Alnylam Pharmaceuticals Inc (ALNY) 2025 Q2 法說會逐字稿

Good morning. Ladies and gentlemen, and welcome to the Alnylam Q2 2025 conference call. (Operator Instructions)

早安.女士們，先生們，歡迎參加 Alnylam 2025 年第二季電話會議。（操作員指示）

This call is being recorded on Thursday, July 31, 2025. I would now like to turn the conference over to the company. Please go ahead.

本次通話於 2025 年 7 月 31 日星期四錄製。現在我想將會議交給公司。請繼續。

Good morning. I'm Christina Kinch, Chief Corporate Communications Officer at Alnylam. With me today are Yvonne Greenstreet, Chief Executive Officer; Tolga Tanguler, Chief Commercial Officer; Pushkal Garg, Chief Research and Development Officer; and Jeff Poulton, Chief Financial Officer.

早安.我是 Alnylam 首席企業傳播長 Christina Kinch。今天與我一起出席的有執行長 Yvonne Greenstreet、首席商務官 Tolga Tanguler、首席研發長 Pushkal Garg 和財務長 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.alnylam.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.alnylam.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 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即將到來的里程碑。

I'd 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 as of the date of this reporting and should not be relied upon as representing our views as of any subsequent date. We specifically declaim any obligation to update such statements.

此外，任何前瞻性陳述均代表我們截至本報告發布之日的觀點，不應被視為代表我們在任何後續日期的觀點。我們明確聲明不承擔更新此類聲明的任何義務。

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. As shown in our Q2 results announced today, Alnylam is firing on all cylinders, and we're swiftly establishing ourselves as a top-tier biotech company. We're doing so by focusing on three core elements of the business that we believe will drive sustainable growth and value creation for years to come.

謝謝，克里斯汀，也謝謝大家今天參加電話會議。正如我們今天公佈的第二季業績所示，Alnylam 正全力以赴，我們正在迅速成為一家頂級生物技術公司。我們透過專注於業務的三個核心要素來實現這一目標，我們相信這三個要素將在未來幾年推動永續成長和價值創造。

The first is TTR leadership. As highlighted in today's press release, the launch is off to a very strong start. And whilst it's still early days, we're encouraged by the pace, and we're deeply focused on laying the groundwork for long-term leadership in TTR.

首先是TTR領導力。正如今天的新聞稿中所強調的那樣，此次發布會開局非常強勁。雖然現在還處於早期階段，但我們對這一進展感到鼓舞，我們非常專注於為 TTR 的長期領導者奠定基礎。

The next is growth through innovation, focused on the potential multibillion-dollar opportunities within our pipeline and an R&D engine set up to deliver sustainable innovation and value creation. To that end, I'd like to acknowledge the recent promotion of Pushkal Garg to Chief Research and Development Officer. Pushkal has been instrumental in progressing our pipeline, and in this role, Pushkal will oversee an integrated R&D organization to drive this exciting pipeline and platform into the future. Congratulations, Pushkal.

下一步是透過創新實現成長，重點關注我們產品線中潛在的數十億美元機會以及為實現永續創新和價值創造而建立的研發引擎。為此，我要對 Pushkal Garg 最近晉升為首席研發長表示感謝。Pushkal 在推動我們的管道建設方面發揮了重要作用，在這個職位上，Pushkal 將負責監督一個綜合研發組織，推動這個令人興奮的管道建設和平台走向未來。恭喜你，普什卡爾。

The third element is strong financial performance, with robust commercial execution and disciplined capital allocation approach, providing us with the opportunity to sustain profitability going forward. As Tolga and Jeff will highlight later, the strong therapeutic profile of AMVUTTRA and ATTR-CM, combined with a large and underserved market, position this as a flagship commercial franchise with robust and durable long-term growth potential.

第三個要素是強勁的財務業績，強勁的商業執行力和嚴謹的資本配置方式，為我們提供了未來保持獲利的機會。正如托爾加和傑夫稍後將強調的那樣，AMVUTTRA 和 ATTR-CM 強大的治療特性，加上龐大且服務不足的市場，使其成為具有強勁而持久的長期增長潛力的旗艦商業特許經營權。

And of course, all of this is underpinned by a best-in-class team and our award-winning culture. Our results this quarter fit within each of these strategic pillars and represent one of the most impactful quarters to date for our [NILM].

當然，所有這一切都建立在一流的團隊和我們屢獲殊榮的文化的基礎之上。本季的業績符合上述每個策略支柱，也是我們迄今為止最具影響力的季度之一。[NILM]。

Our commercial performance was driven by TTR franchise revenues of $544 million, 77% year-over-year growth, with growth largely attributable to the AMVUTTRA-CM launch. This was just the first full quarter of the ATTR-CM launch, and as of June 30, approximately 1,400 cardiomyopathy patients were receiving AMVUTTRA, and this is a remarkable achievement. This performance reflects results from our cardiomyopathy launch in the US only.

我們的商業表現由 TTR 特許經營收入推動，達到 5.44 億美元，年成長 77%，成長主要歸功於 AMVUTTRA-CM 的推出。這只是 ATTR-CM 推出的第一個完整季度，截至 6 月 30 日，約有 1,400 名心肌病變患者正在接受 AMVUTTRA 治療，這是一項了不起的成就。這項業績僅反映了我們在美國推出的心肌病變產品的結果。

International markets are coming online for AMVUTTRA for CM and are expected to begin to contribute to the CM launch in the second half of the year. Kudos to our team for delivering these impressive early results.

AMVUTTRA 的 CM 國際市場即將上線，預計今年下半年開始為 CM 的推出做出貢獻。感謝我們的團隊取得了這些令人印象深刻的早期成果。

In addition to these commercial results, we continue to advance our leading pipeline of RNAi therapeutics. We initiated the TRITON-CM Phase 3 study of nucresiran, further establishing our commitment to leadership in TTR, and are pleased to be announcing today that the FDA has granted fast-track designation to nucresiran for ATTR-CM. We also just shared encouraging Phase 1 multidose data for mivelsiran in Alzheimer's disease and kicked off a Phase 1 study for ALN-4324 in type 2 diabetes earlier in the quarter.

除了這些商業成果之外，我們還繼續推進我們領先的 RNAi 療法產品線。我們啟動了 Nucresiran 的 TRITON-CM 第三階段研究，進一步確立了我們在 TTR 領域的領導地位，今天我們很高興地宣布，FDA 已授予 Nucresiran ATTR-CM 快速通道資格。我們也剛分享了 mivelsiran 治療阿茲海默症的令人鼓舞的 1 期多劑量數據，並在本季度早些時候啟動了 ALN-4324 治療 2 型糖尿病的 1 期研究。

And with regard to financial performance, we're reporting our strongest quarter to date as a company, with $672 million in total net product revenues, or 64% growth year over year. As a result, we've increased our total net product revenues guidance for 2025 from a range of $2.05 to $2.25 billion to a revised range of $2.65 billion to $2.8 billion, representing an increase of $575 million, or 27% at the midpoint, underscoring our confidence in the ATTR-CM launch and our other commercial products in the balance of the year.

就財務業績而言，我們報告了該公司迄今為止表現最強勁的季度，總淨產品收入達 6.72 億美元，年增 64%。因此，我們將 2025 年的總淨產品收入預期從 20.5 億美元至 22.5 億美元範圍上調至 26.5 億美元至 28 億美元的修訂範圍，這意味著增加了 5.75 億美元，即中位數增長 27%，這凸顯了我們對 ATTR-CM 的推出以及今年剩餘時間裡其他商業產品的信心。

So zooming out from the success of Q2, this progress represents stellar execution towards our Alnylam P5x25 goals, which we seek to achieve by the end of this year. Doing so will further establish our Alnylam as a unique, top-tier biotech company, delivering sustainable innovation to patients for many years to come.

因此，從第二季的成功來看，這項進展代表著我們在實現 Alnylam P5x25 目標方面取得了出色的成績，我們希望在今年年底前實現這一目標。這樣做將進一步確立我們的 Alnylam 作為一家獨特的頂級生物技術公司的地位，並在未來許多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 view of our commercial performance. Tolga?

說完這些，現在請容許我將電話轉給托爾加，請他介紹我們的商業表現。托爾加？

Thanks, Yvonne, and good morning, everyone. I'm excited to share with you the results of our Q2 commercial performance. As Ivan indicated, we are firing on all cylinders, and our Q2 performance was exceptional for the full portfolio. On a global basis, our commercial portfolio delivered $672 million in net product revenues, accounting for 64% year over year and 43% quarter-over-quarter growth.

謝謝，伊馮娜，大家早安。我很高興與大家分享我們第二季商業業績的結果。正如伊凡所指出的，我們正在全力以赴，我們第二季的業績對於整個投資組合來說都是非常出色的。在全球範圍內，我們的商業產品組合實現了 6.72 億美元的淨產品收入，年增 64%，季增 43%。

As you will see in a moment, the US TTR performance was the major driver of growth given the ATTR-CM launch for AMVUTTRA. It is also encouraging that we saw very robust double-digit growth compared with Q1 across both our TTR and Rare franchises across the globe. All parts of our business are operating with focus and excellence.

您馬上就會看到，由於 AMVUTTRA 推出了 ATTR-CM，美國 TTR 的表現成為成長的主要動力。同樣令人鼓舞的是，與第一季相比，我們在全球範圍內的 TTR 和 Rare 特許經營權都實現了非常強勁的兩位數增長。我們業務的各個部分都在專注和卓越地運作。

Let's quickly start with our rare franchise. Our GIVLAARI and OXLUMO teams stayed focused and delivered $128 million in combined Q2 sales, up 24% versus last year. Our TTR performance was largely demand driven, with a tailwind from favorable GIVLAARI growth to net adjustments in the US.

讓我們快速開始我們罕見的特許經營權。我們的 GIVLAARI 和 OXLUMO 團隊保持專注，第二季總銷售額達 1.28 億美元，比去年成長 24%。我們的 TTR 表現很大程度上是由需求驅動的，得益於 GIVLAARI 的良好成長和美國的淨調整。

Now turning our attention to TTR franchise, where we delivered $544 million in global net product revenues during the quarter, representing a 77% increase compared with the second quarter of '24, and a robust 51% increase compared with the first quarter of 2025.

現在將注意力轉向 TTR 特許經營權，本季度我們實現了 5.44 億美元的全球淨產品收入，與 24 年第二季度相比增長 77%，與 2025 年第一季相比增長 51%。

In the US, combined Q2 sales of ONPATTRO and AMVUTTRA rose 80%, up roughly $170 million from Q1, driven primarily by AMVUTTRA's ATTR-CM launch. We closed the quarter with approximately 1,400 cardiomyopathy patients on therapy, contributing an estimated $150 million in revenue. This performance was fueled by strong execution and faster than anticipated access across payers and providers.

在美國，ONPATTRO 和 AMVUTTRA 第二季的總銷售額成長了 80%，比第一季增加了約 1.7 億美元，這主要得益於 AMVUTTRA 推出的 ATTR-CM。本季結束時，我們為大約 1,400 名心肌病變患者提供了治療，貢獻了約 1.5 億美元的收入。這一業績得益於強大的執行力以及付款人和提供者之間比預期更快的訪問速度。

Regarding the year-over-year dynamics, the US TTR franchise grew 125% compared with the second quarter of 2024, primarily driven by the significant increase in demand from the ATTR-CM launch that I just highlighted.

就同​​比動態而言，美國 TTR 特許經營權與 2024 年第二季度相比增長了 125%，這主要得益於我剛才強調的 ATTR-CM 發布帶來的需求大幅增長。

Turning to our international markets, we delivered 18% year-over-year growth, driven by continued strength in our HKTTR-PN business, which remains a solid growth engine. Most importantly, we have yet to recognize any ATTR-CM revenue internationally, as launches in Germany and Japan are slated to begin contributing in Q3.

轉向我們的國際市場，我們實現了 18% 的同比增長，這得益於我們 HKTTR-PN 業務的持續強勁增長，該業務仍然是一個強勁的增長引擎。最重要的是，我們尚未在國際上確認任何 ATTR-CM 收入，因為德國和日本的發布計劃在第三季開始貢獻。

Now let me provide some additional perspectives on the US TTR revenue dynamics, where the franchise achieved $383 million in Q2, representing a very robust 80% quarter-over-quarter growth. While we don't have the ability to report revenue by indication, the underlying trend is clear. From Q1 '24 through Q1 '25, the US TTR franchise delivered steady growth of around $15 million to $20 million on average every quarter. In Q2 2025, we saw a pronounced step change, indicating an estimated $150 million contribution from ATTR-CM.

現在，讓我提供一些關於美國 TTR 收入動態的額外觀點，該系列電影在第二季度實現了 3.83 億美元的收入，環比增長非常強勁，達到 80%。雖然我們沒有能力按指標報告收入，但潛在趨勢是顯而易見的。從 2024 年第一季到 2025 年第一季度，美國 TTR 特許經營權平均每季實現約 1,500 萬至 2,000 萬美元的穩定成長。2025 年第二季度，我們看到了明顯的階躍變化，顯示 ATTR-CM 的貢獻估計為 1.5 億美元。

I will now provide some additional launch metrics to further contextualize AMVUTTRA's launch performance in ATTR-cardiomyopathy. Our launch began on March 20, 2025, and Q2 marked our first full quarter post-approval. It is still early, and there is more work to do, but we are very encouraged by the strong momentum we are seeing.

我現在將提供一些額外的啟動指標，以進一步說明 AMVUTTRA 在 ATTR 心肌病變中的啟動性能。我們的發佈於 2025 年 3 月 20 日開始，第二季是我們獲得批准後的第一個完整季度。現在還為時過早，還有很多工作要做，但我們對所看到的強勁勢頭感到非常鼓舞。

As we have described on prior calls, we have been focused on three key enablers around the US launch of AMVUTTRA in ATTR-cardiomyopathy: health system setup, access and affordability, and treatment choice. The headlines are here, and I will go into more detail on each in the following slides.

正如我們在先前的電話會議上所描述的，我們一直專注於美國在 ATTR 心肌病變領域推出 AMVUTTRA 的三個關鍵推動因素：醫療體系的建立、可及性和可負擔性以及治療選擇。標題就在這裡，我將在接下來的幻燈片中對每個標題進行更詳細的介紹。

As we have shared on prior calls, there are approximately 170 priority health systems through which approximately 80% of ATTR cardiomyopathy patient volume flows. The majority of these provider accounts now have AMVUTTRA formulary, enabling therapy initiation throughout these health systems where ATTR-CM patients present. What's more, nearly all of the priority health systems have already begun treating patients with AMVUTTRA for ATTR-cardiomyopathy.

正如我們在先前的電話會議中所分享的，大約有 170 個優先醫療系統，大約 80% 的 ATTR 心肌病變患者透過這些系統就診。目前，大多數提供者帳戶都擁有 AMVUTTRA 處方集，從而能夠在 ATTR-CM 患者所在的整個醫療系統中開始治療。此外，幾乎所有優先醫療系統都已開始為患有 AMVUTTRA 的 ATTR 心肌病變患者進行治療。

This together with the broad network of more than 2,000 alternate sites of care has allowed us to achieve our aspiration. Roughly 90% of patients in the US are able to receive AMVUTTRA treatment within about 10 miles of where they live. Bottom line, our priority was to enable broad provider accounts set up in our first year of launch. This has happened faster than we had initially anticipated. Since now, at the end of our first quarter of launch, we are largely there.

這與超過 2,000 個替代護理站點的廣泛網絡一起使我們能夠實現我們的願望。美國大約 90% 的患者可以在距離其居住地約 10 英里的範圍內接受 AMVUTTRA 治療。歸根結底，我們的首要任務是在推出的第一年就建立廣泛的提供者帳戶。此事發生得比我們最初預期的還要快。從現在起，我們已度過發表會的第一個季度末，基本上已經完成了目標。

In addition, patients are getting first-line access to AMVUTTRA across all payer segments. Coverage is now confirmed by payers covering the majority of US patient lives, inclusive of Medicare fee-for-service, Medicare Advantage, and commercial. We can therefore confirm that the large majority of patients have access to AMVUTTRA as a first-line treatment, meaning without requiring patients to step through another product first.

此外，患者可以透過所有付款人群體獲得 AMVUTTRA 的第一線治療機會。付款人現在已確認該保險涵蓋大多數美國患者的生活，包括醫療保險按服務收費、醫療保險優勢計劃和商業保險。因此，我們可以確認，絕大多數患者可以使用 AMVUTTRA 作為第一線治療，這意味著患者無需先使用其他產品。

Most patients are indeed paying zero in out-of-pocket costs and consistent with what we've seen in cardiomyopathy, there has been very limited use of our quick start program, quite simply because patients are not experiencing delays in coverage.

大多數患者的自付費用確實為零，而且與我們在心肌病變中看到的情況一致，我們的快速啟動計劃的使用非常有限，原因很簡單，因為患者沒有遇到承保延遲。

We're also seeing patient initiations flowing through all payer segments: Medicare fee-for-service, Medicare Advantage, and commercial. These access dynamics are consistent with what we've long seen in hATTR-PN, and we're encouraged to see them replicated in ATTR-CM. This reflects our deep experience engaging with payers and the advantage of our fully integrated in-house patient support services.

我們也看到患者主動性流向所有付款人部分：醫療保險按服務收費、醫療保險優勢和商業。這些訪問動態與我們長期以來在 hATTR-PN 中看到的一致，我們很高興看到它們在 ATTR-CM 中複製。這反映了我們與付款人合作的豐富經驗以及我們完全整合的內部患者支援服務的優勢。

Now, most importantly, physicians and patients are choosing AMVUTTRA, a testament to its highly differentiated and compelling profile, including its rapid knockdown of the disease-causing protein. By the end of the second quarter, approximately 1,400 ATTR-CM patients had initiated treatment.

現在，最重要的是，醫生和患者都選擇了 AMVUTTRA，這證明了其高度差異化和引人注目的特性，包括其對致病蛋白質的快速敲除。截至第二季末，約有 1,400 名 ATTR-CM 患者開始接受治療。

While we don't plan to regularly report patient numbers going forward, we felt it was important to share this clear signal of early momentum in our first full quarter post launch. This strong uptake also gives us early insight into utilization patterns, which so far have been broad and balanced.

雖然我們不打算定期報告未來的患者數量，但我們認為在推出後的第一個完整季度分享這一早期發展勢頭的明確信號非常重要。這種強勁的成長動能也讓我們提前了解了利用模式，迄今為止，這種模式一直廣泛而均衡。

More specifically, very early initial uptake was more pronounced among stabilizer progressors. However, within just three short months, utilization has become relatively balanced between first line, new starts, and stabilizer progressors. We're seeing steady growth across both sources of business, and we have a clear focus on making AMVUTTRA the first line treatment of choice.

更具體地說，穩定器進展者的早期初始吸收更為明顯。然而，在短短三個月內，第一線藥物、新藥和穩定劑進展藥物之間的利用率已經相對平衡。我們看到這兩個業務來源都在穩步成長，我們明確致力於將 AMVUTTRA 打造為首選治療方法。

We also see balanced utilization across academic and community settings. And lastly, physician adoption has been broad. Since launch, the total AMVUTTRA prescriber base has tripled quarter over quarter. This reflects growing awareness and confidence in AMVUTTRA across both cardiology and multidisciplinary practices. Bottom line, we're highly encouraged by the early progress post launch. The trajectory supports sustainable growth and positions us for long-term leadership in TTR amyloidosis.

我們也看到學術和社區環境之間的平衡利用。最後，醫生的採用範圍很廣。自推出以來，AMVUTTRA 處方總數較上季增加了兩倍。這反映出心臟病學和多學科實踐對 AMVUTTRA 的認識和信心不斷增強。總而言之，我們對發布後的早期進展感到非常鼓舞。該軌跡支持永續成長並使我們在 TTR 澱粉樣變性領域保持長期領導地位。

In summary, access ramped faster than expected, and the value proposition is resonating. We've seen rapid payer adoption and broad physician engagement. The clinical differentiator of AMVUTTRA is clearly being recognized.

總而言之，訪問量的成長速度超出了預期，而且價值主張引起了共鳴。我們看到了付款人的快速採用和醫生的廣泛參與。AMVUTTRA 的臨床鑑別特徵已被明確認可。

We're seeing robust growth in an underserved and expanding ATTR-CM population. Look, this is a devastating disease, and we remain deeply committed to advancing care through real-world evidence generation and development of our next generation RNAi therapeutics, Nucleus RAM.

我們看到服務不足且不斷擴大的 ATTR-CM 群體正在強勁成長。看，這是一種毀滅性的疾病，我們仍然堅定地致力於透過真實世界證據的生成和下一代 RNAi 療法 Nucleus RAM 的開發來推進治療。

Finally, global expansion is underway. With regulatory approvals secured in Europe, Japan, and Brazil, we've now launched in Germany and Japan, unlocking access to more patients worldwide. We're also maintaining stable growth in the hATTR pulmonary operative business both in the US and the United States. These drivers underpin our increased revenue guidance and reinforce our conviction in significant revenue growth going forward.

最後，全球擴張正在進行中。在獲得歐洲、日本和巴西監管部門的批准後，我們現已在德國和日本推出該產品，為全球更多患者提供治療服務。我們在美國和美國的hATTR肺部手術業務也保持穩定成長。這些驅動因素支撐了我們提高的收入預期，並增強了我們對未來收入大幅成長的信心。

We're just getting started, and we remain focused on discipline execution, anchored in patient and customer centricity and delivering long-term innovation-driven growth.

我們才剛起步，我們將繼續專注於紀律執行，以患者和客戶為中心，實現長期創新驅動的成長。

I'll now turn it over to Pushkar to share more about our work to advance the science in ATTR and beyond. Pushkar?

現在我將把時間交給 Pushkar，讓他進一步分享我們為推動 ATTR 及其他領域的科學發展所做的工作。普什卡？

Thank you, Tolga, and good morning, everyone. I'm delighted to see the early success of AMVUTTRA in these first few months of the launch. It is a true testament to the outstanding execution of our commercial and medical teams and to AMVUTTRA's unique and compelling profile established in HELIOS-B.

謝謝你，托爾加，大家早安。我很高興看到 AMVUTTRA 在推出後的頭幾個月取得了早期的成功。這真正證明了我們的商業和醫療團隊的出色表現以及 AMVUTTRA 在 HELIOS-B 中建立的獨特而引人注目的形象。

To that end, we continue to generate evidence from the HELIOS-B study that further supports the long-term efficacy and safety of AMVUTTRA with the aim of cementing it as the first line treatment of choice for patients with ATTR-cardiomyopathy. This slide highlights some of the unique and profound benefits of AMVUTTRA's rapid knockdown mechanism of action that are emerging from HELIOS-B.

為此，我們繼續從 HELIOS-B 研究中獲取證據，進一步支持 AMVUTTRA 的長期療效和安全性，旨在鞏固其作為 ATTR 心肌病變患者的一線治療選擇的地位。這張投影片重點介紹了 AMVUTTRA 快速擊倒作用機制在 HELIOS-B 中產生的一些獨特而深遠的好處。

In the left column, you can see the benefits on NT-proBNP and troponin I, important clinical biomarkers of cardiac stress and injury, respectively. Not only do you see a large effect in patients receiving drugs versus those on placebo, but it's interesting to see a reduction compared to baseline in troponin I, suggesting a potential disease-modifying effect on this biomarker.

在左側欄中，您可以看到 NT-proBNP 和肌鈣蛋白 I 的益處，它們分別是心臟壓力和損傷的重要臨床生物標記。與服用安慰劑的患者相比，您不僅可以看到接受藥物治療的患者獲得了顯著的效果，而且有趣的是，您還可以看到肌鈣蛋白 I 與基線相比有所降低，這表明這種生物標誌物具有潛在的疾病修飾作用。

Further to that point, echocardiographic data in the middle column shows improvements in critical aspects of cardiac function, both diastolic and systolic. And ultimately, we saw this translate into substantial improvements in all-cause mortality, as well as cardiovascular mortality of 33% to 36%.

進一步說，中間一列的超音波心動圖數據顯示心臟功能的關鍵方面（舒張和收縮）均有所改善。最終，我們看到這轉化為全因死亡率的大幅改善，以及心血管死亡率降低了 33% 至 36%。

In addition to data coming from the HELIOS-B study, we are continuing to generate evidence to further support the safe and effective use of AMVUTTRA via numerous registry and real-world evidence-based studies and investigator-initiated studies. We look forward to sharing data from these sources over time.

除了 HELIOS-B 研究的數據外，我們還在透過大量註冊和現實世界的實證研究以及研究者發起的研究繼續產生證據，以進一步支持 AMVUTTRA 的安全有效使用。我們期待隨著時間的推移分享這些來源的數據。

Further to our leadership and commitment to innovation in ATTR amyloidosis, we announced in June the initiation of the TRITON-CM Phase 3 study for nucresiran, which may offer greater knockdown, greater efficacy, and greater convenience for patients with ATR cardiomyopathy.

繼我們在 ATTR 澱粉樣變性領域的領導地位和創新承諾之後，我們在 6 月宣布啟動 Nucresiran 的 TRITON-CM 第 3 階段研究，該研究可能為 ATR 心肌病變患者提供更強的敲低效果、更高的療效和更大的便利性。

As a reminder, TRITON-CM is a randomized, double-blind, event-driven outcome study. Patients are allowed to be on background stabilizer therapy. Approximately 1,200 patients will be randomized, and the primary endpoint is a composite of all-cause mortality and cardiovascular events. The primary analysis will be event-driven and will occur a minimum of 24 months after the last patient is enrolled.

提醒一下，TRITON-CM 是一項隨機、雙盲、事件驅動的結果研究。允許患者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，並將在最後一名患者入組後至少 24 個月進行。

If successful, we target launching nucresiran in ATTR cardiomyopathy around 2030. Also, as Yvonne noted earlier, we've announced today that nucresiran has been granted fast-track designation by the FDA, which will enable a more streamlined review process.

如果成功的話，我們的目標是在 2030 年左右推出用於治療 ATTR 心肌病變的 Nucresiran。此外，正如伊馮娜之前提到的，我們今天宣布，Nucresiran 已獲得 FDA 的快速通道資格，這將使審查流程更加簡化。

In parallel, we have the goal to bring nucresiran to patients as quickly as possible and see an opportunity to do so in hereditary ATTR-PM. Though we are not yet prepared to discuss full details for TRITON-PM, we remain on track to initiate a pivotal study for the polyneuropathy indication by the end of 2025 and anticipate the potential to launch in this indication several years ahead of cardiomyopathy. We look forward to sharing more details in due course.

同時，我們的目標是盡快將 Nucresiran 帶給患者，並看到在遺傳性 ATTR-PM 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，但我們仍有望在 2025 年底之前啟動針對多發性神經病適應症的關鍵研究，並預計有可能在心肌病變治療前幾年推出該適應症。我們期待在適當的時候分享更多細節。

Moving on to another exciting program, just a few days ago we presented new multidose data from the Phase I study of mivelsiran in patients with early-onset Alzheimer's disease. Recall previously that we observed marked reductions in A beta 40 and A beta 42, the pathogenic proteins implicated in cerebral amyloid angiopathy and Alzheimer's disease, respectively, with single doses of mivelsiran.

接下來是另一個令人興奮的項目，就在幾天前，我們展示了 mivelsiran 治療早發性阿茲海默症患者 I 期研究的新多劑量數據。回想一下，我們之前曾觀察到，在服用單劑量 mivelsiran 後，Aβ40 和 Aβ42（分別與腦澱粉樣血管病變和阿茲海默症有關的致病蛋白）顯著減少。

We are pleased to see that continue with multiple doses administered every six months. In addition to the durable knockdown observed, the safety and tolerability profile also remains encouraging. The majority of AEs observed were non-serious, mild to moderate, and deemed unrelated to study drugs. Importantly, we saw no evidence of changes in CSF white blood cells, protein, or neurofilament light chain, which bodes well for this program as well as our CNS platform.

我們很高興看到每六個月繼續進行多次劑量注射。除了觀察到的持久擊倒效果外，安全性和耐受性概況也仍然令人鼓舞。觀察到的大多數不良事件都是不嚴重的、輕度至中度的，並且被認為與研究藥物無關。重要的是，我們沒有看到腦脊髓液白血球、蛋白質或神經絲輕鏈變化的證據，這對該計劃以及我們的中樞神經系統平台來說都是好兆頭。

We look forward to further evaluating the profile of mivelsiran in the ongoing cAPPricorn Phase 2 study in CAA as well as the Phase 2 study in Alzheimer's that we expect to start by the end of the year.

我們期待進一步評估 mivelsiran 在正在進行的 CAA cAPPricorn 第 2 階段研究以及我們預計今年年底開始的阿茲海默症第 2 階段研究中的表現。

As Yvonne mentioned earlier, a key element of our journey towards becoming a top-tier biotech company is growth through innovation. Across what is one of the most robust pipelines in the industry, we are making great progress advancing promising programs across a range of therapeutic areas with multiple potential blockbuster opportunities.

正如 Yvonne 先前提到的，我們成為頂尖生技公司的關鍵要素是透過創新來實現成長。在業內最強大的產品線之一中，我們在推進一系列治療領域的有前景的項目方面取得了巨大進展，並擁有多個潛在的重磅機會。

In addition to some of the highlights we've already discussed, in Q2, we also kicked off a Phase 1 trial for ALN-4324 targeting GRB14, an insulin sensitizer for the potential treatment of type 2 diabetes. We also remain on track to start a Phase 2 study of ALN-6400 targeting plasminogen in a bleeding disorder later this year.

除了我們已經討論過的一些亮點之外，在第二季度，我們還啟動了針對 GRB14 的 ALN-4324 的 1 期試驗，GRB14 是一種用於治療 2 型糖尿病的胰島素增敏劑。我們也計劃在今年稍後啟動針對出血性疾病中纖溶酶原的 ALN-6400 第 2 階段研究。

In summary, Alnylam continues to make remarkable progress and deliver unique innovation that puts us in a great position to have a deep, sustainable pipeline that can deliver meaningful impact to patients for many years to come. With that, let me now turn it over to Jeff to review our financial results and upcoming milestones. Jeff?

總而言之，Alnylam 繼續取得顯著進展並提供獨特的創新，這使我們處於有利地位，擁有深度、可持續的管道，可以在未來許多年為患者帶來有意義的影響。現在，讓我將時間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 a summary of Alnylam's Q2 2025 financial results and discussing our full year upgraded guidance.

謝謝，Pushkal，大家早安。我很高興能夠介紹 Alnylam 2025 年第二季的財務表現摘要並討論我們全年的升級指導。

Let's begin with a summary of our P&L results for the second quarter compared with prior year. Total product revenues for the quarter were $672 million, or 64% growth versus 2024, driven by 77% growth in our TTR franchise, with particularly strong performance in the US market, primarily related to an increase in demand associated with the launch of AMVUTTRA and ATTR-cardiomyopathy.

讓我們先總結一下我們第二季與去年同期的損益結果。本季總產品營收為 6.72 億美元，較 2024 年成長 64%，這得益於我們的 TTR 特許經營權成長 77%，其中美國市場表現尤為強勁，這主要與 AMVUTTRA 和 ATTR-cardiomyopathy 的推出帶來的需求成長有關。

Collaboration revenue for the quarter was $61 million, representing a $166 million decrease when compared with last year. The decrease was primarily driven by the modification of our cemdisiran collaboration agreement with Regeneron, which resulted in approximately $185 million of revenue in Q2. 2024. As a reminder, this amendment granted Regeneron an exclusive license to cemdisiran monotherapy.

本季合作收入為 6,100 萬美元，與去年相比減少 1.66 億美元。下降的主要原因是我們與 Regeneron 修改了 cemdisiran 合作協議，導致第二季營收約 1.85 億美元。2024年。提醒一下，該修正案授予了再生元公司對西地西崙單一療法的獨家許可。

Royalty revenue for the quarter was $40 million, representing an $18 million increase compared with last year, driven by higher [LPO] sales. Gross margin on product sales was 79% for the quarter, compared with 84% in the second quarter of 2024. The decrease in margin was primarily driven by increased royalties on AMVUTTRA, as higher revenues in 2025 resulted in an increase in the royalty compared with last year.

本季特許權使用費收入為 4,000 萬美元，比去年同期增加 1,800 萬美元，這得益於 [LPO] 銷售額的增加。本季產品銷售毛利率為 79%，而 2024 年第二季為 84%。利潤率的下降主要是由於 AMVUTTRA 的特許權使用費增加，因為 2025 年的收入增加導致特許權使用費與去年相比有所增加。

For the balance of the year, our gross margin on product sales is expected to decrease as the applicable AMVUTTRA royalty rates increase, driven by higher sales of AMVUTTRA. Our non-GAAP R&D expenses of $274 million increased 11%, primarily due to increases in start-up clinical trial expenses associated with our cardiovascular outcomes trial for cemdisiran and the TRITON-CM Phase 3 study for nucresiran.

在今年剩餘的時間裡，由於 AMVUTTRA 銷售量增加，適用的 AMVUTTRA 專利費率也將隨之提高，預計我們的產品銷售毛利率將會下降。我們的非公認會計準則研發費用為 2.74 億美元，增加了 11%，這主要是由於與西地西蘭心血管結果試驗和紐克西蘭 TRITON-CM 第 3 階段研究相關的啟動臨床試驗費用增加。

Our non-GAAP SG&A expenses of $261 million increased 26% compared to last year, primarily driven by increased headcount and other investments in support of the AMVUTTRA ATTR-cardiomyopathy launch in the US.

我們的非公認會計準則銷售、一般及行政費用為 2.61 億美元，較去年同期增長 26%，主要原因是員工人數增加以及為支持 AMVUTTRA ATTR-心肌病變在美國上市而進行的其他投資。

Our non-GAAP operating income for the quarter was $95 million, representing a $42 million decrease compared with last year, driven primarily by the recognition of collaboration revenue related to the modification of our Regeneron agreement in Q2 2024, as I previously highlighted. We continue to be pleased with the progress we are making towards achieving our non-GAAP profitability guidance in 2025.

本季我們的非公認會計準則營業收入為 9,500 萬美元，比去年同期減少 4,200 萬美元，這主要歸因於與 2024 年第二季修改 Regeneron 協議相關的合作收入的確認，正如我之前所強調的。我們對在實現 2025 年非 GAAP 獲利預期方面取得的進展感到滿意。

Finally, we ended the quarter with cash equivalents and marketable securities of $2.9 billion compared to $2.7 billion as of December 31, 2024, with the increase primarily driven by cash from operations and that proceeds from the issuance of common stock in connection with employee stock option exercises.

最後，本季末我們的現金等價物及有價證券為 29 億美元，而截至 2024 年 12 月 31 日為 27 億美元，成長主要得益於經營活動現金以及與員工股票選擇權行使相關的發行普通股所得。

Now I'd like to turn to our financial guidance for 2025, where we are substantially increasing our net product revenue guidance, driven by the strong early launch performance of AMVUTTRA and ATTR cardiomyopathy, with specific details as follows. We are increasing our net product revenue guidance from a range of $2.05 billion to $2.25 billion to a revised range of $2.65 billion to $2.8 billion, representing a $575 million, or 27% increase from the midpoint of the prior guidance to the midpoint of the updated guidance.

現在，我想談談我們 2025 年的財務指導，在 AMVUTTRA 和 ATTR 心肌病變的強勁早期推出表現的推動下，我們將大幅提高淨產品收入指導，具體細節如下。我們將淨產品收入預期從 20.5 億美元至 22.5 億美元範圍上調至 26.5 億美元至 28 億美元的修訂範圍，這意味著從先前預期的中點到更新後的預期的中點增加了 5.75 億美元，增幅為 27%。

The combined full-year growth compared to 2024 is a 66% increase at the midpoint of the guidance range. On a franchise level, the guidance is broken down as follows. We are modestly increasing the midpoint of our total rare franchise guidance by raising.

與 2024 年相比，全年綜合成長率將達到指導範圍中位數的 66%。在特許經營層面，指導內容細分如下。我們透過提高來適度提高我們的總稀有特許經營指導的中點。

the bottom end of our prior guidance range by $25 million and leaving the top end of our guidance unchanged, resulting in revised rare product sales guidance of $475 million to $525 million. We are materially increasing our total TTR guidance range from $1.6 billion to $1.725 billion to a revised range of $2.175 billion to $2.275 billion, representing a 34% increase, or more than $550 million at the midpoint.

將我們先前指導範圍的下限降低了 2500 萬美元，同時保持指導範圍的上限不變，從而將稀有產品銷售指導修改為 4.75 億美元至 5.25 億美元。我們將 TTR 總指引範圍從 16 億美元至 17.25 億美元大幅提高至 21.75 億美元至 22.75 億美元的修訂範圍，增幅為 34%，或以中間值計算超過 5.5 億美元。

Let me provide some additional context, which highlights the impact of the cardiomyopathy launch on our TTR franchise growth based on our upgraded guidance.

讓我提供一些額外的背景信息，根據我們升級的指導，強調心肌病變的推出對我們的 TTR 特許經營增長的影響。

During 2024, when we only marketed our TTR therapies for hATTR polyneuropathy, our TTR franchise delivered approximately $300 million in revenue growth compared with 2023. In 2025, with the ATTR franchise now including cardiomyopathy sales following the US launch in Q2, the midpoint of our revised 2025 total TTR sales guidance of $2.23 billion represents an approximate $1 billion increase from 2024 total TTR sales of $1.2 billion.

2024 年，當我們僅行銷針對 hATTR 多發性神經病變的 TTR 療法時，與 2023 年相比，我們的 TTR 特許經營權實現了約 3 億美元的收入增長。2025 年，隨著 ATTR 特許經營權在第二季度在美國推出後包括心肌病變銷售，我們修訂後的 2025 年 TTR 總銷售額中位數為 22.3 億美元，比 2024 年 TTR 總銷售額 12 億美元增加約 10 億美元。

And now my last comment on our upgraded sales guidance, which now assumes foreign exchange rates as of June 30 for the balance of the year, resulting in approximately $60 million of our $575 million guidance increase being attributed to changes in FX from our original guidance, which utilized December 31 FX rates.

現在，我對我們升級的銷售指南的最後一條評論是，現在假設今年餘額的外匯匯率為 6 月 30 日，這導致我們 5.75 億美元的指導增加中的約 6000 萬美元歸因於外匯變化，而不是我們最初的指南，該指南採用了 12 月 31 日的外匯匯率。

The remainder of our financial guidance, including collaboration and royalty revenue, combined non-GAAP R&D and SG&A expenses, and non-GAAP operating income remains unchanged.

我們其餘的財務指導，包括合作和特許權使用費收入、合併非公認會計準則研發和銷售、一般及行政費用以及非公認會計準則營業收入保持不變。

Let me now turn from financials and discuss some key goals and upcoming 2025 milestones. In the second half of 2025, we expect to achieve the following. Initiate the Phase 3 CVOT of zilebesiran in hypertension. Note that we also announced today that we'll present KARDIA-3 Phase 2 results at the European Society of Cardiology Congress later this summer. Initiate the TRITON-PN Phase 3 study of nucresiran in hATTRPN, and initiate Phase 2 studies for mivelsiran in Alzheimer's disease and ALN-6400 in a bleeding disorder.

現在，讓我不再談論財務問題，而是討論一些關鍵目標和即將到來的 2025 年里程碑。2025年下半年，我們預計將達成以下目標。啟動齊萊貝斯蘭治療高血壓的 3 期 CVOT 研究。請注意，我們今天也宣布，我們將在今年夏天晚些時候的歐洲心臟學會大會上展示 KARDIA-3 第 2 階段的結果。啟動 nucresiran 在 hATTRPN 中的 TRITON-PN 第 3 階段研究，並啟動 mivelsiran 在阿茲海默症的第 2 階段研究和 ALN-6400 在出血性疾病的第 2 階段研究。

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 questions. (Event Instructions)

謝謝你，傑夫。接線員，我們現在開始提問。（活動須知）

Thank you. Ladies and gentlemen, we will now begin the question-and-answer session. (Operator Instructions)

謝謝。女士們、先生們，我們現在開始問答環節。（操作員指示）

Richter, Salveen, Goldman Sachs.

里克特、薩爾文、高盛。

Good morning. Thanks for taking my question and congratulations here in the quarter. Could you give some details here in the patient profiles for AMVUTTRA with regard to the frontline patients and whether you're seeing mostly mixed phenotype patients or more of a broader population mix? And help us understand from here what the field force is most focused on.

早安.感謝您回答我的問題，並祝賀本季圓滿成功。您能否提供一些有關 AMVUTTRA 一線患者的詳細信息，以及您看到的主要是混合表型患者還是更廣泛的人群組合？並從這裡幫助我們了解現場部隊最關注的是什麼。

Thanks, Salveen. I mean, I'll start by saying, look, you know, it's early days yet, but we're incredibly pleased with where the launch is going, particularly with, you know, broad and robust uptake. So I think it also really shows that the data that we generated from HELIOS-B is really resonating with physicians, the rapid knockdown of TTR, all-cause mortality improvements, infrequent subcutaneous administration, which provides both convenience and security. So we're seeing broad uptake across first-line patients as well as patients that progress on stabilizers.

謝謝，薩爾文。我的意思是，我首先要說的是，看，你知道，現在還為時過早，但我們對發布的進展感到非常高興，特別是你知道，廣泛而強勁的接受度。所以我認為這也確實表明我們從 HELIOS-B 產生的數據確實引起了醫生的共鳴，TTR 的快速降低、全因死亡率的改善、不頻繁的皮下給藥，既提供了便利，又提供了安全性。因此，我們看到第一線患者以及使用穩定劑的患者都得到了廣泛的應用。

We're seeing use across the community of physicians as well as academic physicians, as well as new prescribers, as well as repeat prescribers. So the trends are really very supportive in suggesting continued growth.

我們看到整個醫生群體、學術醫生、新開處方者和重複開處方者都在使用它。因此，這些趨勢確實非常有利於持續成長。

Now I think it's fair to say that the initial pickup has been faster in the stabilizer-progressing patients, because you bring in a new therapy and the patients who've been progressing on stabilizers, it's not surprising that physicians are looking for an orthogonal treatment for these patients. We're now achieving a really healthy share of first-line patients.

現在我認為可以公平地說，穩定劑進展患者的初始恢復速度更快，因為你引入了一種新的治療方法，而對於使用穩定劑不斷進展的患者，醫生正在為這些患者尋找正交治療方法也就不足為奇了。現在，我們的第一線患者比例已經非常健康。

So we have a good mix of first-line stabilizer progressors, and what we're going to be doing is really consolidating and building on the foundation of this very early picture. Tolga, you probably want to add a couple of comments.

因此，我們擁有一線穩定劑進展器的良好組合，而我們要做的實際上是鞏固和建立在這個非常早期的基礎上。Tolga，你可能想添加一些評論。

Actually, you pretty much covered everything. What I would say is, again, we're just one quarter in, and what we're already seeing, what you described validates our clinical thesis and commercial strategy.

實際上，您幾乎涵蓋了所有內容。我想說的是，我們才剛進入一個季度，而我們已經看到的情況、您所描述的情況驗證了我們的臨床論文和商業策略。

Thanks, Tolga. Next question.

謝謝，托爾加。下一個問題。

Tazeen Ahmad, Bank of America.

美國銀行的塔津·艾哈邁德（Tazeen Ahmad）。

I just wanted to get a sense on how you're thinking about net price for AMVUTTRA and growth to net moving forward.

我只是想了解您對 AMVUTTRA 淨價和未來淨成長的看法。

Yeah, no, thanks for that question. Jeff, perhaps you'd like to start off answering that, and if there are any additional perspectives, Tolga and I can follow on from you.

是的，不，謝謝你的提問。傑夫，也許你想先回答這個問題，如果有任何其他觀點，托爾加和我可以繼續回答。

Yeah, just a reminder of what we said back on the approval call in March. We said that we expected that we would reduce net price modestly and gradually over time, and that does hold for our expectation for 2025. 2025 relative to 2024, I would expect mid-single-digit reduction in net price for AMVUTTRA for the year.

是的，只是提醒一下我們在三月的批准電話會議上說過的話。我們說過，我們預期隨著時間的推移，淨價格會適度、逐步地降低，這也符合我們對 2025 年的預期。相對於 2024 年，我預計 2025 年 AMVUTTRA 的淨價格將出現中等個位數的降幅。

Okay. Yeah, I mean, look, I think one thing is also to importantly highlight is the fact that payer dynamics are moving very much in as what we exactly expected. A lot of the payer policies are already out, both on Medicare Advantage as well as in commercial, and what we're seeing is a first-line access to those patients, and patients actually paying minimal, in most cases, zero out-of-pocket costs.

好的。是的，我的意思是，我認為還有一件事需要強調，那就是付款人的動態正在按照我們預期的方式發展。許多付款人保單已經出台，包括醫療保險優勢計劃和商業保險，我們看到的是這些患者可以獲得一線醫療服務，而且患者實際上支付的費用很少，在大多數情況下，自付費用為零。

So we'll obviously manage that with early engagement with payers, and the impact of the gross net is going to be, as Jeff highlighted, will evolve over time.

因此，我們顯然會透過與付款人的早期接觸來解決這個問題，而且正如傑夫所強調的那樣，淨收入總收入的影響將會隨著時間的推移而發展。

Thanks, Jeff and Tolga. Next question.

謝謝，傑夫和托爾加。下一個問題。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特（Maury Raycroft），傑富瑞集團（Jefferies）。

Congrats on the great quarter, and thank you for taking our question. I'm wondering if you can comment on whether there was any bolus effect in cardiomyopathy scripts in second quarter and could you also please clarify to what extent did stocking contribute to the growth of US AMVUTTRA revenue in the second quarter?

恭喜本季的優異成績，感謝您回答我們的問題。我想知道您是否可以評論一下第二季度心肌病變處方中是否存在推注效應，並且您能否澄清備貨對第二季度美國 AMVUTTRA 收入增長的貢獻程度如何？

That's a great question. Look, I think Tolga has touched on this. We've really demonstrated very solid commercial execution, and that means that we've seen a little bit of faster progress than we expected, particularly around health system setup.

這是一個很好的問題。瞧，我認為托爾加已經談到了這一點。我們確實展示了非常紮實的商業執行力，這意味著我們看到的進展比我們預期的要快一些，特別是在醫療系統建立方面。

So I touched on this already, but it's meant that we had initial faster pickup with stabilizer progressives, but as we went through the queue, we now have this very healthy share of first line, and we're just in the first quarter of launch. So I think the key message number one for me is that the results that we're sharing with you today are not just a flash in the pan. We expect continued sustainable growth, and that's the reason why we raised guidance today.

所以我已經談到了這一點，但這意味著我們最初透過穩定器漸進式技術獲得了更快的提升，但隨著我們排隊，我們現在擁有非常健康的一線份額，而且我們正處於發布的第一季。因此，我認為對我來說最重要的訊息是，我們今天與你們分享的結果並非曇花一現。我們預計持續可持續成長，這就是我們今天提高預期的原因。

I think the second key message is really just the durability of the franchise. We expect to see AMVUTTRA deliver continued sustainable growth, but we'll be bringing new creases around forward as well, as Pushkar highlighted, which gives us the potential to deliver franchise growth out into the 2040s.

我認為第二個關鍵訊息實際上就是特許經營的持久性。我們預計 AMVUTTRA 將實現持續永續成長，但正如 Pushkar 所強調的那樣，我們也將帶來新的成長，這使我們有潛力在 2040 年代實現特許經營成長。

I'll comment on the second part of the question, which was about inventory. I think the headline for the quarter is, again, in the US, Tolga, in his prepared remarks, highlighted the $170 million in growth in the TTR franchise in the US, Q2 versus Q1, and far and away, the biggest driver of that was the cardiomyopathy demand, 1,400 patients on therapy, $150 million in cardiomyopathy revenue for the quarter is what we're estimating.

我將對問題的第二部分，即庫存，進行評論。我認為本季的頭條新聞再次在美國，托爾加在他準備好的發言中強調了美國 TTR 特許經營權第二季度與第一季度相比增長了 1.7 億美元，而其中最大的驅動力是心肌病需求，1,400 名患者正在接受治療，我們估計本季度心肌病收入為 1.5 億美元。

On the inventory side, we did see about a $25 million benefit in Q2 compared to Q1. That's not actually because days on hand increased between Q1 and Q2, as it actually stayed constant at around 20 days, which is at about the midpoint of the agreements that we've got in place with our distributors.

在庫存方面，與第一季相比，我們確實看到第二季有約 2500 萬美元的收益。這實際上並不是因為第一季和第二季之間庫存天數增加了，因為它實際上保持在 20 天左右的穩定水平，這大約是我們與分銷商達成的協議的中間值。

What drove the increase in inventory in the quarter was the calculation of what a day of demand is, or a day of inventory is worth, which is based on a 12-week moving average of demand. It was demand that really drove the increase in inventory in the channel in the quarter, which is, again, a high-quality increase in channel stock in the quarter.

推動本季庫存增加的因素是對一天的需求或一天的庫存價值的計算，該計算基於 12 週的需求移動平均值。需求才是本季通路庫存增加的真正推動力，這又是本季通路庫存的高品質成長。

On the gross to net side, we had an opposite movement, so a headwind that roughly offset the benefit that we had in inventory, which is why we're highlighting demand was the key driver of growth in the quarter. On the gross to net side, a couple things.

從總額到淨額，我們出現了相反的走勢，因此逆風大致抵消了我們在庫存方面的優勢，這就是為什麼我們強調需求是本季成長的主要驅動力。從總額到淨額方面，有幾件事。

One is that we had an increase associated with the Part D rebate that we're paying. Anybody that's got a Part D drug at this point is paying rebates on the IRA Medicare redesign. We do have a small portion of our TTR sales that go through the Part D channel, and that's the home care part of the business.

一是，我們支付的 D 部分退款金額增加。此時，任何擁有 D 部分藥物的人都會支付 IRA Medicare 重新設計的回扣。我們的一小部分 TTR 銷售是透過 Part D 管道進行的，這是業務的家庭護理部分。

Historically, that's been about 20% in polyneuropathy, so there is an increased rebate that we're paying there, which was in line with our expectations. We also saw a modestly higher 340B utilization in the quarter. So on price, net price Q2 to Q1 was down slightly, which is consistent with what I said on the earlier question, that we do expect net price '25 versus '24 for AMVUTTRA to be down mid-single digits.

從歷史上看，多發性神經病變的發生率約為 20%，因此我們支付的回扣增加，這符合我們的預期。我們也看到本季 340B 的利用率略有上升。因此，就價格而言，第二季的淨價格相對於第一季略有下降，這與我在先前的問題中所說的一致，我們確實預計 AMVUTTRA 2025 年的淨價格相對於 2024 年將下降中等個位數。

Thanks, Jeff. I think a very important question, and I think you've clarified that for our investors, so thank you. Next question, please.

謝謝，傑夫。我認為這是一個非常重要的問題，我想你已經為我們的投資者澄清了這一點，所以謝謝你。請回答下一個問題。

Jessica Fye, JPMorgan.

潔西卡費伊（Jessica Fye），摩根大通。

Can you speak a little more in a little more detail to the assumptions underpinning the updated TTR franchise guidance as it relates to the pace of new starts? And I guess just in general, can you just provide a little assurance or reaffirm that the new guidance is not somehow aggressive?

您能否更詳細地談談更新後的 TTR 特許經營指導中與新開業速度相關的假設？我想，總的來說，您能否提供一點保證或重申，新的指導方針並不具有侵略性？

Thank you. Okay, so two parts to that question. Maybe, Tolga, if you start with the first part, and then, Jeff, you can follow on from that.

謝謝。好的，這個問題分成兩個部分。也許，托爾加，你可以從第一部分開始，然後，傑夫，你可以接著講下去。

Yeah, absolutely. Hi, Jessica. I mean, look, at the end of the day, what we've already laid out is we're expecting a steady growth in both first line as well as the second line patient flow.

是的，絕對是如此。你好，潔西卡。我的意思是，看看，到最後，我們已經制定的計劃是，我們預計一線和二線患者流量都會穩定增長。

As Yvonne indicated, let me also provide a little additional color. It is expected that we initially saw uptake concentrated in patients who had progressed on stabilizers. And these are often sicker patients, physicians, and actually look for an alternative therapy with a mechanism of action that's unique, that's accessible, easy to administer, and so forth.

正如伊馮娜 (Yvonne) 指出的，讓我也提供一些額外的資訊。預計我們最初看到的吸收集中在使用穩定劑後病情有所進展的患者中。這些通常是病情較重的患者和醫生，他們實際上在尋找一種具有獨特作用機制、易於獲取、易於管理等的替代療法。

But what's been really particularly encouraging, and this is why the guidance we're providing is over $0.5 billion uptake from where we were, is about a month into the quarter, we began seeing a very healthy and accelerating trend in first line use, just as we had positioned from the outset.

但真正令人特別鼓舞的是，這就是我們提供的指導是從原來的水平增加超過 5 億美元的因素，大約在本季度​​開始的一個月後，我們開始看到一線使用呈現非常健康且加速的趨勢，就像我們從一開始就定位的那樣。

And frankly, that makes a lot of sense. This is a progressive and fatal disease. Physicians want to hit the disease early and hit it hard and not hold back their best therapy for later, as they might in less serious conditions.

坦白說，這很有道理。這是一種進行性且致命的疾病。醫生希望儘早發現疾病並採取有力措施，而不是像在病情不太嚴重時那樣，將最佳治療方法留到以後。

So today, and this is where the guidance is really anchored in, we see both first line and second line segments are growing. They're growing rapidly. Uptake is broad across first and second line and academic and community. And more importantly, we're seeing a good expansion of our prescriber base. We've just expanded by threefold, and that continues to move in the right direction.

因此，今天，這也是指導真正紮根的地方，我們看到一線和二線部分都在成長。它們正在快速成長。一線、二線、學術界和社區都廣泛採用。更重要的是，我們的處方醫生群體正在大幅擴大。我們的規模剛剛擴大了三倍，並且繼續朝著正確的方向發展。

So as we move forward, our focus is clear, to continue reinforcing AMVUTTRA is the first line treatment of choice, supported not only by our approved label, but also by growing evidence, as Pushkar highlighted, with new imaging data, emerging cardiac biomarker trends that suggest AMVUTTRA may even help reverse disease progress.

因此，隨著我們不斷前進，我們的重點很明確，即繼續強化 AMVUTTRA 作為首選一線治療藥物的地位，這不僅得到了我們批准的標籤的支持，而且得到了越來越多的證據的支持，正如 Pushkar 所強調的那樣，新的成像數據和新出現的心臟生物標誌物趨勢表明 AMVUTTRA 甚至可能有助於逆轉疾病進展。

So nonetheless, we're just one quarter in and already seeing that behavior that validates our clinical profile as well as our commercial ambitions. And I think the current guidance really reflects that.

儘管如此，我們才剛進入一個季度就已經看到了這種行為，這驗證了我們的臨床概況以及商業抱負。我認為當前的指導確實反映了這一點。

Yeah, look, I think I just want to emphasize that it's early days yet. We've only just achieved our first full quarter here. And when we came up with the guidance, we've given guidance that we expect to achieve. We're going to be focusing our team on continued execution. And as we progress, we will continue to update and share our perspectives.

是的，看，我想我只是想強調現在還太早。我們剛剛完成了第一個完整季度。當我們提出指導意見時，我們給出了我們期望實現的指導。我們將集中團隊的精力持續執行。隨著我們的進步，我們將繼續更新和分享我們的觀點。

Yeah, maybe just a little bit more context on the guidance. Again, if you look at what I highlighted in terms of the midpoint of the guidance and what it implies in terms of year over year growth for TTR, about $1 billion is what I highlighted.

是的，也許只是對指導提供更多的背景資訊。再說一次，如果你看一下我在指導中點方面所強調的內容以及它對 TTR 同比增長的影響，我所強調的是約 10 億美元。

Last year, the PN franchise grew $300 million versus '23 and was growing at about 30%. So if you just sort of assume that that's the growth that we're going to get from PN this year, that would imply $600 million-plus from cardiomyopathy.

去年，PN 特許經營權比 23 年增加了 3 億美元，成長率約為 30%。因此，如果您只是假設這是我們今年從 PN 獲得的成長，那就意味著來自心肌病變的收入將超過 6 億美元。

We just did $150 million in the second quarter, and we feel really good about growth sustaining through the second half of the year. So I do think we have a high level of confidence in the guidance that we provided, Jess.

我們第二季的銷售額剛好達到 1.5 億美元，我們對下半年的成長動能感到非常樂觀。因此我確實認為我們對我們提供的指導有很高的信心，傑西。

Thanks, Jeff. Next question.

謝謝，傑夫。下一個問題。

Paul Matteis, Stifel.

保羅·馬泰斯（Paul Matteis），Stifel。

Hey, great. One for Tolga and the team. As it relates to stabilizer progressors, can you talk a little bit more about the criteria physicians are using?

嘿，太棒了。一個獻給托爾加和他的團隊。由於它與穩定器推進器有關，您能否再多談談醫生使用的標準？

And I guess now that you've been in the market, do you have a sense of what percent of patients who are on a stabilizer currently would be dictated to be a progressor and a good candidate for AMVUTTRA based on the clinical criteria that are being implemented? Thanks so much.

我想，既然您已經進入了市場，您是否知道，根據正在實施的臨床標準，目前使用穩定劑的患者中有多少比例會被判定為進展者並成為 AMVUTTRA 的良好候選人？非常感謝。

Yeah, so we'll start with Tolga, and then I'd like Pushkar to provide a clinical perspective.

是的，我們將從托爾加 (Tolga) 開始，然後我希望普什卡 (Pushkar) 提供臨床觀點。

Yeah. So Paul, I mean, look, based on our research and obviously published data, clinical evidence suggests that anywhere between a third to a half of the patients on stabilizer at one point progress. And what we see that number is continuing to grow. And then obviously the only real option in terms of mechanistically and the clinical evidence suggests that it would be a AMVUTTRA at this point.

是的。保羅，我的意思是，根據我們的研究和已發表的數據，臨床證據表明，使用穩定器的患者中，有三分之一到一半的患者病情有所改善。我們看到這個數字還在持續成長。顯然，從機械和臨床證據的角度來看，目前唯一真正的選擇是 AMVUTTRA。

But let me turn it over to Pushkar. Pushkar can also provide some more clinical perspective about what we're seeing and how those guidelines are actually progressing.

但讓我把它交給普什卡。普什卡還可以提供一些更臨床的觀點，說明我們所看到的情況以及這些指南的實際進展。

Yeah. Thanks, Tolga. Thanks, Paul. Look, I think it's really important. This is a we talk about ATTR cardiomyopathy and the thing here is that it has a clear cause, which is accumulation of TTR protein in the misfolded protein in the myocardium.

是的。謝謝，托爾加。謝謝，保羅。聽著，我認為這真的很重要。這就是我們所說的 ATTR 心肌病變，它有一個明確的病因，即心肌中錯誤折疊的蛋白質中 TTR 蛋白的累積。

But as it clinically presents, it's a form of heart failure. So doctors have been treating heart failure for decades and they know how to modify drug therapy for patients. They might add diuretics or SGLT2s or other agents as patients are progressing. And so I think they're well accustomed to actually looking at a variety of factors. And frankly, you have to rely on a variety of factors.

但從臨床表現來看，這是一種心臟衰竭。因此，醫生幾十年來一直在治療心臟衰竭，他們知道如何調整患者的藥物治療。隨著患者病情的進展，他們可能會添加利尿劑、SGLT2 或其他藥物。所以我認為他們已經習慣考慮各種因素。坦白說，你必須依賴多種因素。

There's not any one specific indicator. An easy way to think about that is when you look at the European guidelines that were put out a couple of years ago and they had a variety of considerations, including biomarkers echocardiographic factors, exercise tolerance, patient's ability to lie flat at night, different things, pedial edema.

沒有任何一個具體的指標。一個簡單的思考方式是，當你查看幾年前發布的歐洲指南時，他們有各種各樣的考慮因素，包括生物標誌物超音波心動圖因素、運動耐受性、患者晚上平躺的能力、不同的事情、足部水腫。

And so I think what we're seeing now in these early days is that doctors are applying that general clinical rubric of looking at a patient, how they present their symptoms, their signs and other factors in terms of determining how patients will progress.

所以我認為我們現在看到的早期情況是，醫生正在應用一般的臨床標準來觀察病人，了解他們如何表現出症狀、體徵和其他因素來確定病人的病情將如何發展。

We do think that over time, more and more guidelines in this category will develop over time. But our expectation is that there will not be some one single factor that clinicians or payers will be able to rely upon to say specifically that a patient's progressing, but we'll rather have to look at the constellation of factors that affect the patient's symptomatology. Thanks, Fusco.

我們確實認為，隨著時間的推移，這一類別的指導方針將會越來越多地發展。但我們的期望是，臨床醫生或付款人將無法依賴某個單一因素來具體判斷患者的病情進展，而是我們必須研究影響患者症狀的一系列因素。謝謝，Fusco。

Thank you. We'll take the next question. Take the next question.

謝謝。我們將回答下一個問題。請回答下一個問題。

Luca Issi, RBC Capital.

伊西（Luca Issi），加拿大皇家銀行資本管理公司（RBC Capital）。

Great. Congrats on the strong quarter. Maybe if I can circle back on the TTR guide, maybe Jeff, like if I assume $200 million in revenue for the year from [Patro], that essentially means $550 million to $650 million in revenues for the next two quarters from AMVUTTRA, which is actually not dissimilar from the $492 million that you already printed today. I guess what I'm trying to say feels to me that this guide has still a good degree of conservatism in it, especially given that you're going to start selling this drug in international markets like Brazil, Europe, UK, Japan, et cetera. But we'd love if you have a different view here. So any thoughts there, much appreciated.

偉大的。恭喜本季業績強勁。也許如果我可以回到 TTR 指南，也許 Jeff，如果我假設 [Patro] 今年的收入為 2 億美元，那基本上意味著 AMVUTTRA 未來兩個季度的收入為 5.5 億至 6.5 億美元，這實際上與您今天已經公佈的 4.92 億美元並沒有什麼不同。我想說的是，這份指南仍然帶有相當程度的保守性，特別是考慮到你將開始在巴西、歐洲、英國、日本等國際市場上銷售這種藥物。但如果您有不同的看法，我們會很高興。因此，如有任何想法，我將不勝感激。

Thanks so much. Yeah, Luca, I appreciate the question. I'll again reiterate what I said to the earlier question here. We're guiding to $1 billion of TTR growth year over year. Last year, PN grew $300 million and it's growing at about 30%. So that gets you to $600 million-plus for cardiomyopathy. We just did $150 million in Q2. I think we feel very confident about that.

非常感謝。是的，盧卡，我很感謝你的提問。我將再次重申我對先前問題的回答。我們預計 TTR 的年增長率將達到 10 億美元。去年，PN 成長了 3 億美元，成長率約 30%。因此，治療心肌病變的費用將超過 6 億美元。我們第二季的銷售額剛好達到 1.5 億美元。我想我們對此非常有信心。

If you look at historically, the guidance that we've given and the consistency with which we either met that or exceeded that, that's how we feel about the guidance that we're providing. I don't know if it's conservative at this point. Honestly, we're one quarter into this and certainly we look forward to coming back at Q3 and reassessing things.

如果回顧歷史，我們給予的指導以及我們達到或超過該指導的一致性，這就是我們對所提供的指導的感受。我不知道現在這是否保守。老實說，我們已經進行了四分之一，當然我們期待在第三季回來並重新評估情況。

Thank you. Next question.

謝謝。下一個問題。

Ellie Merle, UBS.

瑞銀的艾莉·梅爾（Ellie Merle）。

Hey guys. Congratulations on the quarter and thanks so much for taking the question. Just to drill into this a little bit more, how should we think about the rate of new patient starts per quarter from here? 1,400 is obviously a phenomenal number. Should we think of this cadence of new starts continuing in 3Q and beyond? A

嘿，大家好。恭喜本季取得的成績，非常感謝您提出這個問題。為了更深入地探討這個問題，我們應該如何考慮從現在開始每季新患者的數量？1,400顯然是一個驚人的數字。我們是否應該認為這種新開工節奏將在第三季及以後持續下去？一個

nd second, in terms of the mix, you mentioned now seeing more balanced starts mix between the new patient, newly diagnosed and the progressors, whereas initially it was more of the progressors. How do you expect this mix to evolve over time from here?

第二，就組合而言，您提到現在看到新患者、新診斷患者和病情進展者之間的組合更加平衡，而最初更多的是病情進展者。您預計這種組合今後會如何演變？

Okay. So I think two questions, you can probably take both of them, Tolga.

好的。所以我認為有兩個問題，你或許可以回答，托爾加。

Yeah. So thank you. Look, at the end of the day, we're very pleased obviously with 1,400 paid patients within a three-month period. And as you had highlighted, while the patient starts initially was more predominantly stabilizer progressors, very quickly that switched into a balanced and broad patient uptake. We certainly expect to see both of those categories continue to grow.

是的。所以謝謝你。看，最終，我們對三個月內 1,400 名付費患者感到非常高興。正如您所強調的，雖然患者最初主要是穩定劑進展者，但很快就轉變為平衡且廣泛的患者吸收。我們當然希望看到這兩個類別繼續成長。

Now, in terms of the specific numbers, we kind of went out of our way to be able to provide that clarity. As you know, [Albuterol] has a single SKU, so we can't really isolate CM patients with precision. So we're going to continue to provide additional color, and those numbers obviously we expect to go up.

現在，就具體數字而言，我們盡力提供清晰的說明。如您所知，[Albuterol] 只有一個 SKU，因此我們無法精確地隔離 CM 患者。因此我們將繼續提供更多色彩，而且我們顯然預計這些數字將會上升。

But in terms of the specific precision about how it's going to go quarter after quarter, is not going to be, we're not going to be able to report that.

但就每季的具體進展而言，我們無法報告。

Thank you. Next question.

謝謝。下一個問題。

Kostas Biliouris, BMO Capital Market.

Kostas Biliouris，BMO 資本市場。

Congrats on the impressive launch. One question on payers from us, although you already touched a little bit on that, we have seen some commercial payers requiring stabilizer use prior to AMVUTTRA treatment in cardiomyopathy. Can you comment on how common those requirements are across the different plans and what percentage of patients do these plans cover?

祝賀這次令人印象深刻的發布。我們有一個關於付款人的問題，雖然您已經稍微提到了這一點，但我們已經看到一些商業付款人要求在心肌病變的 AMVUTTRA 治療之前使用穩定劑。您能否評論一下這些要求在不同計劃中有多普遍以及這些計劃覆蓋了多少比例的患者？

Yeah, I know that's a great question. I'll just start off by saying that as we look at this, access is just not a barrier. We're seeing broad coverage across Medicare fee for service, Medicare Advantage, commercial payers, and the vast majority of patients are getting first line with no step. This is exactly what we predicted coming into the launch and what we've been working on for quite some time. I think it really speaks to the AMVUTTRA profile as well as the nature of the disease.

是的，我知道這是一個很好的問題。首先我想說的是，當我們看待這個問題時，訪問並不是一個障礙。我們看到醫療保險按服務收費、醫療保險優勢計劃、商業付款人都得到了廣泛的覆蓋，絕大多數患者都無需邁出第一步就能獲得一線治療。這正是我們在發佈時所預測的，也是我們長期以來一直在努力的。我認為這確實說明了 AMVUTTRA 的概況以及疾病的性質。

But, Tolga, you might want to add another perspective.

但是，托爾加，你可能想增加另一種觀點。

You got it, Yvonne. I think the broad headline is really, as predicted, we're not facing a significant headwind in terms of payer coverage.

你明白了，伊馮娜。我認為總體而言，正如預測的那樣，我們在付款人覆蓋方面並沒有面臨重大阻力。

What I'm really pleased to see was within a short three-month period, majority of both. Medicare Advantage as well as commercial payers have published policies. And in those policies, AMVUTTRA in broad strokes are covered first line.

我真正高興地看到的是，在短短三個月內，兩者大部分都實現了。醫療保險優勢計劃以及商業付款人均已公佈了相關政策。在這些政策中，AMVUTTRA 大致上處於第一線覆蓋範圍。

Now, we also had actually flagged that there could be some commercial payers that could actually provide a step edit in their policies. We're seeing that, but it is incredibly minimal. It's in the single digits and frankly, we don't anticipate that to continue to grow as most other large commercial payers have already written policies that cover AMVUTTRA as first line.

現在，我們實際上也已經標記出可能有一些商業付款人實際上可以在他們的政策中提供逐步編輯。我們看到這種情況了，但這種情況極為少見。這個數字是個位數，坦白說，我們預計它不會繼續成長，因為大多數其他大型商業付款人已經制定了將 AMVUTTRA 作為第一線保險的政策。

Now, when it comes to step edits, we have the tools and the support systems that enables us to actually frankly to help patients and providers to circumvent that or make sure that it's managed very, very carefully.

現在，當涉及步驟編輯時，我們擁有工具和支援系統，使我們能夠坦率地幫助患者和提供者規避這種情況，或確保非常非常謹慎地進行管理。

We've actually built over the years a quiet engine driving real impact in terms of our patient services. And I'm really pleased to see how we've been able to pull through on all three segments. Patients are already getting on treatment, whether it's fee-for-service, whether it's Medicare Advantage, also on commercial payers, including those plans that have actually step edits.

多年來，我們實際上已經打造出一個安靜的引擎，為患者服務帶來真正的影響。我很高興看到我們能夠在所有三個方面取得成功。患者已經開始接受治療，無論是按服務收費，還是醫療保險優勢計劃，甚至是商業付款人，包括那些實際上有逐步編輯的計劃。

We don't see that for now and obviously we're going to close the monitor and continue to engage with payers to make sure that these patients that deal with the severe condition are getting a seamless access with our medicines.

目前我們還沒有看到這種情況，顯然我們將關閉監控並繼續與付款人合作，以確保這些患有嚴重疾病的患者能夠無縫地獲得我們的藥物。

Yeah, that looks great, Tolga. And one data point that really struck me was actually just the minimal use we're seeing of our quick start program. We've introduced the quick start program with all of our launches to make sure that we can help patients with access. And we're just not seeing much use, which I think, again, is very encouraging. Next question, please.

是的，看起來很棒，托爾加。真正讓我印象深刻的一個數據點是，我們看到的快速啟動程序的使用率實際上非常低。我們在所有發布中都引入了快速啟動程序，以確保我們能夠幫助患者獲得服務。但我們並沒有看到太多的用途，我認為這再次令人鼓舞。請回答下一個問題。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

I also wanted to congrats on the outstanding quarter. So maybe, Yvonne, I think you mentioned that the vast majority would be the first line patient. Is it fair to say that out of 1,400 patients treated so far, would be over 50% of patients as a first line patient? And then out of this 1,400 patients, how many of them receive free drug?

我也想對本季的出色表現表示祝賀。所以也許，伊馮娜，我想你提到絕大多數都是第一線患者。是否可以這樣說，在迄今為止接受治療的 1,400 名患者中，超過 50% 的患者是第一線患者？那麼在這1400名患者中，有多少人獲得了免費藥物？

Tolga, you love breaking this down.

托爾加，你喜歡分解這個。

Yeah. Look, Gena, good to hear from you. I think what we had said very thoughtfully, I would say, is our uptake has been broad and balanced. So that included, again, early on, some patients that were actually progressing on stabilizers.

是的。瞧，吉娜，很高興收到你的來信。我想，我們已經非常深思熟慮地說過，我們的吸收是廣泛而均衡的。因此，這包括早期一些正在使用穩定劑的患者。

And then what we're seeing is a very, very strong trend of first line indication. We're in the early innings. And I think the job is to, and we're getting, I would say, our fair share of first line patients. But the job is not done yet. What we want to make sure is that we continue to this trend and make sure that we continue to educate both patients as well as prescribers why AMVUTTRA has a compelling product profile to be a first line patient. So I just wanted to reiterate that. Yeah. It's really important that we clarify exactly where we are.

然後我們看到的是第一線跡象的非常非常強勁的趨勢。我們正處於初期階段。我認為我們的工作是，而且我想說，我們正在獲得公平份額的第一線患者。但工作尚未完成。我們希望確保的是，我們能夠繼續保持這種趨勢，並確保我們繼續教育患者和處方醫生，為什麼 AMVUTTRA 具有引人注目的產品特性，可以成為第一線患者。所以我只是想重申這一點。是的。要明確我們目前所處的位置確實非常重要。

Jeff, do you think? She also had a question about the 1,400 patients and how many of them were in the quick start program. It was the minimum, right?

傑夫，你覺得呢？她還對 1,400 名患者以及其中有多少人參加了快速啟動計劃提出了疑問。這是最低限度，對嗎？

It was very, very low. It was very, very low. It will be very minimal.

它非常非常低。它非常非常低。它將非常小。

It will be absolutely very minimal. Next question.

這絕對是極其微小的。下一個問題。

Mike Ulz, Morgan Stanley.

摩根士丹利的麥克烏爾茲。

Congrats on the strong launch as well. Maybe just to follow up on TTR cardiomyopathy, you highlighted you're getting some nice broad use in the front line as well as the stabilizer progressor patients. Just curious if you started to see any combination use early in the launch. I know you're not expecting it, but we've picked up some combination use in some of our KOL goals. Just curious if you've seen it yet.

也祝賀該產品的順利發布。也許只是為了跟進 TTR 心肌病變，您強調了您在前線以及穩定器進展患者中獲得了廣泛的應用。只是好奇您是否在發布初期就開始看到任何組合使用。我知道您沒有想到，但是我們在一些 KOL 目標中選擇了一些組合使用方法。只是好奇你是否已經看過它。

Yeah, no, thank you. Thank you for that question. Tolga, why don't you take that?

是的，不，謝謝。謝謝你的提問。托爾加，你為什麼不接受這個？

Yeah, look. We certainly do see a very small portion of those patients getting a combination use. We would certainly expect that as the families go generics over the years to become more prominent. But right now, it's really difficult to be very specific about looking at the specific combination use. But I think in where it's allowed and where access is permissible, we do some utilization of combo.

是的，看。我們確實看到只有極少數患者採用了合併用藥。我們當然希望，隨著這些家族多年來的演變，仿製藥將變得更加突出。但目前，確實很難具體地看待具體的組合用途。但我認為，在允許的地方和允許訪問的地方，我們會使用一些組合。

Thank you. I think we've got time for one last question.

謝謝。我想我們還有時間回答最後一個問題。

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

Hi, guys. Thanks for squeezing me in and congratulations on the quarter. A quick question on variants. You guys might have addressed the mixed phenotype, but in your first line and first line accent, what X test, what trends are you seeing in the V122I variant population?

嗨，大家好。感謝您抽空給我，並祝賀本季取得佳績。關於變體的一個快速問題。你們可能已經解決了混合表型問題，但是在你們的第一行和第一行口音中，什麼 X 測試，你們在 V122I 變體群體中看到了什麼趨勢？

As KOL feedback, at least on my model, has suggested I'm underestimating that prevalence by about 6x. But it is a more severe phenotypic presentation.

正如 KOL 的回饋，至少在我的模型上，顯示我低估了這種流行程度約 6 倍。但這是一種更嚴重的表型表現。

Just a very quick follow-up. This is probably semantics. You guys, you mentioned step through and step edits. Are they the same thing as prior authorizations or do you have a different set of prior authorizations?

只是一個非常快速的跟進。這可能是語義。你們提到了逐步和逐步編輯。它們與事先授權是同一件事嗎？或是你們有不同的事先授權嗎？

Thanks. Let me take your last part first. The step edit policy that we've seen, again, it's incredibly small. It's in the single digit and it's mostly predominantly in the commercial setting. There are no real specific limitations other than patients putting on a stabilizer first and frankly, there's not even a time limit or duration and it's really up to the physician if the patient is progressing.

謝謝。讓我先講一下你的最後一部分。我們看到的分步編輯策略非常小。它的數量只有個位數，而且主要集中在商業環境。除了患者首先戴上穩定器之外，沒有其他真正的具體限制，坦白說，甚至沒有時間限製或持續時間，是否進展完全取決於醫生。

We find these policies relatively easy to manage for the patients. There are no specific hereditary or V122I indication. And frankly, we're not surprised about that. We have, I think, what we've demonstrated early on with the pulmonary hereditary condition and then later with the broad cardiomyopathy label is thatii is well positioned to be a first-line patient for all diagnosed ATTR-CM patients. And we're really not seeing that trend.

我們發現這些政策對病人來說相對容易管理。沒有特定的遺傳或 V122I 跡象。坦白說，我們對此並不感到驚訝。我認為，我們早期透過肺部遺傳性疾病以及後來的廣泛性心肌病變標籤證明了這一點，即該疾病非常適合成為所有確診的 ATTR-CM 患者的第一線患者。但我們確實沒有看到這種趨勢。

Maybe I'll turn it over to Pushkal if he has any specific commentary on the trial.

如果普什卡爾對審判有任何具體評論，我可能會把它交給他。

I think you said it well. Look, I think what we've seen in HELIOS-B is that AMVUTTRA works equally well in wild-type patients and in V122I patients. And as Tolga mentioned, this is the one class of drugs that's shown actually a benefit in.

我覺得你說得很好。看起來，我認為我們在 HELIOS-B 中看到的是 AMVUTTRA 對野生型患者和 V122I 患者同樣有效。正如托爾加所提到的，這是一類被證明確實有益的藥物。

hereditary patients, which constitutes the wide range of mutations and we've seen benefits across that. Across, I think, all ranges of severity, whether it's NYHA class one, two, three, whether it's hereditary or wild-type, I think that's, I think, what really cements our belief that this is really and what we're hearing from prescribers in terms of the opportunity to treat patients with this drug as a first-line agent for two.

遺傳性患者，其突變範圍很廣，我們已經看到了益處。我認為，無論病情嚴重程度如何，無論是 NYHA 一級、二級還是三級，無論是遺傳性還是野生型，我認為這才是真正鞏固我們信念的關鍵，也是我們從處方醫生那裡聽到的，有機會用這種藥物作為一線藥物治療兩種患者。

I think this brings our call to a close. I'd just like to thank everybody for joining us today on this call. Look, our line must continue to execute strongly across all areas of the business and we're very much looking forward to providing you further updates as we progress throughout the year. Thanks a lot. Good bye.

我想我們的通話到此結束。我只想感謝大家今天參加這場電話會議。你看，我們的產品線必須繼續在所有業務領域強勁表現，我們非常期待在全年進展過程中為您提供進一步的更新。多謝。再見。

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect. Thank you.

女士們、先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。謝謝。