Madrigal Pharmaceuticals Inc (MDGL) 2025 Q3 法說會逐字稿

Good morning, and thank you for standing by. Welcome to the Madrigal Pharmaceuticals Third Quarter 2025 Earnings Conference Call. (Operator Instructions) As a reminder, today's conference call is being recorded.

早上好，感謝您的耐心等待。歡迎參加 Madrigal Pharmaceuticals 2025 年第三季財報電話會議。（操作員說明）提醒各位，今天的電話會議正在錄音。

I'd now like to introduce Ms. Tina Ventura, Chief Investor Relations Officer. Please go ahead.

現在我謹向大家介紹首席投資者關係長蒂娜·文圖拉女士。請繼續。

Thanks, Marvin. Good morning, everyone, and thank you for joining us to discuss Madrigal's third quarter 2025 earnings. We issued a press release this morning and posted a slide deck that accompanies this webcast on the Investor Relations section of our website. On the call with me today is Bill Sibold, Chief Executive Officer; Dave Soergel, Chief Medical Officer; and Mardi Dier, Chief Financial Officer. They will provide prepared remarks, and then we'll take your questions.

謝謝你，馬文。各位早安，感謝各位參加本次關於 Madrigal 2025 年第三季收益的討論。今天早上我們發布了新聞稿，並在我們網站的投資者關係部分發布了與本次網路直播配套的幻燈片。今天和我一起通話的有：執行長 Bill Sibold；首席醫療官 Dave Soergel；以及財務長 Mardi Dier。他們會發表事先準備好的講話，然後我們會回答你們的問題。

Please note on slide 2, we will be making certain forward-looking statements today. We refer you to our SEC filings for a discussion of the risks that may cause actual results to differ from the forward-looking statements.

請注意，在第二張投影片中，我們今天將做出一些前瞻性陳述。有關可能導致實際結果與前瞻性陳述有差異的風險的討論，請參閱我們向美國證券交易委員會提交的文件。

With that, I will now turn the call over to Bill.

接下來，我將把電話交給比爾。

Thanks, Tina. Good morning, and thanks for joining us. We have delivered another excellent quarter as we continue to execute on our strategic priorities. We're maximizing the value of Rezdiffra and building our pipeline, which sets us up for continued value creation. Rezdiffra is quickly becoming one of the most successful specialty launches in the industry with sales now annualizing at greater than $1 billion in only its sixth quarter of launch.

謝謝你，蒂娜。早安，感謝各位的參與。我們繼續推進策略重點工作，又取得了優異的季度業績。我們正在最大限度地發揮 Rezdiffra 的價值並建立我們的產品線，這為我們持續創造價值奠定了基礎。Rezdiffra 正迅速成為業界最成功的特藥上市產品之一，上市僅六個季度，年銷售額就已超過 10 億美元。

More than 29,500 patients are being treated with Rezdiffra and more than 10,000 healthcare providers have prescribed it. We've made great progress on our 2026 payer contracting strategy for first-line access. Our new US Rezdiffra patent was listed in the orange book. It extends Rezdiffra's value into 2045. And we're expanding globally with our launch in Germany following European approval.

目前已有超過 29,500 名患者接受 Rezdiffra 治療，超過 10,000 名醫療保健提供者開立了該藥物的處方。我們在 2026 年第一線醫療服務准入支付方合約策略方面取得了巨大進展。我們新獲得的美國Rezdiffra專利已列入橙皮書。它將 Rezdiffra 的價值延續到 2045 年。在獲得歐洲批准後，我們將在德國推出產品，從而實現全球擴張。

On the pipeline front, we're advancing our Phase 3 MAESTRO-NASH outcomes trial in F4c, where we could once again be first to market this time for compensated MASH cirrhosis. We look forward to sharing more from our F4c open-label cohort at AASLD later this week. We're executing on our Rezdiffra combination strategy, where we completed the transaction of our new oral GLP-1, and we continue to evaluate opportunities to add additional assets to our pipeline through business development.

在研發管線方面，我們正在推動 F4c 患者的 3 期 MAESTRO-NASH 結果試驗，我們有望再次成為首家上市的代償性 MASH 肝硬化患者。我們期待在本週稍後的 AASLD 會議上分享更多關於我們 F4c 開放標籤隊列的研究結果。我們正在執行 Rezdiffra 組合策略，我們已完成新的口服 GLP-1 的交易，並且我們將繼續評估透過業務發展為我們的產品線添加其他資產的機會。

So today, we'll focus on our two key priorities, our top line and our pipeline. Starting with Rezdiffra's third quarter performance on slide 4, we delivered net sales of $287 million, up 35% quarter-over-quarter. The significant demand we're generating is driven by the positive response to Rezdiffra from prescribers and patients and the strong execution by our team.

所以今天，我們將重點放在兩個關鍵優先事項：營收和產品線。從 Rezdiffra 第三季的業績（見投影片 4）開始，我們實現了 2.87 億美元的淨銷售額，季增 35%。我們所創造的巨大需求，源自於處方醫生和患者對 Rezdiffra 的正面迴響，以及我們團隊的出色執行。

As shown on slide 5, we ended the third quarter with more than 29,500 patients on Rezdiffra, up from more than 23,000 patients at the end of the second quarter. This number represents patients actively on therapy accounting for any discontinuations. As we've discussed since the beginning of our launch, we've been steadily adding patients each quarter, and we expect that to continue going forward.

如投影片 5 所示，截至第三季末，接受 Rezdiffra 治療的患者超過 29,500 人，高於第二季末的 23,000 多人。該數字代表正在接受治療的患者人數，已計入任何中止治療的情況。正如我們自公司成立以來一直討論的那樣，我們每個季度都在穩步增加患者數量，我們預計這種情況將持續下去。

It's incredibly gratifying to see Rezdiffra already making a meaningful difference for so many patients. But what's most exciting is that we've only just begun. More than 90% of our 315,000 target population remains untreated. That leaves tremendous room for growth driven by Rezdiffra's highly differentiated profile and our clear first-mover advantage.

看到 Rezdiffra 已經為這麼多患者帶來了顯著的改變，真是令人無比欣慰。但最令人興奮的是，我們才剛開始。在我們31.5萬目標族群中，超過90%的人仍未接受治療。這為 Rezdiffra 帶來了巨大的成長空間，這得益於其高度差異化的市場定位和我們明顯的先發優勢。

Moving to slide 6 and our continued progress on physician penetration. As I've said before, building a strong prescriber base early in the launch is one of the best indicators of long-term success. That's why the pace of adoption has been so encouraging. This quarter, we hit another launch milestone, more than 10,000 prescribers. This breadth achieved this quickly is at the high end of the benchmarks we track, and it reflects the work we've done to wire the system.

接下來是第 6 張投影片，我們將繼續探討醫生普及率的進展。正如我之前所說，在產品上市初期建立強大的處方醫生基礎是長期成功的最佳指標之一。這就是為什麼普及速度如此令人鼓舞的原因。本季度，我們又達到了一個重要的上市里程碑，處方醫生人數超過 10,000 人。如此迅速地達到如此廣度，在我們追蹤的基準中處於較高水平，這反映了我們為建置系統所做的工作。

Looking ahead, our focus will increasingly shift to depth. This metric is already tracking at the high end of best-in-class launches. We're also continuing to enhance our targeting. While our efforts have mostly centered on hepatologists and gastroenterologists, we're seeing growing interest from endocrinologists. These are specialists with a deep expertise in metabolic health who are interested in Rezdiffra's mechanism and its potential in MASH. In response, we've expanded our field team to further target this group. These efforts substantially started in the fourth quarter.

展望未來，我們的焦點將越來越轉向深度研究。該指標已達到同類最佳產品發布水準的高端水準。我們也在不斷改進我們的目標定位。雖然我們的工作主要集中在肝病學家和胃腸病學家身上，但我們看到內分泌學家也越來越感興趣。這些專家在代謝健康領域擁有深厚的專業知識，他們對 Rezdiffra 的作用機制及其在 MASH 中的潛力很感興趣。為此，我們擴大了外勤團隊，以進一步鎖定這群人。這些努力基本上是從第四季開始的。

On slide 7, let's take a look at how we see the MASH market evolving. We see clear parallels between MASH and other large chronic disease markets like IBD, rheumatoid arthritis and psoriasis. Each of these evolved into multibillion-dollar categories through continuous innovation driven by new mechanisms and tailored treatment regimens that address diverse patient needs. We believe MASH will follow that same path.

在第 7 張投影片中，讓我們來看看 MASH 市場的發展趨勢。我們看到 MASH 與其他大型慢性病市場（如 IBD、類風濕性關節炎和乾癬）之間有明顯的相似之處。透過不斷創新，以及新機制和針對不同患者需求的客製化治療方案，這些都發展成為價值數十億美元的類別。我們相信《陸軍野戰醫院》（MASH）也會走上同樣的道路。

Today, this market is still in its early stages, essentially where those categories were two decades ago, but with one important difference, Rezdiffra's profile. As an effective liver-directed well-tolerated oral medicine, it far surpasses that of the other first-to-market products in those diseases. We believe this gives us a durable advantage and a unique opportunity to lead and shape the market's evolution, first with Rezdiffra and next with the pipeline we are building.

如今，這個市場仍處於起步階段，基本上與二十年前的那些類別一樣，但有一個重要的區別，那就是 Rezdiffra 的概況。作為一種療效顯著、耐受性良好的肝臟標靶口服藥物，它遠遠優於其他同類疾病的首批上市產品。我們相信這將為我們帶來持久的優勢和獨特的機遇，引領和塑造市場的發展，首先是 Rezdiffra，接下來是我們正在建立的產品線。

So we welcome new entrants to this evolving market. Wegovy's recent approval in MASH adds momentum to a market that's just starting to take shape. As seen on slide 8, our focus remains on the 315,000 diagnosed patients with moderate to advanced fibrosis. Novo is targeting a much larger population, which will raise awareness and drive more screening, diagnosis and treatment.

因此，我們歡迎新企業進入這個不斷發展的市場。Wegovy 最近在 MASH 中獲批，為這個剛開始成形的市場注入了新的動力。如幻燈片 8 所示，我們的重點仍然是 315,000 名被診斷出患有中度至重度纖維化的患者。諾和諾德的目標族群規模更大，這將提高人們的意識，並推動更多的篩檢、診斷和治療。

As a reminder, GLP-1s aren't new. They have been available for over a decade and are already used to treat the metabolic comorbidities that oftentimes accompany MASH. As we've reported, about 50% of Rezdiffra patients are currently on or have previously been on a GLP-1. We also understand the limitations of GLP-1 monotherapy in MASH. Few patients reach and sustain a therapeutic dose and tolerability remains a real challenge.

需要提醒的是，GLP-1 並不是新發現的物質。這些藥物已經上市十多年了，並且已經用於治療 MASH 常伴隨發生的代謝合併症。正如我們所報導的那樣，約 50% 的 Rezdiffra 患者目前正在接受或曾經接受過 GLP-1 治療。我們也了解 GLP-1 單藥治療在 MASH 的限制。很少有患者能夠達到並維持治療劑量，耐受性仍然是一個真正的挑戰。

Real-world data show that 70% of obese patients discontinue within one year. New data to be presented at AASLD show similar discontinuation rates in patients with MASLD. So looking ahead, we expect Rezdiffra to benefit in two ways: as first-line therapy in a market that will expand and from the high real-world discontinuation rates of GLP-1s. We're in a strong position and are confident in Rezdiffra's growth potential going forward.

真實世界的數據顯示，70%的肥胖患者會在一年內停止治療。AASLD 即將公佈的新數據顯示，MASLD 患者的停藥率與此類似。展望未來，我們預期 Rezdiffra 將從兩個方面受益：作為第一線療法，市場將會擴大，以及 GLP-1 類藥物在現實世界中較高的停藥率。我們目前處於有利地位，並且對 Rezdiffra 未來的成長潛力充滿信心。

As we've already mentioned, it's Rezdiffra's best-in-class profile that gives us such strong confidence as summarized on slide 9. It is a liver-directed medicine that delivers consistent efficacy across F2/F3 fibrosis, BMI, genetic makeup in patient subtypes, including those with type 2 diabetes who comprise approximately 60% of the MASH population. It's also simple to use. It's a once-daily, well-tolerated pill with no titration requirements. That simplicity matters to providers, to patients and ultimately to adherence. We continue to see strong adherence consistent with other well-tolerated oral therapies.

正如我們已經提到的，Rezdiffra 一流的性能讓我們對其充滿信心，正如幻燈片 9 中所總結的那樣。它是一種針對肝臟的藥物，對 F2/F3 纖維化、BMI、遺傳組成等不同患者亞型具有一致的療效，包括約佔 MASH 人群 60% 的第 2 型糖尿病患者。它也很容易使用。這是一種每日服用一次、耐受性良好的藥片，無需逐漸增加劑量。這種簡便性對醫療服務提供者、患者以及最終的依從性都至關重要。我們持續觀察到良好的依從性，這與其他耐受性良好的口服療法一致。

The seriousness of MASH and Rezdiffra's compelling profile continue to resonate with payers. Our objective is to provide first-line access to patients, preserving treatment choice for patients and providers, and we're pleased to share an update on slide 10. We're making great progress with our payer negotiations for 2026, which to date have resulted in contracts for broad first-line access, no step edit requirements and improvements in utilization management criteria that are better aligned with clinical practice.

MASH 的嚴重性和 Rezdiffra 引人注目的案例繼續引起支付方的共鳴。我們的目標是為患者提供第一線治療途徑，同時保障患者和醫護人員的治療選擇權，我們很高興在第 10 張投影片上分享最新進展。我們在與支付方就 2026 年進行的談判中取得了巨大進展，迄今為止，談判已達成了廣泛的一線用藥准入合同，沒有步驟編輯要求，並且改進了利用管理標準，使其與臨床實踐更加一致。

Overall, the dialogue has been collaborative and productive and discussions are progressing really well. Payers understand the seriousness of the disease, the unique clinical value of Rezdiffra and the importance of access and choice for patients and providers. We've already achieved favorable outcomes with several national payers, while continuing constructive dialogue with others. We're encouraged by the progress and expect contracts to be finalized by the end of the year, covering the vast majority of commercial lives.

整體而言，對話富有合作性和成效，討論進展非常順利。支付者了解這種疾病的嚴重性、Rezdiffra 獨特的臨床價值以及患者和醫療服務提供者獲得治療和選擇的重要性。我們已經與幾家國家級支付方取得了令人滿意的成果，同時繼續與其他支付方進行建設性對話。我們對目前的進展感到鼓舞，預計到年底將完成合約簽訂，涵蓋絕大多數商業人壽保險。

Gross to net management remains a core component of our strategy and guides how we approach payer contracting. We started contracting in April of this year. And as we've said, it wasn't everywhere and wasn't all at once. In fact, through the third quarter, contracting had a minimal impact on gross to net, reflecting our disciplined approach.

總淨值管理仍然是我們策略的核心組成部分，並指導我們如何與付款方簽訂合約。我們從今年四月開始簽訂合約。正如我們所說，它並非遍及所有地方，也不是同時發生的。事實上，第三季以來，合約簽訂對毛利潤與淨利的影響微乎其微，這反映了我們嚴謹的經營方式。

Now that we expect to have payer contracts finalized in the fourth quarter for either an immediate or a January 1 implementation, we expect the fourth quarter gross to net to be at the midpoint of the 20% to 30% range we had previously discussed.

鑑於我們預計將在第四季度最終確定付款方合同，以便立即實施或於 1 月 1 日實施，我們預計第四季度毛利與淨利之比將處於我們之前討論過的 20% 至 30% 範圍的中點。

Starting in the first quarter and continuing throughout 2026, we expect our gross to net impact to be in the high 30% range, which is consistent with other innovative multibillion-dollar specialty medicines. So objectively, we're in a great position. We are executing on one of the most successful specialty launches in the industry with less than 10% of our target market treated, the growth opportunity ahead is substantial.

從第一季開始，一直持續到 2026 年，我們預計毛利與淨利之比將達到 30% 以上，這與其他數十億美元的創新專科藥物一致。客觀來說，我們處境非常有利。我們正在執行業界最成功的特藥上市計畫之一，目標市場接受治療的人數不到 10%，未來的成長機會龐大。

We have taken a thoughtful approach to contracting, which provides for outstanding patient access and durable long-term growth. In short, this strategy paves our path to peak sales. Beyond the US, we are expanding access to Rezdiffra as shown on slide 11. We're taking a focused country-by-country approach in Europe and launched in Germany at the end of September.

我們採取了周全的合約簽訂方式，從而為患者提供了良好的就醫機會，並實現了可持續的長期增長。簡而言之，這項策略為我們實現銷售巔峰鋪平了道路。除美國以外，我們正在擴大 Rezdiffra 的使用範圍，如幻燈片 11 所示。我們在歐洲採取了有針對性的、逐個國家推進的方式，並於9月底在德國啟動了該計畫。

Just like in the US, the team is wiring the system for a first-in-disease launch. This requires educating physicians on the risks of MASH and the urgency to treat. We are also driving change in clinical practice to develop processes for patient identification, diagnosis and use of noninvasive tests. This work happens practice by practice to help develop the infrastructure for sustained adoption. The team is off to a great start, and we anticipate our efforts will start to make an impact in 2026.

就像在美國一樣，該團隊正在為率先推出針對特定疾病的療法而進行系統性建構。這就需要對醫生進行教育，讓他們了解 MASH 的風險以及治療的迫切性。我們也在推動臨床實踐的變革，以製定患者識別、診斷和使用非侵入性檢測的流程。這項工作是透過實踐逐步推進的，旨在為持續推廣應用奠定基礎。團隊開局良好，我們預計我們的努力將在 2026 年開始產生影響。

Now I'll turn it to Dave to discuss the second pillar of our strategy, expanding our pipeline to extend our leadership and build long-term value. Dave?

現在我將把話題交給戴夫，讓他來討論我們策略的第二個支柱，即擴大我們的產品線，以鞏固我們的領先地位並創造長期價值。戴夫？

Thanks, Bill. It's an incredibly exciting time to be at Madrigal. Over the past six months, I've had the opportunity to work closely with this exceptional team. And the more I dug into our programs, the more energized I've become about what we're building. We're not just advancing a pipeline, we're laying the foundation to transform how MASH is treated.

謝謝你，比爾。現在加入 Madrigal 真是令人無比興奮。在過去的六個月裡，我有幸與這支傑出的團隊密切合作。我越深入了解我們的項目，就越對我們正在建立的事業充滿熱情。我們不只是在推動一條生產線，我們更是在為改變 MASH 的治療方式奠定基礎。

As shown on slide 12, we already have a robust clinical program for Rezdiffra. Our Phase 3 MAESTRO-NASH outcomes trial in compensated NASH cirrhosis or F4c, is expected to read out in 2027. Positive results could make Rezdiffra the first approved therapy for F4c and support full approval in F2/F3. Our ongoing Phase 3 MAESTRO-NASH trial in F2/F3 MASH is expected to read out in 2028 and would also support full FDA approval.

如投影片 12 所示，我們已經為 Rezdiffra 制定了完善的臨床方案。針對代償性 NASH 肝硬化或 F4c 的 3 期 MAESTRO-NASH 結果試驗預計將於 2027 年公佈結果。正面的結果可能使 Rezdiffra 成為首個獲準用於 F4c 的療法，並支持其在 F2/F3 中得到全面批准。我們正在進行的針對 F2/F3 MASH 的 3 期 MAESTRO-NASH 試驗預計將於 2028 年公佈結果，並有望獲得 FDA 的全面批准。

Beyond Rezdiffra, we're building a pipeline through our business development efforts. To date, we've added an oral GLP-1 now called MGL-2086, which we intend to develop in combination with resmetirom to deliver a best-in-disease, well-tolerated oral combination. As we think about how to build our pipeline further, we're looking for mechanisms that fit scientifically, strategically and commercially, those with complementary biology and combination potential.

除了 Rezdiffra 之外，我們還透過業務拓展工作來建立銷售管道。到目前為止，我們已經添加了一種口服 GLP-1，現在稱為 MGL-2086，我們打算將其與 resmetirom 聯合開發，以提供一種在疾病治療方面最佳、耐受性良好的口服組合。當我們思考如何進一步建立我們的產品線時，我們正在尋找在科學、策略和商業上都合適的機制，以及那些具有互補生物學和組合潛力的機制。

Continued success in treating patients will come from combining mechanisms and tailoring treatment regimens to specific risk factors, much like what we've seen in other chronic complex diseases. With Rezdiffra's patent protection into 2045, we can be thoughtful and disciplined and build the right kind of pipeline that will define the future of MASH care.

治療患者的持續成功將來自於結合各種機制，並根據特定風險因素量身定制治療方案，就像我們在其他慢性複雜疾病中所看到的那樣。由於 Rezdiffra 的專利保護期至 2045 年，我們可以深思熟慮、嚴謹自律，建立正確的研發管線，從而定義 MASH 護理的未來。

The combination of our oral GLP-1 and THR beta agonist is a great example of this approach to building the pipeline. For MAESTRO-NASH, we know that even a modest amount of weight loss enhances resmetirom's efficacy. So unlike incretin monotherapies that strive for double-digit weight loss, we've seen that as little as 5% weight loss can enhance Rezdiffra's efficacy in MASH.

我們的口服 GLP-1 和 THR β 激動劑的組合，正是這種建構產品線方法的一個很好的例子。對於 MAESTRO-NASH，我們知道即使是適度的體重減輕也能增強 resmetirom 的療效。因此，與力求減重兩位數的腸促胰素單藥療法不同，我們發現，即使減重 5%，也能增強 Rezdiffra 在 MASH 中的療效。

This will allow us to dose escalate the MGL-2086 component of the combination with the goal of optimizing both efficacy and tolerability in a once-daily oral pill. It is also important to note that with the combination, patients would be on an effective dose of resmetirom on day 1 as the MGL-2086 dose is being adjusted in contrast to injectable incretin monotherapies that require a lengthy titration period.

這將使我們能夠增加組合藥物中 MGL-2086 成分的劑量，以期在每日一次的口服藥片中優化療效和耐受性。值得注意的是，採用這種聯合療法，患者在第一天就能獲得有效劑量的瑞美替羅，因為 MGL-2086 的劑量正在調整中，這與需要較長滴定期的注射用腸促胰素單藥療法不同。

On slide 13, we see how these mechanisms could work well together. GLP-1 works from the outside in, improving systemic metabolism, insulin sensitivity and weight loss. Rezdiffra works from the inside out, reversing hypothyroidism in the liver, restoring mitochondrial function and increasing fat processing through beta oxidation. The combined mechanisms lead to lower levels of inflammation and inhibition of stellate cell activation and downstream fibrosis. By combining these complementary mechanisms, we expect to see greater reductions in both liver fat and fibrosis. We plan to start a Phase 1 trial for MGL-2086 in the first half of next year.

在第 13 張投影片中，我們可以看到這些機制如何協同運作。GLP-1 由外而內發揮作用，改善全身代謝、胰島素敏感性和減肥效果。Rezdiffra 從內而外發揮作用，逆轉肝臟中的甲狀腺功能減退，恢復粒線體功能，並透過 β 氧化增加脂肪代謝。這些綜合機制可降低發炎水平，抑制星狀細胞活化和下游纖維化。透過結合這些互補機制，我們期望能夠看到肝臟脂肪和纖維化程度的更大程度降低。我們計劃於明年上半年啟動 MGL-2086 的 1 期臨床試驗。

Next, let's move to our Phase 3 MAESTRO-NASH outcomes trial in compensated MASH cirrhosis or F4c on slide 14. People living with F4c MASH today have no effective treatment options that prevent progression of their disease to decompensated cirrhosis. Our two-year open-label extension data presented at EASL earlier this year demonstrates sustained efficacy of Rezdiffra in this population and supports our confidence in the ongoing MAESTRO-NASH outcomes trial.

接下來，讓我們來看看投影片 14 中關於代償性 MASH 肝硬化或 F4c 的 3 期 MAESTRO-NASH 結果試驗。目前患有 F4c MASH 的患者沒有有效的治療方案來阻止病情發展為失代償性肝硬化。我們今年稍早在 EASL 上公佈的兩年開放標籤擴展數據顯示，Rezdiffra 在該族群中具有持續療效，並增強了我們對正在進行的 MAESTRO-NASH 結果試驗的信心。

Knee liver stiffness decreased by 6.7 kilopascals at two years, a statistically significant reduction from baseline. More than half the patients achieved at least a 25% reduction in liver stiffness, a level tied to improved outcomes. And 65% of patients with clinically significant portal hypertension or CSPH, at baseline moved to a lower risk category by year 2.

兩年後，膝關節肝硬度降低了 6.7 千帕，與基線相比有統計學意義上的顯著降低。超過一半的患者肝臟硬度降低了至少 25%，這一水平與治療效果的改善有關。65% 的基線時患有臨床顯著性門靜脈高壓 (CSPH) 的患者，到第 2 年時風險等級降低。

CSPH is a key driver of the most severe outcomes of cirrhosis and marks the tipping point into decompensated disease. Improvement in CSPH suggests Rezdiffra could delay or even prevent life-threatening complications. We'll be presenting new data from this two-year open-label F4c cohort at AASLD later this week, as noted on slide 15.

CSPH 是導致肝硬化最嚴重後果的關鍵因素，也是疾病失代償的轉捩點。CSPH 的改善顯示 Rezdiffra 可以延緩甚至預防危及生命的併發症。如幻燈片 15 所示，我們將在本週稍後在 AASLD 上展示這項為期兩年的開放標籤 F4c 隊列研究的新數據。

And what I'm really excited about is that this data shows promising efficacy in even the most advanced F4c patients who are on the cusp of progressing to liver decompensation. This is the first time any data will be shown in such a severe population, which gives us additional confidence in our outcomes trial. Also at AASLD from our Phase 3 MAESTRO NAFLD-1 trial, we'll highlight how F2/F3 patients progress when Rezdiffra treatment is interrupted, demonstrating the importance of staying on therapy.

真正讓我感到興奮的是，這些數據表明，即使是對於病情最嚴重的 F4c 患者（即將發展為肝功能失代償），該療法也顯示出良好的療效。這是首次在如此嚴重的患者群體中展示任何數據，這讓我們對試驗結果更有信心。此外，在 AASLD 會議上，我們將透過我們的 3 期 MAESTRO NAFLD-1 試驗，重點介紹 F2/F3 患者在 Rezdiffra 治療中斷時的病情進展情況，以此證明堅持治療的重要性。

We'll also share multiple posters that examine early real-world experience with Rezdiffra and the burden of uncontrolled MASH across health systems. In total, MASH will have 15 abstracts, including two oral presentations and two posters of distinction.

我們也將分享多張海報，探討 Rezdiffra 的早期真實世界經驗以及不受控制的 MASH 對整個醫療系統造成的負擔。MASH 會議將總共有 15 篇摘要，其中包括兩篇口頭報告和兩篇優秀海報。

With that, I'll hand over to Mardi.

接下來，我將把麥克風交給瑪蒂。

Yes. Thank you, Dave. Turning to slide 16 and a summary of our financials. Third quarter 2025 net sales totaled $287.3 million, up 35% from the second quarter of 2025. This was another strong demand quarter.

是的。謝謝你，戴夫。請翻到第 16 頁，查看我們的財務狀況摘要。2025 年第三季淨銷售額總計 2.873 億美元，較 2025 年第二季成長 35%。這又是一個需求強勁的季度。

As Bill mentioned, we're making great progress with our contracting discussions for continued broad first-line access to Rezdiffra in 2026, with no step-through requirements and improved utilization management criteria.

正如比爾所提到的，我們在合約談判方面取得了巨大進展，以確保在 2026 年繼續廣泛地獲得 Rezdiffra 的一線治療，沒有過渡要求，並改進了使用管理標準。

As a reminder, there are several components to gross to net, including commercial rebates, government rebates, co-pay assistance costs and channel distribution costs. Across the board, the team has done an exceptional job managing these dynamics, and we're seeing minimal impact through the third quarter of this year.

需要提醒的是，毛利與淨利之間存在多個組成部分，包括商業回扣、政府回扣、共同支付援助成本和通路分銷成本。總體而言，團隊在應對這些動態方面做得非常出色，我們看到今年第三季受到的影響微乎其微。

As certain contracts take effect in the fourth quarter, we anticipate a step-up in the gross to net impact to the midpoint of our 20% to 30% range, resulting in a full year average near the low end of that range, a great outcome for 2025.

隨著某些合約在第四季度生效，我們預計毛利與淨利之比將上升至我們 20% 至 30% 範圍的中點，從而使全年平均值接近該範圍的低端，這對 2025 年來說是一個很好的結果。

Looking ahead to 2026, we expect the full effect of our payer agreements to begin January 1, bringing our total gross to net impact into the high 30% range, consistent with specialty medicine analogs. As noted, we are confident that we will continue to steadily add Rezdiffra patients, and we expect robust net sales growth for Rezdiffra in 2026 and beyond.

展望 2026 年，我們預計支付方協議的全部效力將於 1 月 1 日開始生效，屆時我們的總毛利淨利差將達到 30% 以上，與專科藥物類似物一致。如前所述，我們有信心繼續穩定增加 Rezdiffra 患者數量，並預計 Rezdiffra 在 2026 年及以後將實現強勁的淨銷售額成長。

R&D expenses for the third quarter of 2025 were $174 million compared to $68.7 million in the third quarter of 2024. The increase was primarily due to the one-time $117 million expense associated with the global licensing agreement for MGL-2086. This was expensed in the third quarter and will impact fourth quarter cash flows.

2025 年第三季的研發費用為 1.74 億美元，而 2024 年第三季的研發費用為 6,870 萬美元。此次成長主要是由於與 MGL-2086 全球授權協議相關的一次性 1.17 億美元支出。這筆費用已計入第三季支出，並將影響第四季的現金流。

SG&A expenses for the third quarter of 2025 were $209.1 million compared to $107.6 million in the third quarter of 2024. The increase primarily reflects the annualization of higher commercial investment to support the Rezdiffra launch.

2025 年第三季的銷售、一般及行政費用為 2.091 億美元，而 2024 年第三季為 1.076 億美元。這一成長主要反映了為支持 Rezdiffra 的上市而增加的商業投資的年度化。

Looking ahead, we expect fourth quarter R&D expenses to be modestly higher than third quarter levels, excluding the third quarter one-time expense for our oral GLP-1 and expect fourth quarter SG&A expenses to continue to increase quarter-over-quarter as we continue to support the launch of Rezdiffra.

展望未來，我們預計第四季度研發費用將略高於第三季度水準（不包括第三季口服 GLP-1 的一次性費用），並且預計第四季度銷售、一般及行政費用將繼續環比增長，因為我們將繼續支持 Rezdiffra 的上市。

Turning to our balance sheet. We ended the third quarter of 2025 with $1.1 billion in cash, cash equivalents, restricted cash and marketable securities. The increase reflects the $350 million initial term loan under our senior secured credit facility, a portion of which was used to repay all outstanding obligations under the Hercules loan facility, offset by the funding of operations.

接下來來看看我們的資產負債表。截至 2025 年第三季末，我們持有現金、現金等價物、受限現金及有價證券共 11 億美元。此次成長反映了我們優先擔保信貸安排下的 3.5 億美元初始定期貸款，其中一部分用於償還 Hercules 貸款安排下的所有未償債務，部分被營運資金所抵銷。

With this strong cash position, we continue to be well resourced to support the ongoing launch of Rezdiffra and advance multiple pipeline programs. With that, on slide 17, let me briefly recap our third quarter progress where we remain focused on our top line and our pipeline. We are driving strong performance in our sixth quarter of our launch with Rezdiffra now annualizing over $1 billion in net sales and expect continued strong growth in 2026 and beyond.

憑藉強勁的現金儲備，我們將繼續擁有充足的資源來支持 Rezdiffra 的持續上市，並推動多個在研項目。接下來，在第 17 張投影片上，我將簡要回顧我們第三季的進展，我們將繼續專注於營收和產品線。在公司成立的第六季度，Rezdiffra 的業績表現強勁，年淨銷售額已超過 10 億美元，預計 2026 年及以後將繼續保持強勁成長。

More than 29,500 patients are on therapy, and we expect to continue to steadily add patients going forward. We've reached another major launch milestone with greater than 10,000 prescribers. Our payer discussions are progressing very well, and we expect continued strong access for patients in 2026, and we're working to further expand our pipeline to solidify our leadership in F2 to F4c MASH.

目前有超過 29,500 名患者正在接受治療，我們預計未來患者人數將持續穩定增加。我們又達到了一個重要的上市里程碑，處方醫師人數已超過 10,000 人。我們與支付方的討論進展非常順利，我們預計 2026 年患者將繼續獲得良好的用藥機會，我們正在努力進一步擴大我們的產品線，以鞏固我們在 F2 至 F4c MASH 領域的領先地位。

And now I'll turn the call back over to Tina and open up the Q&A session.

現在我將把電話交還給蒂娜，開始問答環節。

Thanks, Mardi. Let's move into the Q&A portion of the call. Marvin, please go ahead and provide instructions for the Q&A session.

謝謝你，瑪蒂。接下來進入問答環節。馬文，請開始講解問答環節的規則。

Yasmeen Rahimi, Piper Sandler.

亞斯敏·拉希米，派珀·桑德勒。

Congrats to a great quarter. Team, with AASLD right around the corner, would love to learn sort of how this two-year data, especially the NIT-driven responses could further derisk MAESTRO-NASH outcome, which is reading out in 2028? And also maybe also some color on what visibility do you guys get in terms of that it's on track based on event rates to come in at that time point? And I'll jump back in the queue.

恭喜你度過了一個非常棒的季度。AASLD 會議即將召開，團隊很想了解這兩年的數據，特別是 NIT 驅動的回應，如何能進一步降低 MAESTRO-NASH 研究結果的風險（該研究結果將於 2028 年公佈）？另外，你們能否也提供一些信息，說明根據屆時預計發生的事件數量，你們如何判斷項目是否按計劃進行？那我再重新排隊。

Yes. Thanks for the call. And look, we're really, really excited about AASLD. I'll tell you, we're just coming off of the ACG meeting in Phoenix. I guess it was just last week.

是的。謝謝你的來電。說實話，我們對 AASLD 真的非常非常興奮。我告訴你，我們剛從鳳凰城的ACG會議回來。我猜就是上週的事。

And what a difference a year makes when you think about the progress that we've made with the gastroenterologists. I mean a year ago, people didn't know about NITs. They were still putting their pathways in place. And now we're seeing that Rezdiffra has really moved to being the foundational therapy standard of care with that audience and a lot of positive feedback.

一年時間，我們與腸胃病學家合作取得了多大的進步啊！我的意思是，一年前，人們還不知道國家理工學院（NIT）是什麼。他們仍在鋪設道路。現在我們看到，Rezdiffra 已經真正成為該族群的基礎治療標準，並獲得了許多正面的回饋。

So we're headed into the Super Bowl this week with AASLD. We're really excited about it. We have a lot going on. But maybe, Dave, do you want to provide a little bit of context around some of the data and so forth?

所以，本週我們將和 AASLD 一起迎接超級盃的到來。我們對此感到非常興奮。我們有很多事情要做。不過，戴夫，或許你想就一些數據等等提供一些背景資訊？

Yes. I think your question, yes, had to do with the data that we're reading out at AASLD and how it reflects on MAESTRO outcomes. Is that correct?

是的。是的，我認為你的問題與我們在 AASLD 上公佈的數據以及這些數據如何反映 MAESTRO 結果有關。是這樣嗎？

That's correct.

沒錯。

Okay. Great. Yes. So as we presented at EASL and as we showed in the presentation, we have an open-label cohort of individuals from the MAESTRO NAFLD study where we've been able to show sustained efficacy of Rezdiffra in this cohort, both on liver stiffness and on a variety of biomarkers, including LFTs and so forth. So at AASLD, we're looking more deeply into this cohort and examining some of the more severe patients within this cohort and understanding whether Rezdiffra's efficacy in this group as well. And what we see is really exciting and gives us a lot of confidence about, about MAESTRO outcomes.

好的。偉大的。是的。正如我們在 EASL 會議上所展示的，以及我們在報告中所展示的，我們有一個來自 MAESTRO NAFLD 研究的開放標籤隊列，我們已經能夠證明 Rezdiffra 在該隊列中具有持續療效，無論是在肝臟硬度方面，還是在包括肝功能檢查等在內的各種生物標誌物方面。因此，在 AASLD，我們正在更深入地研究這個隊列，並檢查該隊列中一些病情較嚴重的患者，以了解 Rezdiffra 對該組患者的療效是否也有效。我們看到的情況令人振奮，也讓我們對 MAESTRO 的結果充滿信心。

And so the reason why this is important is because when you think about MAESTRO outcomes and you think about this open-label cohort, the patient populations are really very similar. So the baseline characteristics are similar. And so when we see efficacy in the open-label group, it gives us evidence and a lot of confidence that the outcomes trial will end up being positive as well.

因此，這之所以重要，是因為當你考慮 MAESTRO 研究結果和這個開放標籤群組時，你會發現患者群體實際上非常相似。因此，基線特徵相似。因此，當我們看到開放標籤組的療效時，這給了我們證據和很大的信心，即結果試驗最終也會是正面的。

Jay Olson, Oppenheimer.

傑伊·奧爾森，奧本海默。

Congrats on the quarter. Can you talk about the pros and cons of combining resmetirom with MGL-2086 versus some other oral GLP-1 like orforglipron? And then any other potential mechanisms beyond GLP-1 that might be synergistic with resmetirom?

恭喜你本季取得佳績。能否談談瑞美替羅與 MGL-2086 合併用藥與奧格列酮等其他口服 GLP-1 受體激動劑合併用藥的優缺點？除了 GLP-1 之外，還有哪些潛在機制可能與瑞美替羅產生協同作用？

Jay, thanks for the question. Just for clarification as well, our oral GLP-1 is an orforglipron derivative. So we were very, very specific in the criteria that we had for selecting an oral GLP-1, and we wanted to be in an orforglipron derivative. But maybe, Dave, do you want to talk a little bit about it and a little bit about the future mechanisms and just how we're thinking in general about potential combinations?

傑伊，謝謝你的提問。另外要澄清的是，我們的口服 GLP-1 是奧福格列酮衍生物。因此，我們在選擇口服 GLP-1 時制定了非常非常具體的標準，我們希望選擇奧福格列酮衍生物。不過，戴夫，或許你想稍微談談這件事，談談未來的機制，以及我們總體上是如何看待潛在的組合的？

Yes. So I mean first, the GLP-1 mechanism and why one would combine resmetirom with the GLP-1. So what we know from MAESTRO-NASH from the 52-week experience in MAESTRO-NASH is just a little bit of weight loss enhances resmetirom's efficacy. So we see better antifibrotic effects with resmetirom in people who lose as little as 5% of their body weight. So it's a natural sort of extension of that to consider combining with the GLP-1 that can produce a bit of weight loss, have some metabolic benefits and enhance resmetirom's efficacy in a fixed-dose combination.

是的。我的意思是，首先，GLP-1 機制以及為什麼要將瑞美替羅與 GLP-1 結合使用。我們從 MAESTRO-NASH 的 52 週經驗中了解到，稍微減輕體重就能增強 resmetirom 的療效。因此，我們發現，對於體重減輕 5% 的人來說，resmetirom 具有更好的抗纖維化效果。因此，將瑞斯美替羅與 GLP-1 結合使用是一種很自然的延伸，GLP-1 可以減輕一些體重，帶來一些代謝益處，並在固定劑量組合中增強瑞斯美替羅的療效。

So that's the rationale for combining with the GLP-1. But your point is a great one. There are other mechanisms that may also be attractive to combine resmetirom with. And there are multiple pathways in this very complex disease of MASH that lead to hepatic steatosis, fibrosis and ultimately poor outcomes in patients. So as we've said before, we're looking at pretty much every mechanism of action to potentially combine with resmetirom where there's a good scientific rationale for it and where we believe that the combined efficacy is going to be an advantage to patients. So we're casting the net wide, and we're looking for the best opportunities.

所以這就是與 GLP-1 聯合使用的理由。但你的觀點很棒。還有其他一些機制也可能適合與瑞美替羅併用。MASH 是一種非常複雜的疾病，它涉及多種途徑，最終導致肝脂肪變性、纖維化，最終導致患者預後不良。正如我們之前所說，我們正在研究幾乎所有可能與瑞美替羅聯合使用的作用機制，前提是這些機制有充分的科學依據，並且我們認為聯合療效將對患者有利。所以我們正在廣泛撒網，尋找最佳機會。

Yes, Jay, and just also a little context as well here. With the IP to 2045, that gives us time to really thoughtfully think about building this pipeline. We're not in a rush just to try to fix a problem of a pending patent cliff. We can thoughtfully think about building a franchise that's durable because starting with the 2045 IP for Rezdiffra. Thanks for the question.

是的，傑伊，這裡還需要補充一些背景資訊。到了 2045 年，IP 的期限給我們時間認真思考如何建造這條管道。我們並不急於解決即將到來的專利懸崖問題。我們可以認真考慮如何打造一個經久不衰的特許經營權，因為從 Rezdiffra 的 2045 IP 開始。謝謝你的提問。

Michael DiFiore, Evercore ISI.

Michael DiFiore，Evercore ISI。

Congrats on the continued progress. Just two quick one for me. In light of the recent M&A in the space, I would love to get your thoughts on Madrigal's future competitive positioning and market access once large pharma inevitably bundles their MASH assets, if approved.

恭喜你們持續進步。就我這兩個問題。鑑於該領域最近的併購活動，我很想聽聽您對 Madrigal 未來競爭地位和市場准入的看法，一旦大型製藥公司不可避免地將其 MASH 資產打包出售（如果獲得批准）。

And the second question I have is just any thoughts on Sagimet's plans for testing denifanstat with Rezdiffra. I realize your priority is focusing on the combination therapy with your own GLP-1, but would Madrigal be open in principle to combinations such as this? Or is this just too early at this stage?

我的第二個問題是，您對 Sagimet 公司計劃使用 Rezdiffra 測試 denifanstat 有什麼看法？我知道您目前的首要任務是專注於將您自己的 GLP-1 進行聯合治療，但 Madrigal 原則上是否願意接受這樣的聯合治療呢？或者現在討論這個問題還為時過早？

Yes, Mike, thanks for the question. Let me start with that one. We don't know what Sagimet is doing. We haven't spoken with them, don't know any of the plans. So is it a combination that makes sense? Maybe, but we're not involved in that and don't really know. So that's all I'll comment at the moment there.

是的，麥克，謝謝你的提問。我就先從這個問題開始吧。我們不知道Sagimet在做什麼。我們還沒跟他們談過，對他們的計畫一無所知。那麼，這種組合合理嗎？也許吧，但我們沒有參與其中，所以並不清楚。我目前就說這麼多。

Look, the recent M&A really for us is a validation of the MASH market. Ultimately, what we see happening in these markets, and we talked about IBD, RA and psoriasis. You would have -- and we're a little bit like that where you have a company shows that there is a market and an attractive opportunity. And then the investment in innovation, science and ultimately more products really accelerates. And that's what we think is going to happen in MASH. We're leading the way in this case.

你看，最近的併購活動對我們來說其實是 MASH 市場的驗證。最終，我們看到這些市場正在發生的事情，我們談到了發炎性腸道疾病、類風濕性關節炎和乾癬。你會——我們有點像那樣，一家公司的存在表明存在市場和有吸引力的機會。然後，對創新、科學以及最終更多產品的投資將真正加速成長。我們認為《陸軍野戰醫院》（MASH）裡也會發生這樣的事。我們在這方面處於領先地位。

Now the recent moves of the big pharma to get an FGF21, we think validates that. And we're excited about it because that means there's going to be more attention on the space, which ultimately leads to greater diagnosis, treatment. And with the profile that we have with Rezdiffra, we think it ultimately favors us. So we -- in creating our market access strategy, we've taken a very long-term approach, just like we did from day 1 when we announced approval of the product, you almost have to start with 2045 where Rezdiffra's IP goes out to, that we're going to have F4c, that we're going to have a pipeline and there's going to be other products that enter. So everything has been thoughtfully designed with that end in mind to preserve the most value for not only Rezdiffra, but for our franchise of the future. So we feel we're in a really strong place.

我們認為，大型製藥公司最近為獲取 FGF21 而採取的行動，證實了這一點。我們對此感到興奮，因為這意味著該領域將受到更多關注，最終將帶來更好的診斷和治療。鑑於我們與 Rezdiffra 的合作關係，我們認為最終對我們有利。因此，在製定市場准入策略時，我們採取了非常長遠的策略，就像我們從宣布產品獲批的第一天起所做的那樣，幾乎必須從 2045 年 Rezdiffra 的智慧財產權到期時開始考慮，屆時我們將擁有 F4c，我們將擁有產品線，並且還會有其他產品進入市場。因此，所有設計都經過深思熟慮，以達到這個目的，不僅是為了Rezdiffra，也是為了我們未來的特許經營權，從而最大限度地保留價值。所以我們感覺我們現在處境非常有利。

Now Dave just talked a little bit about F4c. We're really excited about the data that we've seen, and we're very confident about hitting in our MAESTRO-NASH outcome study, which we are reading out in 2027. Of course, we've got to read out. It's an event-driven study, and we'll anticipate those results.

戴夫剛才簡單談了一下F4c。我們對目前看到的數據感到非常興奮，並且非常有信心在 MAESTRO-NASH 結果研究中取得成功，我們將在 2027 年公佈研究結果。當然，我們得讀出來。這是一項以事件為導向的研究，我們將對研究結果充滿期待。

We think that from a competitive perspective, our data is going to be the leading data in that space with that population so that we will be the leaders not only in F2/F3, but from F2 to F4c. So all of this is thought out. We're thinking of things in the long term. We think of that how we build a pipeline, how we evolve gross to net and how we interact with the community. Let me just be crystal clear. Our goal is to not be leaders in the short term, but to have long-term leadership in MASH.

我們認為，從競爭的角度來看，我們的數據將成為該領域和該群體中的領先數據，因此我們不僅會在 F2/F3 階段處於領先地位，而且會在 F2 到 F4c 階段都處於領先地位。這一切都是經過深思熟慮的。我們考慮的是長遠問題。我們會思考如何建構供應鏈，如何實現毛利到淨利潤的轉變，以及如何與社區互動。讓我把話說清楚。我們的目標不是在短期內成為領導者，而是在 MASH 領域取得長期的領導地位。

Akash Tewari, Jefferies.

阿卡什‧特瓦里，傑富瑞集團。

So we're hearing feedback that Rezdiffra's adherence rate is meaningfully higher than the kind of 40% to 60% your team cited for drugs in this category, more in the order of 80% plus. Can you confirm that? And then also, how should we think about Rezdiffra net pricing? I know you've talked about -- we've heard GLP-1 players talk about mid-single-digit net price declines annually. Is that a similar dynamic for Rezdiffra? Or should we see stable net pricing after you get into like the high 30s range on gross to net next year?

我們收到的回饋是，Rezdiffra 的依從率明顯高於你們團隊提到的這類藥物的 40% 到 60%，而 Rezdiffra 的遵從率則在 80% 以上。能確認一下嗎？那麼，我們該如何看待Rezdiffra的淨定價呢？我知道你們已經談過——我們也聽過 GLP-1 患者談論每年淨價格出現中位數個位數的下降。Rezdiffra的情況也類似嗎？或者，明年毛利率淨利率達到 30% 以上時，我們會看到穩定的淨利率？

Thanks for the question, Akash. Look, first of all, on the adherence, I think what we've said about -- at the one-year rate, well-tolerated orals are in that 60% to 70% range. So that doesn't -- that hasn't changed our view. And we are -- the data that we have today, remember, there's still only so many patients that are getting to that one-year mark that we are similar to well-tolerated orals. And like you, we've heard very positive feedback from a lot of clinicians that are treating patients and seeing very strong adherence. And I think that again goes back to the profile of the product. So all encouraging and as we would expect.

謝謝你的提問，阿卡什。首先，關於依從性，我認為我們已經說過——一年內，耐受性良好的口服藥物的依從性在 60% 到 70% 之間。所以，這並沒有改變我們的看法。而且，根據我們目前掌握的數據，請記住，只有少數患者能夠堅持到一年後，我們的療效才能與耐受性良好的口服藥物相媲美。和您一樣，我們也從許多治療患者的臨床醫生那裡聽到了非常正面的回饋，他們發現患者的依從性非常高。我認為這又回到了產品定位的問題。一切都令人鼓舞，也正如我們所預期的。

To the question of gross to net and what we would expect to see. Look, I think that you looking ahead to the future, gross to net only goes in one direction, right? And the difference after '26, you don't have this zero to contracting effect. After '26, we'll have contracting right now, we're going to be bidding on 2027 Medicare. We have some Medicare in place for '26. So you expect to see some future decline in gross to net because that's just what happens. But again, we had this effect of zero to contracting in -- as we enter 2026.

關於毛利潤與淨利潤之比以及我們預期會看到的情況。你看，我認為你展望未來，毛利潤到淨利潤只會朝著一個方向發展，對吧？而 2026 年之後的不同之處在於，不再存在這種從零到收縮的影響。2026 年之後，我們將開始簽訂合同，我們現在要競標 2027 年的醫療保險計劃。我們已經為 2026 年的醫療保險做好了準備。所以，你預期未來毛利潤與淨利之間會有一些下降，因為這種情況就是會發生的。但同樣，隨著我們進入 2026 年，我們又一次經歷了零成長到收縮的局面。

So look, we think that we are in a really great place. Our strategy is for broad first-line access, no step edit and improved utilization management criteria. That was the goal. That's what we're achieving. So we're really, really excited about where we are entering 2026.

所以你看，我們認為我們現在處境非常好。我們的策略是廣泛提供第一線治療，無需逐步修改，並改善利用管理標準。這就是我們的目標。這就是我們正在取得的成就。所以，我們對即將邁入 2026 年的前景感到非常非常興奮。

In fact, I would say, in my experience, I really believe that this is as good as you could possibly be for a product of this stature at this point in launch. In fact, I would go as far as to say, I think this is the best market access from a criteria perspective and everything that I've seen with any of the launches that I've done.

事實上，以我的經驗來看，我認為對於一款如此高規格的產品來說，在上市初期階段，這已經是最好的狀態了。事實上，我甚至可以說，從標準的角度來看，我認為這是最好的市場准入，也是我所見過的所有產品發布中最好的。

Thomas Smith, Leerink Partners.

Thomas Smith，Leerink Partners。

And let me add my congrats on the really strong quarter. Another one on coverage. I appreciate the high-level comments here on the payer contracting efforts, I think everyone saw the recent Aetna formulary coverage decision. Could you just comment specifically on that and the potential impact of noncovered decisions?

我還要祝賀你們取得了非常出色的季度業績。又一篇關於報道的文章。我很欣賞大家對支付方合約工作的高層次評論，我想大家都看到了最近安泰保險公司關於藥品目錄覆蓋範圍的決定。您能否具體談談這一點，以及未納入健保範圍的決定可能造成的影響？

And then any comments on kind of where you are with respect to the contracting for commercial lives next year? Is there an explicit goal or expectation for what percent of commercial lives you think will continue to have that broad first-line access to Rezdiffra for 2026?

那麼，對於明年商業人壽保險的合約簽訂情況，您有什麼看法？對於 2026 年商業保險保單中將有多少百分比的保單能夠繼續廣泛地獲得 Rezdiffra 的一線服務，您是否有明確的目標或預期？

Yes. Thanks, Tom. Maybe I'll start there. Look, we're expecting broad commercial live coverage. So we feel really good about that at this point.

是的。謝謝你，湯姆。或許我就從那裡開始。我們預計會有廣泛的商業直播報導。所以目前我們對此感覺非常好。

As it relates to Aetna, let me start with Rezdiffra wasn't on formulary in 2025, and it's not again in 2026. So that is really no change. So we don't expect to see a meaningful impact here. It will be available through prior authorization or medical exception. And so that's not a practical change in access for patients. And our Madrigal patient support team are really experts at helping patients navigate and helping practices navigate through that. So yes, no change, no effect.

就安泰保險而言，首先要說明的是，Rezdiffra 在 2025 年不在健保目錄內，2026 年也不在。所以實際上並沒有什麼變化。因此，我們預計不會對此產生實質影響。需事先獲得授權或醫療豁免方可取得。因此，這對患者來說，在就醫方面並沒有實際的改變。我們的 Madrigal 患者支援團隊在幫助患者和診所應對這些問題方面都是真正的專家。所以，是的，沒有變化，沒有效果。

Andrea Newkirk, Goldman Sachs.

安德里亞·紐柯克，高盛集團。

Bill, recognizing it's still early here, but just curious if you've observed any signs of Novo's marketing campaign broadening the pool of addressable patients to date. Do you still believe that 315,000 patients is the accurate number for Rezdiffra's target population? And then, Mardi, if I can just ask quickly, just in the context of the successful launch that you've seen to date, how are you thinking about the path to profitability from here?

比爾，我知道現在還為時過早，但我只是好奇你是否觀察到諾和諾德的營銷活動有任何跡象表明其目標患者群體已經擴大。您是否仍認為 315,000 名患者是 Rezdiffra 目標族群的準確數字？那麼，瑪蒂，如果我可以快速問一下，就目前為止的成功發布而言，你認為接下來如何實現盈利？

Thanks, Andrea. Well, look, this is the first quarter where we've had Novo in the market. And you saw that we continue to steadily add patients. And I think by all measures, had an absolutely outstanding quarter. So three months in, we haven't really seen too much.

謝謝你，安德里亞。你看，這是我們Novo進入市場的第一個季度。正如你所看到的，我們的患者數量一直在穩定增加。我認為無論從哪個角度來看，這都是一個非常出色的季度。三個月過去了，我們其實還沒看到太多東西。

We know that they seem to be educating PCPs and trying to drive diagnosis, which we think is ultimately great for patients in the market. We're starting to hear some practices say, and this is very anecdotal at this point that they are reporting more referrals that are coming in. But it's a little early to quantify if there is additional growth to the market as we get through the end of the year and be able to do a more proper analysis, we'll come back with any real growth rates.

我們知道他們似乎在教育初級保健醫生並試圖推動診斷，我們認為這最終對市場上的患者來說是件好事。我們開始聽到一些診所表示（目前這只是非常零星的傳聞），他們報告說收到的轉診病例更多了。但現在量化市場是否還有成長還為時過早，隨著年底的到來，我們將進行更恰當的分析，屆時我們將公佈任何真正的成長率。

Now the 315,000, great question. Look, let's just remind people, the 315,000 are the diagnosed patients in the 14,000 prescribers that we're targeting. And we know that we have patients that are on Rezdiffra now that weren't part of that 315 that they were newly diagnosed. And we also know that the diagnosis rate at the moment remains quite low. Originally, we saw it as around 10% diagnosis rate.

現在來說說315000，這是一個很好的問題。聽著，我們提醒大家，這 315,000 人是我們正在重點關注的 14,000 名處方醫生的確診患者。我們知道，現在有一些患者正在接受 Rezdiffra 治療，但他們最初確診時並不屬於那 315 例新病例。我們也知道，目前的診斷率仍然很低。最初，我們認為診斷率約為 10%。

So we know that there are more prevalent patients out there. And I think what we will see and what we're excited about is having somebody else that is going to help us carry the load of increasing diagnosis. It's not something that's been a focus of ours. It still remains not a focus of ours. But when we have somebody else who needs to have literally millions of patients that are diagnosed in order to serve their needs, that ultimately helps us. That's why we said in the script, it's also -- it's the 315,000 that we win from and the increased diagnosis and ultimately people that can't tolerate or have an effect with a new competitor that will ultimately come to us.

所以我們知道，實際患病人數遠不止這些。我認為我們將會看到，也讓我們感到興奮的是，會有人幫助我們分擔日益增長的診斷負擔。這並非我們關注的重點。這仍然不是我們關注的重點。但是，當有其他機構需要診斷數百萬名患者才能滿足其需求時，這最終會幫助我們。這就是為什麼我們在劇本裡說，這也是——我們從315,000個病例中贏得的，診斷率的提高，以及最終那些無法忍受或受到新競爭對手影響的人最終會轉向我們。

So a little early to quantify. We'll do so in later quarters, but we see some signs that we're starting to see additional growth. Novo, we just don't really have a lot of information, haven't seen them too much out there. But clearly, they are there and starting to drive a little bit more diagnosis.

現在量化還為時過早。我們將在之後的幾個季度這樣做，但我們已經看到一些跡象表明，我們開始看到進一步的成長。Novo，我們真的沒有太多訊息，也沒怎麼見過他們。但很顯然，它們已經存在，並且開始推動更多的診斷。

Great. Yes, go ahead. Yes. Thanks, Andrea, for the question on the path to profitability. And our focus right now and into 2026 is really focused on driving our top line and then building out our pipeline, which Dave described.

偉大的。好的，請繼續。是的。謝謝安德里亞提出的關於獲利之路的問題。而我們現在以及到 2026 年的重點，確實是提高我們的營收，然後建立我們的產品線，正如戴夫所描述的那樣。

That's going to be our focus going forward. It doesn't mean profitability won't happen at some point. But again, we're focused on the top line and building out R&D and continuing to support our efforts in building out the MASH -- our leadership in MASH.

這將是我們未來工作的重點。但這並不意味著盈利在某個時候不會實現。但是，我們仍然專注於營收成長，加大研發投入，並繼續支持我們在 MASH 領域的發展——我們在 MASH 領域的領導地位。

Andy Chen, Wolfe Research.

Andy Chen，Wolfe Research。

It's Emma on for Andy. Rezdiffra uptake has been strong so far, and you mentioned the strong 60% to 70% adherence rate. I know it's still very early days in the launch, but I guess how do these dynamics inform your view of the drug's chronic use potential and just steady-state demand over the long term?

艾瑪代替安迪上場。Rezdiffra 目前為止的接受度很高，您也提到了 60% 到 70% 的高遵從率。我知道現在距離上市還處於非常早期的階段，但我想知道這些動態如何影響您對該藥物長期使用潛力和長期穩定需求的看法？

Thanks, Emma. Look, I think that this is where we win. We have a profile once-a-day pill that is well tolerated and the feedback, some have reported extremely high adherence rates. So we feel extremely well positioned for this to be a long-term chronic therapy. It's really one of the exciting parts of Rezdiffra.

謝謝你，艾瑪。你看，我認為這就是我們贏球的關鍵。我們有一款每日一次的藥丸，耐受性良好，據反饋，一些患者表示依從性非常高。因此，我們感覺自己處於非常有利的位置，可以將其作為長期慢性療法。這確實是 Rezdiffra 最令人興奮的部分之一。

And as I said, versus other categories, which have become really multibillion over $20 billion categories, the profiles, especially the profiles initially of products to launch were kind of hairy, right? They just -- they weren't orals. They had tolerability issues, sometimes safety issues. We feel that we have got -- and you've heard me refer to it in the past as what I believe is kind of like a holy grail profile. That's something which is where we win in this category, frankly. At the end of the day, profiles matter. This is a product which is really designed for chronic use. So we feel really good.

正如我所說，與其他已經發展成為價值超過 200 億美元的數十億美元類別相比，這些類別的概況，特別是最初要推出的產品的概況，相當棘手，對吧？它們只是——它們不是口頭的。它們存在耐受性問題，有時還存在安全問題。我們覺得我們已經得到了——你以前也聽我說過，我認為它就像是聖杯般的個人資料。坦白說，這正是我們在這個類別中獲勝的地方。歸根結底，個人資料很重要。這款產品確實是為長期使用而設計的。我們感覺非常好。

Can I just add on one thing. The other part that also, of course, matters is sustained efficacy. And I think what we're showing at AASLD gives us a lot of confidence in the sustained efficacy of resmetirom in this group. And in fact, what we show in the F2/F3 population is that if you come off of therapy, you have reversion of your disease, which is, of course, a big challenge. So I think those two facets, both the efficacy, sustained efficacy and the sustained tolerability are two.

我可以補充一點嗎？當然，另一個同樣重要的面向是持續療效。我認為我們在 AASLD 上展示的結果讓我們對 resmetirom 在該族群中的持續療效充滿信心。事實上，我們在 F2/F3 族群中發現，如果停止治療，病情就會逆轉，這當然是一個很大的挑戰。所以我認為療效、持續療效和持續耐受性是兩個面向。

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

I wanted to ask, well, 1.5 questions. One on this growth forward given the two strategies, Bill, that you outlined, one, sales force expansion and marketing to the endocrinologists. But at the same time, you mentioned that you want depth in the going-forward marketing strategy. So can you help us reconcile the two and what sort of metrics and current targets for depth that you hope to report and how GLP-1s figure into all this? And this is a very quick e-mail that we've been getting from clients.

我本來想問，嗯，1.5個問題。鑑於比爾，你概述的兩種策略，這種成長勢頭得以實現，一是擴大銷售隊伍，二是向內分泌科醫生進行行銷。但同時，您也提到您希望未來的行銷策略更具深度。那麼，您能否幫助我們協調這兩者，您希望報告哪些指標和當前的深度目標，以及 GLP-1 在這一切中扮演什麼角色？這是我們最近收到的一些客戶發送的簡短電子郵件。

We're having a problem sort of stretching the patient numbers with the revenue numbers. Are there any elements to either stocking or Europe or some other aspect of those numbers that need to be addressed in our models to reconcile everything reported this morning?

我們目前遇到的問題是，如何將患者數量與收入數量相匹配。為了使今天早上公佈的所有數據相符，我們的模型中是否需要考慮庫存、歐洲或其他方面的因素？

Yes. For the quarter, nothing to do with inventory, nothing to do with Europe. I mean, just to be crystal clear, US demand is the driver of the success for the quarter. So let me take that one.

是的。本季與庫存無關，也與歐洲無關。我的意思是，說得更清楚些，美國的需求是本季業績成功的驅動力。那我就來吧。

Next, let's talk about growth going forward and your question about how do we manage expansion, if you will, of into endocrinology and death otherwise.

接下來，我們來談談未來的發展，以及你提出的關於我們如何管理向內分泌學和死亡領域擴張的問題。

We can walk and chew gum at the same time, so to speak. We have to continue to be building for the future as well. Remember, we've got 20 years ahead of us from an IP perspective. So we are going to look for where to currently focus and where do we want to explore. And that's exactly what we're doing here.

我們可以一心二用，邊走邊嚼口香糖。我們也必須繼續為未來建設。記住，從智慧財產權的角度來看，我們還有 20 年的時間。所以我們要看看目前應該要專注在哪些方面，以及我們想要探索哪些方面。而這正是我們在這裡所做的。

We've already from -- and you know we've been always looking at a basket of products in the last 10 years that have been great specialty launches, and we look at each metric, and we're kind of at or near the top on a number of those. Breadth, we're doing great as well.

我們已經——你知道，在過去的 10 年裡，我們一直在關註一系列優秀的特色產品，我們會查看每一項指標，而我們在許多指標上都處於領先地位或接近領先地位。廣度方面，我們也做得很好。

But you need to continue to grow your depth of prescribing, right? I mean we have 10,000-plus prescribers. Now your next step, and I consider that like a checkmark, now you go deeper and deeper into that set of core physicians, which are gastroenterologists and hepatologists. Now the pursuit now of the endocrinologists, that we had endocrinologists targeted as part of the 14,000. But what we've seen is additional endocrinologists have come forward and said, you know what, I'm still seeing a lot of MASH and would like to learn more about Rezdiffra.

但你需要不斷加深你的處方深度，對吧？我的意思是，我們有超過1萬名處方醫生。現在，你的下一步，我認為這就像打勾一樣，現在你要越來越深入地了解這群核心醫生，也就是腸胃病學家和肝病學家。現在，我們開始追蹤內分泌學家，因為我們已經將內分泌學家列為 14,000 名目標人員之一。但我們看到，越來越多的內分泌學家站出來說，你知道嗎，我仍然看到很多 MASH 病例，並且想了解更多關於 Rezdiffra 的資訊。

So there was enough interest that we said, let's put a dedicated team on that opportunity. Just to give you a sense, it's not a huge number. It's a couple of thousand physicians that we add to the target list. And that can be handled with a very concentrated dedicated effort. And we'll see how that evolves.

因此，大家對此表現出了濃厚的興趣，所以我們決定組建一個專門的團隊來負責這個專案。簡單來說，這個數字並不大。我們將數千名醫生加入目標名單。而這可以透過高度集中精力來解決。我們將拭目以待事態發展。

And one of the interesting things is, as you talk about GLP-1s, if GLP-1s were truly solving MASH, there wouldn't be a need in this prescriber group that uses GLP-1s predominantly that another product would be needed. So I think that that is a very good sign for us as well that GLP-1s aren't the solution. They've been on the market for over 10 years. You've got a specialty that uses them, and they still are looking for Rezdiffra.

有趣的是，正如你談到 GLP-1 時所說，如果 GLP-1 真的能解決 MASH 問題，那麼主要使用 GLP-1 的處方醫生群體就不需要其他產品了。所以我認為這對我們來說也是一個非常好的跡象，表明 GLP-1 並非解決方案。它們已經在市場上銷售超過10年了。你們的專業領域需要使用它們，而且他們仍在尋找 Rezdiffra。

So we're putting an effort there. So this is a little bit of a -- we have our present focus, which is driving breadth, and we are starting with these endocrinologists, which you have to wind the clock back to even before '24 because they're not familiar with NITs. They're not -- they don't have their system wired at all. So that's going to take a very long time for them to really get catch up to where gastroenterologists and hepatologists are now. But we think it's worth effort, resource, and we think there's promise for the future there as well.

所以我們正在努力。所以這有點像——我們目前的重點是擴大範圍，我們從這些內分泌學家開始，你必須把時間倒回到 2024 年之前，因為他們不熟悉 NIT。他們沒有──他們的系統根本就沒有連結。所以，他們還需要很長時間才能真正趕上胃腸病學家和肝病學家現在的水平。但我們認為這是值得投入精力和資源的，而且我們認為它在未來也很有發展前景。

Jon Wolleben, Citizens.

Jon Wolleben，市民。

Bill, wondering if you could comment a little bit as we look down the road at expected GLP price erosion how that might affect access and payer decisions for Rezdiffra?

Bill，我想請你談談，隨著 GLP 價格預期下降，Rezdiffra 的取得和支付方決策可能會受到怎樣的影響？

Thanks, Jon. Well, look, I think if you -- I'll take you back to the comments that we made on the call that in January, we would expect to be in the high 30% range. That is in the presence of a rapidly, I would say, eroding gross to net of GLP-1s. So we believe that we are well positioned for the future. As I said, gross to net only goes in one direction.

謝謝你，喬恩。嗯，你看，我認為如果你——我帶你回顧一下我們在電話會議上發表的評論，即我們預計一月份的比例將在 30% 以上。而同時，GLP-1 的總和卻在快速下降，我認為這種下降趨勢是不可逆轉的。因此，我們相信我們已經為未來做好了充分準備。正如我所說，毛利潤到淨利潤的轉換是單向的。

But I think you have to start with the problem that we're trying to solve. This is an expensive disease. I think if you take a look at ICER recently commented again on products that they have recently reviewed. And we're seeing that once again, Rezdiffra is highlighted as a product that is looked at as cost effective and really is offsetting the very costly disease without intervention.

但我認為，我們必須從我們試圖解決的問題開始。這是一種治療費用昂貴的疾病。我認為，如果你看一下ICER最近再次對他們最近評測的產品發表評論，你會發現這一點。我們再次看到，Rezdiffra 被譽為一款經濟高效的產品，它無需幹預就能真正抵消這種代價高昂的疾病。

So I think that you have to start with the problem you're trying to solve. This is an expensive disease. I think payers understand that. Certainly, the system is starting to understand that. So you're always going to have products that have different prices within the category.

所以我認為，你必須從你想要解決的問題著手。這是一種治療費用昂貴的疾病。我認為付款方能夠理解這一點。當然，系統已經開始意識到這一點了。所以，同一類別的產品價格總是會有所不同。

And we've seen even with the categories that I mentioned today, IBD, RA and psoriasis, there's huge variability. But there's a need for more than one medication. There's a need for multiple mechanisms, and you ultimately have to try to solve the problem in front. And we, through an independent third party, ICER, have proven twice now about the cost effectiveness of Rezdiffra.

我們看到，即使是今天我提到的這些疾病類別，如發炎性腸道疾病、類風濕性關節炎和乾癬，也存在著很大的差異。但需要的藥物不只一種。需要多種機制，最終你必須嘗試解決眼前的問題。我們透過獨立的第三方機構 ICER 已經兩次證明了 Rezdiffra 的成本效益。

Prakhar Agrawal, Cantor Fitzgerald.

普拉哈·阿格拉沃爾，坎托·菲茨杰拉德。

And congrats on another strong quarter. So appreciate the clarity on the gross to net for 4Q and 2026. But maybe if you can talk about your expectations for 4Q growth and comfort around 2026 consensus estimates with this set? And maybe second question, what percentage of Rezdiffra volume currently is Medicare? And how are you thinking about the implications of semaglutide IRA pricing decision on the long-term prospects for that channel?

恭喜又一個季度業績出色。非常感謝您對第四季和 2026 年毛利潤與淨利潤的明確說明。但或許您可以談談您對第四季成長的預期，以及您對 2026 年普遍預期的看法？或許還可以問第二個問題，目前 Rezdiffra 的交易量中，有多少百分比是來自 Medicare？您如何看待司美格魯肽 IRA 定價決策對該通路長期前景的影響？

Great. So let me just give you -- I'll give you the quick answer on what the distribution is. We're anticipating it's 50% to 55% commercial, 30% to 35% Medicare and then about 10% Medicaid and other. We're still -- remember, we're at less than 10% penetration here. So that's going to evolve a little bit in time, but we're staying in that range at the moment.

偉大的。那麼，讓我簡單地告訴你一下分佈。我們預計其中 50% 到 55% 為商業保險，30% 到 35% 為聯邦醫療保險，約 10% 為醫療補助和其他保險。記住，我們目前的滲透率還不到 10%。所以隨著時間的推移，情況會略有變化，但目前我們仍維持在這個範圍內。

Maybe, Mardi, do you want to talk about Q4?

瑪蒂，你想聊聊第四季嗎？

Yes, definitely. Hi, Prakhar, thanks for the question. So listen, we've had a great 2025 so far in fourth quarter. We expect that to continue in terms of steadily adding patients, really sort of the driver for our business. We don't see any change there.

是的，當然。你好，普拉哈爾，謝謝你的提問。所以聽著，到目前為止，我們在2025年第四季取得了巨大的成功。我們預計患者數量將持續穩定成長，這實際上是我們業務發展的驅動力。我們沒有看到任何變化。

We did have a very high base in our revenue coming into third quarter that was very much patient demand. We did have some favorability in gross to net, which we discussed in a high demand quarter from an inventory standpoint. So we're in a very strong position.

第三季我們的收入基數非常高，這很大程度上是由於患者的需求所致。我們確實在毛利與淨利方面取得了一些優勢，我們之前討論過，在高需求季度，從庫存角度來看，情況就是如此。所以我們處於非常有利的地位。

But going into fourth quarter, working off that base and taking into effect that there's fewer selling days in the fourth quarter in general, and that as we discussed, the gross to net begins to -- we'll see the commercial rebating starting to take effect in the fourth quarter. So we'll be at the midpoint of that 20% to 30% range. All that put together, we think we'll see high single-digit growth quarter-over-quarter going into the fourth quarter, but still a very strong quarter. And of course, we're on over $1 billion run rate in revenue. So fantastic.

但進入第四季度，在此基礎上，考慮到第四季度銷售天數總體較少，而且正如我們討論的那樣，毛利與淨利開始——我們將看到商業返利在第四季度開始生效。所以我們將處於 20% 到 30% 範圍的中間點。綜合所有因素，我們認為進入第四季後，環比成長率將達到個位數高位，但第四季仍然會非常強勁。當然，我們的年化營收已經超過10億美元。太棒了。

And Prakhar, maybe just one comment there as well. I think more and more the measure turns to patients and patients being treated. And as you can see, we are doing really, really great in our steadily adding patients, and that's something that is going to, we've said, remain to be steadily adding in the future and feel really, really great. Again, where we are, it's less than 10% penetration. There's a ton of patients that are out there that still need to be treated, and that represents a great opportunity for us.

Prakhar，或許也可以在這裡發表一下看法。我認為衡量標準越來越傾向於患者和接受治療的患者。正如你所看到的，我們在穩定增加患者方面做得非常出色，而且正如我們所說，未來還會繼續穩步增加患者數量，這感覺真的非常棒。再說一遍，在我們這裡，滲透率不到10%。還有很多病人需要治療，這對我們來說是一個絕佳的機會。

Yes. And I just wanted to come back to 2026 that Prakhar asked about, too. So again, everything Bill just said for the steadily adding patients, we see that going into 2026 as well. So steadily adding patients, we anticipate and we said in the script, robust net sales growth in 2026. But if you think about -- just think about the phasing, right?

是的。我也想回到普拉卡爾問的 2026 年的問題。所以，比爾剛才提到的患者數量穩定增加的情況，我們也認為這種情況會持續到 2026 年。因此，隨著患者數量的穩定增加，我們預計（正如我們在腳本中所說），2026 年淨銷售額將實現強勁增長。但如果你仔細想想——想想階段性問題，對吧？

So we're going to have the impact of the gross to net starting in January right at the beginning of the year. So you're going to see that step up from the contracting and we will be in the high 30s. And of course, we always have the Q1 effect on top of that, right? So in terms of the phasing, you'll see some of that play through in 2026. But net-net, we see robust growth going into 2026.

因此，從一月份年初開始，我們將面臨毛利潤與淨利轉換的影響。所以你會看到合約金額逐步增加，我們將達到30%以上。當然，我們也要考慮第一季的影響，對吧？所以就分階段實施而言，你會在 2026 年看到一些成果。但總的來說，我們預計到 2026 年將保持強勁成長。

Srikripa Devarakonda, Truist Securities.

Sriripa Devarakonda，Truist 證券公司。

Congratulations on the quarter. I was wondering if you can talk a little bit on the expected cadence for EU launch and how that -- when we think about 2026, that might add to the growth? I know it takes time for EU launches. And also the SG&A that was reported, does that include sales force in Europe? Or should we be thinking about slight increase in SG&A over the next several months to reflect sales force on the ground in Europe?

恭喜你本季取得佳績。我想請您談談歐盟市場預計的推出節奏，以及到 2026 年，這將如何促進市場成長？我知道歐盟地區的產品發布需要時間。另外，報道中提到的銷售、一般及行政費用是否包括歐洲的銷售團隊？或者我們應該考慮在未來幾個月內略微提高銷售、管理及行政費用，以反映歐洲第一線銷售團隊的情況？

Mardi, do you want to take that first?

瑪蒂，你想先吃那個嗎？

Yes, I'll definitely answer the SG&A question first, and we can talk about just EU launch in general. So SG&A for building out Germany, right? So that where we're only launching there as of right now is included in our SG&A expenses. And you'll continue to see that included in SG&A. But as we said, when we move into country by country, we're going to be very disciplined, and we look at a two- to three-year positive contribution metric for each country. So the spend will increase with Europe. But again, we're mindful with each country.

是的，我一定會先回答銷售、管理及行政費用的問題，之後我們可以再討論歐盟市場的整體情況。所以，德國市場的銷售、管理及行政費用是用來支付這些費用的，對吧？所以，目前我們只在那裡推出的產品，其銷售、一般及行政費用已包含在我們的銷售、一般及行政費用中。而且，您還會繼續在銷售、一般及行政費用中看到這些費用。但正如我們所說，當我們逐個國家進行評估時，我們會非常嚴謹，我們會關注每個國家兩到三年的積極貢獻指標。因此，隨著歐洲的崛起，支出將會增加。但是，我們始終對每個國家的情況保持謹慎。

And then just the EU launch, let's just talk about that. I'll start and Bill, I don't know if you want to add? But we did start launching in the third quarter, but really, we were just testing the channel. So just de minimis amount of revenue for 2025, we believe, and where we said we can start that -- we can start seeing some impact in 2026. So I would say the robust sales growth that we're talking about 2026 is by far and predominantly the US sales growth and adding patients, which we've discussed. And Europe, again, it's going to play out. It is slow. We have to build the system. We have to wire the system in countries in Europe. It will just be Germany next year. So it will be -- it will add, but not a significant amount.

然後就說說歐盟的發佈吧。我先來，比爾，不知道你願不願意補充？但我們確實在第三季開始推出，但實際上，我們只是在測試這個管道。因此，我們認為 2025 年的收入將微乎其微，而我們之前說過，我們可以從 2026 年開始看到一些影響。所以我認為，我們所說的 2026 年強勁的銷售成長，主要還是指美國銷售成長和病患數量的增加，我們已經討論過這一點。歐洲的情況也一樣，這一切終將再次上演。速度很慢。我們必須建立這個系統。我們需要在歐洲各國鋪設這套系統。明年就只有德國了。所以確實如此——它會增加一些，但不會增加很多。

Yes. I think that's really, really great comment. It is Germany right now, and we're really excited. I mean, first of all, we've hired an outstanding team there. The team is great. The feedback that we're getting is that MASH is -- needs to be treated. It's prevalent, very similar to the US in that sense, but it takes time, right? You got to wire the system. It's practice by practice, it's prescriber by prescriber.

是的。我覺得這個評論真的非常棒。現在這裡是德國，我們感到非常興奮。首先，我們在那裡聘請了一支非常優秀的團隊。這個團隊很棒。我們得到的回饋是，MASH（陸軍野戰醫院）需要被重視。這種情況很普遍，從這個意義上與美國非常相似，但這需要時間，對吧？你得給系統接線。這是逐一實踐、逐一開藥的醫生之間的比較。

And we're taking all the steps in the usual next countries to look at as well. We've started putting teams in place that are evaluating the market and our launch strategy there. And again, just absolutely high-quality team that's in place. So we feel really good about the long-term prospects, but we also know that there's a lot of wiring to do, and we've got to navigate the reimbursement process in each country, which takes some time, but we got a great team to do that.

我們也正在採取一切必要措施，對接下來要關注的國家進行同樣的觀察。我們已經開始組建團隊，負責評估市場以及我們在當地的上市策略。再次強調，我們擁有一支絕對高素質的團隊。所以我們對長期前景感到非常樂觀，但我們也知道還有很多工作要做，而且我們必須處理每個國家的報銷流程，這需要一些時間，但我們有一個很棒的團隊來做這件事。

Kaveri Pohlman, Clear Street.

卡維裡·波爾曼，克利爾街。

Congrats on the progress. Are there any systemic differences or challenges in insurance approval rates for Rezdiffra depending on whether the prescription comes from an endocrinologist versus a hepatologist or gastroenterologist. And maybe just like a connected question to that. Besides the clinical data that you showed on slide 14, is there any real-world evidence that you have collected or showing that Rezdiffra can prevent or delay the progression of F4 cirrhosis perhaps based on the feedback from its current use by physicians? In other words, is there like any evidence leading to the preference of Rezdiffra or GLP-1s in F2/ F3 MASH patient?

恭喜你取得進展。Rezdiffra 的保險審批率是否有系統性差異或挑戰，取決於處方是由內分泌科醫師開立還是由肝病科醫師或胃腸科醫師開立。也許可以把它看作是一個相關的問題。除了您在第 14 張投影片上展示的臨床數據之外，您是否收集或收集了任何真實世界的證據，表明 Rezdiffra 可以預防或延緩 F4 肝硬化的進展，或許可以根據醫生目前使用該藥物的反饋來證明這一點？換句話說，是否有任何證據表明 Rezdiffra 或 GLP-1s 在 F2/F3 MASH 患者中更受歡迎？

Yes. Thanks for the question. Maybe starting there. We're seeing more and more real-world evidence that's coming to life. Some of it will be presented at AASLD this week or this week into next week.

是的。謝謝你的提問。或許可以從那裡開始。我們看到越來越多的現實世界證據正在變成現實。部分內容將在本週或下週的AASLD會議上發表。

And we expect as more patients start to hit the one-year mark and beyond that there will be more. Anecdotally, we're hearing really, really great feedback. When you launch a product, you never know what's going to happen in the real world. You have your clinical data and you're not sure what real-world experience is going to be. So far, the anecdotal feedback has been extremely strong by prescribers, and they're seeing effects on, obviously, liver fat.

我們預計，隨著越來越多的患者達到一年及以上的追蹤期，人數還會增加。據我們了解，回饋非常好。產品上市時，你永遠無法預知現實世界會發生什麼事。您擁有臨床數據，但不確定現實世界的經驗會是什麼樣的。到目前為止，處方醫生的回饋非常積極，他們顯然看到了對肝臟脂肪的影響。

They're seeing effects on fibrosis and all the other myriad of other things, LSTs, lipids, et cetera. So we're really excited about the real-world evidence reading out. And we've done work with claims databases, et cetera. So more to come, but early indicators are extremely strong. So really excited about that.

他們發現對纖維化以及其他無數方面都有影響，例如 LST、脂質等等。所以我們對現實世界的證據解讀感到非常興奮。我們也做過理賠資料庫等方面的工作。後續還有更多消息，但目前的跡象非常強勁。我真的非常興奮。

To your first question, it really is payer to payer about, this is this utilization management criteria, who can prescribe, et cetera. And for the most part, it is -- it refers to specialists. And in the specialists, that can be hepatologists and gastroenterologists. And then in some cases, it may or may not name endocrinologists. So it's usually either a requirement to be prescribed by a specialist or in consultation with a specialist.

對於你的第一個問題，這實際上是付款方之間的問題，即醫療資源利用管理標準、誰可以開處方等等。而且在大多數情況下確實如此——它指的是專家。而專科醫生則包括肝病學家和腸胃科醫生。在某些情況下，它可能會提及內分泌學家的名字，也可能不會。因此，通常需要由專科醫生開立處方或諮詢專科醫生後才能服用。

But again, that's something which really varies on a plan-by-plan basis. We don't see that as any kind of a hindrance now. And remember, our focus is the specialists. We believe Rezdiffra should be prescribed by these specialists. Now in time, that may change, but we think that this is a very serious disease. It is a very serious disease, and we want to have the specialists get experience with Rezdiffra in treating these patients before it would ever extend beyond that. And that's crystal clear we make that crystal clear with payers as well. That is our intent.

但同樣，這實際上是因計劃而異的。我們現在並不認為這會構成任何障礙。記住，我們的重點是專家。我們認為Rezdiffra應該由這些專科醫生開處方。隨著時間的推移，這種情況可能會改變，但我們認為這是一種非常嚴重的疾病。這是一種非常嚴重的疾病，我們希望專家在使用 Rezdiffra 治療這些患者之前累積經驗，然後再推廣到其他地區。這一點非常明確，我們也向付款方明確說明了這一點。這就是我們的意圖。

Great. Thanks, Bill. And thank you all for your time and interest today. This now concludes our call. A replay of this webcast will be available on our website in approximately two hours. Thanks for joining us.

偉大的。謝謝你，比爾。感謝各位今天抽出時間並對此感興趣。通話到此結束。本次網路直播的回放將在大約兩小時後發佈在我們的網站上。謝謝您的參與。

Ladies and gentlemen, thank you for your participation in today's conference. You may now disconnect. Have a wonderful day.

女士們、先生們，感謝各位參加今天的會議。您現在可以斷開連線了。祝您有美好的一天。