Alnylam Pharmaceuticals, Inc. (ALNY) 2026 Q2 法說會逐字稿

Thank you for standing by. My name is Frilla, and I will be your conference operator today. At this time, I would like to welcome everyone to the Alnylam Pharmaceuticals Q2 earnings conference call. (Operator Instructions)

感謝各位稍候。我叫 Frilla，今天將擔任各位的電話會議接線員。此刻，我謹代表公司歡迎各位參加 Alnylam Pharmaceuticals 2026 年第二季財報電話會議。（接線員指示）

Thank you. I would now like to turn the conference over to the company. You may begin.

謝謝。我現在將會議交給公司方。您可以開始。

Good morning. I'm Josh Brodsky, Vice President of Investor Relations at Alnylam. With me today are Yvonne Greenstreet, Chief Executive Officer; Jeff Poulton, Chief Financial Officer; Tolga Tanguler, Chief Commercial Officer; and Pushkal Garg, Chief Research and Development Officer.

各位早安。我是 Josh Brodsky，Alnylam 投資人關係副總裁。今天與我一同出席的有執行長 Yvonne Greenstreet；財務長 Jeff Poulton；商務長 Tolga Tanguler；以及研發長 Pushkal Garg。

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，隨附簡報可至我們網站投資人頁面的活動（events）區瀏覽：investors.alnylam.com/events。

During today's call, as outlined on slide 2, Yvonne will offer introductory remarks and provide some general context. Jeff will review our financials and guidance. Tolga will provide an update on our global commercial progress, and Pushkal will discuss our TTR franchise, our confidence in Triton CM, and upcoming pipeline milestones, before we open the call for your questions.

在今天的電話會議中，如投影片第 2 頁所示，Yvonne 將先致開場致詞並提供整體背景。Jeff 將回顧我們的財務表現與財測指引。Tolga 將更新我們全球商業化進展，Pushkal 將討論我們的 TTR 產品組合、我們對 Triton CM 的信心，以及即將到來的研發管線里程碑，之後我們將開放提問。

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. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important risks and uncertainties, including those discussed under the heading Risk Factors in our most recent periodic report available on our website and on file with the SEC. We disclaim any obligations to update such statements.

提醒各位，本次電話會議將包含關於 Alnylam 未來預期、計畫與前景的評論，這些內容構成安全港條款所定義的前瞻性陳述。由於各項重要風險與不確定性，實際結果可能與這些前瞻性陳述所示有重大差異，包括我們最近一期定期報告中「風險因素」章節所討論者；該報告可於我們網站及向美國證券交易委員會（SEC）申報之文件中取得。我們不承擔更新此等陳述的任何義務。

And with that, I'll now turn the call over to Yvonne. Yvonne?

接下來，我把電話交給 Yvonne。Yvonne？

Thanks, Josh, and thank you everyone for joining the call today.

謝謝 Josh，也謝謝各位今天加入電話會議。

During the second quarter, we demonstrated strong performance across all aspects of the business. Notably, it marked the first time Amvutra revenues exceeded $1 billion in a single quarter, representing an annual run rate of more than $4 billion just 15 months into the ATTR Cardiomyopathy Lodge, a testament to both the commercial opportunity and our NIHM execution.

在第二季，我們在業務各方面都展現了強勁表現。值得注意的是，這是 Amvutra 單季營收首次突破 10 億美元，換算年化營收動能超過 40 億美元；而這距離 ATTR 心肌病（Cardiomyopathy）適應症上市僅 15 個月，充分證明了商業機會以及我們 NIHM 的執行力。

As we reflect on the launch, several insights reinforce our confidence in the durability of Ambutra growth over the years ahead.

回顧此次上市，我們得到的幾項洞見進一步強化了我們對 Ambutra 未來多年成長韌性的信心。

First, this has been an impressive launch by industry benchmarks when looking across market share, access, and revenue generation.

第一，若以市占率、給付可近性與營收創造等指標來看，這次上市以產業基準衡量都相當亮眼。

Second, the fundamentals of our TTR business are strong, and they include Ambutra's compelling clinical profile and label.

第二，我們 TTR 業務的基本面強勁，其中包括 Ambutra 具吸引力的臨床特性與核准標籤（label）。

Strong access that we established at launch, which continues to improve, and our robust and expanding provider network.

我們在上市時建立的強勁可近性持續改善，以及我們強健且持續擴大的醫療提供者網絡。

Third, patient demand for Ambutra continues to grow robustly, particularly in the first-line setting, which has been our focus as we aspire to market leadership, given Ambutra's clinical differentiation and desirability as a foundational therapy for newly diagnosed patients.

第三，患者對 Ambutra 的需求持續強勁成長，尤其是在第一線治療情境，這一直是我們的重點；鑑於 Ambutra 的臨床差異化與作為新診斷患者基礎治療（foundational therapy）的吸引力，我們以成為市場領導者為目標。

Toko will discuss how we are now further investing in broadening our Ambutra prescriber base and supporting overall category growth, the latter of which has been accelerating.

Tolga 將說明我們目前如何進一步加大投資，以擴大 Ambutra 的開立醫師基礎並支持整體品類成長，而後者的成長正在加速。

Finally, our geographic expansion strategy continues to gain momentum. And today, we are pleased to announce our collaboration with B1, through which they will have exclusive commercialization and distribution rights for Ambutra in mainline China and Macau, subject to Ambutra receiving marketing authorization.

最後，我們的地理擴張策略持續累積動能。今天我們也很高興宣布與 B1 的合作；在 Ambutra 取得上市許可的前提下，B1 將擁有 Ambutra 在中國大陸與澳門的獨家商業化與經銷權。

Together with B1, we aim to help advance awareness and support diagnosis of ATTR amyloidosis, and if approved. Bring the strength of TTR silencing with AMVUTRA to patients in these underserved regions.

我們將與 B1 攜手提升對 ATTR 類澱粉沉積症的認知並支持診斷；若獲核准，把 AMVUTRA 的 TTR 沉默（silencing）優勢帶給這些醫療資源相對不足地區的患者。

As Jeff will describe shortly, we are lowering our 2026 revenue guidance today to reflect a better understanding with hindsight of the first few quarters of our US launch.

如 Jeff 稍後將說明，我們今天下調 2026 年營收指引，以反映我們在回頭檢視美國上市最初幾季後所獲得的更佳理解。

Specifically, that early second-line demand growth in 2025 benefited significantly from pent-up demand for a new therapy that has since normalized.

具體而言，2025 年早期第二線需求成長在很大程度上受益於市場對新療法的累積（遞延）需求，而該需求目前已趨於正常化。

With that learning and our strong 2026 second-quarter performance, our confidence in Amvutra's growth trajectory has never been stronger.

基於這些學習以及我們 2026 年第二季的強勁表現，我們對 Amvutra 的成長軌跡信心前所未有地強。

First-line new patient starts are now responsible for about 80% of category growth in this accelerating market, and we believe we're making great progress in establishing Ambutra as a foundational therapy.

在這個加速成長的市場中，第一線新患者起始用藥目前約占品類成長的 80%；我們相信我們在將 Ambutra 建立為基礎治療方面正取得重大進展。

I will now turn to recent developments in the competitive landscape, specifically the negative outcome of the cardio-transform study of Eplon-Tersa.

接下來我將談談競爭態勢的最新發展，特別是 Eplon-Tersa 的 cardio-transform 研究出現負面結果。

We recognize investor interest in understanding any potential implications of that study's failure for our probability of success in Triton-CM, our Phase III cardiovascular outcomes trial of mucrisiram.

我們理解投資人關切該研究失敗是否會對我們在 Triton-CM（我們針對 mucrisiram 的第三期心血管臨床結局試驗）的成功機率造成任何潛在影響。

Let me be clear: this outcome does not alter our conviction in the Triton-CM study. And as Pushkal was shared in greater detail, our strong confidence is grounded in the established clinical evidence for RNAI therapeutics in TTR and the track record of our clinical organization.

我想說清楚：這一結果不會改變我們對 Triton-CM 研究的信念。而且如 Pushkal 將更詳細分享，我們的高度信心建立在 RNAi 治療在 TTR 領域既有的臨床證據，以及我們臨床團隊的執行紀錄之上。

At the same time, we have a variety of options at our disposal to potentially adapt the study and position it for optimal success. We will carefully review the full EPLON-certain dataset when it becomes available and adapt our study plan if appropriate.

同時，我們也有多種選項可用，以便在必要時調整研究設計並使其更有利於達成最佳成功機率。待 EPLON-certain 的完整資料集可取得後，我們將審慎檢視，並在適當時調整我們的研究計畫。

We have successfully navigated complex TTR development before and believe we are exceptionally well-positioned to do so again with MFESRAM.

我們過去已成功因應複雜的 TTR 研發挑戰，並相信我們同樣具備極佳條件，再次以 MFESRAM 做到這一點。

Additionally, in the quarter, we were pleased to announce a series of strategic AI collaborations across the enterprise, including with Inceptiv, to expand the next frontier in the discovery of RNAi therapeutics.

此外，本季我們也很高興宣布一系列橫跨全公司的策略性 AI 合作（包括與 Inceptiv 合作），以拓展 RNAi 治療藥物發現的下一個前沿。

And A collaboration we're pleased to announce today was a large healthcare system in California aimed at supporting early identification of ATTR cardiomyopathy in routine care.

而我們今天也很高興宣布另一項合作：與加州一家大型醫療體系合作，目標是在常規照護中支持 ATTR 心肌病的早期辨識。

This builds on our previously announced partnerships with VisAI and Komodo Health.

這是在我們先前已宣布與 VisAI 與 Komodo Health 合作的基礎上進一步延伸。

Altogether. This cohesive AI strategy from discovery and evidence generation to disease identification, clinical practice, and commercial execution reflects our long-term conviction that AI will fundamentally reshape how medicines are discovered, developed, and ultimately delivered to patients.

總而言之。這套從藥物發現與證據生成，到疾病辨識、臨床實務與商業執行的整合式 AI 策略，反映了我們長期的堅定信念：AI 將從根本上重塑藥物如何被發現、開發，並最終交付給患者。

Finally, we also continue to progress our deep pipeline of investigational medicines, initiating a Phase II trial of ALN-6400 in von Wiedebrand's disease. And a Phase II trial of myvalturan in Down syndrome-associated Alzheimer's disease. And we look forward to a series of clinical data readouts in the back half of this year, including presentation of initial Phase I results of ALN-HTTO2 in patients with Huntington's disease at EHDN in October.

最後，我們也持續推進深厚的研發管線，已在 von Wiedebrand 氏病啟動 ALN-6400 的第二期試驗。並在唐氏症相關阿茲海默症啟動 myvalturan 的第二期試驗。我們也期待今年下半年一系列臨床數據讀出，包括在 10 月 EHDN 會議上發表 ALN-HTTO2 於亨丁頓氏病患者的第一期初步結果。

All of this progress. Builds our momentum towards accelerating innovation and scaling our impact as we look to deliver on our five-year vision online in 2030. And our strategy is anchored around three pillars. The first pillar is to establish global leadership in TTR while continuing to build a doable franchise.

所有這些進展。都在推動我們的動能，讓我們在邁向加速創新與擴大影響力的道路上持續前進，並以在 2030 年實現我們的五年願景為目標。而我們的策略以三大支柱為核心。第一個支柱是在持續打造可行的產品組合（franchise）的同時，建立我們在 TTR 領域的全球領導地位。

The momentum we have built at ATTR cardiomyopathy to date. Along with recent developments in the competitive landscape, including the CardioTransform Phase III top-line results and the delay in expected U.S. Generic entry for Tafamidis until mid-2031, further reinforce the strength of our position and the significant opportunity ahead to establish Ambutra as a foundational therapy and realize our TTR leadership ambitions.

我們迄今在 ATTR 心肌病領域所建立的動能。再加上競爭格局的近期發展，包括 CardioTransform 第三期臨床試驗的主要結果（top-line results），以及 Tafamidis 預期在美國的學名藥進入時間延後至 2031 年年中，進一步強化了我們的有利地位，以及未來在建立 Ambutra 作為基礎治療並實現我們在 TTR 領域領導願景方面的重大機會。

The second pillar is growing through sustainable innovation, where we aim to deliver therapies that not only slow the progression of disease but prevent, halt, or reverse it. And the third pillar is scaling with discipline and agility to enable durable, profitable growth.

第二個支柱是透過可持續的創新來成長，我們的目標是提供不僅能減緩疾病進展，且能預防、阻止或逆轉疾病的療法。第三個支柱則是以紀律與敏捷性擴大規模，以實現持久且具獲利性的成長。

Our NADM 2030 represents our commitment to becoming the leading science-driven, fully integrated global biopharmaceutical company and to maximize the full potential of RNA therapeutics for patients. With that, let me now turn the call over to Jeff for a review of our second-quarter financial results and 2026 guidance. Jeff.

我們的 NADM 2030 代表我們致力於成為以科學驅動、完全整合的全球生物製藥領導公司，並為患者最大化 RNA 治療的全部潛力。接下來，我把電話交給 Jeff，請他回顧我們第二季的財務結果以及 2026 年的財測指引。Jeff。

Thanks, Yvonne, and good morning, everyone. This morning, I'll be presenting a summary of Elm Island's second-quarter 2026 financial results and discussing updates to our full-year guidance.

謝謝你，Yvonne，各位早安。今天早上，我將簡要說明 Elm Island 2026 年第二季的財務結果，並討論我們對全年指引的更新。

Let's begin with a summary of our P&L results for the second quarter.

我們先從第二季損益表（P&L）結果摘要開始。

Total global net product revenues were approximately $1.2 billion, representing 74% growth versus Q2 last year, driven by the continued uptake of AMBUTRA and ATTR cardiomyopathy.

全球產品淨營收總計約 12 億美元，較去年第二季成長 74%，主要由 AMBUTRA 在 ATTR 心肌病領域的持續放量所帶動。

Second quarter of 2026 marks the first time we achieved more than $1 billion of TTR revenue. These results reflect a substantial improvement in quarter-on-quarter growth compared with growth in Q1 this year, consistent with the phasing expectations we discussed on our year-end and Q1 earnings calls earlier this year. Olga will share more details on our TTR performance in the quarter.

2026 年第二季是我們 TTR 營收首次突破 10 億美元。相較於今年第一季的成長，本季結果反映出季對季成長的顯著改善，符合我們在今年稍早的年終與第一季法說中所討論的分期（phasing）預期。Olga 將分享更多本季 TTR 表現的細節。

In Q2, collaboration revenue was $47 million or a 23% decrease compared with the same period last year due to lower revenue recognized from our Regeneron collaboration, partially offset by increased revenue from our Roche collaboration, driven by higher reimbursable development activities related to the Zenith Phase III clinical trial, azabistiran.

第二季合作收入為 4,700 萬美元，較去年同期下降 23%，原因是我們與 Regeneron 合作案認列的收入較低；部分被與 Roche 合作案收入增加所抵銷，該增加主要由與 Zenith 第三期臨床試驗 azabistiran 相關、可報銷的研發活動增加所帶動。

Royalty revenue for the second quarter increased 79% to $72 million, driven by higher Lectio sales by Novartis.

第二季權利金收入成長 79% 至 7,200 萬美元，主要由 Novartis 的 Lectio 銷售增加所帶動。

Gross margin on product sales was 75% or 4% lower than Q2 last year. The decrease in margin was primarily driven by increased royalties on Embutra as higher revenues in 2026 resulted in an increase in the average royalty rate payable to Sanofi.

產品銷售毛利率為 75%，較去年第二季低 4 個百分點。毛利率下降主要是因 Embutra 的權利金增加所致；2026 年營收提高使得需支付給 Sanofi 的平均權利金率上升。

Our non-GAAP R&D expenses of $377 million increased 38% compared to last year, primarily driven by costs associated with our three ongoing Phase III clinical studies, including the Xenith Phase III cardiovascular outcomes trial for zilviziran and the Triton-CM and PN studies for nucrisiran.

我們的非 GAAP 研發費用為 3.77 億美元，較去年增加 38%，主要由三項進行中的第三期臨床研究相關成本所驅動，包括 zilviziran 的 Xenith 第三期心血管結局試驗，以及 nucrisiran 的 Triton-CM 與 PN 研究。

Beyond the pivotal studies, we also continue to increase investment to support important programs for bleeding disorders, Huntington's disease and CAA.

除關鍵性研究外，我們也持續加大投資，以支持出血性疾病、亨丁頓舞蹈症以及 CAA 等重要計畫。

Non-GAAP SG&A expenses of $297 million increased 14% compared to last year, driven primarily by investments in support of the EMBUTRA ATTR cardiomyopathy launch in the U.S. And key international markets.

非 GAAP 銷售、一般及行政（SG&A）費用為 2.97 億美元，較去年增加 14%，主要由支持 EMBUTRA 在美國及主要國際市場的 ATTR 心肌病上市推廣之投資所帶動。

We achieved non-GAAP operating income of $318 million, more than triple the amount we achieved last year, driven primarily by the strong top-line results that I previously highlighted.

我們的非 GAAP 營業利益為 3.18 億美元，較去年增加逾三倍，主要由我先前強調的強勁營收表現所驅動。

Finally, we ended the second quarter with cash equivalents and marketable securities of $3.3 billion compared with $2.9 billion as of year-end 2025. The primary driver of the increase in cash year-to-date is our strong operating performance.

最後，我們在第二季末的現金及約當現金與有價證券為 33 億美元，較 2025 年底的 29 億美元增加。今年迄今現金增加的主要原因是我們強勁的營運表現。

Now turning to our full year 2026 guidance.

接下來談 2026 年全年指引。

As Ivan noted, we are revising our total net product revenue guidance to $4.7 billion to $5.1 billion, driven fully by an update of our TTR revenue guidance to $4.2 billion to $4.5 billion, representing a $200 million reduction from our original TTR guidance at the midpoint and still reflects a robust 75% growth year-over-year.

如 Ivan 所提，我們將產品淨營收總額指引修訂為 47 億至 51 億美元，完全是因將 TTR 營收指引更新為 42 億至 45 億美元；以中位數計較原先 TTR 指引下調 2 億美元，但仍反映年增 75% 的強勁成長。

Guiding the market's expectations appropriately is important, and we didn't get it right with our original guidance. We own that. Revised guidance we are sharing today reflects a better understanding of the evolution of second-line demand as our launch has progressed.

適當引導市場預期很重要，而我們原先的指引並不正確。這點我們承擔責任。我們今天分享的修訂指引，反映了隨著上市推進，我們對第二線需求演變有了更好的理解。

Let me provide some additional color on the basis for this revision. Overall, the AMVUTRA cardiomyopathy launch continues to perform ahead of analogs, and importantly, we are pleased with uptake in the first-line portion of the market, which has been and remains the primary focus of our commercial efforts, given the importance of this segment to driving long-term growth.

我再補充一些此次修訂的背景。整體而言，AMBUTRA 心肌病上市表現仍優於同類產品（analogs）；更重要的是，我們對第一線市場的採用情況感到滿意，而這一直是、也仍將是我們商業化工作的主要重點，因為該區隔對推動長期成長至關重要。

When Ambutra was launched in April 2025, the compelling Helios V data and our team's success in establishing access enabled physicians to rapidly transition existing patients who are progressing on stabilizers onto Ambutra.

Ambutra 於 2025 年 4 月上市時，具說服力的 Helios V 數據以及團隊在建立給付可近性方面的成功，使醫師能迅速將在穩定劑（stabilizers）治療下仍持續惡化的既有患者轉換至 Ambutra。

As a result, second-line demand volumes remained consistently robust throughout 2025, which informed our original 2026 guidance.

因此，第二線需求量在 2025 年全年持續維持強勁，並成為我們原先 2026 年指引的依據。

However, as the launch progressed into 2026 and with the benefit of hindsight, it is now clear that a greater than understood proportion of early second-line volume growth was driven by pent-up demand from patients who are waiting for a new treatment option.

然而，隨著上市進入 2026 年並回頭檢視，我們現在清楚看到：早期第二線需求量成長中，有高於原先理解的比例是由「累積待釋放需求」所驅動，也就是等待新治療選項的患者所帶來的需求。

Consistent with the trend we highlighted in our Q1 2026 earnings call, growth in second-line volumes began to moderate in early 2026 to what we now recognize as a normalized level.

與我們在 2026 年第一季法說中所強調的趨勢一致，第二線需求量的成長在 2026 年初開始放緩，並回到我們如今認知的常態化水準。

This normalization of second-line demand is the driver of the $200 million reduction in TTR guidance that we are announcing today.

第二線需求的這種常態化，正是我們今天宣布將 TTR 指引下調 2 億美元的原因。

Hogle will share more perspective in just a few moments on our confidence in future TTR growth, which is grounded in three key elements. The strength of our current market fundamentals, positive impact we expect from new investments we're making based on early launch learnings, and lastly, the favorable competitive developments that Yvonne mentioned in her opening remarks.

Hogle 將在稍後分享更多觀點，說明我們對未來 TTR 成長的信心，其基礎來自三個關鍵要素：我們目前市場基本面的強勁、基於早期上市學習而進行的新投資所預期帶來的正面影響，以及最後 Yvonne 在開場致詞中提到的有利競爭動態發展。

Now back to updating our guidance.

接著回到指引更新。

We are also updating our guidance for collaboration and royalty revenues to a revised range of $575 million to $625 million, representing a $150 million increase at the midpoint of the range, driven primarily by strong performance of Lecvio and the resulting royalties from Novartis, as well as higher cost reimbursement from Roche, favorably impacting collaboration revenue, driven by the pace of enrollment in our Xenith Phase III study with Lvisiran Remainder of our non-GAAP financial guidance remains.

我們也將合作收入與權利金收入指引更新至 5.75 億至 6.25 億美元區間，以中位數計增加 1.5 億美元；主要由 Lecvio 的強勁表現及其帶來自 Novartis 的權利金所驅動，同時 Roche 的成本補償提高亦有利於合作收入，該提升與我們 Xenith 第三期研究的收案速度相關，研究藥物為 Lvisiran。我們其餘的非 GAAP 財務指引維持不變。

Let me now turn it over to Tolga to provide more color on our commercial performance in the second quarter. Tolga.

接下來我把時間交給 Tolga，請他就第二季的商業表現提供更多說明。Tolga。

Thanks, Jeff, and good morning.

謝謝你，Jeff，各位早安。

I'm pleased to share our continued progress in bringing Alnylam therapies to patients globally.

我很高興與各位分享我們在將 Alnylam 療法帶給全球患者方面所取得的持續進展。

Almutray is delivering a category-defining ATTRCM launch and is on track toward delivering on our Alnylam 2030 ambitions.

Almutray 正在推動一項具類別定義意義的 ATTRCM 上市，並正按計畫朝著實現我們 Alnylam 2030 願景邁進。

As Yvonne and Jeff mentioned.

正如 Yvonne 和 Jeff 所提到的。

We have gained valuable insights as the launch has progressed.

隨著上市推進，我們獲得了寶貴的洞見。

These learnings have sharpened our understanding of demand dynamics while also reinforcing our confidence in the fundamental drivers of sustainable growth.

這些學習讓我們對需求動態的理解更為清晰，同時也進一步強化了我們對可持續成長基本驅動因素的信心。

Overall, we remain highly confident in our path to achieving TTR leadership.

整體而言，我們對達成 TTR 領導地位的路徑仍然高度有信心。

The momentum of the business, coupled with an increasingly favorable competitive landscape.

業務動能，加上競爭格局日益有利。

Reinforce our conviction in achieving our long-term ambitions.

進一步強化我們實現長期目標的信念。

Q2 marked another quarter of strong commercial execution and growth.

第二季再度展現強勁的商業執行力與成長。

Specifically, we delivered $1.17 billion in combined net product revenues, up 74% year-over-year and 13% over Q1 2026.

具體而言，我們合計實現 11.7 億美元的產品淨收入，年增 74%，較 2026 年第一季成長 13%。

In just five quarters since our CM launch, we have generated over $4 billion in total revenue, reflecting both a strong base and a clear growth trajectory.

自我們 CM 上市以來僅五個季度，我們已創造超過 40 億美元的總收入，反映出強勁的基礎與清晰的成長軌跡。

Our rare disease portfolio also continues to deliver meaningful impact for patients and consistent performance for our business. In Q2, we generated $142 million in rare disease net revenue, up 11% year over year.

我們的罕見疾病產品組合也持續為病患帶來顯著影響，並為公司業務提供穩健表現。第二季，我們的罕見疾病淨收入為 1.42 億美元，年增 11%。

Turning to our TTR franchise, global TTR net revenues reached $1.03 billion in the second quarter, increasing 13% versus Q1 and 89% year over year, reflecting the continued strength of the launch.

再看我們的 TTR 產品線，第二季全球 TTR 淨收入達 10.3 億美元，較第一季成長 13%，年增 89%，反映上市持續強勁。

And the robust execution of our global teams.

以及我們全球團隊的有力執行。

In the U.S., TTR revenues increased 15% versus Q1 and 114% year-over-year, reflecting robust underlying demand with reported revenue partially held back by changes in inventory days on hand during Q2.

在美國，TTR 收入較第一季成長 15%，年增 114%，反映強勁的基本需求；但第二季因庫存持有天數變動，部分已認列收入受到抑制。

Access remained broad, pull-through was strong.

可近性仍然廣泛，拉動（pull-through）表現強勁。

And ATRs continued to exceed 90%. Outside the U.S., TTR revenues increased 7% versus Q1 and 31% year-over-year.

且 ATR 持續超過 90%。在美國以外，TTR 收入較第一季成長 7%，年增 31%。

Continued ATTR CM uptake in Japan, the UK, and Germany, along with strong pulse neuropathy performance across our international markets, drove Q2 growth.

日本、英國與德國的 ATTR CM 持續採用，加上我們國際市場中脈衝神經病變（pulse neuropathy）業務的強勁表現，帶動第二季成長。

Despite pricing handwinds related to ongoing CM launches in several countries.

儘管在多個國家持續推進 CM 上市，帶來與定價相關的逆風。

Double-clicking on our Q2 TTR performance in the U.S., underlying demand was exceptionally strong, increasing by $129 million in the quarter, more than doubling the demand growth achieving Q1.

進一步聚焦我們第二季在美國的 TTR 表現，基本需求異常強勁，本季增加 1.29 億美元，需求增量較第一季翻倍以上。

A portion of that demand was offset by inventory dynamics, which reduced reported growth by $21 million and to a lesser extent by the continued and anticipated modest reduction in net price.

其中一部分需求被庫存動態所抵銷，使已認列成長減少 2,100 萬美元；此外，淨價格持續且如預期的小幅下滑也在較小程度上造成影響。

As a reminder, our Q1 USTTR growth was more modest and was impacted by several seasonal phasing dynamics.

提醒一下，我們第一季美國 TTR 成長較為溫和，並受到多項季節性時點（phasing）因素影響。

And we are therefore pleased by the robust re-acceleration in demand in Q2 and the continuing strength of the business.

因此，我們對第二季需求強勁再加速以及業務持續強勢感到滿意。

Almutra's differentiated clinical profile underpins our confidence in the long-term growth opportunity.

Almutra 具差異化的臨床特徵，是我們對長期成長機會保持信心的基礎。

We believe that Almutra stands apart as a first-line choice on attributes that matter to physicians and patients.

我們相信，Almutra 在醫師與病患重視的關鍵屬性上，作為第一線選擇具有明顯優勢。

It is the first and only product approved in the US for both ATT-RCM and hereditary ATT-RPM.

它是在美國首個且唯一同時獲准用於 ATT-RCM 與遺傳性 ATT-RPM 的產品。

It works upstream at the source, delivering rapid, deep, and sustained knockdown of the disease-causing protein.

它在源頭上游發揮作用，能快速、深度且持續地降低致病蛋白。

In the pivotal HELIOS-B study, AUTRA met 10 out of 10 endpoints and demonstrated robust treatment effects in the primary endpoint of all-cause mortality. And recurring CV events and secondary endpoints of functional capacity and health-related quality of life.

在關鍵性 HELIOS-B 研究中，AUTRA 達成 10 項終點中的 10 項，並在主要終點「全因死亡率」上展現強勁治療效果。以及反覆發生的心血管（CV）事件，與次要終點中的功能能力與健康相關生活品質。

Across all of these endpoints, consistent treatment effects with or without background stabilizers were observed.

在所有這些終點上，無論是否合併背景穩定劑治療，皆觀察到一致的治療效果。

Combined with the convenience of once quarterly healthcare provider administration and real-world data that suggests greater than 90% adherence.

再加上每季一次由醫療照護提供者施打的便利性，以及真實世界數據顯示超過 90% 的依從性。

We believe Almutra is uniquely positioned to address the needs of the growing ATTRCM patient population. The first five quarters of launch have provided valuable insights that are informing where we increase investment and how we position the business for its next phase of growth. During the initial quarters following approval.

我們相信 Almutra 具備獨特優勢，可滿足不斷成長的 ATTRCM 病患族群需求。上市前五個季度帶來的寶貴洞見，正指引我們在哪些領域加大投資，以及如何為下一階段成長定位業務。在核准後的最初幾個季度。

Many of our high-volume early adopters transitioned a substantial number of stabilizer-treated progressing patients to Ombutra. While those transitions continue, we are now seeing that portion of demand volume growth normalize toward a more sustainable underlying rate, and we continue to capture leadership share of second-line starts.

我們許多高用量的早期採用者，將相當數量使用穩定劑但仍進展的病患轉換至 Ombutra。雖然這些轉換仍在持續，我們目前看到該部分需求量的成長正趨於正常化，回到更可持續的基本增速；同時我們仍持續取得第二線起始治療的領先市占。

Today, approximately 80% of new treatment initiations are first-line starts. Establishing Almutra as first-line treatment choice has been our priority since launch, and we continue to strengthen our competitive position. What's more, while our strategy has never depended on competitors' outcomes, two favorable developments in the external landscape have cleared the path. For us to be even more competitive in the first line setting. First, we now anticipate Tafamidis U.S. loss of exclusivity in 2031. Amutra is already challenging the seven-year incumbent for leadership share of new patient starts, and we see a significant opportunity to continue strengthening that position years ahead of generalization of the stabilizer class. Second. Based on the CARDIO transform study top-line results, we now anticipate one fewer branded ATTR-CM competitor in both the first line and stabilizer progressive segments. Finally, category growth continues to accelerate. And our competitive first-line share, coupled with this clear competitive path to greater first-line penetration, aligns well with where we see the largest opportunity. With an estimated 80% of patients still untreated and additional physicians and health systems initiating treatment of ATT-RCM, we expect the robust growth in first-line starts to continue.

目前，約 80% 的新治療啟動為第一線起始。自上市以來，將 Almutra 建立為第一線治療選擇一直是我們的優先事項，我們也持續強化競爭地位。此外，雖然我們的策略從未依賴競品結果，但外部環境出現兩項有利發展，已掃清道路。使我們在第一線情境中更具競爭力。第一，我們目前預期 Tafamidis 在美國將於 2031 年失去獨占性。Amutra 已在新病患起始治療的領先市占上挑戰這位七年既有領導者；我們看到在穩定劑類別普及（generalization）之前的多年內，仍有顯著機會持續強化此一地位。第二。基於 CARDIO transform 研究的主要結果（top-line results），我們目前預期在第一線與穩定劑進展族群兩個區隔中，將少一個品牌化的 ATTR-CM 競爭者。最後，類別成長仍在加速。而我們具競爭力的第一線市占，加上這條清晰的競爭路徑以提升第一線滲透率，與我們所見的最大機會高度一致。在估計仍有 80% 病患未接受治療、且更多醫師與醫療體系開始啟動 ATT-RCM 治療的情況下，我們預期第一線起始治療的強勁成長將持續。

And we're helping to drive that category growth. More specifically, we're accelerating our investments in diagnosis-enabling initiatives, investments to identify patients earlier, to expand its treatable population, and ultimately to improve patient outcomes. Taken together, these insights provide great confidence in our ability to expand leadership across both ATTRCM.

而我們也正協助推動該類別成長。更具體而言，我們正加速投入促進診斷的計畫、提早識別病患的投資，以擴大可治療族群，並最終改善病患預後。綜合而言，這些洞見讓我們對於在 ATTRCM 兩個領域擴大領導地位充滿信心。

Hereditary TTRPN and deliver on our 2030 ambitions of TTR leadership and a 25% revenue CAGR during the period. As we shared today, our differentiated profile has translated into exceptional launch momentum and that experience has sharpened our understanding of what will drive the next phase of growth. First, after five quarters in the market.

遺傳性 TTRPN，並實現我們 2030 年的目標：取得 TTR 領導地位，且在此期間達成 25% 的營收年複合成長率（CAGR）。如同我們今天分享的，我們的差異化特徵已轉化為卓越的上市動能，而這些經驗也讓我們更清楚理解將驅動下一階段成長的因素。第一，在市場上五個季度之後。

Almutra's compelling profile and our focused efforts have driven broad coverage and efficient patient access with no meaningful reimbursement headwinds. We believe the Strong Access Foundation will continue to support physician confidence and patient adoption as we expand the franchise. Second, we continue to deepen adoption among physicians who have already incorporated Almutra into their practice.

Almutra 具吸引力的特徵與我們聚焦的努力，帶來廣泛的給付覆蓋與高效率的病患可近性，且沒有實質性的報銷逆風。我們相信，強勁的可近性基礎將在我們擴大產品線時，持續支持醫師信心與病患採用。第二，我們持續深化已將 Almutra 納入臨床實務之醫師的採用程度。

Among prescribers using Almutra, it now represents more than 50% of new patient starts, underscoring the strong physician preference that develops with experience. And from ATTRCM launch through the end of Q2, we have added over 1,700 new prescribers. Third, and perhaps most importantly. We have significant opportunity to expand the breadth of prescribers who have experience with Albutra, which we estimated about a third of the growing pool of TTR prescribers. While we know that experience drives preference, there are many more physicians, including many who are new to the category who have not yet prescribed Albutra. To capture that opportunity.

在使用 Almutra 的開立醫師中，它目前占新病患起始治療的 50% 以上，凸顯隨著使用經驗累積而形成的強烈醫師偏好。且自 ATTRCM 上市至第二季末，我們已新增超過 1,700 位新開立醫師。第三，或許也是最重要的。我們在擴大具備 Albutra 使用經驗的開立醫師廣度方面仍有重大機會；我們估計目前約占持續成長的 TTR 開立醫師池的三分之一。我們知道經驗會驅動偏好，但仍有更多醫師（包括許多新進入此類別者）尚未開立過 Albutra。為了掌握這個機會。

We are intensifying our focus and increasing our investment in customer-facing activities to expand the breadth of prescribing. We are already seeing early progress from these efforts. With accelerated growth in new Almuter prescribers during the second quarter, we believe we are in the early stages of that expansion opportunity. While we are still early in the commercialization journey. We believe AMBUTRA is well positioned to capture the significant opportunity ahead as we bring this differentiated therapy to more patients living with ATTR-CM. With that, I will now turn it over to Pushkar.

我們正加強聚焦並增加對面向客戶之活動的投資，以擴大處方覆蓋面。我們已經從這些努力中看到初步進展。隨著第二季新 Almuter 處方醫師的加速成長，我們相信我們正處於該擴張機會的早期階段。儘管我們仍處於商業化旅程的早期。我們相信，隨著我們將這項具差異化的療法帶給更多 ATTR-CM 患者，AMBUTRA 已具備良好定位，可把握前方重大的機會。接下來，我把時間交給 Pushkar。

Thank you, Tolga, and good morning, everyone. As Tolga just highlighted, we believe AMBUTRA has a remarkable clinical profile that supports it being the first-line treatment of choice for patients with ATTR cardiomyopathy.

謝謝你，Tolga，各位早安。正如 Tolga 剛才強調的，我們相信 AMBUTRA 具備卓越的臨床特徵，支持其成為 ATTR 心肌病患者的首選一線治療。

These key attributes are highlighted here with data from the landmark Helios B study. First and foremost, we've seen substantial benefits with regard to improving clinical outcomes, both all-cause mortality and cardiovascular events, with reductions of nearly 40% over 48 months across these two endpoints. Second, the treatment effects are largest when we intervene early.

這些關鍵特點在此以里程碑式的 Helios B 研究數據加以凸顯。首先也是最重要的，我們看到在改善臨床結局方面具有顯著效益，包含全因死亡率與心血管事件；在這兩個終點上，於 48 個月內降幅接近 40%。第二，當我們及早介入時，治療效果最大。

You can see that in the fourth plot on the bottom left, where patients with lower BNP, greater walking ability, and younger age have had even greater reductions in the composite endpoint of 47%, 42%, and 45% respectively. And importantly, in data recently presented at ESC heart failure and shown on the lower right quadrant, we see that the treatment effect is preserved irrespective of background medications, including TGR stabilizers. These attributes, along with the quarterly dosing that supports adherence, in our view, represents an ideal profile for first-line agent for patients with ATTR cardiomyopathy.

你可以在左下角的第四張圖看到：BNP 較低、步行能力較佳以及年齡較輕的患者，在複合終點上的降幅分別更高，達 47%、42% 與 45%。而且重要的是，在近期於 ESC 心衰會議發表、並顯示於右下象限的數據中，我們看到不論背景用藥為何（包含 TGR 穩定劑），治療效果都能維持。我們認為，這些特點加上每季一次給藥以支持依從性，構成了 ATTR 心肌病患者理想的一線用藥特徵。

Now the strength of these Helios B results, along with our many learnings from our deep experience in TTR amyloidosis, provide us with staunch conviction in the value of nucrisiran, our next-generation investigational RNAi TTR silencer, which we believe has the potential for even greater improved efficacy by a greater knockdown, over 95% with just two doses per year.

如今，這些 Helios B 結果的強勁表現，加上我們在 TTR 類澱粉沉積症領域深厚經驗所累積的諸多洞見，使我們對 nucrisiran——我們下一代研發中的 RNAi TTR 沉默劑——的價值抱持堅定信心；我們相信它有潛力透過更高幅度的抑制帶來更佳療效：每年僅兩次給藥即可達到超過 95% 的 knockdown。

As you're aware, we continue to advance Nucresiran in the Triton Phase 3 program. Triton CM is a randomized, double-blind, event-driven outcome study of Nucresiran versus placebo. We announced last quarter that we utilized a pre-specified option in our protocol to expand enrollment by approximately 500 patients to 1,715 total, further mitigating the potential risk of low event rates while maintaining or potentially even accelerating timelines for this important study.

如各位所知，我們持續在 Triton 第三期計畫中推進 Nucresiran。Triton CM 是一項隨機、雙盲、以事件驅動的結局研究，比較 Nucresiran 與安慰劑。我們在上一季宣布，已依照方案中預先規劃的選項，將收案人數擴增約 500 名至總計 1,715 名，進一步降低事件率偏低的潛在風險，同時維持、甚至可能加速這項重要研究的時程。

Now, given recent competitor data and given that many patients in TRITON CM will be on a background stabilizer, we understand that there have been many questions raised about the feasibility of delivering positive results from this clinical trial. While we still have more to learn about the Eplintercin results, we believe they're likely attributable to a combination of molecule and study-specific issues. And as we compare what we know about Nucrisiran with what's been reported about Eplintercin, I want to assure you that we remain highly confident. Nucrisuran and Tritonsium. I'll explain more in a moment, but first let me share what we'll be looking for in the upcoming data presentations of the CardioTransform results at ESC to better understand the reasons why the study did not meet its primary endpoint. First, we'll be interested to learn more about the population baseline characteristics of the CardioTransform study.

鑑於近期競品數據，且 TRITON CM 中許多患者將合併使用背景穩定劑，我們理解外界對於此臨床試驗能否取得正向結果提出了許多疑問。雖然我們對 Eplintercin 的結果仍有更多需要了解之處，但我們認為其很可能可歸因於分子本身與研究設計/執行層面的多重因素。當我們把已知的 Nucrisiran 與外界報導的 Eplintercin 進行比較時，我想向各位保證，我們仍然高度有信心。Nucrisuran 和 Tritonsium。我稍後會進一步說明；但首先，讓我分享我們將在 ESC 即將發表的 CardioTransform 結果數據中重點關注哪些面向，以更好理解該研究未達主要終點的原因。第一，我們會希望更深入了解 CardioTransform 研究族群的基線特徵。

Particularly in the two key subgroups of monotherapy and in the patients on background stabilizers. As I noted, in Helios-B, we saw that treatment effects with ONVUTRA were greatest in early patients. And so a drug signal may be obscured if many advanced patients were enrolled. We already know from published data that the CARDIOTRANSFORM study enrolled 17% NYHA Class III patients, nearly double that in Helios-B.

特別是兩個關鍵亞組：單藥治療，以及合併背景穩定劑的患者。如我所提，在 Helios-B 中，我們看到 ONVUTRA 的治療效果在早期患者中最大。因此，若納入許多晚期患者，藥物訊號可能會被掩蓋。我們已從已發表數據得知，CARDIOTRANSFORM 研究納入了 17% 的 NYHA 第 III 級患者，幾乎是 Helios-B 的兩倍。

Patients with higher NAC stage and patients with higher BNPs. Importantly, as I'll explain further in a moment, we believe deep, rapid knockdown of TTR is critical to improving outcomes in ATTR cardiomyopathy. Grafts in the primary manuscript for the Efluentersen PN study indicated it took longer to get to peak knockdown than Embutra, but the depth and variability of knockdown are also important, so we'll be looking for those details.

此外還包括 NAC 分期較高以及 BNP 較高的患者。重要的是，正如我稍後會更進一步說明，我們相信 TTR 的深度且快速 knockdown 對於改善 ATTR 心肌病的結局至關重要。Efluentersen PN 研究的主要論文中的圖表顯示，其達到峰值 knockdown 所需時間比 Embutra 更長；但 knockdown 的深度與變異性同樣重要，因此我們會關注這些細節。

Safety will be important given what we know about ASOs in the past and the frailty of the ATTR cardiomyopathy population. Did patients stay on drug? And were there any competing risks that impacted study outcomes? We'll also want to look at study execution and completeness of follow-up. And finally, we'll want to take a much deeper look at the outcomes data. For example, how did the individual components of their primary endpoint, CV mortality and CV events, look?

考量到我們過去對 ASO 的認識，以及 ATTR 心肌病族群的脆弱性，安全性將是重點。患者是否能持續用藥？是否存在任何影響研究結局的競爭風險？我們也會檢視研究執行與追蹤的完整性。最後，我們將更深入檢視結局數據。例如，他們主要終點的個別組成項——心血管死亡率與心血管事件——表現如何？

And what about all-cause mortality, which is part of our primary endpoint? How did these accrue over time and did the results vary in particular subgroups, particularly by disease severity? Bottom line is there are a lot of details not yet known about the failure of CardioTransform. However, we are in an ideal position to learn from it.

那全因死亡率呢？這也是我們主要終點的一部分。這些事件隨時間如何累積？結果是否在特定亞組（尤其依疾病嚴重度）有所差異？總而言之，關於 CardioTransform 失敗的原因，目前仍有許多細節尚未明朗。然而，我們處於理想位置，可以從中學習。

With enrollment ongoing and a projected launch for an increase in 2030 for ATTR cardiomyopathy, we have plenty of time to digest this information, thoroughly consider our options, and implement appropriate changes to Triton CM, assuming any are even warranted. Let me return now to why we remain confident in Triton CM following the CardioTransform top-line release. The reasons come down to three key factors. The specific attributes of our molecule, nacrisiran, key design elements of the Triton CM study, and the track record of our team here at Al Nyla. Starting with the molecule. First, RNAi therapeutics are fundamentally different than antisense olivonucleotides. In our hands, RNAi has been able to deliver rapid, deep, and durable TTR knockdown, which we believe has implications on treating the course of disease.

在收案仍持續進行、且針對 ATTR 心肌病的預計上市時間為 2030 年左右的情況下，我們有充足時間消化這些資訊、全面評估我們的選項，並在必要時對 Triton CM 做出適當調整——前提是確實需要調整。現在我回到為何在 CardioTransform 公布頂線結果後，我們仍對 Triton CM 保持信心。原因可歸結為三個關鍵因素。包括我們分子 nacrisiran 的特定屬性、Triton CM 研究的關鍵設計要素，以及我們在 Al Nyla 團隊的過往實績。先從分子談起。第一，RNAi 治療在本質上不同於反義寡核苷酸（ASO）。在我們的經驗中，RNAi 能夠實現快速、深度且持久的 TTR knockdown，我們相信這對於改變疾病進程具有意義。

There are now several recent examples of ASOs and RNAIs silencing the same genetic target with various. Different profiles. We've also seen that the safety profiles of these two approaches differ as well. Second, Nucrisran's depth of TTR knockdown is expected to be best in class based on preliminary Phase I results showing over 95% TTR knockdown with much tighter interpatient variability. I'll explain why we believe that will result in strong efficacy in a moment. And finally.

近期已有多個例子顯示，ASO 與 RNAi 針對相同的基因靶點進行沉默時，會呈現不同的特徵。不同的特徵。我們也看到這兩種方法的安全性特徵同樣有所差異。第二，根據第一期初步結果，Nucrisran 的 TTR knockdown 深度預期將為同類最佳，顯示可達超過 95% 的 TTR knockdown，且病人間變異更小、更緊密。我稍後會說明為何我們相信這將帶來強勁療效。最後。

We have data from two prior studies evaluating RNAi in ATTR cardiomyopathy patients, Apollo-B and Helios-B, both of which generated data supporting a combination benefit. You've seen the Helios-B data and label, which shows a clear benefit of RNAi-mediated TTR silencing in a population that included heavy stabilizer use and consistent effects in combination in monotherapy. But as I'll show you in a moment, we saw the same effect with patisran as well.

我們有來自兩項先前研究的資料，這兩項研究評估了 RNAi 在 ATTR 心肌病變患者中的效果：Apollo-B 與 Helios-B；兩者皆產生支持「合併治療具益處」的數據。各位已看過 Helios-B 的數據與標示（label），其顯示在一個包含大量穩定劑使用者的族群中，RNAi 介導的 TTR 沉默具有明確益處，且在合併治療與單藥治療中效果一致。但正如我稍後將展示的，我們在 patisran 上也看到了相同的效果。

Moving to the study. TRITON-CM now with 1,750 patients will be the largest study conducted in ATTR-CM, which will allow us to accrue more outcome events.

接著談到這項研究。TRITON-CM 目前規劃納入 1,750 名患者，將是 ATTR-CM 領域迄今規模最大的研究，這將使我們能累積更多結局事件。

And further to that point, we designed Triton CM as an event-driven study. Given the evolving treatment landscape, patients with somewhat milder disease on baseline on average and other dynamics, we determined that a time-based primary endpoint was not ideal. Instead, we'll continue to study until we have enough endpoint events to ensure sufficient study power. Third, we've used our insights to define entry criteria that enrich for patients who are most likely to benefit based on our prior learnings.

此外，我們將 Triton CM 設計為一項以事件驅動（event-driven）的研究。鑑於治療版圖持續演變、基線時平均病情較輕的患者比例增加，以及其他動態因素，我們判定以時間為基礎的主要終點並不理想。相反地，我們將持續研究，直到累積足夠的終點事件，以確保研究具備充分的統計力（power）。第三，我們運用既有洞見來界定入組標準，以富集（enrich）最可能受益的患者族群，這是基於我們先前的學習。

And finally, we have an outstanding experienced team here at Alnyla. We've been focused on TTR drug development for well over 15 years, delivering two approved products. We've amassed tremendous experience across study design, execution, and analysis to maximize the probability of success of a trial in this area. Part of this experience and history of conducting TTR trials is our vast database of deep patient-level insights that we can leverage to optimize study design and conduct.

最後，我們在 Alnyla 擁有一支傑出且經驗豐富的團隊。我們專注於 TTR 藥物開發已超過 15 年，並成功推出兩項已獲核准的產品。我們在研究設計、執行與分析方面累積了極為豐富的經驗，以最大化此領域試驗成功的機率。這段經驗與進行 TTR 試驗的歷史之一部分，是我們擁有龐大的資料庫，包含深入的患者層級洞見，可用以最佳化研究設計與執行。

And to that last point, we have a track record of meticulous execution to ensure study success. This was most recently exemplified by how we optimized the endpoint structure and analytic plan for Helios B to deliver remarkable results resulting in the strong label that Tolga highlighted earlier. Before I move on, I'd like to underscore a few of the points I just made by sharing some clinical data that support the additive benefits of RNAi mediated silencing on top of the stabilizer.

呼應最後一點，我們有一貫嚴謹執行以確保研究成功的紀錄。最近的例子是：我們如何為 Helios B 最佳化終點架構與分析計畫，交出卓越成果，並促成 Tolga 先前強調的強勁標示（label）。在我繼續之前，我想透過分享一些臨床數據，強調我剛才提到的幾點，這些數據支持在穩定劑之上再加上 RNAi 介導沉默所帶來的加成效益。

As you'll recall, the HELIOS-B study demonstrated an approximately 41% reduction in the risk of all-cause mortality up to 42 months when Amvutril was given to patients on a stabilizer at baseline, highlighting both the residual unmet need in these stabilizer-treated patients as well as the additive benefit of vutresiran. But what you may not know is that we saw a nearly identical effect in Apollo B. As shown here, with just 24 months of follow-up in a comparable population in that study, we saw an estimated 44% reduction in all-cause mortality. Hence, we have data from two different molecules in two different studies showing comparable improvements in outcomes, which provides the strongest evidence of a combo effect. We believe these clinical data result from the knockdown profile of these two medicines. There are many ways to look at TTR knockdown, but what we believe matters is the speed and depth of knockdown and particularly getting as many patients as possible to deep knockdown. Here we show TTR knockdown from our polyneuropathy studies, which had the richest sampling of TTR levels. Both show median knockdown of approximately 90% at steady state.

各位或許記得，HELIOS-B 研究顯示：當 Amvutril 用於基線即使用穩定劑的患者時，在最長 42 個月內，全因死亡風險約降低 41%，這凸顯了這些接受穩定劑治療患者仍存在未被滿足的需求，以及 vutresiran 的加成效益。但各位可能不知道的是，我們在 Apollo B 中也觀察到幾乎相同的效果。如圖所示，在該研究中、於相近族群且僅 24 個月追蹤下，我們看到估計全因死亡降低 44%。因此，我們有來自兩種不同分子、兩項不同研究的數據，顯示相近的結局改善，這提供了合併效應最有力的證據。我們相信這些臨床數據源自這兩種藥物的 knockdown（下調）特徵。評估 TTR knockdown 有許多方式，但我們認為關鍵在於下調的速度與深度，尤其是讓盡可能多的患者達到深度下調。此處我們展示來自多發性神經病變研究的 TTR knockdown，該研究對 TTR 水平的取樣最為豐富。兩者在穩態時的中位數下調皆約為 90%。

Now, we don't know exactly what level of knockdown is critical for efficacy in cardiomyopathy, but we have robust data in hereditary ATTR, where we have more sensitive endpoints. It suggests on a population basis, achieving 80% knockdown or greater is associated with halting of polyneuropathy. And based on our depth, speed, and variability of knockdown, the large majority of patients, about 82% to 84% of Boutrisa transferred patients, reached that threshold at steady state.

目前我們尚不清楚在心肌病變中，何種下調程度對療效至關重要，但在遺傳性 ATTR（hereditary ATTR）方面我們有扎實數據，因為那裡有更敏感的終點。這些數據顯示，就族群層面而言，達到 80% 或以上的下調與多發性神經病變的停止進展相關。並且基於我們在下調深度、速度與變異性方面的表現，絕大多數患者——約 82% 至 84% 的 Boutrisa 轉入（transferred）患者——在穩態時達到該門檻。

So how does this compare to other molecules? Here we've plotted the same data as on the prior slide for vitresiran, now shown as bar graphs. You see 91% median knockdown with about 82% of patients achieving that 80% threshold of deep knockdown. So how does that compare to the data reported for ampluntersen?

那麼這與其他分子相比如何？在此我們將前一張投影片中 vitresiran 的相同數據改以長條圖呈現。你可以看到中位數下調為 91%，約 82% 的患者達到 80% 這個深度下調門檻。那麼這與 ampluntersen 所報告的數據相比又如何？

Our team used published data from the Epilon-Tersen PN study, which showed median knockdown of 84% at steady state, as well as available data on variability to model the expected proportion of patients who will reach that same 80% knockdown threshold. Our model estimates that only about 67% of Epilon-treated patients would reach that same deep level of knockdown. Or said another way. One-third of patients may not reach the threshold of knockdown we've seen to be associated with strong efficacy, nearly double that calculated for batresirab. These are estimates and should be interpreted with appropriate caution, but they highlight that the TTR knockdown data in cardio transform will be critical to review, and insufficient knockdown is one plausible contributor to the failure of that study.

我們的團隊使用已發表的 Epilon-Tersen PN 研究數據（顯示穩態時中位數下調為 84%），並結合可得的變異性資料，建立模型以推估能達到同樣 80% 下調門檻的患者比例。我們的模型估計，只有約 67% 的 Epilon 治療患者能達到同樣的深度下調。換句話說。約三分之一的患者可能無法達到我們所觀察到、與強勁療效相關的下調門檻；這一比例幾乎是對 batresirab 所計算值的兩倍。這些為估計值，應以適當審慎態度解讀，但它們凸顯：在 cardio transform 中的 TTR 下調數據將是必須檢視的關鍵，而下調不足是該研究失敗的一個合理可能因素。

We ran the same modeling exercise for nucrisiran using the same dose and regimen that we are using in the Triton CM and PN studies. And the good news is that by these same metrics, nucrisiran has the potential to be even better than vutrisiran's high mark. With median knockdown of 95% and low variability, over 99% of patients choose nucrisiran are expected to surpass this deep knockdown threshold. So in sum.

我們也以相同方式對 nucrisiran 進行建模，使用與 Triton CM 與 PN 研究相同的劑量與給藥方案。好消息是，依照同樣的衡量指標，nucrisiran 甚至有潛力優於 vutrisiran 的高標準。在中位數下調 95% 且變異性低的情況下，預期超過 99% 選用 nucrisiran 的患者將可超越此深度下調門檻。因此總結而言。

We don't believe that the top-line results shared a few weeks ago negate the hypothesis and rationale of using a silencer for ATTRCM patients who are already on a stabilizer. More likely, as we see it, they may demonstrate that the type and depth of silencing, along with aspects of the study design, are what really matter.

我們不認為幾週前分享的整體（top-line）結果否定了：對於已使用穩定劑的 ATTRCM 患者，採用沉默劑（silencer）的假說與理據。更可能的是，如我們所見，這些結果顯示真正重要的是沉默的類型與深度，以及研究設計的若干面向。

That, I'd like to remind you that we're progressing a broad pipeline of medicines beyond TTR with over 25 clinical programs spanning multiple therapeutic areas across rare specialty and prevalent indications. This robust pipeline represents a tremendous opportunity to improve patient health and create value in the years ahead. To that end, we look forward to a lot of pipeline momentum in the next few years. This year in 2026, we continue to execute on our three ongoing pivotal studies.

另外，我想提醒各位，我們正在推進一條廣泛的產品線，涵蓋 TTR 以外的藥物，擁有超過 25 個臨床計畫，橫跨多個治療領域，涵蓋罕見專科與常見適應症。這條強健的產品線代表未來數年改善患者健康並創造價值的巨大機會。為此，我們期待未來幾年產品線將有大量進展動能。今年（2026 年），我們持續推進三項正在進行的關鍵性（pivotal）研究。

Including two cardiovascular outcomes trials. We also anticipate four key data readouts in the second half, which I'll outline on the next slide. And looking ahead, we anticipate many more data readouts and pivotal trial starts in '27 and '28. Additionally, in 2028, we anticipate the launch of nacresiran in HATTR polyneuropathy, assuming positive Phase III data and regulatory approval.

其中包括兩項心血管結局試驗。我們也預期在下半年會有四項關鍵數據讀出（readouts），我將在下一張投影片中概述。展望未來，我們預期在 2027 與 2028 年將有更多數據讀出以及關鍵性試驗啟動。此外，若第三期數據為正且獲得監管核准，我們預期於 2028 年在 HATTR 多發性神經病變適應症推出 nacresiran。

And of course, we'll continue to build the pipeline through the filing of three to four new INDs each year as we scale to meet our Al Nitem 2030 ambitions. Coming back to '26 and our pipeline goals for the remainder of the year, we're looking forward to four important data readouts from three key programs. For ALN6400, we plan to share healthy volunteer data from the ongoing Phase I study, as well as initial results from the Phase II study in patients with hereditary hemorrhagic telangiectasia.

當然，隨著我們擴大規模以達成 Al Nitem 2030 的雄心目標，我們將持續透過每年提交三到四項新的 IND 申請來建構研發管線。回到 2026 年以及我們今年剩餘期間的管線目標，我們期待來自三個關鍵專案的四項重要數據讀出。就 ALN6400 而言，我們計畫分享正在進行的第一期研究之健康受試者數據，以及在遺傳性出血性毛細血管擴張症患者中第二期研究的初步結果。

We also expect to initiate Phase 1 data from both ALN HD202, our Huntington Disease Program, and ALN 2,232 in development for obesity and weight management. With that, let me turn it back to Josh to coordinate our Q&A session. Josh?

我們也預期將啟動兩項專案的第一期數據：ALN HD202（我們的亨丁頓氏病專案）以及正在開發用於肥胖與體重管理的 ALN 2,232。接下來我把時間交還給 Josh 來協調我們的問答環節。Josh？

Thank you, Pushkul. Operator, we'll now open the call for questions. To those dialed in, we'd 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，Pushkul。接線員，我們現在開放提問。對於撥入的各位，我們想請大家每人先提一個問題；若還有其他問題，請回到隊列重新排隊。

(Operator Instructions) Paul Matteis, Stifel.

(接線員指示) Paul Matteis，Stifel。

Great. Good morning. Thanks so much for taking my question. I appreciate it.

很好。早安。非常感謝讓我提問。我很感激。

I wanted to just talk about like the change in guidance.

我想談談指引變更的部分。

By our math, under the new guide, you're growing around 50-ish percent at the midpoint in the second-half of this year. And for 2030, I think you still guided to this 25% CAGR. Given this drop-off versus your original expectations and when you gave this long-term guidance, I was wondering if you could talk a little bit more about the next sort of 12 to 24-month outlook. And your confidence that you can keep the growth rate on track likely above that 25% number for a while and still meet your long-term goals.

按我們的計算，在新的指引下，今年下半年以中位數來看，你們的成長大約是 50% 左右。而對於 2030 年，我想你們仍然指引為 25% 的年複合成長率（CAGR）。鑑於相較於你們原先預期、以及當初給出長期指引時的假設，現在出現了這樣的落差，我想請你們多談一點未來 12 到 24 個月的展望。以及你們對於能讓成長率維持在軌道上、可能在一段時間內高於 25% 並仍能達成長期目標的信心。

Thank you.

謝謝。

Thanks for the question. Look, clearly, we're not pleased to be learning guidance. As Jeff said, we own it. But I think it's really important to emphasize that we believe that the fundamentals driving our opportunity are really strong, particularly market growth and our first-line momentum. And it's difficult to know every single factor when you kick off a launch from the get-go. But we are very pleased with the outlook that we have in front of us, both in the.

謝謝你的問題。你看，很明顯地，我們對於下修指引並不滿意。如 Jeff 所說，這是我們的責任，我們承擔。但我認為非常重要的是要強調，我們相信推動我們機會的基本面非常強勁，特別是市場成長以及我們在第一線治療的動能。而當你從一開始啟動產品上市時，很難掌握每一個因素。但我們對於眼前的展望感到非常滿意，無論是在。

Near future, but also in the longer-term in reaching our 2030 goals. Jeff, do you want to add some comment?

近期，或是在更長期達成我們 2030 年目標方面。Jeff，你要補充一些看法嗎？

I mean, I'll just comment on the second-half of 26 and what the revised guidance implies, and then maybe Tolga would like to make some comments on longer-term confidence in the On Island 23rd guide. The revised guidance that we've given of $4.2 billion to $4.5 billion, in terms of the midpoint of that, just relative to the growth that we just put up in the second quarter, the midpoint to achieve the midpoint, we would need to deliver growth in Q3 and Q4 that's consistent with what we just put up in Q2. And I think we do have confidence in that, given some of the things that Tolga talked about, particularly strength in the first-line part of the market in terms of demand we saw in the quarter in the US. But Tolga, any more comments on the. In the longer-term. Yeah, maybe I'll.

我的意思是，我先就 2026 年下半年以及修訂後指引所代表的意涵做個評論，然後也許 Tolga 想就對 On Island 23rd 指引的長期信心做些補充。我們給出的修訂指引為 42 億到 45 億美元；就其中位數而言，相對於我們在第二季剛交出的成長表現，若要達到中位數，我們需要在第三季與第四季交出與第二季一致的成長。我認為我們對此有信心，基於 Tolga 提到的一些因素，特別是美國市場第一線部分在本季所看到的需求強勁。但 Tolga，對於。在更長期方面，還有其他補充嗎？是的，也許我會。

Combine both Ivan and Jeff's points, which is first and foremost, we are competing in a highly untapped market. 80% of patients remain untreated.

把 Ivan 和 Jeff 的重點結合起來：首先也是最重要的，我們是在一個高度尚未被充分開發的市場中競爭；仍有 80% 的患者未接受治療。

And within that category, in a short 15 months, we've already been able to actually build a very strong base for our business. And what's exciting about that, frankly, to me is while we're obviously normalizing our second line.

而在這個類別中，在短短 15 個月內，我們其實已經為業務建立了非常強的基礎。而令我感到興奮的是，坦白說，雖然我們的第二線。

Second-line new business, our first-line business is really rapidly replacing that. And if you think about the fact that 80% in this category comes in as new patients as first line, we really like how we're positioned.

第二線新增業務正在明顯回歸常態，但我們的第一線業務正在快速補上並取代那部分。而如果你想到這個類別中有 80% 的患者是以第一線的新患者形式進入，我們非常喜歡我們目前的定位。

With the existing prescriber basis. And as I highlighted in my remarks, one of the areas where we still need to do some work, which I believe we'll be able to do, is continue to expand our prescriber basis. And that's where we're really investing our efforts. And we've already done that. So given matching that with actually the access that we've been able to secure and good achievements rates.

以現有的開立處方醫師基礎而言。而如我在發言中強調的，我們仍需要再做一些工作、而我相信我們能做到的，是持續擴大我們的處方醫師基礎。這正是我們投入資源的重點。而我們也已經在做了。因此，將這點與我們已經爭取到的給付可近性，以及良好的核准率相結合。

Our ability to demonstrate 25% CAGR growth year-over-year is definitely within our reach.

我們逐年展現 25% CAGR 成長的能力，絕對在可達範圍之內。

And if I can add, we're actually even more confident now with the results of the CARDIO TRANSFORM study. I mean, there's likely to be one less branded competitor on the market. And Pushkar such and all the reasons why our confidence in new Korea and Triton CM is undiminished. So I think if anything, actually, we're sort of more confident about our future outlook. In these developments.

另外補充一下，隨著 CARDIO TRANSFORM 研究結果出爐，我們其實更有信心。也就是說，市場上很可能會少一個品牌競爭者。而 Pushkar 也提到各種原因，說明我們對新 Korea 和 Triton CM 的信心絲毫未減。所以我認為，如果有什麼不同的話，我們其實對未來展望更有信心。在這些進展之下。

Thank you very much for my question.

非常感謝回答我的問題。

Next question, please.

請下一題。

It's from Salvine. Salvine.

下一題來自 Salvine。Salvine。

Thanks for taking our question. This is Tommy on for Salvine. I'm curious on if you're seeing a slower rate of second-line patients, TAF progressors per year, given trends in earlier diagnosis and potentially patients staying on TAF for longer. And also, if you could maybe comment on how you expect the timing for your diagnosis. Awareness efforts to start, playing a key role in first-line capture?

謝謝讓我們提問。我是 Tommy，代 Salvine 提問。我想了解，隨著更早期的診斷趨勢、以及患者可能在 TAF 上維持更久，你們是否看到第二線患者（每年 TAF 進展者）的速度變慢？另外，也想請你們評論一下，你們預期診斷。宣導/提升認知的努力在何時開始，並在第一線患者取得上扮演關鍵角色？

Thank you.

謝謝。

That's a great question. First to talk.

這是個很好的問題。先談。

Yeah. So it's a good question around the early diagnosis. Frankly, when we started, just like any launch, when you have an orthogonal mechanism of action product like we do, we knew that there was going to be a level of pent-up demand.

是的。關於早期診斷，這確實是個好問題。坦白說，當我們開始時，就像任何產品上市一樣，當你擁有像我們這樣作用機轉正交（不同）的產品時，我們知道會有一定程度的累積需求（pent-up demand）。

And it's certainly over time, we've seen that being normalizing. So we're still seeing actually a healthy number of patients that are coming into the category. That's about 20%, both switch and combo.

而且確實隨著時間推進，我們看到那部分正在回歸常態。因此，我們仍然看到實際上有相當健康的患者數進入這個類別。大約是 20%，包含轉換（switch）與合併治療（combo）。

That will continue to be the same. What's even more important to me is these early diagnosis is actually going to hopefully help increase the category growth and accelerating that category growth. We've already seen that, it's gone up.

這部分將會維持不變。對我而言更重要的是，這些早期診斷實際上希望能幫助提升類別成長，並加速該類別的成長。我們已經看到這點，它已經上升了。

From the prior years into since we launched an acceleration of these new patients. So, in fact, those patients that are getting treated early is going to be a nice tailwind for us.

從前幾年一路到我們啟動以來，我們加速了這些新病患的導入。因此，事實上，那些能夠及早接受治療的病患，將會成為我們一股不錯的順風。

Thank you.

謝謝。

Next question, please.

請下一題。

Tazeen Ahmad, Bank of America.

Tazeen Ahmad，美國銀行。

Good morning. Thanks for taking my question. I wanted to get a little bit more color about your comments about frontline is now about 80% of new starts.

早安。謝謝讓我提問。我想更了解一些您提到的一點：一線治療目前約占新啟用的 80%。

Can you just tell me what the split is for use in community physician practices versus centers of excellence? And I guess the question that a lot of people are asking is if.

您能否說明一下，在社區醫師診所與卓越中心（centers of excellence）之間的使用占比各是多少？另外，我想很多人都在問的問題是，如果……

For better or for worse right now, physicians are looking at stabilizers as being similar in efficacy to silencers. How do you kind of maintain that growth that you're seeing in the frontline with needing to balance educating physicians, presumably community-based physicians, on the real differences between silencers and stabilizers? Thanks.

不論好壞，就目前而言，醫師把穩定劑（stabilizers）視為在療效上與沉默劑（silencers）相近。在需要平衡對醫師（推測多為社區型醫師）教育、讓他們了解沉默劑與穩定劑之間真正差異的同時，您要如何維持目前在一線治療看到的成長？謝謝。

So I'll say a few words, maybe I'll...

我先說幾句，或許我會……

Look, I mean, first and foremost, we continue to compete for category leadership against the product that's been in the market for approximately 7 years, and obviously we remain ahead of the other recent entrants.

你看，首先也是最重要的，我們持續與已在市場上約 7 年的產品競爭品類領導地位，且顯然我們仍領先其他近期進入者。

But more importantly, the...

但更重要的是……

How the business is evolving beneath the overall share I think is really important. Early in the launch, growth was more balanced between first and second-line patients. Today, a second-line demand, as we described, has moved toward a more sustainable rate. An increasing proportion of our growth is not coming from first-line patients, which represents the larger and the more durable opportunity.

我認為，在整體市占之下，業務如何演進其實非常重要。在上市初期，成長在一線與二線病患之間較為均衡。如今，如我們所述，二線需求已轉向較可持續的成長速度。我們成長中愈來愈高的比例來自一線病患，這代表更大且更具持久性的機會。

At the same time, I think this is really important, we are deepening adoption within existing accounts and rapidly expanding that prescriber base.

同時，我認為這點非常重要：我們正在既有客戶中加深採用度，並快速擴大開立處方的醫師基礎。

So we're essentially maintaining a strong overall share while improving the underlying composition of the business through a broader physician adoption. Now you brought up the point around the COEs and community experts. What's been really encouraging for us is as we establish that early base business. That business didn't just come from the CoEs. We actually had a very healthy balance of CoEs, academic centers, as well as community experts. What we need to continue to do is to actually expand out those community expert centers, and we know how to do that.

因此，我們基本上是在維持強勁整體市占的同時，透過更廣泛的醫師採用來改善業務的底層組成。你也提到了卓越中心（COEs）與社區專家這一點。令我們非常振奮的是，當我們建立早期的基礎業務時，那個業務並不只來自 COEs。我們其實在 COEs、學術中心以及社區專家之間，取得了非常健康的平衡。我們接下來需要做的，是進一步擴大那些社區專家中心，而我們知道該怎麼做。

Some of the challenges we faced with them early on was, well, okay, I don't know what the differences are between the silencers and stabilizers. Now those physicians have actually adopted Ambutra and all other stabilizers. We actually have a significantly higher market share.

我們早期在他們那裡遇到的一些挑戰是：好吧，我不知道沉默劑與穩定劑之間有什麼差異。現在那些醫師其實已經採用了 Ambutra 以及其他所有穩定劑。而我們的市占其實顯著更高。

When it comes to, oh, well, I don't know how to buy and build this product. Particularly on the community expert centers, we know how to bring them along with that, whether through building their own, helping their own practice or creating alternative sites of care for their injections. So it is something we've done already, and now we're essentially intensifying our efforts to make sure that actually that adoption curve continues to get deeper.

至於「我不知道要怎麼採購並在院內備藥（buy and build）這個產品」這件事，特別是在社區專家中心，我們知道如何協助他們上手：不論是讓他們自行建置、協助其診所運作，或是為其注射建立替代照護場域。所以這是我們已經做過的事，而現在我們基本上是在加大力道，確保採用曲線能持續加深。

And Tazeema, I'll just add to what Tolga said in response to your question. Look, there's no head-to-head data, of course, we know between these different classes of medicines. But as tried to highlight in the main presentation, we think we have actually an incredibly unique profile for AMVUTRA. It starts with the outcomes data, which we think are really quite remarkable. I've shown you substantial impact on outcomes. And importantly, the fact that.

Tazeema，我再補充 Tolga 對你問題的回應。你看，當然，這些不同藥物類別之間沒有頭對頭（head-to-head）數據，我們也知道這點。但如同我在主簡報中試圖強調的，我們認為 AMVUTRA 其實具備極其獨特的特性。首先是結局（outcomes）數據，我們認為相當令人驚豔。我已向各位展示了對結局的重大影響。而且重要的是……

We've seen now in two studies additive benefits on top of stabilizers, which suggest there is efficacy left that's not fully addressed by the stabilizers alone. It's indirect evidence, but we think it's very strong and reproducible evidence. We've also seen that starting these class of agents early, silencers, has the greatest treatment effect and even approaching almost 45% reductions in mortality, which I think is. Quite remarkable. And we're seeing evidence of disease remodeling when we look at echocardiographic parameters, we look at cardiac MRI, et cetera. So look, our job, as Tolga has highlighted, is to continue to educate on those attributes, continue to generate evidence. You've seen at recent meetings more and more that we're putting out and to continue to educate. And so as Tolga has talked about expanding the prescriber base, an important aspect is educating these prescribers on the attributes of this class of medicines. And we've seen.

我們現在在兩項研究中看到，在穩定劑之上仍有額外的加成效益，這暗示僅靠穩定劑並未完全解決所有療效空間。這是間接證據，但我們認為這是非常強且可重現的證據。我們也看到，及早使用這一類藥物（沉默劑）具有最大的治療效果，甚至死亡率降低幅度接近 45%，我認為這……相當值得注意。此外，當我們觀察心臟超音波參數、心臟 MRI 等，我們也看到疾病重塑（remodeling）的證據。所以，你看，我們的工作，如 Tolga 所強調的，是持續就這些特性進行教育、持續產生證據。你也在近期會議上看到我們發布的資料愈來愈多，並持續教育。因此，當 Tolga 談到擴大處方醫師基礎時，其中一個重要面向就是教育這些開立處方者了解這一類藥物的特性。而我們也看到……

That once they gain experience with it, that they find that it actually becomes a dominant part of their practice in terms of prescribing. So that's going to be our effort.

一旦他們累積使用經驗，就會發現就處方而言，它實際上會成為其臨床實務中的主導部分。所以這將是我們的努力方向。

Very good.

很好。

Thank you.

謝謝。

Next question.

下一題。

Kostas Biliouris, Oppenheimer.

Kostas Biliouris，Oppenheimer。

Thanks for taking our question. One on Europe.

謝謝讓我們提問。有一題關於歐洲。

Given that Vyndakel will soon be generic in Europe, to what extent do you think the commercial dynamics between Ambutra and a generic drug in Europe will reflect what may happen in the U.S. Post-2071 when Tafamidis goes genetic?

鑑於 Vyndakel 很快會在歐洲成為學名藥，您認為歐洲 Ambutra 與學名藥之間的商業動態，在多大程度上會反映美國在 2071 年後（Tafamidis 轉為學名藥之後）可能發生的情況？

Thank you.

謝謝。

Thank you very much.

非常感謝。

So thank you, Costas, for that question. First and foremost, I think we've always highlighted that the contribution of growth for Europe is going to be relatively modest, similar to the growth that we had last year. And that had a lot to do with the fact that we were going to actually make the appropriate price adjustments in order to capture a larger cardiomyopathy volume. Now, in terms of.

謝謝你，Costas，提出這個問題。首先也是最重要的，我想我們一直強調，歐洲對成長的貢獻將相對溫和，與我們去年看到的成長類似。這在很大程度上是因為我們將進行適當的價格調整，以便掌握更大的心肌病（cardiomyopathy）用量。現在，就……而言。

Tefamidis, the 80 milligram, the four pills a day option is going to be going generic. I believe 61 milligram will continue to be available for a while. Now, in respect to our ability to actually capture those reimbursements, since these are single-payer systems.

Tefamidis 的 80 毫克、每日四顆的選項將會轉為學名藥。我相信 61 毫克還會繼續供應一段時間。至於我們實際取得這些給付（reimbursements）的能力，因為這些是單一支付者（single-payer）體系。

These systems have already anticipated that genericization transition. And what I'm pleased to say is that we've actually, in most cases, been able to secure premium pricing versus Tefaminus, and quite pleased with the ongoing negotiations we have, whether it's Germany, Spain, Italy, and Japan. We highlighted the fact that we are competing very effectively, essentially exceeding all analogs.

這些體系其實已經預期到學名化（genericization）的轉換。我很高興地說，在多數情況下，我們實際上已能取得相較於 Tefaminus 的溢價定價（premium pricing），而且我們對正在進行的談判也相當滿意，不論是在德國、西班牙、義大利或日本。我們也強調過，我們的競爭非常有效，基本上表現優於所有同類產品（analogs）。

And a good uptake. So while, again, because of the pricing changes, we're going to have a modest growth contribution, particularly in '26, we see '27 and beyond the launches is going to have a meaningful impact on our overall business.

而且採用情況良好。因此，再次強調，由於定價變動，我們的成長貢獻將會是溫和的，特別是在 '26 年；我們認為 '27 年以及之後的上市產品，將對我們整體業務帶來顯著影響。

Eli Merle, Barclays.

Eli Merle，巴克萊。

Hey, guys. Thanks for taking the question. Just curious if you could give us more color on what a steady state level of second-line starts look like. I think you said 80% of starts in 2Q were from the frontline. So is 20% a steady state for second-line starts? Or do you expect that to decline over time?

嗨，各位。謝謝讓我提問。想請教能否更具體說明第二線治療啟用（starts）在穩態下大概會是什麼水準。我記得你們說 2Q 的啟用有 80% 來自第一線。那麼第二線啟用的 20% 會是穩態水準嗎？還是你們預期隨時間會下降？

And then I guess what drives your confidence that the frontline starts will continue at this cadence going forward?

另外，我想問是什麼讓你們有信心第一線啟用未來能以這樣的節奏持續？

And specifically, if you could give us more color on if we strip out. Starts, have you seen growth in first-line starts or a stable number of first-line starts each quarter? Thanks.

更具體地說，如果我們把……剔除。就啟用而言，你們看到第一線啟用有成長，還是每季第一線啟用數量維持穩定？謝謝。

I thank you for that question. I mean, just to be clear, when we talk about the 80/20 perspective, that's mainly driven by the overall category. And what we've seen essentially is not a market share loss on second lines, but the overall volume.

謝謝你的問題。我的意思是，先說清楚，當我們談 80/20 的觀點時，主要是由整體品類所驅動。我們基本上看到的並不是第二線的市占流失，而是整體量能（volume）。

Shift into a lesser contribution of the new brands from Switch Pizz for the entire category. What I'm really pleased about is while we're continuing to maintain and having a nice gradual progression of our market share, that market share growth is actually being contributed by the first-time shares. So that's actually a very healthy sign of our business. And in respect to the first-time contributions.

整個品類中，來自 Switch Pizz 新品牌的貢獻占比轉為較低。讓我非常高興的是，在我們持續維持並且讓市占呈現良好、逐步的提升之際，這個市占成長其實是由首次使用者（first-time）所貢獻。所以這對我們的業務而言是非常健康的訊號。至於首次使用者的貢獻。

As I alluded to earlier, those physicians that actually use all three products predominantly use Omutra as their first time choice. That's the analysis that we have.

如我先前提到，那些實際上三種產品都會使用的醫師，主要會把 Omutra 作為他們的首次選擇。這是我們所做的分析。

So now the question is how can we actually continue to expand the prescriber base so more physicians actually test and understand and experience Omutra because they experience.

所以現在的問題是，我們要如何持續擴大開立醫師基礎，讓更多醫師實際試用、理解並體驗 Omutra，因為他們體驗到。

Preference. And this is where we're really honing our efforts in. And we've been able to expand that prescriber base at 1,500 new prescribers since the launch. And we believe we're going to be able to continue to do that. And again, the goal has always been actually on the first line. And this normalization is just a question, actually, frankly, not just the dynamic, but also the strategy.

偏好。而這正是我們真正聚焦投入的地方。自上市以來，我們已新增 1,500 位新的開立醫師。我們相信我們能夠持續做到這點。而且再次強調，我們的目標一直都是第一線。而這種常態化其實不只是動態的問題，坦白說，也是一個策略問題。

Luca Issi, RBC.

Luca Issi，RBC。

Oh, great. Thanks so much for taking my question. Maybe a quick one for Tolga.

太好了。非常感謝讓我提問。我可能有個簡短問題想問 Tolga。

Pretty clear that AstraZeneca did not show any additive effect between stabilizer and balancers in their trial based on the press release. It got appreciated that's a different molecule as push calls, nicely articulated. But are you seeing any impact commercially based on that data? Are you seeing payers forcing docs to pick one versus the other and. No longer allowing patients to be on the combo. And he called there, much appreciated. And then super quickly, can you comment on the evolution of net price in the U.S. For the rest of the year? Thanks so much.

從新聞稿來看很清楚，AstraZeneca 在他們的試驗中並未顯示 stabilizer 與 balancers 之間有任何加成效果。也理解那是不同分子，正如 Pushkal 很清楚地闡述。但你們在商業端是否看到該數據帶來任何影響？你們是否看到付款方（payers）要求醫師二選一，不再允許病人使用合併療法（combo）？若能說明將非常感謝。另外非常快地，能否評論一下今年剩餘期間美國淨價格（net price）的走勢？非常感謝。

That's true. That's a three-parter, I guess.

沒錯。我想這是三個問題。

So maybe I'll start. I mean, obviously, Pushkal laid it out very clearly. I would believe what we believe.

那我先開始。我的意思是，很明顯 Pushkal 已經講得非常清楚。我會相信我們所相信的。

Look, in terms of the payer pushback, obviously, it's too early to say, but what I can tell you is this.

你看，就付款方的反彈而言，顯然現在下結論還太早，但我可以告訴你的是這個。

Oral access to Omotra remains very strong.

Omotra 的口服給付可近性（oral access）仍然非常強。

Some Medicare Advantage policies that are already in place that already puts limitation on combination use.

有些已經生效的 Medicare Advantage 保單，已經對合併使用設有限制。

And in fee-for-service coverage always follows the label. And frankly, physicians continue to have pathways to pursue access when they believe a particular treatment approach is medically appropriate given the severity of this disease. What's also very important is. CardioTransform does not change ANBUTRA's evidence or its label. It was a study of a different molecule. We would not expect payers to alter ANBUTRA coverage based on those results. Our priority remains ensuring appropriate patients can access ANBUTRA, whether they're initiating first-line therapy or switching from another treatment. So we're not seeing any pushback, again, given the fact that actually the policies are already in place, and yet when the physician wants.

而在按服務計費（fee-for-service）的給付中，一向是依照標籤適應症（label）走。坦白說，當醫師認為在此疾病嚴重程度下，某種治療方式在醫學上是適當的，他們仍然有途徑去爭取取得給付。另外非常重要的是，CardioTransform 並不會改變 ANBUTRA 的證據或其標籤。那是一項針對不同分子的研究。我們不預期付款方會因為那些結果而改變 ANBUTRA 的給付。我們的優先事項仍是確保合適的病人能取得 ANBUTRA，不論他們是啟動第一線治療或是從其他治療轉換。所以我們沒有看到任何反彈；同樣地，考量到相關政策其實已經存在，而當醫師想要。

To have access, they obtain it if they provide the right appropriate materials.

取得給付時，只要提供正確且適當的資料，他們就能取得。

Yeah, thanks for that. Look, I think there are many examples of drugs, in similar classes where one drug fails and the other succeeds. And we really believe what we have here are two distinct molecules with different mechanisms, as well as, different profiles and a different study. And really our job is to get out there and talk of this saying and educate physicians on the compelling benefits that we.

是的，謝謝。你看，我想在相似藥物類別中，有很多例子是一個藥失敗、另一個成功。我們確實相信，我們這裡的是兩個不同分子，具有不同機轉，也有不同的特徵（profiles），而且研究也不同。我們真正的工作是走出去，談論這些並教育醫師，讓他們了解我們所看到的具說服力的效益。

The focus on first line because we believe this should be a foundational therapy as well as explaining the benefits that we've seen in two separate studies as well as explained with respect to combination use.

聚焦第一線，因為我們相信這應該是一個基礎性治療（foundational therapy）；同時也說明我們在兩項獨立研究中看到的效益，並且就合併使用的部分加以說明。

There was one question on net price in terms of what we expect and I think the slide that told us showed that showed the first half dynamics showed the modest. Quarter-to-quarter decreases in net price, we expect that will continue for the second-half. And if we were to show you that on a year-over-year basis, the way we had guided was mid-single-digit net price decrease year-over-year. We're still on track for that, Luca.

有一個關於淨價格的問題，談到我們的預期；我想投影片已經告訴我們、也呈現了上半年動態，顯示淨價格每季有溫和的下降。我們預期下半年會延續這個趨勢。如果以年對年來看，我們先前的指引是淨價格年對年下降中個位數百分比（mid-single-digit）。Luca，我們仍然在這個軌道上。

Jessica Fye, JPMorgan.

Jessica Fye，摩根大通。

Hey, guys. Good morning. Thanks for taking my question. Question for Pushkal.

嗨，各位。早安。謝謝讓我提問。我有個問題想問 Pushkal。

Recognizing that this is hypothetical, can you elaborate on some of those potential changes available to you with Triton CM to maximize its probability of success?

我知道這是假設性的，但你能否更詳細說明，針對 Triton CM，為了最大化其成功機率，你們有哪些可能可採取的變更？

And then maybe as a follow-up to that, are there potentially other paths to approval for nucrisaran in ATTRCM beyond Triton CM? For example, would it be feasible to run a non-inferiority trial against AMBUTRA?

接著作為追問，對於 nucrisaran 在 ATTRCM 的核准，除了 Triton CM 之外，是否可能還有其他路徑？例如，是否可行針對 AMBUTRA 進行一項非劣性（non-inferiority）試驗？

Thank you.

謝謝。

Yeah, thanks, Jess, for your question. Look, again, we feel really good about what we have in our hands, both in terms of the molecule Nucreaseran for all the reasons I talked about and the.

是的，謝謝你，Jess，提出問題。你看，再次強調，我們對目前手上的進展感到非常有信心，無論是就我先前提到的各項原因而言的分子 Nucreaseran，還是就……

And the study that we have. So again, I want to reinforce, we may not need to do anything different from what we already have ongoing.

以及我們現有的研究而言。所以再次重申，我們可能不需要做任何不同於目前已在進行中的事情。

That said, we do have options at our disposal. We'll look at the data and we'll consider. I think they broadly fall into a couple of buckets. One is whether we. Modify enrollment in certain subpopulations, for instance, and enrich in certain ways for those. Again, we've done that already in the context of study, but we could potentially further do that based on information that we see. The other thing would be to make modifications around the analytic plan in terms of how we think about various endpoints, the hierarchy, etc.

話雖如此，我們確實有一些可用的選項。我們會檢視數據並加以考量。我認為大致可歸納為幾個面向。其中之一是我們是否要……例如，調整特定亞族群的入組，並以某些方式進行富集。同樣地，我們在本研究的設計脈絡中已經做過這些，但我們也可能根據所看到的資訊進一步調整。另一個則是針對分析計畫做修改，也就是我們如何看待各個終點、層級排序等。

And so they're largely in those two big buckets. I mean, to the second part of your question, is there a possibility that if we wanted to, we could do additional studies? Yes, certainly those things are potential.

因此主要就是這兩大類。至於你問題的第二部分，如果我們想的話，是否有可能再做額外研究？是的，當然，這些都是可能的選項。

I'm not going to speculate though further on what those might look like, but I think broadly speaking, I think there's a variety of options that are in. Again, we're playing the long game here. I think our commitment is to deliver a successful study. We've done that in the past. We think Nucreciran has the opportunity to be an amazing medicine for patients and we're committed to delivering a positive study for that. And so we will consider all the potential options at hand. As I said, they fall into several key buckets.

不過我不會進一步臆測那些研究可能會長什麼樣子，但我認為整體而言，有各式各樣的選項可供……再次強調，我們是在打長期戰。我們的承諾是交付一項成功的研究。我們過去做到了。我們認為 Nucreciran 有機會成為對病患非常出色的藥物，我們也致力於為此交付一項正向的研究結果。因此，我們會考量手上所有潛在選項。如我所說，它們可歸納為幾個關鍵面向。

And we'll kind of consider all those opportunities and see if anything at all is warranted.

我們會逐一評估所有這些機會，看看是否有任何事情確實值得採取。

Whitney Ijem, Canaccord Genuity.

Whitney Ijem，Canaccord Genuity。

Hey, guys. Thanks very much for taking my question.

嗨，各位。非常感謝讓我提問。

Sorry if I missed it, but can you remind us on any updated thinking, I guess, around the total U.S. Patient population or TAM for ATT-RCM and where you are with diagnosis rates currently? And then just as a point of comparison ahead of the 6,400 Phase 2 data later this year, what are the comparable numbers for HHT-US TAM in terms of patient numbers and diagnosis rates? Thanks.

如果我漏聽了很抱歉，但你們能否提醒我們，關於 ATT-RCM 在美國的總病患人數或可服務市場（TAM）的最新看法，以及目前診斷率的進展到哪裡？另外，作為今年稍晚 6,400 期第 2 期數據公布前的比較，HHT-US 的 TAM（就病患人數與診斷率而言）可比的數字是多少？謝謝。

For TTR, what I can tell you is in our less estimates, if you go back to our TTR webinar, we've highlighted, we estimate around 200,000 patients and about 80% of those remain untreated. What to me is sort of a good confirmatory data set is the fact that you're seeing around 40% year-over-year growth of the category with a single.

就 TTR 而言，我能告訴你的是，依我們的估算，如果你回去看我們的 TTR 網路研討會，我們曾強調我們估計約有 200,000 名病患，其中約 80% 仍未接受治療。對我來說，一個相當好的佐證數據集是：你看到在只有單一……的情況下，該類別仍有約 40% 的年增長。

Option on the table that has actually accelerated since we launched, and that remains very robust. So we believe more competitors, more awareness, more education, and frankly, some of those initiatives that we've just actually laid. Will continue to help accelerate those patients getting diagnosed. And as you all know, we have excellent data that demonstrates those patients that are treated earlier end up actually getting more benefits from Omutra. So we're very actually excited about that. And again, our position on first line gives us the confidence that we can actually continue to be the leading.

而且自我們上市以來，這個增速其實還加快了，且依然非常強勁。因此我們相信，更多競爭者、更高的認知度、更多教育，以及坦白說，我們剛剛提出的部分倡議……將持續幫助加速這些病患獲得診斷。而且各位都知道，我們有非常好的數據顯示，越早接受治療的病患，實際上能從 Omutra 獲得更多益處。所以我們對此其實非常興奮。再者，我們在一線治療的定位也讓我們有信心，能夠持續成為領先的……

Leading option on the table in this growing category.

在這個成長中的類別裡，持續成為桌面上的領先選項。

Yeah, and with regard to hereditary hemorrhagic telangiectasia, there really are no approved treatments for this disease. It's actually the second most common rare bleeding disorder that's out there. I think globally there's about one and a half million patients with this disease. I think when we think about the addressable population in the United States, I think, again, those estimates vary. I think there's a number of these patients who don't actually get to medical attention. But we think there's probably about 70,000 or so patients in the United States who may be addressable with this condition. But, again, that epidemiology will firm up. Again, as we've seen with rare diseases where there aren't treatments, once there are effective treatments, more and more come to attention. So that's probably a ballpark, though, for you.

是的，至於遺傳性出血性毛細血管擴張症（hereditary hemorrhagic telangiectasia），目前確實沒有任何獲批的治療可用於這個疾病。它其實是第二常見的罕見出血性疾病。我想在全球大約有 150 萬名病患罹患此病。當我們思考美國可觸及的人群時，我認為同樣地，這些估算會有所差異。我想其中有不少病患其實並未就醫。但我們認為，美國大概有約 70,000 名左右的病患可能屬於此病況的可觸及人群。不過，再次強調，這些流行病學數據會逐步更明確。同樣地，正如我們在沒有治療選項的罕見疾病中所見，一旦出現有效治療，會有越來越多病患被發現並進入醫療體系。所以這大概是一個供你參考的概略數字。

Thank you.

謝謝。

And that concludes our question-and-answer session. I will hand it back to the company for closing remarks.

以上為我們的問答環節。我將把時間交回公司進行結語。

Thank you. So to close, we continue to build momentum across our business as we execute against our strategy and advance towards our 2030 goals. And I'd like to thank everyone who's joined us today.

謝謝。最後，我們在執行策略並朝 2030 年目標邁進的同時，持續在整體業務上累積動能。也感謝今天所有與會者的參與。

Thank you.

謝謝。

Thank you, presenters. And ladies and gentlemen, this concludes today's conference call.

謝謝各位簡報者。各位女士、先生，今天的電話會議到此結束。

Thank you all for joining. You may now disconnect.

感謝各位參與。您現在可以掛線。