over with our cardiomyopathy indication in most cases.

所以我認為這是我們多年來建立的最佳實踐之一。我們預計，在大多數情況下，這將延續我們的心肌病變指徵。

Mani Foroohar, Leerink Partners.

Mani Foroohar，Leerink Partners。

Congrats on great results commercially and otherwise. I know that there's probably two more questions about AMVUTTRA and pricing in the line. So I'm going to ask actual financial question. Could you clarify the driver of the tax benefit that was noted here? And would that be recurring?

恭喜您在商業和其他方面都取得了巨大的成就。我知道可能還有兩個關於 AMVUTTRA 及其定價的問題。所以我要問實際的財務問題。您能否澄清一下這裡提到的稅收優惠的驅動因素？這種情況會重複發生嗎？

Is this an NOL dynamic OUS, if you could just dig into what drove that benefit and how it might recur or not flash over the course of the year?

這是一個 NOL 動態 OUS 嗎，如果您可以深入研究是什麼推動了這種好處，以及它在一年內可能如何重現或不閃現？

A question for you --

向您提問--

Good question, Mani. We noted in the press release that we had a release of a valuation allowance ex US, and that's really related to our Swiss entity. This is something that we have to do every quarter with our deferred tax assets as we have to assess whether or not it's more likely than not that, that value is going to ultimately be recognized.

問得好，馬尼。我們在新聞稿中指出，我們已經釋放了美國的估值準備金，這實際上與我們的瑞士實體有關。這是我們每季都要對遞延稅務資產進行的操作，因為我們必須評估該價值是否最終有可能被確認。

And the Swiss entity has had profitability for a number of periods now. So that gave us the confidence to release that. We've not released all the valuation allowances either in Switzerland, and we've not released anything in the US yet. It's very difficult this point to predict further, Mani. So I'd probably just leave it at that for now.

該瑞士實體目前已連續多個時期保持獲利。因此這給了我們發布該產品的信心。在瑞士，我們尚未公佈所有的計價準備，在美國，我們也尚未公佈任何內容。這一點很難進一步預測，馬尼。所以我現在可能就先這樣吧。

I think we've got time for one more question. I think we couple of last questions coming up.

我想我們還有時間再回答一個問題。我想我們還有最後幾個問題。

Luca Issi, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Luca Issi。

Great. Maybe I'll follow Mani here I guess. But Jeff, how should we think about gross margin here going forward? I mean the same of the oral TC is very meaningful at 15%, 30%, but we obviously don't know the exact hearing of the royalty fee. Do you think that modeling gross margin compressing from 80% now, I think it's a low 80s now to like low 70s, so even upper 60s. Is that a reasonable assumption in your mind. Any call there much appreciated.

偉大的。我想，也許我會跟著 Mani 來這裡。但是傑夫，我們該如何看待未來的毛利率呢？我的意思是，口服 TC 的費率同樣在 15%、30% 左右，非常有意義，但我們顯然不知道特許權使用費的具體金額。您是否認為建模毛利率從現在的 80% 壓縮到了現在的 80% 以下，我認為是 70% 以下，甚至是 60% 以上。您認為這是一個合理的假設嗎？任何來電均非常感激。

Yes, I appreciate the question. So in my prepared remarks, I mentioned that we expect -- gross margin on product sales to be lower in 2025. You're right. 2024, our gross margin on product sales was 81%. And I do think that will be the direction of travel for a period of time, really driven by two things that relate to AMVUTTRA.

是的，我很感謝你提出這個問題。因此，在我準備好的發言中，我提到，我們預計 2025 年產品銷售毛利率將會下降。你說得對。 2024年，我們的產品銷售毛利率為81%。我確實認為這將是一段時期內的旅行方向，實際上受到與 AMVUTTRA 相關的兩件事的推動。

One is -- it's our lowest margin product right now, given the royalty burden to Sanofi, and it's our fastest-growing product. So that will put pressure on margins as we move forward. And secondly, as that business grows, we also start to move up higher in the royalty tiers.

一是－考慮到賽諾菲的專利使用費負擔，它是目前我們利潤率最低的產品，也是我們成長最快的產品。因此，這將對我們未來的利潤造成壓力。其次，隨著業務的成長，我們的特許權使用費等級也開始上升。

So the average royalty rate will likely also increase over time. The royalty that we paid on average across 2024 for AMVUTTRA was 21%. Again, my expectation as this moves forward is, over time, that number is going to probably be mid- to high 20s. So that's just sort of the incremental amount that I would expect. Now there's a couple of things that will move the other way, I would say, on margins. If you look at our gross margin on a total revenue basis, that also includes the impact of collaboration and royalty revenue. that's revenue that's very high margin, probably close to 100%.

因此，平均版稅率也可能隨著時間的推移而增加。2024 年我們平均為 AMVUTTRA 支付的特許權使用費為 21%。再次，我預計隨著時間的推移，這個數字可能會達到 25% 左右。這只是我預期的增量。現在我想說，在利潤率方面，有幾件事會朝著相反的方向發展。如果從總收入的角度來看我們的毛利率，其中還包括合作和特許權使用費收入的影響。這是利潤率非常高的收入，可能接近 100%。

As an example, in 2024, the margin on product sales was 81%. But if you looked at margin on total revenue, it was 86%. So that uplifted it. And then secondly, I think the most important thing is that the issue with this high royalty burden, if we're successful in developing Nucresiran, we'll hear more about that at R&D Day, as Pushkal said, there's no royalty burden to Sanofi on that. So that would obviously offset this in the future if we're successful in bringing that to market. So hopefully, that gives you a little more clarity on direction of travel on margins.

例如，2024 年產品銷售利潤率為 81%。但如果你看一下總收入的利潤率，它是86%。這讓它振奮起來。其次，我認為最重要的是這個高額特許權使用費負擔的問題，如果我們成功開發出 Nucresiran，我們會在研發日聽到更多有關這方面的信息，正如 Pushkal 所說，賽諾菲在這方面沒有特許權使用費負擔。所以如果我們成功將其推向市場，這顯然會在未來抵消這一影響。所以希望，這能讓您更清楚地了解邊際的移動方向。

That's super helpful.

這非常有幫助。

Well, look, thanks, everybody, for joining the call. 2024 is really a very good year for Alnylam. As I said, just the beginning of the success we believe we're on track to realize in 2025. So thanks, everybody, and have a great day.

好吧，謝謝大家參加電話會議。 2024 年對 Alnylam 來說確實是非常好的一年。正如我所說，這只是成功的開始，我們相信我們有望在 2025 年實現成功。謝謝大家，祝大家有個愉快的一天。

Goodbye. Ladies and gentlemen, the conference has now ended. Thank you all for joining. You may all disconnect your lines.

再見。女士們、先生們，會議現已結束。感謝大家的加入。你們都可以斷開自己的線路。