Alnylam Pharmaceuticals Inc (ALNY) 2025 Q1 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Alnylam Pharmaceuticals Q1 2025 earnings conference call. (Operator Instructions) This call is being recorded on Thursday, May 1, 2025.

女士們、先生們，早安，歡迎參加 Alnylam Pharmaceuticals 2025 年第一季財報電話會議。（操作員指示）本次通話於 2025 年 5 月 1 日星期四錄製。

I would now extend the conference over to Alnylam. Please go ahead.

我現在想將會議延伸至 Alnylam。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.

早安.我是 Christine Lindenboom，Alnylam 首席企業傳播長。今天與我一起的還有首席執行官 Yvonne Greenstreet； Tolga Tanguler，首席商務官； Pushkal Garg，首席醫療官；以及首席財務官 Jeff Poulton。

For those of you participating via conference call, the accompanying slides can be accessed by going to the events section of the Investors page of our website, investors.alynylam.com/events.

對於透過電話會議參與的各位，可以透過造訪我們網站投資者頁面的活動部分 investors.alynylam.com/events 來存取隨附的幻燈片。

During today's call, as outlined in slide 2, Yvonne will offer introductory remarks and provide some 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 our upcoming milestones before we open the call to your questions.

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些一般背景資訊。托爾加將提供我們全球商業進展的最新情況。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我們即將實現的里程碑。

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. 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 report on file with the SEC.

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案》安全港條款所指的前瞻性陳述。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。

In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements.

此外，任何前瞻性陳述僅代表我們截至本紀錄之日的觀點，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?

說完這些，我想把電話轉給伊馮娜 (Yvonne)。伊馮娜？

Thanks, Christine, and thank you everyone for joining the call today. 2025 is off to a strong start at Alnylam. In the first quarter, we made notable progress towards our goal of becoming the global TTR leader, which will play a critical role in driving sustainable growth and value creation this year and beyond.

謝謝，克莉絲汀，也謝謝大家今天參加電話會議。 2025 年對 Alnylam 來說是一個好的開始。第一季度，我們朝著成為全球TTR領導者的目標取得了顯著進展，這將在推動今年及以後的可持續成長和價值創造方面發揮關鍵作用。

Commercially, we delivered $469 million in combined to net product revenues, and this represents 28% growth year over year. This was driven primarily by the robust 45% year-over-year growth of our US TTR franchise, which in the first quarter consisted solely of continued uptake in the hereditary polyneuropathy population.

商業方面，我們實現了 4.69 億美元的淨產品收入，年增 28%。這主要得益於我們美國 TTR 特許經營權同比增長 45%，第一季該業務僅由遺傳性多發性神經病人群的持續增長所驅動。

We also have several exciting portfolio advancements in the quarter, most notably the expanded indication of AMVUTTRA in ATTR cardiomyopathy, with approvals in the US and Brazil. And earlier this week, we received a positive CHMP opinion in the EU.

本季度，我們還取得了幾項令人興奮的產品組合進展，最引人注目的是 AMVUTTRA 在 ATTR 心肌病變中的適應症擴大，並已獲得美國和巴西的批准。本週早些時候，我們收到了歐盟 CHMP 的積極意見。

We also saw approval of the 6th Alnylam-discovered RNAi therapeutic, Qfitlia, for hemophilia A or B secured by our partners at Sanofi. Lastly, we are reiterating our guidance for the year, underscoring our confidence and continued growth and a strong launch in ATTR cardiomyopathy. This also includes our goal of achieving sustainable non-GAAP profitability in 2025.

我們還看到，我們的合作夥伴賽諾菲已批准 Alnylam 發現的第 6 種 RNAi 療法 Qfitlia 用於治療血友病 A 或 B。最後，我們重申今年的指導方針，強調我們的信心、持續的成長以及在 ATTR 心肌病變領域的強勁推出。這也包括我們在 2025 年實現永續非 GAAP 獲利的目標。

Now, before I move on, I'd like to take just a brief moment to acknowledge the uncertainty that exists related to potential evolution in certain policies, including tariffs, FDA personnel, reorganization, and other biotech industry initiatives being discussed.

現在，在我繼續之前，我想花一點時間來承認與某些政策的潛在演變相關的不確定性，包括關稅、FDA 人員、重組和正在討論的其他生物技術行業舉措。

While much is yet to be clarified and finalized, we've taken a comprehensive look across our business, and we believe that Alnylam is well positioned and pretty well insulated from any potential impacts associated with the key initiatives that have been announced to date. We feel that we're completely able to focus on the key tasks at hand, executing on a strong launch in ATTR cardiomyopathy and continuing to advance our robust high value pipeline.

雖然還有很多事情尚未澄清和最終確定，但我們已經對我們的業務進行了全面的審視，我們相信 Alnylam 已經做好了準備，並且能夠很好地抵禦迄今為止宣布的關鍵舉措所帶來的任何潛在影響。我們覺得我們完全能夠專注於手頭上的關鍵任務，在 ATTR 心肌病變領域強勢推出新產品，並繼續推進我們強大的高價值產品線。

Our achievements in early 2025 underpin the three core elements of our business that we believe will drive sustainable growth and value creation for years to come. The first is TTR leadership. Tolga will provide color on our launch of AMVUTTRA in ATTR-CM, but at a high level we're very pleased with our early progress, which is focused on securing broad access, driving awareness, and supporting treatment initiation for patients in the initial few weeks since approval.

我們在 2025 年初的成就鞏固了我們業務的三大核心要素，我們相信這些要素將在未來幾年推動永續成長和價值創造。首先是TTR領導力。Tolga 將為我們在 ATTR-CM 中推出 AMVUTTRA 提供色彩，但總體而言，我們對我們的早期進展感到非常滿意，我們的重點是確保廣泛的使用機會、提高認識，並在批准後的最初幾週內支持患者開始治療。

The next is growth through innovation, including a pipeline with numerous multi-billion-dollar opportunities and an R&D engine set up to deliver sustainable innovation and value creation. The third element is strong financial performance with robust commercial delivery and a disciplined approach to capital allocation to enable us to sustain profitability going forward.

其次是透過創新實現成長，包括擁有眾多價值數十億美元的機會的管道和為實現永續創新和價值創造而建立的研發引擎。第三個要素是強勁的財務表現、強勁的商業交付和嚴謹的資本配置方法，使我們能夠維持未來的獲利能力。

And of course, all of this is underpinned by a best-in-class team and our award winning culture. And this all represents tremendous progress against Alnylam's [P5x25] goals, and we continue to work to turn these goals into reality by the end of the year. Doing so will further establish Alnylam as a unique top tier biotech company, delivering sustainable innovation to patients for years to come.

當然，這一切都建立在一流的團隊和屢獲殊榮的文化的基礎上。這一切都代表著 Alnylam 在實現 [P5x25] 目標方面取得了巨大進展，我們將繼續努力，爭取在今年年底前將這些目標變為現實。此舉將進一步確立 Alnylam 作為一家獨特的頂級生物技術公司的地位，並在未來幾年為患者提供可持續的創新。

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

現在，請容許我將電話轉給托爾加 (Tolga)，讓他回顧一下我們的商業表現。托爾加？

Thanks, Yvonne, and good morning, everyone. I am particularly excited to share our commercial update on this call today. I am as encouraged as I've ever been, not only by the impact we're already having for patients affected by the conditions our medicines are indicated to treat, but also by the potential that is just beginning to unfold now that our ATTR-CM launch is on the way in the US.

謝謝，伊馮娜，大家早安。我特別高興在今天的電話會議上分享我們的商業更新。我感到前所未有的鼓舞，不僅因為我們已經為受我們藥物所針對的疾病影響的患者帶來了積極影響，還因為我們的 ATTR-CM 即將在美國上市，其潛力才剛開始顯現。

I'll review our performance in Q1 and also provide some early perspective on our ATTR-CM launch, which only begun in the final days of this quarter and will take shape over the quarters ahead.

我將回顧我們在第一季的表現，並對我們的 ATTR-CM 發布提供一些早期的看法，該產品於本季度的最後幾天才開始推出，並將在未來幾個季度內逐漸成形。

Our Q1 performance continues to be strong. Altogether, our portfolio delivered nearly $0.5 million in combined net product revenues, representing 28% growth year over year and 4% versus Q4 2024. This is tremendous growth across our portfolio, several years after our initial launches. Quite simply, this means helping more patients affected by each of these devastating diseases.

我們第一季的業績持續保持強勁。總體而言，我們的投資組合實現了近 50 萬美元的綜合淨產品收入，年增 28%，與 2024 年第四季相比成長 4%。這是我們產品組合在首次推出幾年後的巨大成長。很簡單，這意味著幫助更多受到這些毀滅性疾病影響的患者。

Before we dive into our TTR franchise and the exciting progress with our new CM launch, let me briefly update you on our rare disease franchise. Our rare franchise, GIVLAARI and OXLUMO, together delivered $109 million in combined product sales in the first quarter, representing 8% growth compared with the first quarter of 2024.

在我們深入了解我們的 TTR 特許經營權以及新 CM 推出的令人興奮的進展之前，讓我先簡單介紹一下我們的罕見疾病特許經營權。我們的稀有特許經營權 GIVLAARI 和 OXLUMO 在第一季共實現了 1.09 億美元的綜合產品銷售額，與 2024 年第一季相比成長了 8%。

On a year-over-year basis, the growth in GIVLAARI patients on therapy was approximately 15% and growth in OXLUMO patients on therapy was approximately 20%. Revenue growth for OXLUMO was less than growth in patients on therapy, primarily due to gross adjustments in European markets and the timing of orders in partner markets. We continue to expect full-year product sales growth of approximately 15% for our rare franchise, consistent with the midpoint of our 2025 rare product sales guidance.

與去年同期相比，接受 GIVLAARI 治療的患者數量增加了約 15%，接受 OXLUMO 治療的患者數量增加了約 20%。OXLUMO 的收入成長低於接受治療的患者數量的成長，主要原因是歐洲市場的整體調整和合作夥伴市場的訂單時間。我們繼續預計我們的稀有特許經營權的全年產品銷售額將增長約 15%，與我們 2025 年稀有產品銷售指導的中點一致。

Moving now to our TTR franchise, we continue to see strong performance in Q1. The franchise delivered $359 million in global net revenues, representing a 36% increase compared with the first quarter of 2024. Importantly, this represents continued and robust growth from our base business in hereditary ATTR-PN since the CM indication approval came in the final days of the quarter.

現在轉向我們的 TTR 特許經營權，我們繼續看到第一季的強勁表現。該系列電影的全球淨收入為 3.59 億美元，與 2024 年第一季相比成長了 36%。重要的是，這代表了自本季度最後幾天獲得 CM 適應症批准以來，我們在遺傳性 ATTR-PN 領域的基礎業務持續強勁成長。

In the US, combined sales of ONPATTRO and AMVUTTRA in the first quarter increased by a robust 45% compared with the first quarter of 2024, continue to drive strong growth momentum. The 45% year-over-year growth was primarily driven by the following: a 32% increase in demand driven by the strength of ongoing AMVUTTRA patient uptake.

在美國，ONPATTRO 和 AMVUTTRA 第一季的合併銷售額與 2024 年第一季相比強勁成長 45%，繼續推動強勁的成長動能。45% 的年成長主要得益於以下因素：AMVUTTRA 患者接受度持續強勁成長帶動需求成長 32%。

We are pleased with the growth in demand, which has been consistent over the past five quarters, despite new competition entering the market at the end of 2023, which we believe is reflective of the leadership position we have established in a growing PN market over the last six years. The remaining growth in the quarter, 13%, is related to favorable adjustments in gross to net deductions, combined with stocking dynamics as inventory in the distribution channel modestly increased in Q1.

我們對需求的成長感到滿意，儘管 2023 年底有新的競爭對手進入市場，但過去五個季度需求一直保持穩定成長，我們相信這反映了我們在過去六年中在不斷增長的 PN 市場中確立的領導地位。本季剩餘的 13% 的成長與總扣除額到淨扣除額的有利調整有關，再加上庫存動態，因為第一季分銷通路的庫存適度增加。

I will share additional detail on our PN performance in the US on the next slide. Now, let me turn to our international markets for just a quick moment, where the TTR franchise grew 24% compared with the first quarter of 2024.

我將在下一張投影片中分享我們在美國 PN 表現的更多細節。現在，讓我簡單介紹一下我們的國際市場，與 2024 年第一季相比，TTR 特許經營權成長了 24%。

Similar to the US, the year-over-year growth was primarily driven by increased demand for AMVUTTRA as patient uptake remained robust. Bottom line, our TTR base business is very strong and continues to grow. Before I provide additional color on early days of our TTR-CM launch, let me touch briefly on the dynamics we're seeing in the US hATTR-PN markets.

與美國類似，年成長主要得益於患者接受度保持強勁，對 AMVUTTRA 的需求增加。總而言之，我們的 TTR 基礎業務非常強勁且持續成長。在我對 TTR-CM 發布的早期階段提供更多細節之前，讓我先簡單談談我們在美國 hATTR-PN 市場看到的動態。

A full year after the launch of a new competitor, AMVUTTRA remains the clear market leader in the US, maintaining a majority of new patient starts, with AMVUTTRA capturing approximately 70% of new patient starts in the first quarter of 2025. This results from a strong brand value proposition, coupled with continued discipline execution by our commercial teams.

在新的競爭對手推出整整一年後，AMVUTTRA 仍然保持著美國市場的明顯領先地位，保持了大多數新患者就診數量，AMVUTTRA 在 2025 年第一季佔據了約 70% 的新患者就診數量。這是強大的品牌價值主張以及我們商業團隊持續的紀律執行的結果。

What's more, as anticipated, we are finding that in categories where the majority of patients remain untreated, more treatment options mean more voices helping to raise disease awareness, ultimately accelerating category growth and increasing the number of patients on therapy.

此外，正如預期的那樣，我們發現，在大多數患者仍未得到治療的類別中，更多的治療選擇意味著更多的聲音有助於提高疾病意識，最終加速類別的增長並增加接受治療的患者數量。

In other words, this continues to be a growth story and patients are benefiting. With similar dynamics anticipated across hATTR-PN and ATTR-CM, we believe about 80% of the global addressable population remains untreated. This bodes well for the opportunity ahead in ATTR-CM.

換句話說，這將繼續是一個成長故事，患者也將從中受益。由於預計 hATTR-PN 和 ATTR-CM 會出現類似的動態，我們認為全球約 80% 的可尋址人口仍未得到治療。這預示著 ATTR-CM 未來將迎來良好的機會。

Now, on to our new indication. Momentum is building fast and the team is laser focused on delivering a successful launch. On March 20, we received FDA approval for AMVUTTRA as the first and only [silencer] approved in the US for ATTR-CM, and the only treatment indicated in the US for both the polyneuropathy manifestations of hereditary ATTR and cardiomyopathy manifestations of ATTR.

現在，談談我們的新適應症。勢頭正在快速增強，團隊正全神貫注於成功發布。3 月 20 日，我們獲得 FDA 批准 AMVUTTRA，這是美國首個也是唯一一個獲批用於治療 ATTR-CM 的 [消音器]，也是美國唯一一個同時適用於治療遺傳性 ATTR 的多發性神經病表現和 ATTR 的心肌病表現的藥物。

Though it's still early days, we are very encouraged about what we're seeing. Our first priority out of [Yates] was the access setup, and we're pleased to say it's progressing exactly to plan, thus enabling the second-half growth story that we have described on our prior calls.

儘管現在還處於早期階段，但我們對所看到的情況感到非常鼓舞。我們從 [Yates] 那裡得到的首要任務是訪問設置，我們很高興地說它正在按照計劃進行，從而實現了我們在之前的電話會議上描述的下半年增長故事。

Though it's of course, early to quantify trends, I would like to share some examples of the very encouraging progress we're already seeing, particularly with regard to the access and health system formulary reviews that we have shared would be the early priorities and key enablers of our second-half launch momentum.

雖然現在量化趨勢還為時過早，但我想分享一些我們已經看到的非常令人鼓舞的進展的例子，特別是關於我們所分享的獲取和醫療系統藥典審查，這將是我們下半年啟動勢頭的早期優先事項和關鍵推動因素。

Let me explain why we believe this launch is of an exceptional start with some specific examples. First, we're seeing robust patient initiations across all payer segments, Medicare fee for service, Medicare Advantage, and commercial. We are continuing payer engagements, and a majority of contracted lives are covered by value agreements that include the cardiomyopathy line accession.

讓我用一些具體的例子來解釋為什麼我們認為這次發布是一個特別的開始。首先，我們看到所有付款人群體、醫療保險服務費、醫療保險優勢計劃和商業保險的患者主動性都十分強勁。我們正在繼續與付款人合作，大多數簽約生命都受到包括心肌病線接入在內的價值協議的保障。

As expected, the majority of AMVUTTRA patients to date pay $0 co-pay in ATTR-CM like with hATTR-PN, and we continue to have widespread payer coverage exactly in line with our expectations. Second, and this is important, about 80% of [CTR] volume flows through approximately 170 health systems.

正如預期的那樣，迄今為止大多數 AMVUTTRA 患者在 ATTR-CM 中支付的共付額為 0 美元，就像 hATTR-PN 一樣，而且我們繼續擁有廣泛的付款人覆蓋，這與我們的預期完全一致。第二，這一點很重要，大約 80% 的 [CTR] 流量流經大約 170 個醫療系統。

Our team's focused efforts enabled inclusion of AMVUTTRA on formulary in more than half of these health systems within short four weeks of label expansion. In fact, the majority of these accounts have already initiated a motor treatment for ATTR-CM patients, underscoring that with the proper setup, these accounts do indeed come online.

我們團隊的專注努力使得 AMVUTTRA 在標籤擴展後的短短四周內就被納入了超過一半醫療系統的處方集。事實上，這些帳戶中的大多數已經開始針對 ATTR-CM 患者的運動治療，這強調了只要設定得當，這些帳戶確實可以上線。

And finally, in terms of treatment choice, we're seeing healthy demand across both prior AMVUTTRA prescribers as well as first time AMVUTTRA prescribers, and what we're hearing from prescribers is that the AMVUTTRA disruptive value proposition resonates and is enabling this early and encouraging launch momentum.

最後，在治療選擇方面，我們看到先前使用 AMVUTTRA 的處方者和首次使用 AMVUTTRA 的處方者都對這一療法有著健康的需求，而且我們從處方者那裡聽到的是，AMVUTTRA 顛覆性的價值主張引起了共鳴，並促成了這一早期且令人鼓舞的上市勢頭。

Early feedback from patients and physicians indicates clear excitement for a new mechanism of action in ATTR-CM that can rapidly knock down TTR. HCPs further highlighted that AMVUTTRA has clinically and statistically significant benefits in stand-alone, all-cause mortality coupled with demonstrated preservation of functional capacity and quality of life where AMVUTTRA makes significant impact on KCCQ, a six-minute walk distance are highly differentiating.

患者和醫生的早期回饋表明，人們對 ATTR-CM 中能夠快速降低 TTR 的新作用機制感到興奮。HCP 進一步強調，AMVUTTRA 在獨立全因死亡率方面具有臨床和統計上的顯著優勢，同時也證明了功能能力和生活品質的保留，其中 AMVUTTRA 對 KCCQ 產生了重大影響，六分鐘的步行距離具有很大的差異。

Furthermore, physicians they appreciate how quarterly HCP-administered dosing gives peace of mind for verified adherence. In terms of early utilization, here too, we are very pleased by early signals. We see broad views in line with our expectations. More specifically, we're seeing AMVUTTRA using first line. We're also seeing stabilizer, progressive patients switch to AMVUTTRA. We're seeing broad utilization, including an academic and community settings, supported by the broad alternate site of care networks that's been established.

此外，醫生們欣賞 HCP 每季給藥的方式，因為這能讓他們在驗證依從性方面感到安心。就早期利用而言，我們對早期訊號感到非常高興。我們看到廣泛的觀點符合我們的預期。更具體地說，我們看到 AMVUTTRA 使用第一行。我們也看到穩定劑、進展型患者轉向使用 AMVUTTRA。我們看到了廣泛的利用，包括學術和社區環境，並得到了已建立的廣泛的替代護理網絡站點的支持。

Simply put, the mechanism of action and the well-established safety and tolerability of AMVUTTRA hit home. Our consistent data speaks volumes. HCP administered, verify adherence is real, and patients are getting on therapy on AMVUTTRA, most with zero co-pay. In conclusion, the launch is off to an exceptional start.

簡而言之，AMVUTTRA 的作用機制和已被充分證實的安全性和耐受性令人深受震撼。我們一致的數據說明了一切。HCP 管理，驗證依從性是真實的，患者正在接受 AMVUTTRA 治療，大多數患者無需共同支付。總而言之，此次發表會開局非常好。

These are, of course, the early days of launch. We will continue to share more as the launch progresses, including both qualitative and quantitative launch indicators. We've provided full-year guidance, projecting robust 36% year-over-year growth in our TTR franchise revenues at the midpoint of the guidance. This reflects our confidence in the launch and the future potential of this franchise.

當然，現在還處於發布的初期。隨著發布的進展，我們將繼續分享更多信息，包括定性和定量的發布指標。我們提供了全年指導，預計在指導中期，我們的 TTR 特許經營收入將比去年同期強勁增長 36%。這反映了我們對該系列產品的推出及其未來潛力的信心。

Now, with a few early weeks of experience since launch, we remain as confident as ever. In conclusion, we are pleased with the results in the first quarter with both our TTR and rare franchises delivering strong growth in patients on therapy as well as delivering robust year-over-year growth in revenues, giving us confidence in our ability to deliver substantial growth, achieve profitability, and most importantly, deliver our highly differentiated and transformative medicines to more patients in need around the world.

現在，憑藉推出以來的幾週經驗，我們仍然像以往一樣充滿信心。總而言之，我們對第一季的業績感到滿意，我們的 TTR 和罕見病特許經營權均實現了治療患者數量的強勁增長，同時收入也實現了強勁的同比增長，這使我們有信心實現大幅增長、實現盈利，最重要的是，向全球更多有需要的患者提供高度差異化和變革性的藥物。

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

現在，我將把時間交給 Pushka 來回顧我們最近的研發和管道進展。普什卡？

Thanks, Tolga, and good morning, everyone. To echo my colleagues, I'm very excited about the launch of AMVUTTRA in ATTR-CM at the end of Q1, and that we've hit the ground running to educate physicians and patients and drive awareness. And I'm delighted by the early progress that Tolga had just described, which is based on great execution by our commercial and medical teams and the impressive HELIOS-B results summarized here.

謝謝，托爾加，大家早安。與我的同事們一致，我對第一季末在 ATTR-CM 中推出 AMVUTTRA 感到非常興奮，並且我們已經開始對醫生和患者進行教育並提高認識。我對托爾加剛剛描述的早期進展感到非常高興，這是基於我們的商業和醫療團隊的出色執行以及這裡總結的令人印象深刻的 HELIOS-B 結果。

In a population representative of today's ATTR-CM patients, nearly half of whom were already being treated with a stabilizer, we saw a substantial benefit AMVUTTRA on cardiac outcomes, including a 35% to 36% reduction in the risk of all-cause mortality alone.

在代表當今 ATTR-CM 患者的人群中，近一半患者已經接受穩定劑治療，我們發現 AMVUTTRA 對心臟結果有顯著益處，其中僅全因死亡風險就降低了 35% 至 36%。

We saw broad benefits on a series of other important clinical parameters such as cardiac biomarkers, echocardiographic measures, and disease progression. These, together with an encouraging safety profile and an infrequent HCP administered dosing regimen that enables a high degree of adherence, support the potential for AMVUTTRA to become a first-line therapy in this disease.

我們看到了一系列其他重要臨床參數（如心臟生物標記、超音波心動圖測量和疾病進展）的廣泛益處。這些，加上令人鼓舞的安全性和能夠實現高度依從性的低頻率 HCP 給藥方案，支持了 AMVUTTRA 成為該疾病的一線療法的潛力。

Based on these exceptional data, we quickly submitted filings to regulatory agencies in key geographies, and we're pleased with the pace of progress thus far. We of course achieved US approval of the sNDA in March, followed shortly thereafter by approval in Brazil.

基於這些出色的數據，我們迅速向主要地區的監管機構提交了文件，我們對迄今為止的進展速度感到滿意。當然，我們在三月獲得了美國對 sNDA 的批准，隨後不久又獲得了巴西的批准。

And earlier this week, we announced that the Committee for Medicinal Products for Human Use of the European Medicines Agency has adopted a positive opinion recommending approval of vutrisiran in ATTR-CM. This should enable the European Commission to approve AMVUTTRA in Europe in Q3, and possibly in Q2.

本週早些時候，我們宣布歐洲藥品管理局人用藥品委員會已採納積極意見，建議批准 vutrisiran 用於 ATTR-CM。這將使歐盟委員會能夠在第三季度，甚至可能在第二季度批准 AMVUTTRA 在歐洲的實施。

So things are progressing swiftly and we look forward to launching other important territories in the coming quarters. Now beyond those primary results that discussed a moment ago, we continue to share additional insights from the HELIOS-B data set. At ACC last month, we shared a few new analyses that further support vutrisiran's compelling profile.

所以事情進展迅速，我們期待在未來幾季開拓其他重要領域。現在，除了剛才討論的主要結果之外，我們還繼續分享更多來自 HELIOS-B 資料集的見解。上個月在 ACC 上，我們分享了一些新的分析，進一步支持了 vutrisiran 引人注目的形象。

In one, we highlighted echocardiographic data which demonstrated that treatment with vutrisiran led to significant improvements in diastolic function and attenuation of declines in left ventricular and right ventricular systolic function at month 18 compared to placebo.

其中一項研究強調了超音波心動圖數據，該數據表明，與安慰劑相比，使用 vutrisiran 治療 18 個月後，患者的舒張功能得到顯著改善，左心室和右心室收縮功能下降得到減緩。

These indicate that vutrisiran is favorably impacting cardiac function, which is truly remarkable. We also shared an exploratory subgroup analysis which demonstrated vutrisiran and reduced all-cause mortality and recurrent CV events across a range of baseline heart failure severity in patients with this disease.

這些表明 vutrisiran 對心臟功能有積極的影響，這確實非常了不起。我們還分享了一項探索性亞組分析，證明了 vutrisiran 可降低該疾病患者的一系列基線心臟衰竭嚴重程度的全因死亡率和復發性心血管事件。

And lastly, a separate analysis confirmed that vutrisiran significantly maintained or improved functional capacity and patient reported health status and quality of life compared to placebo over 30 months. These last two analyses were also published in the Journal of the American College of Cardiology.

最後，一項單獨的分析證實，與 30 個月內的安慰劑相比，vutrisiran 顯著維持或改善了功能能力以及患者報告的健康狀況和生活品質。最後兩項分析也發表在《美國心臟病學會雜誌》。

We look forward to continuing our analysis of this landmark study and educating the ATTR amyloidosis community about the differentiated profile of AMVUTTRA.

我們期待繼續分析這項具有里程碑意義的研究，並向 ATTR 澱粉樣變性社區介紹 AMVUTTRA 的差異化特徵。

Further to our leadership and commitment to innovation in this disease and to these patients, at R&D Day in February, we shared updated plans for pivotal studies of nucresiran, our next generation RNA therapeutic targeting TTR with the potential for deeper knockdown and biannual dosing.

進一步發揮我們在這種疾病和這些患者中的領導作用和創新承諾，在二月份的研發日上，我們分享了對 nucresiran 關鍵研究的最新計劃，nucresiran 是我們針對 TTR 的下一代 RNA 治療藥物，具有更深層次的敲低和每半年給藥的潛力。

TRITON-CM will be a randomized double-blind events-driven outcome study in ATTR-CM patients with either hereditary or wild type disease and a medical history of symptomatic heart failure. NYHA Class I through III. All patients will be allowed to be on background stabilizer therapy. Approximately 1,200 patients will be randomized, and the primary endpoint will be a composite of all-cause mortality and CV events. The primary analysis will be event-driven and will for a minimum of 24 months after the last patient enrolled.

TRITON-CM 將是一項針對患有遺傳性或野生型疾病且有症狀性心臟衰竭病史的 ATTR-CM 患者的隨機雙盲事件驅動結果研究。NYHA I 至 III 級。所有患者都將被允許接受背景穩定劑治療。大約 1,200 名患者將被隨機分配，主要終點將是全因死亡率和心血管事件的綜合。主要分析將由事件驅動，並將在最後一位患者入組後至少持續 24 個月。

If successful, we target launching nucresiran in ATTR-CM around 2030. In parallel, we have the goal of bringing nucresiran to patients as quickly as possible and see an opportunity to do so in hereditary ATTR-PN. Though we're not yet prepared to discuss the full details of TRITON-PM, we plan to initiate the pivotal study by the end of this year and anticipate the potential to launch in this indication several years ahead of ATTR-CM. We look forward to sharing more details in due course.

如果成功的話，我們的目標是在 2030 年左右在 ATTR-CM 中發射 Nucresiran。同時，我們的目標是盡快將 Nucresiran 帶給患者，並看到了在遺傳性 ATTR-PN 中實現這一目標的機會。雖然我們尚未準備好討論 TRITON-PM 的全部細節，但我們計劃在今年年底前啟動這項關鍵研究，並預計有可能比 ATTR-CM 提前幾年推出這一適應症。我們期待在適當的時候分享更多細節。

R&D Day also showcased a number of exciting advancements earlier in our pipeline that underscore the bright future for RNA therapeutics across a broad range of diseases. Key among these updates, we disclosed two new clinical programs. ALN-4324 targets GRB14 for the treatment of type 2 diabetes with a novel mechanism of action. It acts as an insulin sensitizer, addressing a tremendous unmet need in diabetes where insulin resistance is a major issue. We're pleased to announce today that we've initiated the Phase 1 study for ALN-4324.

研發日也展示了我們早期研發過程中取得的許多令人興奮的進展，這些進展凸顯了 RNA 療法在多種疾病治療中的光明前景。這些更新中最關鍵的是，我們揭露了兩個新的臨床項目。ALN-4324 以 GRB14 為靶點，透過新的作用機制治療第 2 型糖尿病。它充當胰島素增敏劑，解決了糖尿病中胰島素抗性這一主要問題的巨大未滿足需求。今天我們很高興地宣布，我們已經啟動了 ALN-4324 的第一階段研究。

The second [parameter] that targets liver-derived plasminogen, and this molecule represents a potential universal hemostatic agent for the treatment of bleeding disorders without the risk of thrombosis. Another key highlight was our update on delivery solutions with best-in-class potential for adipose, muscle, heart, and kidney tissue, as well as a new approach to crossing the blood-brain barrier.

第二個[參數]針對的是肝源性纖溶酶原，這種分子代表了一種潛在的通用止血劑，可用於治療出血性疾病，而沒有血栓形成的風險。另一個重要亮點是我們對輸送解決方案的更新，該解決方案具有針對脂肪、肌肉、心臟和腎臟組織的一流潛力，以及穿越血腦屏障的新方法。

As we announced in our R&D day, our goal is to achieve delivery of RNAi therapeutics to every major tissue by 2030. Lastly, I'd like to congratulate our partners at Sanofi for securing FDA approval for Qfitlia (fitusiran) for hemophilia A or B, with or without factor VIII or IX inhibitors. With this approval, Qfitlia becomes the [6,000-island] discovered RNAi therapeutic approved by the Food and Drug Administration.

正如我們在研發日上所宣布的那樣，我們的目標是到 2030 年實現將 RNAi 療法輸送到所有主要組織。最後，我要祝賀賽諾菲的合作夥伴獲得 FDA 批准 Qfitlia（fitusiran）用於治療 A 型或 B 型血友病，無論是否含有因子 VIII 或 IX 抑制劑。憑藉此項批准，Qfitlia 成為美國食品藥物管理局批准的首個 [6,000 島] RNAi 療法。

In summary, this remarkable and unique pace of innovation puts us in a great position to have a deep, self-sustainable pipeline that can continue to deliver meaningful impact to patients for many years to come.

總而言之，這種非凡而獨特的創新步伐使我們處於有利地位，擁有深厚的、可自我維持的研發管道，可以在未來許多年繼續為患者帶來有意義的影響。

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

現在，請容許我把時間交給傑夫來回顧我們的財務表現和即將到來的里程碑。傑夫？

Thanks, Pushkal. Good morning, everyone. I'm pleased to be presenting a summary of Alnylam's Q1 2025 financial results and discussing our full-year guidance. Before turning to the details on our Q1 financial performance, I'd like to further some of Tolga's comments on the early observations of our cardiomyopathy launch.

謝謝，普什卡爾。大家早安。我很高興能夠介紹 Alnylam 2025 年第一季的財務表現摘要並討論我們的全年指導。在介紹我們第一季財務表現的細節之前，我想進一步談談托爾加對我們心肌病變研究發布的早期觀察結果的一些評論。

I'm extremely pleased with the commercial execution demonstrated by the US TTR team thus far. They have guided CM revenue being a second-half story with the second quarter focusing on continuing to build awareness, unlocking patient access, and supporting treatment initiation for patients. Given the early progress that Tolga described, I am confident in reiterating our financial guidance, including TTR product sales, which I will discuss later.

我對美國 TTR 團隊迄今為止所展現的商業執行力感到非常滿意。他們指導 CM 收入成為下半年的故事，第二季度的重點是繼續提高意識、解鎖患者訪問權限以及支持患者開始治療。鑑於托爾加所描述的早期進展，我有信心重申我們的財務指導，包括 TTR 產品銷售，我將在稍後討論。

With that, let's begin with a summary of our P&L results for Q1 2025 compared with prior year. Total product revenues for the quarter were $469 million or 28% growth versus last year, driven by the 36% growth in our TTR franchise, with particularly strong performance in the US market as Tolga described. As Tolga also noted, AMVUTTRA was approved for ATTR cardiomyopathy with only one week remaining in the first quarter, so it did not contribute to our Q1 results.

首先，讓我們總結一下 2025 年第一季與去年同期的損益結果。本季產品總營收為 4.69 億美元，較去年同期成長 28%，這得益於我們的 TTR 特許經營權成長 36%，正如 Tolga 所述，美國市場的表現尤為強勁。托爾加也指出，AMVUTTRA 獲批用於治療 ATTR 型心肌病變時，第一季僅剩一週時間，因此它對我們的第一季業績沒有貢獻。

Collaboration revenue for the quarter was $99 million or 16% decrease compared to the first quarter of last year. The decrease was primarily driven by the $65 million Roche milestone achieved Q1 '24 related to the first patient being dosed in the KARDIA-3 study, partially offset by the $30 million milestone achieved from [VR] and reimbursements from our collaboration with Regeneron in Q1 '25.

本季合作收入為 9,900 萬美元，與去年第一季相比下降 16%。下降的主要原因是羅氏在 2024 年第一季度實現了 6500 萬美元的里程碑，該里程碑與 KARDIA-3 研究中第一位接受給藥的患者有關，但被 [VR] 實現的 3000 萬美元里程碑以及 2025 年第一季度與 Regeneron 合作獲得的報銷部分抵消。

Royalty revenue for the quarter was $26 million, representing a $16 million increase compared to last year, driven by Novartis's increased LEQVIO sales. Gross margin on product sales was 85% for the quarter, which was consistent with the first quarter of 2024, as the AMVUTTRA royalty rate payable to Sanofi recess at the beginning of each calendar year. For the balance of the year, our gross margin on product sales is expected to decrease as the AMVUTTRA average royalty rate escalates, driven by annual sales of AMVUTTRA reaching higher royalty tiers.

本季特許權使用費收入為 2,600 萬美元，比去年同期增加 1,600 萬美元，這得益於諾華 LEQVIO 銷售額的成長。本季產品銷售毛利率為 85%，與 2024 年第一季一致，因為每年年初向賽諾菲支付的 AMVUTTRA 特許權使用費率都會降低。在今年剩餘時間裡，隨著 AMVUTTRA 平均特許權使用費率的上升（受 AMVUTTRA 年銷售額達到更高特許權使用費率等級的推動），我們產品銷售的毛利率預計會下降。

Our non-GAAP R&D expenses were $241 million, were in line with prior year as increases in clinical trial expenses associated with our KARDIA-3 study for zilebesiran and the mivelsiran Phase 2 CAA study were offset by reductions related to the wind down of the HELIOS-B Phase 3 study. We do expect that R&D expenses will increase compared to 2024 for the balance of the year as Phase 3 studies for both zilebesiran an increase in ramp up.

我們的非公認會計準則研發費用為 2.41 億美元，與前一年持平，因為與 zilebesiran 的 KARDIA-3 研究和 mivelsiran 第 2 階段 CAA 研究相關的臨床試驗費用增加，但被 HELIOS-B 第 3 階段研究結束相關的減少所抵消。我們確實預計，由於 zilebesiran 的 3 期研究將增加，因此今年剩餘時間的研發費用將比 2024 年增加。

Our non-GAAP SG&A expenses increased 12% in the first quarter compared to the same period last year, primarily driven by increased investments in support of AMVUTTRA for the cardiomyopathy launch. Our non-GAAP operating profit for the quarter was $75 million representing a $73 million improvement compared to last year, driven by the strength of our top-line growth combined with more moderate growth in operating expenses.

我們第一季的非公認會計準則銷售、一般及行政費用與去年同期相比增加了 12%，這主要由於對 AMVUTTRA 心肌病變上市支持的投資增加。本季我們的非公認會計準則營業利潤為 7,500 萬美元，比去年同期增加了 7,300 萬美元，這得益於我們強勁的營收成長和較為溫和的營業費用成長。

Finally, we ended the quarter with cash, cash equivalents, and marketable securities of $2.6 billion compared to $2.7 billion at the end of 2024. Now turning to our guidance, where, as I previously mentioned, we are reiterating our 2025 guidance as presented during our last earnings call and is summarized on our guidance slide. Additionally, I'd like to provide two additional points of perspective.

最後，本季末我們的現金、現金等價物和有價證券為 26 億美元，而 2024 年底為 27 億美元。現在談談我們的指導，正如我之前提到的，我們重申我們在上次收益電話會議上提出的 2025 年指導，並在我們的指導幻燈片中進行了總結。此外，我想提供另外兩個觀點。

Our guidance continues to assume foreign exchange rates as of December 31, 2024, which are noted in the footnote of our guidance slide. As you are aware, the US dollar has weakened considerably in recent weeks. If the current FX rates continue through the remainder of the year, we expect currency upside relative to our current product sales guidance of approximately $50 million.

我們的指導繼續假設截至 2024 年 12 月 31 日的外匯匯率，這在我們的指導幻燈片的腳註中註明。正如您所知，最近幾週美元大幅貶值。如果目前的外匯匯率在今年剩餘時間內持續下去，我們預計相對於我們目前的產品銷售指導，貨幣匯率將上漲約 5000 萬美元。

We will re-evaluate our full-year guidance for FX [2]. Secondly, I'd like to make some brief remarks on the potential impact of recently announced tariffs, as well as pharma tariffs that are currently being contemplated. As it relates to the tariffs that are now in place, we do not see a material impact on our business and believe we can absorb any resulting cost increases within our existing 2025 financial guidance.

我們將重新評估全年外匯預期[2]。其次，我想簡要談談最近宣布的關稅以及目前正在考慮的藥品關稅的潛在影響。就目前實施的關稅而言，我們認為這不會對我們的業務產生重大影響，並相信我們可以在現有的 2025 年財務指導範圍內吸收由此產生的任何成本增加。

As it relates to the pharma tariffs that are being considered, there's obviously still uncertainty as we await the drafting of the final rules. However, we are comfortable sharing some high-level perspective that reflects our positioning as a company.

由於它與正在考慮的藥品關稅有關，在我們等待最終規則的起草時，顯然仍存在不確定性。然而，我們很樂意分享一些反映我們公司定位的高層觀點。

Our commercial supply chain is global in nature, but the majority of our products are manufactured through third-party contract manufacturing organizations in the US. Additionally, our intellectual property is also primarily based in the US. We think both of these factors position us well in terms of limiting exposure to potential future pharma tariffs. We will provide further updates as we get more clarity on tariff policy.

我們的商業供應鏈本質上是全球性的，但我們的大多數產品都是透過美國的第三方合約製造組織生產的。此外，我們的智慧財產權也主要位於美國。我們認為，這兩個因素都使我們在限制未來潛在的藥品關稅風險方面處於有利地位。隨著關稅政策的進一步明朗，我們將提供進一步的更新。

Let me now turn from financials and discuss some key goals in upcoming 2025 milestones. We intend to initiate the TRITON-CM Phase 3 study of nucresiran in ATTR-CM in the first half of 2025. TRITON-PM is expected to initiate by the end of 2025.

現在，讓我不再談論財務問題，而是討論即將到來的 2025 年里程碑中的一些關鍵目標。我們計劃於 2025 年上半年啟動 ATTR-CM 中 Nucresiran 的 TRITON-CM 第 3 期研究。TRITON-PM 預計將於 2025 年底啟動。

We expected additional approvals of AMVUTTRA in ATTR cardiomyopathy in Japan in Q2 and the European Union in Q3. Planned report data from the KARDIA-3 Phase 2 trial of the zilebesiran in the second half of the year. These results will help inform the final design for the Phase 3 CVOT of zilebesiran, which we also expect to initiate in the second half of 2025.

我們預計日本將於第二季、歐盟將於第三季批准 AMVUTTRA 用於治療 ATTR 心肌病變。計劃於下半年報告zilebesiran的KARDIA-3第2階段試驗的數據。這些結果將有助於為 zilebesiran 第三階段 CVOT 的最終設計提供參考，我們預計設計也將在 2025 年下半年啟動。

Let me now turn it back to Christine to coordinate our Q&A session. Christine?

現在讓我把話題轉回給克里斯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 your questions to 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 additional questions.

謝謝你，傑夫。接線員，我們現在將向撥入的各位提問。我們希望你們每次只問一個問題，如果有其他問題，請回到隊列。

(Operator Instructions) Tazeen Ahmad, Bank of America.

（操作員指示） Tazeen Ahmad，美國銀行。

Thanks for taking my question. I'm sorry if I missed this on the prepared remarks, but I just wanted to get a little bit of additional color of the initial patients that are starting treatments. Who are the prescriber based? Are they people that have already had previous experience with AMVUTTRA, or are you seeing a mix of doctors that are also completely new to the drugs?

感謝您回答我的問題。如果我在準備好的發言中遺漏了這一點，我很抱歉，但我只是想對開始接受治療的初始患者有一點額外的了解。處方者是誰？他們是否已經有使用 AMVUTTRA 的經驗，或者您是否正在接受對這些藥物完全陌生的醫生的治療？

Yeah, that's a great question and one to talk about, but I think what's really encouraging about the launch and cardiomyopathy is that really kind of all the indicators are flashing green and we're really seeing broad and balanced views across all aspects, but Tolga, perhaps you can speak specifically to the prescriber base.

是的，這是一個很好的問題，值得討論，但我認為關於發布和心肌病真正令人鼓舞的是，所有指標都閃爍著綠色，我們確實看到了各個方面的廣泛和平衡的觀點，但是托爾加，也許你可以具體談談處方者群體。

Yeah, I mean, the way we see this is a really good broad uptake. We see cardiologists that have been familiar with the product, but we're also seeing a pretty good uptake in terms of those cardiologists that have not tried AMVUTRRA. So that's really encouraging.

是的，我的意思是，我們認為這是一個非常好的廣泛接受度。我們看到心臟科醫生已經熟悉該產品，但我們也看到那些尚未嘗試 AMVUTRRA 的心臟科醫生的接受度相當高。這確實令人鼓舞。

But the most, I think, encouraging part is that what I highlighted, our number one priority, which was at the gate to set up and enable [second] health momentum by actually setting up these institutions to be formally ready. And within a short four weeks, we've been able to get into formulary of half of those accounts, and that to me is really opening up an incredible opportunity for us.

但我認為最令人鼓舞的是，我強調了我們的首要任務，即透過實際建立這些機構並使其正式做好準備，建立並實現[第二個]健康勢頭。在短短的四周內，我們就能夠獲得其中一半帳戶的處方，對我來說，這確實為我們打開了一個難以置信的機會。

Thanks, Tazeen. Next question?

謝謝，Tazeen。下一個問題？

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

So I think we saw first full-quarter revenue from, I think, [$79 million] for (inaudible) and the $37 million for (inaudible) ATTR cardiomyopathy. So which one do you think it's a good benchmark for AMVUTTRA first-quarter revenue and also my quick calculation for your ATTR franchise this quarter versus the last quarter of roughly [$17 million] quarter-over-quarter growth, any revenue was contributed from ATTR cardiomyopathy revenue.

因此，我認為我們看到第一季的完整收入來自（聽不清楚）的 [7,900 萬美元] 和（聽不清楚）ATTR 心肌病變的 3,700 萬美元。那麼您認為哪一個是 AMVUTTRA 第一季營收的良好基準？同時，我對本季 ATTR 特許經營權與上一季相比的快速計算顯示，環比增長約為 [1700 萬美元]，任何收入都來自 ATTR 心肌病變收入。

[Well], I think that's really for you. It was actually quite hard to hear you, Gena, but I'll try, I think there was one question around how we think about benchmarks for the CM launch.

[嗯]，我認為這真的適合你。吉娜，實際上很難聽到您的回答，但我會盡力的，我認為有一個問題與我們如何考慮 CM 發布的基準有關。

Yeah. I'm happy to take that, Gena. Look, first and foremost, we've already laid out our year-end guidance, so that's really important to demonstrate and that mid-year point of the -- the midpoint of the total growth is going to be about 36%. That's obviously our goal, is to meet and hopefully exceed that year-end guidance.

是的。我很高興接受這個，吉娜。首先，我們已經制定了年終指引，因此展示這一點非常重要，年中點——總成長的中點將達到 36% 左右。這顯然是我們的目標，即達到並希望超越年底的預期。

Now in respect to the first-quarter results of those two stabilizers, I think it's really important to highlight the categories growing. If you take out the [IR] impact of [fameters], both products have grown. In fact, I think [tefamis] had let that growth. So that's a clear, good early sign of how this category remains untapped in terms of growth.

現在，就這兩個穩定器的第一季業績而言，我認為強調成長類別非常重要。如果剔除 [fameters] 的 [IR] 影響，這兩種產品都會成長。事實上，我認為[tefamis]已經允許這種增長。所以這是一個明顯的、良好的早期訊號，表明這一類別在成長方面仍未開發。

So I mean, that's great talk. I mean, look, we really are excited to be in a class of our own in this market with a sort of orthogonal mechanism and a differentiated profile. So, Gena, I'll just come back to you because I'm not sure, I heard all of your questions.

所以我的意思是，這是一次很棒的對話。我的意思是，我們真的很高興能夠在這個市場上獨樹一幟，擁有一種正交機制和差異化形象。所以，吉娜，我再來找你，因為我不確定，我聽到了你所有的問題。

Sorry, yeah, so I think that -- yeah, sure. Can you hear me better now? Okay, so yeah, the second question is regarding the -- this quarter number, quarter-over-quarter growth, when we look at the ATTR franchise, it's about [$17 million]. Just wondering any revenue contribution from the ATTR cardiomyopathy.

抱歉，是的，所以我認為——是的，當然。現在你能聽清楚我的話了嗎？好的，是的，第二個問題是關於這個季度的數字，環比增長，當我們看 ATTR 特許經營權時，它是關於[1700萬美元]。只是想知道 ATTR 心肌病變能帶來什麼收入貢獻。

No, we actually made those points in our prepared remarks. It's all TTR polyneuropathy, and I think that this speaks to, again, the profile of AMVUTTRA that we have in polyneuropathy and the quality of commercial execution. I'm really delighted actually by the strength of our polyneuropathy business with terrific growth. Tolga, do you want to add anything?

不，我們實際上在準備好的發言中提出了這些觀點。這都是 TTR 多發性神經病變，我認為這再次說明了 AMVUTTRA 在多發性神經病變方面的概況以及商業執行的品質。我對我們的多發性神經病變業務的強勁成長感到非常高興。托爾加，你還有什麼要補充嗎？

Thank you, Gena. Next question.

謝謝你，吉娜。下一個問題。

Greg Harrison, Scotiabank.

加拿大豐業銀行的格雷格·哈里森。

This is [Theresa Vitale] on for Greg Harrison. Congrats on all of the progress this quarter and thanks for taking our question. Curious to hear how you're leveraging your commercial expertise and maybe what additional strategic efforts are you making on the commercial front to be competitive in capturing the (inaudible).

我是 [Theresa Vitale]，為 Greg Harrison 報道。恭喜本季取得的所有進展，並感謝您回答我們的問題。我很想知道您如何利用您的商業專業知識，以及您在商業方面正在做出哪些額外的策略努力，以便在獲得市場競爭力方面保持領先地位。（聽不清楚）。

It's a great question. Tolga, I think it's -- goes straight to you.

這是一個很好的問題。托爾加，我認為這是－－直接給你。

Yeah, I mean, first and foremost, as I indicated, we come with an entirely new mechanism of action that clearly sets us apart in terms of any stabilizers are out there, given that we work in upstream. And that rapid knockdown clearly actually manifested itself with HELIOS-B results where half the patients were both on placebo, as well as on the (inaudible) study arm, were actually already on a stabilizer, and the results are obviously quite compelling.

是的，我的意思是，首先，正如我所指出的，我們採用了一種全新的作用機制，鑑於我們在上游工作，這種機制顯然使我們在任何穩定劑方面脫穎而出。這種快速的抑製作用實際上明顯地體現在 HELIOS-B 的結果中，其中一半的患者既服用安慰劑，又在（聽不清楚）研究組中，實際上已經在服用穩定劑，而且結果顯然非常引人注目。

But frankly, when you think about the disease itself, given that it's a rapidly progressing fatal disease, physicians are first and foremost interested in treating the disease early, and actually treating with the best possible option they have. In that case, we believe actually AMVUTTRA provides a real clear first line option.

但坦白說，當你考慮這種疾病本身時，考慮到它是一種快速發展的致命疾病，醫生首先感興趣的是儘早治療這種疾病，並採用他們所擁有的最佳治療方案。在這種情況下，我們相信 AMVUTTRA 實際上提供了真正清晰的一線選擇。

Now, in terms of those physicians who are considering a switch, we're already seeing that in our broad patient uptake, and we believe that's going to continue to be the case given that half the patients in the most recently published ACC study that shows that patients do progress on stabilizer. So we believe actually we're going to remain a very important option for those patients are progressing on any stabilizer.

現在，對於那些正在考慮轉換治療方案的醫生來說，我們已經在廣大患者中看到了這一點，我們相信這種情況將持續下去，因為最近發表的 ACC 研究表明，一半的患者在使用穩定劑後確實取得了進展。因此，我們相信，對於那些使用任何穩定劑的患者來說，我們仍將是一個非常重要的選擇。

Thank you, Tolga. Next question?

謝謝你，托爾加。下一個問題？

Eli Merle, UBS.

瑞銀的 Eli Merle。

Thanks for taking the question and congrats on the early launch progress. Just in terms of AMVUTTRA, I guess what do you expect or what are you seeing in terms of the use of the first injection free versus those going straight to paid drug, maybe assuming that more would go straight to paid drug considering your comments on the formulary access.

感謝您提出這個問題，並祝賀早期發布進展順利。就 AMVUTTRA 而言，我想您期望什麼，或者您看到第一次注射免費與直接付費藥物的使用情況如何，考慮到您對處方集訪問的評論，也許假設更多的人會直接購買付費藥物。

And then just a follow up on your commentary on formulary access, I guess since you're already on formulary and more than half of these, 170 priority centers, are you seeing any change to the price used for polyneuropathy from these centers and just your latest expectation on how this pricing will play out between polyneuropathy versus cardiomyopathy?

然後，再跟進一下您對處方集訪問的評論，我想既然您已經進入了處方集，並且其中一半以上（170 個優先治療中心）的治療中心，您是否看到這些中心用於治療多發性神經病的價格有任何變化，以及您對多發性神經病和心肌病之間的定價將如何變化的最新預期？

So two questions I think one about our Quick Start Program and the second around formulary and --

所以我想有兩個問題，一個是關於我們快速啟動計劃的，另一個是關於處方集和--

Yeah, I mean, maybe I'll take the second question first. We have a single price and we don't see any price difference between our -- both of our indications which are both rare conditions. Now, in terms of our -- I think you're referring to our Quick Start Program. Look, I mean, if you take a step back, we have plethora of services that is actually developed by our in-house patient support program helping patients to actually navigate a very complex US healthcare system.

是的，我的意思是，也許我會先回答第二個問題。我們有一個單一的價格，我們沒有發現我們的兩種適應症之間存在任何價格差異，這兩種適應症都是罕見的情況。現在，就我們的而言——我想您指的是我們的快速啟動計劃。你看，我的意思是，如果你退一步來看，我們有大量服務實際上是由我們的內部患者支援計劃開發的，幫助患者真正駕馭非常複雜的美國醫療保健系統。

And frankly, if you look at our track records, our conversion rates, when a patient comes into those patient op programs is actually very fast and it is very effective and patients stay on [for therapy]. Now that program itself it includes a Quick Start Program, and we had it frankly for that program for years. And so far we're seeing a very limited use of this Quick Start Program, as we have seen in polyneuropathy.

坦白說，如果你看看我們的記錄，我們的轉換率，當病人進入這些病人手術計畫時，實際上非常快，而且非常有效，病人會繼續留在[用於治療]。現在該程序本身包括一個快速啟動程序，坦白說，我們已經使用這個程序很多年了。到目前為止，我們看到這個快速啟動計劃的使用非常有限，就像我們在多發性神經病變中看到的那樣。

And what we're really pleased is, frankly, those patients that are coming into the program across a different payer mix are getting on therapy, whether it's through Medicare fee for service, Medicare Advantage, as well as in commercial. And I must also add, as we anticipated, those -- most of those patients are paying zero co-pay as we had seen in polyneuropathy as well.

坦白說，我們真正感到高興的是，那些透過不同付款人組合進入該計劃的患者正在接受治療，無論是透過醫療保險服務費、醫療保險優勢計劃，還是商業治療。我還必須補充一點，正如我們預期的那樣，大多數患者都沒有支付共同支付費用，就像我們在多發性神經病變中看到的那樣。

Very important. We're getting good patient access. Next question?

非常重要。我們獲得了良好的患者就診體驗。下一個問題？

Gary Nachman, Raymond James.

蓋瑞納赫曼、雷蒙詹姆斯。

Thanks for taking the question and congrats on the progress. So with the TruB in the early launch phase and getting some traction, is that creating a headwind for AMVUTTRA's launch in CM or is it helping create more noise for the entire category? So what's the early read on position receptivity to a new sound serve versus a new stabilizer out there?

感謝您提出這個問題，並祝賀您的進展。那麼，TruB 處於早期發布階段並獲得了一些關注，這是否會對 AMVUTTRA 在 CM 中的發布造成阻力，還是會為整個類別帶來更多關注？那麼，對於新的聲音發球和新的穩定器，位置接受度的早期解讀是什麼？

And then just, maybe specifically on the reimbursement side, how are the dynamics playing out as a Part D drug versus the stabilizers that are Part D drugs.

然後，也許具體到報銷方面，D 部分藥物與 D 部分藥物的穩定劑之間的動態表現如何。

Yeah, those are two great questions. I think Tolga has made the point that we really are in a category growth story, and you know what we're just seeing is actually continued evidence of a large growing and frankly unsatisfied market, and I think, we're very excited to be able to participate in this market with a recent launch of AMVUTTRA in cardiomyopathy. I think the second question was around the [Part B, Part D] dynamics and how that plays through.

是的，這是兩個很好的問題。我認為 Tolga 已經指出我們確實處於一個類別增長的故事中，你知道，我們所看到的實際上是一個巨大增長和坦率地說不滿意的市場的持續證據，我認為，我們非常高興能夠通過最近推出的用於治療心肌病的 AMVUTTRA 來參與這個市場。我認為第二個問題是關於[B 部分，D 部分]的動態及其如何發揮作用。

So look, I mean, I think a good example of how we've been managing Part D, Part B dynamics, frankly, is what we've already demonstrated in polyneuropathy. We just shared with you in this past quarter, after one year of launch the Part B product, we've actually been able to achieve 70% of all new patients and continue to grow actually in an accelerated phase based from a larger base of business.

所以，我的意思是，我認為我們如何管理 D 部分、B 部分動態的一個很好的例子，坦白說，就是我們在多發性神經病變中已經證明的。我們剛剛與大家分享了上個季度的情況，在推出 B 部分產品一年後，我們實際上已經能夠覆蓋 70% 的新患者，並且在更大的業務基礎上繼續加速成長。

Now, in terms of what we're seeing in this new line extension we have, we're seeing no headwinds and thankfully with the value-based agreements we have and we're seeing this uptake across all payer mixes, so there are no signals that we can iterate right now that would suggest otherwise.

現在，就我們在這條新的產品線擴展中看到的情況而言，我們沒有看到任何阻力，而且幸運的是，我們擁有基於價值的協議，並且我們看到所有付款人組合都在接受這種服務，因此現在沒有任何跡象表明情況並非如此。

And in terms of differentiation and whether we're actually seeing any headwinds, look, what really sets us apart is the strength of our data. It's complete, consistent, and cohesive. We're presenting the full picture with scientific rigor. And in contrast, we're seeing some in the space selectively highlighting data points with creative interpretations.

至於差異化以及我們是否真的遇到任何阻力，看看吧，真正讓我們脫穎而出的是我們數據的力量。它是完整的、一致的、有凝聚力的。我們以科學嚴謹的態度呈現全貌。與此相反，我們看到一些人選擇性地突出具有創造性解釋的數據點。

And we already see and believe investors and physicians alike value the clarity and integrity of a comprehensive data set, and that's exactly what we're delivering.

我們已經看到並相信投資者和醫生都重視全面數據集的清晰度和完整性，而這正是我們所提供的。

And yeah, it's what we've been doing for the past several years as we focused on meeting the needs of patients. Next question?

是的，這就是我們過去幾年一直在做的事情，因為我們專注於滿足患者的需求。下一個問題？

Jessica Fye, JPMorgan.

潔西卡費伊（Jessica Fye），摩根大通。

Thanks for taking my questions. You mentioned providing additional launch indicators with Q2 results. Can you just touch on what those will be? And then of those 170 priority health systems, I think you mentioned more than half already have AMVUTTRA on formulary. Can you just speak to your goal of where you want that number to stand maybe next quarter and by year end?

感謝您回答我的問題。您提到要透過第二季業績提供額外的發布指標。能否簡單介紹一下這些是什麼？然後，我想您提到，在這 170 個優先醫療系統中，超過一半已經在處方集中加入了 AMVUTTRA。您能否談談您希望下個季度和年底這個數字達到的目標？

Yeah, look, I mean, I think we've been very consistent about how we're describing in the way we're updating the investors and, in this case, our goal, frankly, was to complete the inclusion of formulary by year end.

是的，看，我的意思是，我認為我們對於如何向投資者更新資訊的方式的描述非常一致，在這種情況下，坦率地說，我們的目標是在年底前完成處方集的納入。

As you can see, we're taking our progress has been faster and we're very pleased with that. So it's absolutely by year end we want to be able to get there so that we have access. What's most encouraging, frankly, about the most recent development is a big majority of these accounts, not only included in the formulary, but those accounts that have included the formulary are already actually initiating patients on therapy, and that's incredibly encouraging.

正如您所看到的，我們的進展速度更快了，我們對此感到非常高興。因此，我們絕對希望在年底前能夠到達那裡，以便我們能夠進入。坦白說，最近的發展最令人鼓舞的是，這些帳戶中的絕大多數不僅被納入了處方集，而且那些已經納入處方集的帳戶實際上已經開始幫助患者接受治療，這是非常令人鼓舞的。

Now in terms of our Q2 data, I think the biggest update is going to be our revenue uptake and the pull through and how we're actually seeing them and obviously we're committed to providing additional color in terms of the broad patient uptake and what that really looks like and prescriber update and so on and so forth.

現在就我們的第二季度數據而言，我認為最大的更新將是我們的收入增長和拉動，以及我們如何實際看到它們，顯然我們致力於在廣泛的患者吸收方面提供額外的色彩，以及實際情況和處方更新等等。

That's great. Yeah, we're looking forward to showing much more to our next earnings call. Next question?

那太棒了。是的，我們期待在下次財報電話會議上展示更多內容。下一個問題？

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

You mentioned that you're seeing first line use already. Tolga, can you speak a little to the type of patient or profile of patient that is making up that first line use, and the next, kind of clarification on formulary inclusion. When you have formulary inclusion, is that where any prior authorization requirements sort of get set for use in the health system as well? And if so, how should we be thinking about what you're seeing for prior auths in formulary inclusion?

您提到您已經看到了第一線的使用。托爾加，您能否簡單談談構成第一線用藥的患者類型或患者概況，以及關於處方集納入的說明。當您有處方集時，是否也需要事先授權要求才能在醫療系統中使用？如果是這樣，我們應該如何看待您在處方集納入方面所看到的先前授權？

Yeah, I'm way too high. I'm grateful for your question. Let me take the last one first, meaning the type of formulating and whether that would require actually prior auth. So we're talking about two types of access here. One is the access where, you're dealing with the payers, that's the Medicare fee for service, Medicare Advantage, as well as commercial.

是的，我太高了。我很感謝你的提問。讓我先談談最後一個問題，即制定的類型以及是否需要事先授權。我們在這裡討論兩種類型的訪問。一是與付款人打交道的管道，即醫療保險服務費、醫療保險優勢計劃以及商業費用。

They're actually -- all products go through a medical exception process and it's usually essentially if you're a Part D product, the prior authorization is in almost all circumstances that is required. What makes us unique is the Medicare fee for service, there are no prior art requests.

實際上 — — 所有產品都要經過醫療例外程序，通常基本上，如果您是 D 部分產品，則幾乎所有情況下都需要事先授權。我們的獨特之處在於醫療保險服務費，並且沒有現有技術要求。

The second part, which I was alluding to is the 170 healthcare systems, and these systems is just a question of the organization saying we're actually going to be buying this product because now it's actually included with this new indication that requires no prior authorization. So I just wanted to make that very clear. Now, in terms of the type of patients that we see in the first line. What's really exciting about this is when doctors believe actually that AMVUTTRA and understand the AMVUTTRA's profile that is clearly differentiated as a rapid knockdown agent, they don't actually make a lot of differences in terms of what patients they want to put in.

第二部分，也就是我所指的 170 個醫療保健系統，這些系統只是組織的一個問題，表示我們實際上將購買該產品，因為現在它實際上包含了這種不需要事先授權的新適應症。所以我只是想把這一點說清楚。現在，就我們在第一線看到的患者類型而言。真正令人興奮的是，當醫生真正相信 AMVUTTRA 並了解 AMVUTTRA 作為快速擊倒劑的明確特徵時，他們在選擇治療哪些患者時實際上並不會產生太大差異。

What they see is if the patient is progressing on a stabilizer, they immediately put that patient on AMVUTTRA. If they see a new patient, whether that's early onset or actually they're already progressive, they immediately put that patient on the first line. So it's not so much about the type of patient, but it's also whether the doctor have clearly understood the compelling data set that we get to present with HELIOS-B and additional real world evidence.

他們發現，如果患者在使用穩定器後病情好轉，就會立即讓患者使用 AMVUTTRA。如果他們看到新病人，無論是早期發病還是病情已經惡化，他們都會立即將該病人安排在第一線。因此，這不僅與患者的類型有關，還與醫生是否清楚地理解了我們透過 HELIOS-B 和其他現實世界證據呈現的令人信服的數據集有關。

Thank you. Next question?

謝謝。下一個問題？

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Hi, this is [Tommy] on for Salveen. Thank you for taking our question. We just want to confirm some of the metrics that you gave out, so 170 health systems over half on formularies and over 75 initiated, one per system around 65 patients give or take, is that accurate to think about? And just to follow up, we're wondering if you're seeing some more standardized guidelines for identifying stabilizer progressors among HCPs now that we have new options.

大家好，我是 Salveen 的 [Tommy]。感謝您回答我們的問題。我們只是想確認您給出的一些指標，因此 170 個醫療系統中超過一半已製定處方集，超過 75 個已啟動處方集，每個系統大約有 65 名患者，這樣想準確嗎？為了跟進，我們想知道，既然我們有了新的選擇，您是否看到了一些更標準化的指南，用於在 HCP 中識別穩定劑進展者。

Tolga, why don't you take the first question and then I think Pushka will take the second.

托爾加，你先回答第一個問題，然後我認為普什卡會回答第二個問題。

Yeah, I mean, just to be clear, we clearly laid those out on the slide which essentially says 80% of the TTR treatments are initiated through these 170 US healthcare systems. These are some regional networks, maybe local networks, as well as national networks.

是的，我的意思是，為了清楚起見，我們在幻燈片上清楚地列出了這些內容，基本上說 80% 的 TTR 治療是透過這 170 個美國醫療保健系統發起的。這些是一些區域網絡，可能是本地網絡，也可能是國家網絡。

Once those institutions include a product, because it's a buy and build product, in their formula, that means actually that institution can acquire and can initiate therapy. And what we're alluding to is of those 170 within three to four weeks, those systems are already set up as online.

一旦這些機構將某種產品納入其配方中（因為這是一種購買和建造的產品），這實際上意味著該機構可以獲得並可以啟動治療。我們所指的是，在這 170 個系統中，三到四周內，這些系統就已經設定成在線狀態。

Now the big majority of those systems are already initiating treatments in the setting. That's what we're referring to. I don't know if that captures --

現在，絕大多數系統已開始在環境中進行治療。這就是我們所指的。我不知道這是否捕捉到了--

I think that covers the question. Maybe we get on to the second question, Pushka.

我想這涵蓋了這個問題。也許我們可以討論第二個問題，Pushka。

Tommy, in terms of the stabilizer progressors, but maybe just a couple of points on this because it does come up not infrequently. Doctors are well-trained cardiologists to evaluate patients with heart failure and whether they're doing well or not well on therapy. That's why you've seen over the years, many studies that have said, hey, how are patients doing on stabilizers, and they report 30% to 50% of patients do progress on those therapies.

湯米，就穩定器進展器而言，但也許只是幾點，因為它確實經常出現。醫生都是訓練有素的心臟科醫生，可以評估心臟衰竭患者的治療效果以及他們的治療效果是否良好。這就是為什麼多年來你會看到許多研究都說，嘿，患者使用穩定劑後情況如何，他們報告說 30% 到 50% 的患者在這些療法上取得了進展。

And so that's -- I think that's where that's coming from. And so I think they're well trained. I think if you look, for example, at ESC heart failure guidelines that were set up for ATTR-CM, they show that doctors look at factors like clinical symptoms or are they hospitalized? What's their walking ability, what's their shortness of breath? What's happening on imaging like echocardiograms, for example, what's happening with critical biomarkers like NT-proBNP and troponin.

所以這就是——我認為這就是它的由來。所以我認為他們訓練有素。例如，我認為，如果你看一下為 ATTR-CM 制定的 ESC 心臟衰竭指南，你會發現醫生會考慮臨床症狀等因素，或者他們是否住院？他們的行走能力如何，呼吸困難程度如何？例如，超音波心動圖等影像學檢查中發生的情況，以及 NT-proBNP 和肌鈣蛋白等關鍵生物標記中發生的情況。

And so I think doctors are well attuned to looking at those factors and examining and I think, once again, really heartening to us about the profile of AMVUTTRA is that on actually, every one of those parameters, we see a benefit in terms of delaying and favorably impacting these progression. I think that's a core aspect of this disease, as I mentioned, we just published data showing that actually there's actually improvements in aspects of cardiac function with this drug, which indicates the potential for a disease modifying profile.

因此，我認為醫生非常善於觀察和檢查這些因素，而且我認為，AMVUTTRA 的概況再次讓我們感到振奮，因為實際上，在每一個參數上，我們都看到了延緩和積極影響這些進展的好處。我認為這是這種疾病的一個核心方面，正如我所提到的，我們剛剛發布的數據表明，這種藥物確實可以改善心臟功能，這表明它具有改變疾病的潛力。

So that's what's compelling about this. I think there will be more guidelines, et cetera around this, but I think really what we're seeing is that doctors know how to recognize heart failure and heart patients who aren't doing well and then reaching for the best therapy for their patients.

這就是這件事引人注目的地方。我認為將會有更多關於此方面的指導方針等等，但我認為我們真正看到的是，醫生知道如何識別心臟衰竭和病情不佳的心臟病患者，然後為患者找到最好的治療方法。

Great. Thanks, Pushkal. Next question?

偉大的。謝謝，普什卡爾。下一個問題？

Kostas Biliouris, BMO Capital Markets.

Kostas Biliouris，BMO 資本市場。

Thanks for taking our question and congrats on the progress. One question from us on AMVUTTRA, I'll try to push my luck here a little bit for some more granularity. [BridgeBio] recently mentioned that they saw an impact from AMVUTTRA loans on the number of (inaudible), and this impact was particularly from Swiss patients. So that said, I wonder whether you see the majority of the early AMVUTTRA [take] coming from Swiss patients or new patients. Any quantitative or directional color there would be very helpful.

感謝您回答我們的問題，並祝賀取得的進展。我們在 AMVUTTRA 上有一個問題，我會嘗試在這裡稍微碰碰運氣，以獲得更詳細的資訊。 [BridgeBio] 最近提到，他們看到 AMVUTTRA 貸款對（聽不清楚）數量產生了影響，這種影響尤其來自瑞士患者。所以，我想知道您是否認為早期 AMVUTTRA 的大部分收入來自瑞士患者還是新患者。任何定量或方向性的顏色都會非常有幫助。

I'll take that question. Look, I think the way we best describe, given that still early days is broad. What I'm really excited is, again, we're taking all kinds of patients, including definitely first line patients, as well as switch patients, and look, those physicians that choose to switch, they also start new patients on AMVUTTRA, and that's definitely an early trend that we start seeing.

我來回答這個問題。你看，我認為我們最好的描述方式是，考慮到仍處於早期階段，描述範圍很廣。我真正興奮的是，我們再次接收各類患​​者，包括第一線患者以及轉換患者，而且，那些選擇轉換的醫生也會開始使用 AMVUTTRA 治療新患者，這絕對是我們開始看到的早期趨勢。

By the way, before I -- before we move on, I also want to take a quick moment since I know the team is always listening in to call out their phenomenal work, what they've done. Honestly, what I've witnessed leading up to this launch and in these early days has been nothing short of world class.

順便說一句，在我們繼續之前，我還想花一點時間，因為我知道團隊一直在傾聽，並讚揚他們的傑出工作和所做的事情。說實話，在這次發表會之前以及初期，我所見證的一切都是世界級的。

Our customer facing and patient support teams are really firing on all cylinders, bringing the exceptional profile to AMVUTTRA to our patient community that's long waited for a breakthrough medicine, and the early momentum, Kostas, as I shared, is strong, and all signs point to us being right on track to deliver something truly impactful.

我們面向客戶和患者支持的團隊正在全力以赴，將 AMVUTTRA 的卓越品質帶給我們長期等待突破性藥物的患者群體，正如我分享的那樣，科斯塔斯，早期勢頭強勁，所有跡像都表明我們正走在正確的軌道上，交付真正有影響力的東西。

Tolga, thanks for those perspectives. Next question, please?

托爾加，謝謝你的觀點。請問下一個問題？

Luca Issi, RBC Capital Markets.

伊西 (Luca Issi)，加拿大皇家銀行資本市場部。

Thanks so much for taking my question. Congrats on the progress. Maybe, Tolga, quick one here on access, at least based on our checks, it sounds like step edits are likely going to be implemented for commercial patients but are much, much less likely on the Medicare fee for service patients. One, is that a fair characterizations; and two, if so, how should we think about the Medicare Advantage patients, the one kind of in between the two buckets? Are they conceptually closer to commercial patients where [step edits] are likely, or are they closer to fee for service patients where step edits are less likely? Any thoughts there are much appreciated.

非常感謝您回答我的問題。恭喜你取得進展。托爾加，也許，至少根據我們的檢查，這裡快速詢問一下訪問權限，聽起來步驟編輯可能會針對商業患者實施，但對服務患者的醫療保險費用實施的可能性則要小得多。一、是公正的定性；第二，如果是這樣，我們該如何看待醫療保險優勢患者，也就是介於兩者之間的一種患者？從概念上講，他們是否更接近可能進行 [逐步編輯] 的商業患者，還是更接近不太可能進行分步編輯的按服務收費患者？任何想法都值得感激。

Yeah, I know, I appreciate the question. Look, first and foremost, what we've already seen is a very nice broad uptake on all payer mix. So we're really not seeing any headwinds in terms of any restrictions on the product. Now, when it comes to fee for service, surely, there won't be any limitations. So definitely half of the Medicare patients will be able to have access very seamlessly and we're seeing that with zero co-pay, I must say, in most of the patients.

是的，我知道，我很感謝你提出這個問題。首先，我們已經看到，所有付款人組合都得到了非常廣泛的接受。因此，我們確實沒有看到任何產品限制的阻力。現在，說到服務費，當然不會有任何限制。因此，肯定有一半的醫療保險患者將能夠非常無縫地獲得服務，而且我們必須說，我們看到大多數患者的共同支付額為零。

In terms of commercial and Medicare Advantage, we're not seeing any step edits so far, and we obviously have established a great infrastructure through our value-based agreements that enables us to be able to actually demonstrate clinical value. And that clinical value provides us that similar advantage.

在商業和醫療保險優勢方面，到目前為止我們還沒有看到任何步驟編輯，而且我們顯然已經透過基於價值的協議建立了良好的基礎設施，使我們能夠真正展示臨床價值。這種臨床價值為我們提供了類似的優勢。

Now if there were to be any step edits, we certainly have the tools to be able to address that if that were to be the case. But look, we have seen it in polyneuropathy. We're [now seeing] in CM. We have the patients getting on treatment in a very quick short amount of time and staying on treatment thanks to, again, the product profile and the support that we provide.

現在，如果有任何步驟需要編輯，我們當然有工具可以解決這個問題。但是你看，我們在多發性神經病變中看過它。我們[現在看到]在CM。患者可以在很短的時間內接受治療並堅持治療，這再次要感謝我們提供的產品和支援。

Thanks, Tolga. (inaudible) Next question please.

謝謝，托爾加。（聽不清楚）請問下一個問題。

Paul Matteis, [Alma Lane].

保羅·馬泰斯，[阿爾瑪巷]。

Paul from Stifel. I appreciate you taking the time. As it relates to uptake so far, Tolga, when we had dinner five weeks ago, you talked about how there are certain physicians who they actually can use the drug without going through a [P&C] committee. Any metrics there like what percent of the prescriber base is that and what have you seen from that population? And then as it relates to Medicare fee for service patients, given the ease of access, is this the kind of thing where over time you think a patient who has -- who's insured who's covered by Medicare fee for service could actually get drug -- the first dose of drug the same day that it's prescribed?

來自 Stifel 的 Paul。感謝您抽出時間。就目前的吸收情況而言，托爾加，當我們在五週前共進晚餐時，您談到某些醫生實際上可以在不經過 [P&C] 委員會的情況下使用該藥物。有沒有指標，例如處方者群體的百分比是多少，以及您從這個群體中看到了什麼？然後，就其與醫療保險按服務收費患者相關而言，考慮到獲取醫療服務的便利性，您是否認為隨著時間的推移，擁有醫療保險按服務收費保險的患者實際上可以在開具處方的當天獲得第一劑藥物？

Yeah, I mean, maybe I'll take care of your last question first. Look, at the end of the day, this is a healthcare professionally administered product, which requires actually injection by and bill, and that requires some level of coordination. So it will never be a one-day administration, but it's certainly very quick, given the kind of support that we provide and we obviously track those patients.

是的，我的意思是，也許我會先回答你的最後一個問題。看看，歸根結底，這是一種由醫療保健專業人員管理的產品，需要實際注射和計費，這需要一定程度的協調。因此，這絕對不會是一天就能完成的，但考慮到我們提供的支持類型以及我們對這些患者的跟踪，這肯定非常快。

What's also very encouraging is whether you're a fee for service advantage or commercial patients. These patients come in through a [start form] where we don't actually see any distinction based on their insurance coverage. We are neutral to the payer mix, and despite that, those patients start getting on therapy. And the main reason is, and I really want to underline this, whether it's step edit or prior auth, this is a rare and a very severe disease that rapidly progressing.

同樣令人鼓舞的是，無論您是按服務優勢收費還是按商業患者收費。這些病人透過[開始表格]進來，我們實際上沒有看到基於他們的保險範圍的任何差異。我們對付款人組合持中立態度，儘管如此，那些患者還是開始接受治療。主要原因是，我真的想強調這一點，無論是逐步編輯還是事先授權，這是一種罕見且非常嚴重的疾病，而且進展迅速。

And because of this, we see really great coverage of this category as a whole, and given what we have to offer, and based on the value-based agreements that we've established, we believe actually we have the ability to have the appropriate patients put on therapy as the physician requires.

正因為如此，我們看到整個類別的覆蓋範圍非常廣，並且考慮到我們所提供的服務，以及基於我們已經建立的基於價值的協議，我們相信我們實際上有能力根據醫生的要求讓合適的患者接受治療。

Thanks, Tolga. I think we've got time for one last question.

謝謝，托爾加。我想我們還有時間回答最後一個問題。

Mike Ulz, Morgan Stanley.

摩根士丹利的麥克烏爾茲。

Thanks for taking the question. Maybe just another one in cardiomyopathy. I wonder if you can talk about the rate of diagnosis and maybe if you've noticed a shift since the beginning of the year now that there's two additional products on the market. And then maybe just secondly, with about 20% of patients currently diagnosed, what do you think that could look like at the end of the year?

感謝您回答這個問題。也許只是又一個心肌病變。我想知道您是否可以談談診斷率，以及您是否注意到自今年年初以來由於市場上又增加了兩種產品而發生了變化。其次，目前約有 20% 的患者得到確診，您認為到年底的情況會如何？

Two great questions.

兩個很好的問題。

No, thank you. Look, I think we actually have empirical evidence now. What you see in polyneuropathy from 50% growth rate to 60% just with another product in polyneuropathy already accelerated that, and we remain the market leader. Now when you look at actually the Q1 results of both stabilizers, actually, in the US, the stabilizer has grown the fastest ever in the quarter.

不，謝謝。看，我認為我們現在確實有經驗證據。您所看到的多發性神經病變的成長率從 50% 上升到 60%，而多發性神經病變的另一種產品的出現已經加速了這一進程，我們仍然是市場的領導者。現在，當您實際查看這兩個穩定器的第一季結果時，實際上，在美國，穩定器在本季度的增長速度是有史以來最快的。

I think that's somewhat also supported by IRA changes as well, but we see this category growth only accelerating. We used to provide analogies with multiple sclerosis and other products. Now we see it in our own category. So there's definitely evidence of that.

我認為 IRA 變化也在一定程度上支持了這一點，但我們看到這一類別的成長只會加速。我們過去常常提供與多發性硬化症和其他產品的類比。現在我們在我們自己的類別中看到了它。所以肯定有證據證明這一點。

Now in terms of how large the category and how much diagnosis rate is going to go up, it's going to be very difficult for us to predict that now, but I think we will all see, and I'm sure all voices in this category is going to help accelerate that in the future.

現在就該類別的規模和診斷率將上升多少而言，我們現在很難預測，但我想我們都會看到，而且我相信這一類別中的所有聲音都將有助於在未來加速這一進程。

Good. Okay. Well, look, thank you, everyone, for joining us on the call. As you can hear, 2025 is off to a great start at Alnylam, and we look forward to providing you with further updates as the year progresses. Thanks, everybody.

好的。好的。好吧，看，謝謝大家參加我們的電話會議。正如您所聽到的，2025 年對 Alnylam 來說是一個很好的開端，我們期待在新的一年為您提供進一步的更新。謝謝大家。

Ladies and gentlemen, this is your conference call for today. We thank you for participating and we ask that you please disconnect your lines.

女士們、先生們，這是你們今天的電話會議。感謝您的參與，請您斷開線路。