Madrigal Pharmaceuticals Inc (MDGL) 2025 Q4 法說會逐字稿

Good morning, and thank you for standing by. Welcome to Madrigal Pharmaceuticals' fourth quarter and full year 2025 earnings conference call. (Operator Instructions)

早上好，感謝您的耐心等待。歡迎參加 Madrigal Pharmaceuticals 2025 年第四季及全年業績電話會議。（操作說明）

As a reminder, today's conference call is being recorded. I would now like to introduce Ms. Tina Ventura, Chief Investor Relations Officer. Please go ahead.

再次提醒，今天的電話會議正在錄音。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。

Thank you, Michelle. Good morning, everyone, and thank you for joining us to discuss Madrigal's fourth quarter and full year 2025 earnings. We issued a press release this morning and posted a slide deck to accompany this webcast on the Investor Relations section of our website.

謝謝你，米歇爾。各位早安，感謝各位參加本次會議，共同探討 Madrigal 2025 年第四季及全年收益。今天早上我們發布了新聞稿，並在我們網站的投資者關係版塊發布了與本次網路直播配套的幻燈片。

On the call with me today is Bill Sibold, Chief Executive Officer; David Soergel, Chief Medical Officer; and Mardi Dier, Chief Financial Officer. They will provide prepared remarks, followed by Q&A. 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.

今天和我一起通話的有：執行長 Bill Sibold；首席醫療官 David Soergel；以及財務長 Mardi Dier。他們將發表準備好的講話，然後進行問答環節。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 on slide 3.

接下來，我會把電話交給比爾，請看投影片 3。

Thanks, Tina. Good morning, and thanks for joining us. Today, I'll provide an update on the Rezdiffra launch, where we ended our first full year on the market at nearly $1 billion in net sales and solidified Rezdiffra as the foundational therapy in MASH. We'll discuss the significant growth in the US MASH market, which is up nearly 50% since the end of 2023 and growing at a double-digit pace. And then Dave will provide an update on our R&D strategy, where we now have more than 10 programs in our pipeline. Before turning to our fourth quarter results, I want to reflect on what we accomplished in 2025 and in just the first six weeks of this year.

謝謝你，蒂娜。早安，感謝各位的參與。今天，我將介紹 Rezdiffra 的上市情況，我們在上市後的第一個完整年度實現了近 10 億美元的淨銷售額，並鞏固了 Rezdiffra 作為 MASH 基礎療法的地位。我們將討論美國 MASH 市場的顯著成長，自 2023 年底以來成長了近 50%，並以兩位數的速度成長。然後，Dave 將介紹我們的研發策略的最新進展，目前我們有 10 多個專案正在研發中。在介紹我們第四季業績之前，我想回顧一下我們在 2025 年以及今年前六週所取得的成就。

In a remarkably short period of time, we've built the leading company in MASH and assembled a pipeline we believe will help define the future of this category. We continue to execute on a fantastic US launch, extended Rezdiffra's patent exclusivity to 2045, and initiated our ex-US rollout beginning in Germany. We're advancing our F4c trial for Rezdiffra, and we're accelerating evidence generation to further differentiate the product.

在極短的時間內，我們打造了 MASH 領域的領先公司，並建立了我們認為將有助於定義該領域未來的產品線。我們繼續在美國成功推出產品，將 Rezdiffra 的專利獨佔期延長至 2045 年，並​​開始在美國以外地區推廣，首先從德國開始。我們正在推進 Rezdiffra 的 F4c 試驗，並加快證據生成，以進一步凸顯該產品的差異化優勢。

At the same time, we moved quickly to build a high-quality pipeline around Rezdiffra, completing three transactions in roughly six months, adding an oral GLP-1, a late-stage DGAT-2 inhibitor, and a portfolio of six preclinical siRNA targets, each designed to be studied in combination with Rezdiffra. The reason we're moving with this level of urgency is simple: assets like Rezdiffra don't come along often. We have a high-quality, high-growth, foundational therapy driving strong top-line performance with patent protection into 2045.

同時，我們迅速圍繞 Rezdiffra 構建了一條高品質的研發管線，在大約六個月內完成了三筆交易，新增了一種口服 GLP-1、一種後期 DGAT-2 抑製劑和六個臨床前 siRNA 靶點組合，每個靶點都旨在與 Rezdiffra 聯合研究。我們如此緊急地採取行動的原因很簡單：像 Rezdiffra 這樣的資產並不常見。我們擁有高品質、高成長的基礎療法，該療法推動了強勁的營收成長，並擁有專利保護至 2045 年。

When you have an asset like that, you have an opportunity to build a sustainable and durable franchise for the long term. That's exactly what we're doing. Rezdiffra gives us a unique ability to pursue combinations, to attract high-quality assets, and to shape a market in ways other companies simply can't. As a result, we are fundamentally a different company today than just six months ago, transitioning from a single-asset launch story into a fast-growing biotech with a pipeline designed to extend our leadership for years to come. Let's turn to net sales performance on slide 5.

擁有這樣的資產，你就有機會建立一個可持續發展的、持久的長期特許經營體系。這正是我們正在做的。Rezdiffra 賦予我們獨特的能力，讓我們能夠以其他公司無法做到的方式合併、吸引高品質資產並塑造市場。因此，如今的我們與六個月前相比，已經發生了根本性的變化，我們從一家單一資產上市的公司轉型為一家快速發展的生物技術公司，並擁有旨在鞏固我們未來幾年領先地位的產品線。讓我們來看看第 5 張投影片中的淨銷售業績。

We delivered fourth quarter 2025 net sales of $321 million, more than tripling fourth quarter 2024. For our first full year on the market, net sales totaled $958 million, an exceptional launch by any industry standard. That nearly billion-dollar result took a lot of work. We didn't just launch a product, we built a market from scratch. Let's take a second and really think about that.

我們實現了 2025 年第四季淨銷售額 3.21 億美元，是 2024 年第四季的三倍多。上市第一年，我們的淨銷售額達到 9.58 億美元，以任何行業標準衡量，這都是一個非凡的開局。這一近十億美元的成果背後付出了大量努力。我們不僅推出了一款產品，我們也從零開始打造了一個市場。讓我們花點時間認真思考。

Remember, MASH was long viewed as the graveyard of drug development. No treatments, no market, and skepticism that one would ever exist, particularly with GLP-1s on the horizon. We took a different view. The unmet need was substantial, and demand for an effective therapy was real. We believed in the science and Rezdiffra's ability to become the standard of care. We built the right team, people who have created categories and launched blockbuster brands, and we got to work. We executed with a long-term mindset, wiring the system practice by practice, educating prescribers, establishing care pathways, expanding prescriber breadth and depth, and securing first-line access through disciplined contracting. And we continued to iterate and improve.

別忘了，MASH 長期以來一直被視為藥物研發的墳場。沒有治療方法，沒有市場，而且人們懷疑這種治療方法是否會存在，尤其是在 GLP-1 療法即將問世的情況下。我們持不同觀點。未被滿足的需求很大，對有效療法的需求是真實存在的。我們相信科學，也相信Rezdiffra有能力成為治療標準。我們組建了一支合適的團隊，成員都是曾經開創品類並推出過爆款品牌的人，然後我們就開始工作了。我們以長遠的眼光執行，逐一實踐地建立系統，教育處方醫生，建立護理路徑，擴大處方醫生的廣度和深度，並透過嚴格的合約確保一線准入。我們不斷迭代改進。

The results speak for themselves. We were first to market, and that matters. Rezdiffra, with its liver-directed and differentiated profile, has established itself as the foundational therapy in MASH. The market is real and only beginning to take shape. GLP-1s are here, and as we expected, we're still steadily adding patients. There is room for competition, which we believe will further expand the market, and we are building a pipeline designed to extend our leadership over time.

結果不言而喻。我們率先進入市場，這一點很重要。Rezdiffra 具有肝臟標靶和分化特性，已成為 MASH 的基礎療法。市場是真實存在的，並且才剛開始成形。GLP-1 療法已經問世，正如我們所預期的那樣，我們仍在穩步增加患者數量。市場存在競爭空間，我們相信這將進一步擴大市場，我們正在建立一個旨在隨著時間的推移鞏固我們領先地位的管道。

As a result of the foundation we've built and our large base of prescribers, we continue to steadily add patients quarter over quarter, as seen on slide 7. Remember, the number we report reflects the net of new starts and discontinuations at the end of each quarter.

由於我們已建立的基礎和龐大的處方醫生群體，我們每個季度都在穩步增加患者數量，如幻燈片 7 所示。請記住，我們報告的數字反映的是每個季度末新開工項目和停工項目的淨額。

We continued to steadily add patients, ending the fourth quarter with more than 36,250 patients on Rezdiffra, up from more than 29,500 at the end of the third quarter. That tells us two things. First, Rezdiffra's profile is exceptional and resonates very well with prescribers and patients. Second, this large and expanding market is capable of supporting multiple therapies. This represents a small fraction of the growing addressable population, and we expect to continue to steadily add patients quarter over quarter going forward. Let me spend a moment on the US MASH market on slide 8.

我們持續穩定增加患者數量，到第四季末，接受 Rezdiffra 治療的患者超過 36,250 人，高於第三季末的 29,500 多人。這說明了兩件事。首先，Rezdiffra 的療效非常出色，深受處方醫生和患者的歡迎。其次，這個龐大且不斷擴大的市場能夠支持多種療法。這僅佔不斷增長的目標人群的一小部分，我們預計未來每季患者數量將繼續穩步增長。讓我花點時間在第 8 張投影片上介紹美國的 MASH 市場。

We are still in the early stages of what we expect to become a large specialty market. In just the last two years, the F2, F3 target population of 315,000 representative patients seen by our target specialists has expanded nearly 50%, and we expect this market to grow at a double-digit pace for the foreseeable future.

我們目前仍處於發展初期，但我們預計未來將成為一個龐大的專業市場。在過去的兩年裡，我們目標專科醫生接診的 315,000 名 F2、F3 目標患者群體增長了近 50%，我們預計在可預見的未來，該市場將以兩位數的速度增長。

Rezdiffra's approval and increased industry investment across the ecosystem has fundamentally changed the market dynamic, driving increased awareness, diagnosis, referrals, specialist involvement, and patients seeking care. This is a category in its very early stages, where Rezdiffra is now established as the standard of care. As the market expands, we expect to benefit from its growth, increased penetration, and ultimately, the introduction of additional therapies from our pipeline.

Rezdiffra 的批准以及整個生態系統中行業投資的增加，從根本上改變了市場動態，推動了人們對該疾病的認識、診斷、轉診、專家參與以及患者尋求治療的增加。這是一個尚處於早期階段的類別，目前 Rezdiffra 已成為該類別的標準治療方案。隨著市場擴張，我們期望從其成長、滲透率提高以及最終從我們的研發管線中推出更多療法中受益。

MASH is a rare opportunity in biotech. Few therapeutic areas offer this combination of scale and high growth potential. That's why we expect MASH to follow the trajectory of other large specialty markets, as shown on slide 9.

MASH是生物技術領域一個難得的機會。很少有治療領域能同時具備如此大的規模和高成長潛力。因此，我們預期 MASH 將遵循其他大型專業市場的軌跡，如投影片 9 所示。

Markets that support 10 to 15 plus therapies and have grown over decades to exceed $20 billion in annual sales. We believe MASH will evolve the same way, with one important difference. We are first to market with a product that has an unmatched profile. As an effective liver-directed, safe, and well-tolerated oral medicine, it far surpasses the profile of first-to-market products in those other categories. And we continue to hear from our prescribers that Rezdiffra is performing even better than expected in the real world. This profile positions us well to expand into compensated MASH cirrhosis or F4c, the next phase of our growth strategy outlined on slide 11.

支持 10 到 15 種以上療法的市場，經過幾十年的發展，年銷售額已超過 200 億美元。我們認為 MASH 的發展方向也相同，但有一個重要的差異。我們率先將一款擁有無可比擬優勢的產品推向市場。作為一種有效、安全、耐受性良好的肝臟標靶口服藥物，它遠遠超過了其他類別中首批上市產品的性能。我們也不斷收到處方醫生的回饋，表示 Rezdiffra 在現實世界中的表現甚至比預期還要好。該概況使我們能夠很好地擴展到代償性 MASH 肝硬化或 F4c，這是我們在第 11 張投影片中概述的下一階段成長策略。

We believe F4c could double Rezdiffra's opportunity with approximately 245,000 patients, no approved therapies, and a significantly higher urgency to treat. Assuming regulatory approval, we expect to be first to market in F4c. Importantly, our F4c trial focuses on clinically meaningful outcomes, preventing decompensation rather than relying on biopsy. Rezdiffra would be the only medicine with outcomes data, solidifying it as the standard of care in MASH and supporting full approval across F2 to F4c. Before I turn it over to Dave, I want to briefly outline how we see the MASH market evolving and why Madrigal is uniquely positioned to lead it by building on the pipeline strategy that I described earlier.

我們相信，F4c 可以讓 Rezdiffra 的機會翻一番，因為大約有 245,000 名患者，沒有核准的療法，而且治療的緊迫性要高得多。假設獲得監管部門批准，我們預計將率先在 F4c 領域進入市場。重要的是，我們的 F4c 試驗著重於具有臨床意義的結果，防止失代償，而不是依賴活檢。Rezdiffra 將成為唯一擁有療效數據的藥物，鞏固其作為 MASH 治療標準的地位，並支持其在 F2 至 F4c 階段獲得全面批准。在將發言權交給戴夫之前，我想簡要概述我們對 MASH 市場發展的看法，以及 Madrigal 如何憑藉我之前描述的管道策略，在獨特的地位上引領這一市場。

MASH is a complex, heterogeneous disease. Over time, we expect distinct patient subpopulations to emerge, each requiring different mechanisms, combinations, and sequencing approaches, all anchored by Rezdiffra. We've seen this evolution before in other diseases, where progress was driven by matching the right combinations to the right patients. That's the model we're pursuing in MASH, and it's why we've moved quickly to add these specific assets to our portfolio.

MASH是一種複雜的、異質性疾病。隨著時間的推移，我們預計會出現不同的患者亞群，每個亞群都需要不同的機制、組合和定序方法，所有這些都以 Rezdiffra 為基礎。我們以前在其他疾病中也看到過這種演變，進步的驅動力在於將正確的藥物組合與正確的患者相匹配。這就是我們在 MASH 中追求的模式，也是我們迅速將這些特定資產添加到我們的投資組合中的原因。

And the reason we can execute on this strategy is our high confidence in the growth potential of Rezdiffra. We're able to build an industry-leading MASH pipeline because we have an outstanding product, one that is performing exceptionally well today and is positioned for continued strong growth. That strong foundation allows us to develop the next generation of MASH therapies for patients. That's exciting, and it's a true differentiator for Madrigal.

我們之所以能夠執行這項策略，是因為我們對 Rezdiffra 的成長潛力充滿信心。我們能夠建立業界領先的 MASH 產品線，因為我們擁有出色的產品，目前表現優異，並有望繼續保持強勁成長。這一堅實的基礎使我們能夠為患者開發下一代 MASH 療法。這令人興奮，也是 Madrigal 的真正差異化優勢。

Dave, I'll turn it over to you to walk through our R&D strategy.

戴夫，接下來就交給你來介紹一下我們的研發策略。

Thanks, Bill. Our objective in R&D at Madrigal is straightforward: build the industry-leading pipeline in MASH to make better therapies for patients. We're doing that through targeted business development and smart clinical execution, leveraging the expertise of an R&D team that pioneered modern MASH drug development. Our strategy has four goals: deliver outcomes, data, and full approval for Rezdiffra from F2 through F4c; advance complementary mechanisms for combination with Rezdiffra to deliver the best efficacy across the MASH spectrum; remain modality agnostic, keeping development of the best combination regimens as our strategic aim; note our recent addition of injectable siRNAs; everage our experience to evolve the science; design smarter, more informative clinical trials enabled by our extensive data and operational experience in MASH. Our aim is to use capital efficiently to take more shots on goal and advance only the most promising programs for patients.

謝謝你，比爾。Madrigal 的研發目標很明確：在 MASH 領域建立業界領先的研發管線，為病患提供更好的治療方案。我們透過有針對性的業務拓展和巧妙的臨床執行來實現這一目標，充分利用了率先開發現代 MASH 藥物的研發團隊的專業知識。我們的策略有四個目標：從 F2 到 F4c 階段，為 Rezdiffra 提供結果、數據和全面批准；推進與 Rezdiffra 聯合使用的互補機制，以在 MASH 治療領域實現最佳療效；保持治療方式中立，將開發最佳聯合治療方案作為我們的戰略目標；注意我們最近的注射型 siRNA利用我們在註射的經驗；領域豐富的數據和營運經驗，設計更聰明、資訊量更大的臨床試驗。我們的目標是有效率地利用資金，爭取更多機會，只推動最有希望的患者治療計畫。

The first pillar of our R&D strategy is delivering outcomes data in F4c. The basis of our high confidence in our outcomes study are the data from our 2-year open-label study. The importance of the 2-year data is better understood in the context of how cirrhosis progresses.

我們研發策略的第一個支柱是提供 F4c 的結果資料。我們對結果研究的高度信心源自於我們為期 2 年的開放標籤研究的數據。了解肝硬化的進展情況，就能更能理解兩年數據的重要性。

Development of clinically significant portal hypertension, or CSPH, is a critical inflection point in the disease. It marks a transition from compensated cirrhosis towards decompensated disease and is when the most serious complications, like variceal bleeding and development of ascites, begin to occur. Crossing the threshold into decompensated cirrhosis predicts poor prognosis, with an average survival time of 2 to 3 years without a liver transplant.

臨床上顯著的門靜脈高壓（CSPH）的發生是該疾病的關鍵轉折點。它標誌著從代償性肝硬化到失代償性疾病的過渡，也是最嚴重的併發症（如食道靜脈曲張出血和腹水形成）開始出現的時候。肝硬化發展到失代償期預示著預後不良，若未進行肝臟移植，平均存活期為 2 至 3 年。

From the literature, it's clear that patients with CSPH have meaningfully higher rates of liver-related events, and reducing CSPH risk lowers liver-related events.. That's why the 2-year open label, 122-patient F4C data from our NAFLD-1 trial are so exciting.

從文獻中可以明顯看出，CSPH 患者的肝臟相關事件發生率顯著較高，降低 CSPH 風險可降低肝臟相關事件的發生率。這就是為什麼我們 NAFLD-1 試驗中為期 2 年、122 名患者的 F4C 數據如此令人興奮的原因。

As shown here on slide 14, 65% of patients with CSPH at baseline moved into lower risk categories by year two. These data support Rezdiffra's potential in F4C and reinforce confidence in our outcomes trial, particularly given that both trials have very similar patient populations.

如投影片 14 所示，基線時患有 CSPH 的患者中有 65% 在第二年轉入風險較低的類別。這些數據支持 Rezdiffra 在 F4C 中的潛力，並增強了我們對結果試驗的信心，特別是考慮到這兩個試驗的患者群體非常相似。

The second pillar of our R&D strategy is advancing combination therapies anchored by Rezdiffra. Slide 15 shows many of the known mechanisms involved in MASH. MASH is driven by excess free fatty acid delivery to the liver, leading to steatosis, inflammation, and fibrosis. While there are many potential points to intervene in the disease, it took decades and more than 20 industry failures before Madrigal cracked the code with Rezdiffra.

我們研發策略的第二個支柱是推動以 Rezdiffra 為核心的聯合療法。第 15 張投影片展示了 MASH 中涉及的許多已知機制。MASH 是由過量的遊離脂肪酸輸送到肝臟引起的，導致脂肪變性、發炎和纖維化。雖然有許多潛在的干預點可以治療這種疾病，但 Madrigal 花了數十年時間，經歷了 20 多次行業失敗，才最終用 Rezdiffra 破解了這個難題。

To date, only two mechanisms have crossed the finish line: THR-β agonism, addressing MASH at its source in the liver, and indirect-acting GLP-1 agonism. But MASH is a heterogeneous chronic disease, and therefore, we expect treatment to evolve toward combinations. Rezdiffra gives us a unique, solid foundation on which to build combinations to achieve better efficacy overall or in certain patient subpopulations.

迄今為止，只有兩種機制取得了成功：THR-β激動劑，從肝臟的源頭解決MASH；以及間接作用的GLP-1激動劑。但 MASH 是一種異質性慢性疾病，因此，我們預期治療將朝著聯合治療的方向發展。Rezdiffra 為我們提供了一個獨特、堅實的基礎，在此基礎上我們可以建立組合療法，從而在整體上或在某些患者亞群中實現更好的療效。

Our combination strategy is simple: prioritize validated, mechanistically complementary approaches that enhance efficacy while preserving Rezdiffra's strong safety and tolerability profile. In orange, you see where we've already acted, an oral GLP-1, a late-stage DGAT-2 inhibitor, and multiple targets using siRNA. Let's discuss why we're excited about these new mechanisms, starting with siRNA on Slide 16.

我們的聯合策略很簡單：優先採用已驗證的、機制互補的方法，以提高療效，同時保持 Rezdiffra 良好的安全性和耐受性。在橘色部分，您可以看到我們已經採取行動的領域，包括口服 GLP-1、後期 DGAT-2 抑制劑以及使用 siRNA 的多個標靶。讓我們討論為什麼我們對這些新機制感到興奮，首先從第 16 張投影片上的 siRNA 開始。

First, siRNAs target validated genes that drive MASH progression. Using precise mRNA knockdown, we can either enhance efficacy broadly or develop more tailored approaches for defined patient subpopulations.

首先，siRNA 靶向驅動 MASH 進展的已驗證基因。利用精確的 mRNA 敲低，我們可以廣泛提高療效，或為特定的患者亞群開發更有針對性的方法。

Second, the modality. GalNAc conjugated siRNA is well established and highly liver-targeted. The clinical safety of the platform is supported by multiple marketed products. We acquired six preclinical siRNA assets that are highly complementary to resmetirom, positioning us for next generation, more personalized combination regimens. Slide 17 covers our DGAT2 inhibitor, which we're excited about for a number of reasons.

其次，是表達方式。GalNAc 偶聯的 siRNA 是一種成熟的、高度標靶肝臟的 siRNA。該平台的臨床安全性已得到多種上市產品的支持。我們收購了六項與resmetirom高度互補的臨床前siRNA資產，使我們為下一代更個人化的聯合治療方案奠定了基礎。第 17 張幻燈片介紹了我們的 DGAT2 抑制劑，我們對此感到非常興奮，原因有很多。

First, DGAT2 inhibition is a complementary mechanism to THR beta agonism. Ervogastat prevents free fatty acids from being incorporated into triglycerides, and resmetirom restores mitochondrial function to allow those free fatty acids to be turned into energy through beta oxidation. The two mechanisms together, therefore, address both the production and clearance of excess hepatic fat.

首先，DGAT2 抑制是 THR β 激動劑的補充機制。Ervogastat 可防止遊離脂肪酸摻入三酸甘油酯中，而 resmetirom 可恢復粒線體功能，使這些遊離脂肪酸透過 β 氧化轉化為能量。因此，這兩種機制共同作用，既能解決肝臟中過量脂肪的產生問題，又能解決肝臟中過量脂肪的清除問題。

Second, we know a lot about Ervogastat. It's already completed a Phase 2B trial in MASH, demonstrating a robust MRI-PDFF reductions and clean safety. In the MYRNA study, 72% of patients at the 150 mg dose achieved at least a 30% reduction in PDFF, and 61% achieved a 50% reduction, what many experts now consider a super response, predicting a greater likelihood of a reversal of fibrosis.

其次，我們對 Ervogastat 了解很多。該藥物已在 MASH 中完成了 2B 期試驗，結果顯示其能顯著降低 MRI-PDFF 值，且安全性良好。在 MYRNA 研究中，72% 的 150 毫克劑量組患者的 PDFF 至少降低了 30%，61% 的患者降低了 50%，許多專家現在認為這是超強療效，預示著纖維化逆轉的可能性更大。

The combination of these two mechanisms has the potential to move more patients into that super responder category and drive better antifibrotic efficacy and better outcomes. We plan to initiate a drug-drug interaction study this year and expect to begin a Phase 2 combination program in 2027 following FDA discussions. Next, our oral GLP-1 on Slide 18.

這兩種機制的結合有可能使更多患者進入超級反應者類別，並提高抗纖維化療效和改善治療效果。我們計劃今年啟動一項藥物交互作用研究，並預計在與FDA討論後於2027年啟動2期聯合用藥計畫。接下來，我們將介紹投影片 18 的口服 GLP-1。

Let's start by acknowledging that there's strong real-world enthusiasm for combining GLP-1s with resmetirom, with an understanding of the mechanistic complementarity of GLP-1 and resmetirom. GLP-1s act outside the liver by improving systemic metabolism and reducing free fatty acid delivery to the liver. This complements resmetirom's liver-directed mechanism of action. Importantly, our focus for this program is on developing a better treatment for MASH, not maximal weight loss, and therefore, our goal is to balance the right amount of weight loss to potentiate resmetirom's antifibrotic effect.

首先，我們要承認，在了解 GLP-1 和 resmetirom 的機制互補性的基礎上，現實世界對將 GLP-1 與 resmetirom 結合使用表現出了強烈的熱情。GLP-1 蛋白在肝臟外發揮作用，透過改善全身代謝和減少遊離脂肪酸向肝臟的輸送來發揮作用。這與瑞美替羅針對肝臟的作用機轉相輔相成。重要的是，我們這個計畫的重點是開發一種更好的 MASH 治療方法，而不是最大限度地減輕體重，因此，我們的目標是平衡適當的減重幅度，以增強 resmetirom 的抗纖維化作用。

So what is the right amount of weight loss to achieve better efficacy in MASH? In MAESTRO-NASH, we saw that as little as 5% weight loss meaningfully potentiated Rezdiffra's fibrosis benefit. So our aim is a once-daily, well-tolerated, oral fixed-dose combination that optimizes efficacy while maintaining good tolerability. A Phase 1 single-ascending dose study of MGL-2086 is expected to start in the second quarter.

那麼，在 MASH 治療中，減重多少才算適合才能達到更好的療效呢？在 MAESTRO-NASH 研究中，我們發現即使體重減輕 5%，也能顯著增強 Rezdiffra 對纖維化的益處。因此，我們的目標是研發一種每日一次、耐受性良好的口服固定劑量複方製劑，在維持良好耐受性的同時優化療效。MGL-2086 的 1 期單次遞增劑量研究預計將於第二季開始。

Putting it all together on slide 19, we are translating our leadership into action with one goal in mind: build the leading MASH pipeline. This is really just the beginning of an exciting journey. With Rezdiffra protected into 2045, we have a long runway to invest and innovate, building a pipeline that will define the future of MASH care.

在第 19 張投影片中，我們將所有內容整合起來，把我們的領導轉化為行動，目標只有一個：建立領先的 MASH 人才培養體系。這只是一段令人興奮的旅程的開始。由於 Rezdiffra 的保護期延長至 2045 年，我們有很長的時間進行投資和創新，建立一個將定義 MASH 護理未來的產品線。

With that, I'll hand it over to Mardi.

這樣，我就把它交給瑪蒂了。

Thanks, Dave, and good morning. Turning to slide 20 and a summary of our financials. Fourth quarter 2025 net sales totaled $321.1 million, reflecting another quarter of strong demand and bringing full year 2025 net sales to $958.4 million. As we've discussed, we've made excellent progress contracting for first-line access in 2026, with some contracts taking effect in the fourth quarter of last year, as anticipated. As a result, our gross to net impact increased from the third quarter to the fourth quarter. As a reminder, gross to net includes several components: commercial rebates, government rebates, co-pay assistance, and channel distribution costs.

謝謝你，戴夫，早安。接下來請看第 20 張投影片，了解我們的財務狀況摘要。2025 年第四季淨銷售額總計 3.211 億美元，反映出另一季強勁的需求，使 2025 年全年淨銷售額達到 9.584 億美元。正如我們所討論的，我們在 2026 年一線准入合約的簽訂方面取得了非常好的進展，一些合約已於去年第四季如期生效。因此，我們的毛利與淨利之比從第三季到第四季有所成長。提醒一下，毛利到淨利包括以下幾個部分：商業回扣、政府回扣、共同支付援助和通路分銷成本。

The team did an exceptional job managing these dynamics, resulting in a full year average at the low end of the 20%-30% range we previously outlined, an excellent outcome for 2025. We're off to a strong start this year and continue to steadily add patients. As indicated last year, last quarter, we expect our payer agreements to bring our full year 2026 gross to net impact into the high 30% range, consistent with specialty medicine analogs. Looking ahead, we expect robust net sales growth in 2026, despite the step-up in gross to net from contracting that begins in Q1, plus the typical first quarter dynamics related to benefit plan changes and insurance re-verifications. The fundamentals of the business are strong, and we're looking forward to another outstanding year of performance.

團隊出色地管理了這些動態，使得全年平均成長率達到了我們之前概述的 20%-30% 範圍的低端，這對 2025 年來說是一個極好的結果。今年我們開局良好，患者數量持續穩定成長。正如去年上個季度所指出的那樣，我們預計我們的支付方協議將使我們 2026 年全年毛利淨利差達到 30% 以上，與專科藥物類似物一致。展望未來，儘管從第一季開始的合約簽訂導致毛利潤與淨利潤之間的差距擴大，加上第一季常見的福利計劃變更和保險重新核實等因素，我們預計 2026 年淨銷售額將實現強勁增長。公司基本面強勁，我們期待又一個業績斐然的年份。

Moving briefly to operating expenses, R&D expenses for the fourth quarter and full year 2025 were $116.3 million and $388.5 million, respectively. The increase over the prior year periods was primarily due to business development. In the third quarter, this included a $120 million upfront payment for our oral GLP-1, and in the fourth quarter, a $50 million upfront payment for Ervogastat and our two additional early-stage MASH pipeline assets. Of note, the upfront payment of $60 million for our siRNA targets will be paid and included as an R&D expense in the first quarter of 2026.

簡單來說，營運費用方面，2025 年第四季和全年的研發費用分別為 1.163 億美元和 3.885 億美元。與上年同期相比的成長主要是由於業務發展。第三季度，我們收到了 1.2 億美元的口服 GLP-1 預付款；第四季度，我們收到了 5,000 萬美元的 Ervogastat 預付款以及另外兩項早期 MASH 管線資產的預付款。值得注意的是，我們為 siRNA 標靶支付的 6,000 萬美元預付款將在 2026 年第一季支付，併計入研發費用。

SG&A expenses for the fourth quarter and full year 2025 were $240 million and $813.8 million, respectively. The increase over the prior periods was expected to support the Rezdiffra launch. Looking ahead, we expect 2026 R&D expenses to be roughly the same as 2025, as we build our organization and begin to invest in our pipeline programs. We anticipate SG&A expenses to increase next year as we continue to support the launch of Rezdiffra and build the foundation for exceptional long-term growth.

2025 年第四季及全年的銷售、一般及行政費用分別為 2.4 億美元及 8.138 億美元。與前期相比，此次成長預計將支持 Rezdiffra 的推出。展望未來，我們預計 2026 年的研發支出將與 2025 年大致相同，因為我們將建立我們的組織並開始投資我們的在研項目。我們預計明年的銷售、管理及行政費用將會增加，因為我們將繼續支持 Rezdiffra 的推出，並為卓越的長期成長奠定基礎。

Turning to our balance sheet, we ended the fourth quarter of 2025 with $988.6 million in cash, cash equivalents, restricted cash, and marketable securities. With this strong cash position, we continue to be well resourced to support the ongoing launch of Rezdiffra and the advancement of multiple pipeline programs and continued business development. So to close, slide 21 captures why we're so confident about where Madrigal is headed.

從資產負債表來看，截至 2025 年第四季末，我們擁有 9.886 億美元的現金、現金等價物、受限現金和有價證券。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、多個在研項目的推進以及業務的持續發展。最後，第 21 張投影片說明了我們為什麼對 Madrigal 的發展方向如此有信心。

Rezdiffra is the foundational therapy in F2, F3 MASH, and it's just getting started. F4c represents another meaningful growth driver that could double our commercial opportunity. Our pipeline, now more than 10 programs deep, positions us to extend our leadership position as a durable, category-leading franchise. Taken together, this is a company built for sustained value creation across our launch, indication expansion, and pipeline. We believe we're exceptionally well positioned to lead in MASH in 2026 and beyond.

Rezdiffra 是 F2、F3 MASH 的基礎療法，而且它才剛起步。F4c 代表著另一個重要的成長動力，它有可能使我們的商業機會翻倍。我們目前擁有超過 10 個專案儲備，這使我們能夠鞏固自身作為持久的、行業領先的特許經營品牌的領導地位。綜上所述，這是一家旨在透過產品上市、適應症擴展和產品線建設實現持續價值創造的公司。我們相信，我們擁有得天獨厚的優勢，能夠在 2026 年及以後引領 MASH 的發展。

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

現在我將把電話轉回給蒂娜，讓她開始問答環節。

Thanks, Mardi. Let's move into the Q&A part of the call. [Michelle], 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。 [Michelle]，請先介紹問答環節的規則。

(Operator Instructions) Ellie Merle, Barclays.

（操作說明）Ellie Merle，巴克萊銀行。

Thanks for taking the question. So you're seeing meaningful growth in the number of diagnosed patients. Can you elaborate on the drivers here and talk about your expectations for category growth in 2026?

感謝您回答這個問題。所以，確診患者人數出現了顯著成長。您能否詳細說明一下這裡的驅動因素，並談談您對 2026 年該類別成長的預期？

And then second, you're also seeing an acceleration in patient starts despite the launch of Wegovy. Can you elaborate on the types of patients you're seeing starting on Rezdiffra now, versus, say, in the past, and any trends you're seeing across the types of different prescribers? Thanks.

其次，儘管 Wegovy 已經推出，但患者數量仍在加速成長。您能否詳細說明現在開始服用 Rezdiffra 的患者類型與過去相比有何不同，以及您在不同類型的處方醫生中觀察到的任何趨勢？謝謝。

Great. Ellie, thanks for the question. Yeah, we are seeing really strong growth. As you saw on the slides, which say a lot, almost 50% growth over a 2-year period. And this, you know, we had talked about the market is in a position to grow, right? The 315,000 diagnosed patients was diagnosed sitting in the offices of the target specialists that we were calling on. And what we're seeing is our efforts are really paying off on a couple of fronts.

偉大的。艾莉，謝謝你的提問。是的，我們看到了非常強勁的成長。正如你在投影片上看到的（幻燈片內容豐富），兩年內成長了近 50%。你知道，我們之前討論過，市場處於成長的有利位置，對吧？這 315,000 名確診患者都是在我們拜訪的目標專家的辦公室確診的。我們看到，我們的努力在幾個方面確實取得了成效。

Number one, as awareness goes up, there's going to be more people that are diagnosed. I think that having another company in the mix, Novo, who's really trying to drive, I would say, broad awareness and uptake in the primary care offices, et cetera, is leading to more diagnosis. Our focus has always been the $315, as we see a path to peak, essentially, through what's already available.

第一，隨著人們意識的提高，確診的人數也會增加。我認為，Novo 的加入，這家公司正在努力提高人們對基層醫療機構等的認識和接受度，從而促進了更多診斷的出現。我們一直關注的是 315 美元這個價位，因為我們認為可以透過利用現有資源來實現價格高峰。

Now, inevitably, though, as you bring products to market, you see higher growth in that space, and that's where we've seen the 50% and double-digit growth we're expecting into the foreseeable future. So we're really quite excited about it, and it gives us not only a clearer path to peak, but also perhaps it gives us a greater opportunity than we had even anticipated and planned around. So growth you see in all these markets, you're going to see patient growth for really years and years. And you know, I'll leave that there.

不過，隨著產品不斷推向市場，該領域的成長勢頭必然會更加強勁，而我們也正是在這個領域看到了 50% 甚至兩位數的增長，並預計在可預見的未來，這一增長勢頭仍將持續。所以我們對此感到非常興奮，這不僅讓我們更清楚地看到了達到巔峰的路徑，而且或許也給了我們比我們預期和計劃的更大的機會。所以，你在所有這些市場看到的成長，將會是持續多年的穩定成長。好了，我就說到這裡吧。

The question on patient adds, you know, we've been staying, and we continue to steadily add patients, and we've seen really no difference in the type of patients that is being prescribed Rezdiffra. They tend to be a pretty even mix between F2 and F3. And as it relates to, I think you mentioned a little bit about endocrinology, or how our efforts are just in general with growing, you know, we're seeing prescriptions mostly in the hep GI space. That is the predominant number of physicians, obviously more gastroenterologists than endocrinologists. They've just gone deeper into the deck, I would say.

關於患者的問題，你知道，我們一直在堅持，並且繼續穩定增加患者，但我們發現，服用 Rezdiffra 的患者類型並沒有什麼變化。F2 和 F3 的比例通常比較均衡。至於這方面，我想你剛才提到了一些關於內分泌學的內容，或者說我們總體上是如何努力發展壯大的，你知道，我們看到處方主要集中在肝病胃腸道領域。這是醫生中的絕大多數，顯然腸胃科醫生比內分泌科醫生多。可以說，他們只是深入了甲板的更深處。

You know, we've said that we've established really great breadth of prescribing, and now it's a matter of going deeper into their patient population. And I think what we're seeing is proof points that this is becoming the standard of care. Patients are being put on Rezdiffra, having great experiences, staying on the drug, and you see that reflected in the patient adds.

你知道，我們已經建立了非常廣泛的處方範圍，現在的問題是如何更深入地了解他們的患者群體。我認為我們現在看到的種種跡象表明，這正在成為護理標準。患者開始服用Rezdiffra，體驗很好，並且堅持服用該藥物，這一點從患者的補充資訊中就能看出。

Great. Thanks, Ellie. Next question, please.

偉大的。謝謝你，艾莉。下一個問題。

Thomas Smith, Leerink Partners.

Thomas Smith，Leerink Partners。

Good morning. Congrats on the quarter, and thanks for taking our questions. Maybe just one quick clarification question on, I just wanted to ask about the contribution of the Germany launch to the worldwide revenues and patient numbers, and maybe if you could expand a little bit on expectations for 2026.

早安.恭喜您本季取得佳績，感謝您回答我們的問題。或許我還有一個需要澄清的問題，我想問德國上市對全球收入和病患數量的貢獻，以及您能否稍微詳細談談對 2026 年的預期。

And then, on the pipeline combo programs, I know you're starting to look, and you've guided today to a Phase 2 study with Ervogastat next year. Could you just elaborate on how you're thinking about sort of mid-stage Phase 2 studies from here? Do you think these studies will need to evaluate liver histology via biopsy before you progress into pivotal studies, or is there potential for a more accelerated path that perhaps leverages NITs? Thanks so much.

然後，關於管道組合項目，我知道你們已經開始關注，而且你們今天也表示明年將進行 Ervogastat 的 2 期研究。您能否詳細說明一下您接下來對二期中期研究的設想？您認為這些研究是否需要在進入關鍵性研究之前透過活檢評估肝臟組織學，還是有可能透過利用非侵入性技術（NITs）等更快捷的途徑來實現？非常感謝。

Tom, thanks for the question. I'll start off with answering Germany. Germany contribution in 2025 was negligible, and we don't see actually a lot in 2026 as well. You know, really, part of the driver of that is as we're launching into an MFN world, it is still uncertain how ex-US is going to evolve. And that's not a Madrigal issue; that's for the whole industry.

湯姆，謝謝你的提問。我先回答德國的問題。德國在 2025 年的貢獻微乎其微，我們預期在 2026 年也不會有太多貢獻。你知道，這背後的部分原因是，隨著我們進入最惠國待遇的世界，美國以外的地區將如何發展仍然不確定。這不是 Madrigal 的問題，而是整個產業的問題。

So negligible in 2025. We're just getting started really in 2026. Don't expect a lot of contribution from Germany or ex-US in 2026. This is -- US is the base business. US is -- has exceptionally strong dynamics to it, as you've seen, not only from a performance perspective, but from an outlook perspective. We're very, very comfortable being able to have robust growth in 2026, the way 2026 is unfolding from an international market perspective.

因此，到2025年，其影響可以忽略不計。2026年我們才真正開始。不要指望德國或前美國國家在 2026 年做出太多貢獻。這是－美國是基礎業務。正如你所看到的，美國具有非常強勁的活力，不僅從表現的角度來看，而且從前景的角度來看也是如此。從國際市場的角度來看，2026 年的發展趨勢讓我們非常有信心在 2026 年實現強勁成長。

Maybe I'll just put on a finer point about our 2026, Tom. We really do expect robust growth. And where consensus is coming out for 2026 already, we feel really good about that, which reflects very good growth from where we ended up with the $958 for 2025.

湯姆，或許我應該再補充一點關於我們 2026 年的更具體觀點。我們確實預期會有強勁成長。對於 2026 年的共識已經形成，我們對此感到非常樂觀，這反映出與我們先前預測的 2025 年 958 美元相比，成長非常顯著。

Dave, do you want to...

戴夫，你想…

Yeah, sure. For the combination -- thanks for the question, Tom. So you know, it's a bit early to be definitive about our program in Phase 2 at this point, because, you know, we do need to go to the FDA and have a conversation about their expectations for the Phase 2B program, you know, then leading into the Phase 3 program.

當然可以。關於組合的問題——謝謝你的提問，湯姆。所以你知道，現在就對我們的二期臨床試驗項目下定論還為時過早，因為我們需要與FDA進行溝通，了解他們對二期B試驗項目的期望，然後再進入三期臨床試驗項目。

However, what I'll say with respect to NITs is that, you know, clinical care has moved well past biopsy. You know, biopsy is not used in clinical care anymore, and FDA has shown more and more interest in qualifying non-invasive tests for use in drug development. I'd say in Phase 2, our expectation is that NITs will play a major role in our assessment. As you know, as we show in the slides, we have a strong understanding of the relationship between PDFF reduction and a potential improvement in fibrosis. So as you can see, we're anchoring a lot of how we're looking at the program around evaluation of NITs in Phase 2.

但是，關於 NIT，我想說的是，你知道，臨床治療已經遠遠超越了活檢階段。你知道，活檢在臨床護理中已經不再使用，而FDA對用於藥物研發的非侵入性檢測表現出越來越濃厚的興趣。我認為在第二階段，我們預計 NIT 將在我們的評估中發揮重要作用。如您所知，正如我們在幻燈片中所示，我們對 PDFF 減少與纖維化潛在改善之間的關係有著深刻的理解。所以正如你所看到的，我們在第二階段將許多工作圍繞著對 NIT 的評估。

Great. Thanks, Dave. [Michelle], next question, please.

偉大的。謝謝，戴夫。 [米歇爾]，請問下一個問題。

Yasmeen Rahimi, Piper Sandler.

亞斯敏·拉希米，派珀·桑德勒。

Good morning. This is Emma on for Yas. Thanks for taking our questions. Firstly, maybe help us understand for MAESTRO-NASH outcomes in F4C, how are you tracking blinded event rates, and how is this like tracking for on-time data? At what point in this year might you tighten guidance in that regard? And is there any additional cirrhosis, open label, NAFLD data follow-up that we could get to further strengthen conviction and success? Thank you.

早安.這是 Emma 為 Yas 帶來的報導。謝謝您回答我們的問題。首先，能否請您幫助我們了解 F4C 中 MAESTRO-NASH 的結果，您是如何追蹤盲法事件發生率的，以及這與追蹤及時數據有何不同？今年何時您會收緊這方面的指導意見？是否有其他關於肝硬化、開放標籤、NAFLD 的數據後續研究可以讓我們進一步增強信心和成功率？謝謝。

Great. Thanks for the question. Dave, I'll turn that over to you.

偉大的。謝謝你的提問。戴夫，這事就交給你了。

Yeah, sure. I guess for -- thanks for the question. I think on the -- let's start with the last part. Is there going to be any additional open label data? I mean, I think we've shown quite a bit already. So we've gotten quite a lot of information out of those 122 patients in the open label, NAFLD-1 study.

當然可以。我想應該是這樣——謝謝你的提問。我認為——讓我們從最後一部分開始。是否會有額外的開放標籤資料？我的意思是，我覺得我們已經展示了很多了。因此，我們從開放標籤的 NAFLD-1 研究中的 122 名患者那裡獲得了相當多的信息。

And I think what you can see from that, that experience is that, even patients with the most severe disease, so individuals with clinically significant portal hypertension, we see what look like positive effects of Rezdiffra in that population. You can move people into lower risk categories of CSPH over a 2-year timeframe. So we've already gotten a lot out of this, out of this open label experience.

我認為從那次經驗中可以看出，即使是病情最嚴重的患者，也就是患有臨床上顯著的門靜脈高壓的患者，我們也看到了 Rezdiffra 在該族群中似乎具有積極作用。在兩年的時間範圍內，可以將人們轉移到 CSPH 風險較低的類別。所以，我們已經從這次開放標籤試驗中獲益良多。

With respect to the progress of MAESTRO outcomes, we are seeing events track in the range that were expected. So as we've talked about, historically, if you look at natural history data, you see about a 5% to 10% annual event accrual in patients with cirrhosis. We estimate in the placebo group somewhere in that range, and we are seeing events track with expectation to deliver data in 2027.

關於 MAESTRO 研究結果的進展，我們看到各項事件都在預期的範圍內進行。正如我們之前討論過的，從歷史數據來看，如果你查看自然史數據，你會發現肝硬化患者的年事件累積率約為 5% 至 10%。我們估計安慰劑組的情況也在這個範圍內，而且我們看到事件進展符合預期，預計在 2027 年提供數據。

With respect to guidance, we need to get a little bit further along to get more precise on our, on our timing.

關於指導方針，我們需要再進一步，才能更精確地掌握時間安排。

Great. Thanks, Dave. [Michelle], next question, please.

偉大的。謝謝，戴夫。 [米歇爾]，請問下一個問題。

Prakhar Agrawal, Cantor Fitzgerald.

普拉哈·阿格拉沃爾，坎托·菲茨杰拉德。

Good morning, and thank you for taking my questions, and congrats on another strong quarter. Maybe firstly, on gross to net, if you could comment on gross to net for Q1 and cadence for the rest of 2026. Will you still expect broad first line access without step edits for Rezdiffra in 2026, now that we're seeing no contract? Maybe just another follow-up, if you can comment on compliance, persistence, and discontinuation rates that you're seeing, especially since Wegovy's launch in the market. Thank you.

早安，感謝您回答我的問題，恭喜您又一個季度取得了優異的成績。首先，關於毛利潤到淨利潤的轉換，您能否評論一下 2026 年第一季的毛利潤到淨利潤轉換情況以及剩餘時間的節奏？既然目前還沒有合同，您是否仍然期望 Rezdiffra 在 2026 年能夠獲得廣泛的一線使用權而無需進行任何修改？或許可以再補充一點，您能否就您觀察到的依從性、持續性和停藥率發表一些看法，特別是自 Wegovy 進入市場以來的情況。謝謝。

Great. So maybe I'll start a little bit with just the payer contracts. They're complete. They were in place January 1 or earlier. And as we previously said, we were contracting for broad first line access, no step edits, and improved utilization criteria where where it's possible. So that holds true. We are in a really great place for contracting.

偉大的。所以，或許我可以先從付款方合約著手。它們都完成了。它們於1月1日或更早之前就已到位。正如我們之前所說，我們簽訂的合約旨在爭取廣泛的一線准入，不進行任何步驟修改，並在可能的情況下改進利用標準。確實如此。我們目前所處的環境非常適合承包業務。

I think this, when I think about kind of the accomplishments, the way we've managed contracting and gross to net is absolutely best in industry that I've seen, certainly any launch I've been a part of. Remember, we came out of the gates, we didn't contract. It's now only entering into the eighth quarter of launch that you're going to be having broad contracting. So the focus really has been preservation of gross to net, and I think we've done a great job at it, and we've set ourselves up exceptionally well for 2026.

我認為，就我們所取得的成就而言，我們在合約管理和毛利潤到淨利潤的管理方式絕對是業內我見過的最好的，當然也是我參與過的所有產品發布會中最好的。記住，我們是直接進入市場的，我們沒有收縮戰線。現在才進入產品上市的第八季度，才會出現大規模的合約簽訂。因此，我們的重點一直是保持毛利潤與淨利潤的平衡，我認為我們在這方面做得非常出色，並且為 2026 年做好了非常充分的準備。

Before turning it over to Mardi for gross to net, let me finish the compliance and persistence questions. Same as what we've said, well-tolerated oral. You know, a well-tolerated oral at the 1-year mark is in this 60% to 70% range. Certainly, we're continuing to see that strong performance and, you know, really encouraged.

在將問題轉給 Mardi 進行毛利到淨利的計算之前，讓我先完成合規性和持續性方面的問題。正如我們所說，口服耐受性良好。你知道，一年後耐受性良好的口服藥物的有效率在 60% 到 70% 之間。當然，我們持續看到這種強勁的表現，這真的令人鼓舞。

As I said, we've seen some institutions have been able to have persistence up in the 90% range. We're doing everything we can to learn from kind of the best performance and how to apply that to the broader population. We've got an outstanding patient services team that is all over this. We work closely with specialty pharmacy and providers and patients to work on that.

正如我所說，我們已經看到一些機構的留存率達到了 90% 左右。我們正在盡一切努力學習最佳表現，並思考如何將其應用到更廣泛的人群中。我們擁有一支非常優秀的病患服務團隊，負責處理所有相關事宜。我們與專科藥房、醫療服務提供者和患者密切合作，共同解決這個問題。

You asked the question about Wegovy, and you know, what's the impact that we're seeing there? Well, you know, look, Wegovy's being used, but certainly not to the detriment of Rezdiffra. In fact, we just had our best NBRX week since launch, which says to me that just as we had said, you can have multiple products in the space, but that Rezdiffra really is the winning profile. So maybe with that one, why don't I turn it over to Mardi to talk about gross to net evolution.

你問了關於 Wegovy 的問題，你知道，我們在那裡看到了什麼影響？你知道，你看，Wegovy 正在被使用，但肯定不會對 Rezdiffra 造成損害。事實上，我們剛剛經歷了自推出以來 NBRX 最好的一周，這對我來說意味著，正如我們所說，你可以在這個領域擁有多個產品，但 Rezdiffra 確實是獲勝的產品。所以，或許我該把話題交給瑪蒂，讓她來談談毛利到淨利的演變。

Great. Thanks, Bill. Yeah, let's break down gross to net a little bit. Prakhar, thanks for the question, and maybe a little comment on Q1 as well. So nothing's really changed from what we discussed last quarter with respect to gross to net. So we ended the fourth quarter exactly where we thought we'd be, which was the midpoint of our 20% to 30% range. And that was a bit of an increase from third quarter, as anticipated, as some of the commercial contracting, which remember, is one component of gross to net, took hold in the fourth quarter. But so again, ending fourth quarter in that midpoint of the 20% to 30% range, as expected.

偉大的。謝謝你，比爾。是的，我們來稍微分析一下毛利潤和淨利潤之間的差異。Prakhar，謝謝你的提問，也想對問題1做一些補充說明。所以，就毛利和淨利而言，和我們上個季度討論的情況相比，並沒有什麼真正的改變。因此，在第四季度結束時，我們達到了預期目標，即 20% 到 30% 範圍的中點。正如預期的那樣，這比第三季度略有增長，因為一些商業合約（請記住，這是毛利潤與淨利潤的組成部分之一）在第四季度站穩了腳跟。但正如預期的那樣，第四季末的佔比再次落在了 20% 到 30% 區間的中間位置。

Now, going into 2026, none of our messages have changed here either. With the basically zero to contracting that we've been discussing, as we put those commercial contracts into effect as of 1/1/2026, that moves our gross to net discount, our overall gross net discount, with all the components into the high 30s for 2026.

現在，進入2026年，我們在這裡傳達的訊息也沒有任何改變。鑑於我們一直在討論的從零到簽訂合約的情況，隨著我們從 2026 年 1 月 1 日起實施這些商業合同，這將使我們的毛利淨利差、整體毛利淨利差（包括所有組成部分）在 2026 年達到 30% 以上。

And we've broken that down really by quarter. It really stays in that high 30s for each of the quarters for 2026. There's always interquarter variability because there's so many components, but generally in the high thirties, for gross to net, all as expected. And remember, as Bill just said, we get that excellent first line access, no step edits, et cetera. So we are in very good shape and have always taken our gross to net, our diligence around gross to net very seriously.

我們已經按季度進行了細分。2026 年每個季度，該數值都將保持在 30% 以上。由於構成要素眾多，季度之間總會有波動，但總體而言，毛利潤與淨利潤之比都在 30% 以上，一切都在預期之中。記住，正如比爾剛才所說，我們可以獲得極佳的第一行訪問權限，無需逐步編輯等等。所以我們目前狀況非常好，而且我們一直非常重視毛利和淨利潤，我們在這方面一直非常認真負責。

But you know, for -- as we discuss about Q1, looking at Q1 and what our expectations are for Q1, not much has changed there either. So we have to take into effect, which is different than most companies, that we have this zero to contracting impact to gross to net for Q1, in addition to just the normal Q1 effect. So if we look at our analogs, all the specialty medicine analogs that we refer to frequently and have since launch, if we look at what the typical first quarter impact is, it's a decline in net sales of, you know, mid- to high-single digits. And that takes into effect the reverifications of the insurance plans and sort of the typical Q1 effect.

但你知道，就我們討論第一季的情況，展望第一季以及我們對第一季度的預期而言，情況也沒有太大變化。因此，我們必須考慮到，與大多數公司不同的是，除了正常的 1 季度影響之外，我們還有 1 季度毛利潤到淨利潤的零到收縮的影響。所以，如果我們看看我們的同類產品，所有我們經常提及且自上市以來就有的專科藥物同類產品，如果我們看看典型的第一季度影響是什麼，那就是淨銷售額下降了，你知道，是中高個位數。這其中涉及了保險計劃的重新核實以及典型的第一季效應。

And that's really reflective of where we believe our first quarter will be as well. But you have to consider not only do we have the Q1 effect, we're never immune to that, but we also have this in this quarter, the zero to contracting impact on gross to net that we just discussed. So we feel that that's pretty impressive, considering that we've been able to steadily add patients and still have a strong Q1 with the typical Q1 effect and zero to contracting. So we think we're going to be in good shape overall for 2026, and as I already mentioned, we'll have robust sales growth in 2026.

這也確實反映了我們對第一季業績的預期。但你不僅要考慮到第一季的影響（我們永遠無法免受其影響），還要考慮到本季度毛利潤與淨利潤之間零增長或收縮的影響，正如我們剛才討論的那樣。考慮到我們能夠穩定增加患者數量，並且第一季業績依然強勁，具有典型的第一季效應，並且從零到收縮，我們認為這相當令人印象深刻。所以我們認為 2026 年整體情況良好，而且正如我之前提到的，2026 年我們的銷售額將實現強勁增長。

Great. Thanks, Mardi. Next question, please, [Michelle].

偉大的。謝謝你，瑪蒂。下一個問題。[米歇爾]

Akash Tewari, Jefferies.

阿卡什‧特瓦里，傑富瑞集團。

This is Manoj on for Agas. Thanks for taking our question. Just one from our end. So you mentioned about like 60%-70% persistence rate. When we looked at the AASLD data, there were, like, some presentations showing more than 90% adherence rate in the real world. How important is to keep the adherence rate to that 90% to maintain the current patient adds and the revenue growth?

這裡是 Manoj 為您報道 Agas。感謝您回答我們的問題。我們這邊只有一條。你提到大約有 60%-70% 的持續率。當我們查看 AASLD 數據時，發現有些報告顯示，在現實世界中，依從率超過 90%。維持90%的依從率對於維持現有病患數量和收入成長有多重要？

And also, do you expect any acceleration in patient adds going forward now with all the contracts in place, or should we think about like probably around 6,000 to 7,000 patients net patient adds every quarter? Just to trying to understand that point. Thanks.

另外，鑑於所有合約都已到位，您預計未來患者新增數量會加速成長嗎？還是我們應該預期每個季度淨新增患者數量在 6000 到 7000 人左右？只是想弄清楚這一點。謝謝。

Great. So thanks for the question. Let me start with the patients. Look, we've said that we have been steadily adding patients, and we expect to steadily add patients going forward. And I think that is, and it's certainly an important measure as we show you this quarter, how we did, in light of having another product on the market.

偉大的。謝謝你的提問。讓我先從病人說起。你看，我們已經說過我們一直在穩定增加患者數量，而且我們預計未來患者數量也會穩定增加。我認為這一點非常重要，因為我們本季要向大家展示，在市場上又推出了一款產品的情況下，我們的業績表現如何。

So you know, the fundamentals are really, really great, and we would expect in this environment to continue to steadily add. The contracting -- remember, we've had great access from the beginning. The contracting doesn't really accelerate anything, because, if there was no policy in place, if you had a medical exception, those were flowing through very quickly.

所以你知道，基本面真的非常好，我們預計在這種環境下會繼續穩定成長。合約簽訂－記住，我們從一開始就擁有極大的便利。簽訂合約並不會真正加快任何事情的進程，因為如果沒有相關政策，如果你有醫療豁免，這些豁免也會很快得到批准。

But in this next phase of launch, you know, we've partnered with the payers. I think we've had some really great discussions. I think they've understood the value of Rezdiffra. They see the cost of these patients in their systems, and, you know, I think we've landed in a really good place for the future with them, and you know, we do appreciate the partnership that we have.

但在下一階段的推廣中，我們已經與支付方建立了合作關係。我認為我們進行了一些非常棒的討論。我認為他們已經理解了Rezdiffra的價值。他們看到了這些患者為他們的系統帶來的成本，而且，你知道，我認為我們與他們建立了非常良好的合作關係，這對未來非常有利，我們也十分珍惜我們之間的這種夥伴關係。

Now, regarding persistence, you know, we are in that well-tolerated oral range, as I said, the 60% to 70%. And yes, as you point out, there are some institutions that have reported rates all the way up to 90%. Now, what we will always try to do is look for ways to, you know, help appropriate patients stay on product as long as they need it.

至於持久性，你知道，我們處於口服耐受性良好的範圍內，正如我所說，60% 到 70%。是的，正如你所指出的，有些機構報告的利率高達 90%。現在，我們將始終努力尋找方法，幫助合適的患者在需要時能夠持續使用產品。

I think that sense of urgency has increased coming out of AASLD, where we presented data from both the F2, F3 population and the F4c population. If you discontinue therapy, disease comes back, and it comes back quickly. So you know, we do believe this is a chronic therapy and that it's in patients' best interest, obviously prescribers' best interest, and overall for the system best interest, that they stay on therapy. So we have a lot of initiatives underway that we're doing with our own patient services group, partnering with specialty pharmacy and institutions, and working with patients as well directly to try to help that persistence rate improve to a level which is even higher than the well-tolerated oral range.

我認為，在 AASLD 會議上，我們展示了 F2、F3 群體和 F4c 群體的數據，這加劇了緊迫感。如果停止治療，疾病就會復發，而且復發速度很快。所以，我們確實認為這是一種慢性療法，為了病人的最大利益，顯然也為了處方醫生的最大利益，以及整個系統的最大利益，讓他們堅持治療是符合病人最大利益的。因此，我們正在進行許多舉措，包括與我們自己的患者服務團隊合作，與專科藥房和機構合作，以及直接與患者合作，以期幫助提高藥物的持續使用率，使其達到甚至高於耐受性良好的口服藥物範圍的水平。

But that takes a lot of work, and, you know, there's just -- you know, people -- look, they regardless of whether it's for, regardless of the type of indication, people tend to drop off of drugs in time. But we're going to do everything we can to educate, to keep people on appropriately.

但這需要付出很多努力，而且，你知道，人們——你看，不管是為了什麼，不管是什麼適應症，人們往往會隨著時間的推移而停止服用藥物。但我們將盡一切努力進行教育，讓人們遵守相關規定。

Great. Thanks so much. Next question, please.

偉大的。非常感謝。下一個問題。

Michael DiFiore, Evercore.

Michael DiFiore，Evercore。

Thanks so much for taking my questions, and congrats on the continued progress. Two for me. The first, over the past several months, you've added multiple combination assets around Rezdiffra, including DGAT2, GLP-1, and siRNA programs. My question is: How do you avoid diminishing return from putting too many synergistic mechanisms into the pipeline? And what is your go -- no-go criteria for advancing a second agent, both clinically and commercially?

非常感謝您解答我的問題，也恭喜您持續的進步。我兩個。首先，在過去的幾個月裡，你們圍繞著 Rezdiffra 增加了多個組合資產，包括 DGAT2、GLP-1 和 siRNA 專案。我的問題是：如何避免在產品線中引入過多協同機製而導致收益遞減？那麼，你們在臨床和商業上推進第二種藥物研發的准入和不准入標準是什麼？

And then my second question is briefly: Has there been any change in expected timing of MAESTRO-NASH outcomes now that the FDA has approved AI-supported pathology reads? Thank you.

我的第二個問題簡要地問一下：既然 FDA 已經批准了 AI 支持的病理判讀，MAESTRO-NASH 結果的預期時間是否有任何變化？謝謝。

Okay, Dave, I'm going to pass over to you in a second, but just, you know, let's just take a step back, what we're trying to do here, Mike, and thanks for the question because I think this is really important. So with Rezdiffra, we have what has become standard of care and is truly a foundational therapy. And that's just not from use.

好的，戴夫，我馬上就把麥克風交給你，但是，你知道，我們先退一步，回顧一下我們在這裡要做的事情，麥克，謝謝你的提問，因為我認為這真的很重要。因此，Rezdiffra 已成為標準療法，並且是一種真正的基礎療法。而且這不僅僅是使用造成的。

Looking at the clinical data, one of the things that is really striking is that across all subgroups, you have essentially a consistent effect. So in other words, it tends to be that, you know, all these F2, F3 patients do well. It's not as though one group does, you know, like a super responder group. Now, that is a great therapy, and you know, rarely do you see something that has that type of results.

從臨床數據來看，最引人注目的一點是，在所有亞組中，效果基本上是一致的。換句話說，通常情況下，所有這些 F2、F3 期患者的情況都很好。並不是說某個團體，你知道，就像一個超級應急小組那樣。那是一種非常有效的療法，你知道，很少有療法能達到這樣的效果。

Now, if we can, through the addition of new mechanisms of action, find a way to have the whole population or a subpopulation do better, then that really provides an opportunity for better patient outcomes. And that's how we're thinking about this. So when we're going out and looking at any of the mechanisms we're bringing in, it starts with, we believe that there's a strong mechanistic rationale that in combination, we could see a better effect for all or some patients.

現在，如果我們能夠透過增加新的作用機制，找到一種方法讓整個人群或某個亞群的情況得到改善，那麼這確實為改善患者的治療效果提供了機會。我們就是這樣考慮這個問題的。所以，當我們研究引入的任何機制時，首先要相信，這些機制具有很強的機制原理，結合起來，可以對所有或部分患者產生更好的效果。

Now, we have to test that theory, and that's why we're going to do these trials to quickly determine whether if there's and we will kill or move forward quickly. The goal is not to have a lot of straggling things in the pipeline that never do anything except for suck up resource. We're not doing that. We're going to try to only take forward what is meaningful for patients.

現在，我們必須檢驗這個理論，所以我們要進行這些試驗，以便迅速確定是否存在這樣的理論，以及我們是會終止試驗還是迅速推進試驗。我們的目標是避免流程中出現大量無關緊要、只會消耗資源而毫無作用的項目。我們不會那樣做。我們將盡量只推進對患者有意義的工作。

Now, we also see the market evolving, though, where various subpopulations, or, or let's call them segments, may emerge. And we're well-positioned not only with Rezdiffra, but now as we make these combo programs, to provide a better product for those segments. So this is extremely, when I say well thought out, it's well thought out. It's deliberate. It is based on mechanism, what we like, and it all starts with the fact that Rezdiffra is a foundational therapy that is really one which is amenable to either fixed those combinations or combinations, for instance, with siRNA, where you may have a pill and an injectable, but in a very favorable regimen. So that's just to give you the thinking of it.

不過，現在我們也看到市場正在發生變化，各種次群體，或者我們稱之為細分市場，可能會出現。我們不僅憑藉 Rezdiffra 佔據了有利地位，而且現在隨著我們推出這些組合方案，我們也能為這些細分市場提供更好的產品。所以，我說這是經過深思熟慮的，那絕對是經過深思熟慮的。這是故意的。它基於機制，我們喜歡什麼，這一切都始於Rezdiffra是一種基礎療法，它確實適用於固定組合或組合，例如與siRNA，其中您可能需要服用藥丸和注射劑，但在一個非常有利的方案中。以上只是給你一些思路。

Dave, maybe just over to you for a little bit more color around it.

戴夫，或許應該請你再補充一些細節。

I think the only thing I would add there is that when you start with a solid foundation that works in everybody, that's not necessarily true of every combination partner you add, right? So it could be that a particular combination partner, for example, DGAT or the GLP-1 or one of the siRNAs, does better for certain patient subtypes, whether they're a genetic predilection to disease progression, or they have some comorbidity that sort of the combination partner happens to target more effectively.

我覺得我唯一要補充的是，當你從一個對每個人都適用的堅實基礎開始時，這並不一定適用於你添加的每一個組合夥伴，對吧？因此，某些特定的組合夥伴，例如 DGAT、GLP-1 或 siRNA，可能對某些患者亞型效果更好，無論他們是具有疾病進展的遺傳傾向，還是患有某種合併症，而組合夥伴恰好能更有效地針對這些合併症。

So there -- the other thing I think that's really important about our strategy is that it's adaptable, right? It's adaptable to the science. So as we run our Phase 2 studies, we'll be able to determine whether or not, you know, the drug is kind of going to be broadly applicable in the population and broadly does something, you know, that's going to be meaningful for patients with MASH, or a subsegment within that, the MASH population is going to be a better target for that combination treatment. So I would just add the adaptability part for how we're thinking about pursuing these agents.

所以，我認為我們策略中另一個非常重要的方面是它的適應性，對吧？它能夠適應科學發展。因此，在我們進行 2 期研究的過程中，我們將能夠確定該藥物是否具有廣泛的適用性，是否能夠對 MASH 患者產生有意義的影響，或者該藥物是否能更好地幫助 MASH 患者，或者 MASH 患者群體是否更適合接受這種聯合治療。因此，我只想補充一點，關於我們如何考慮追捕這些代理人，我們需要考慮適應性問題。

Then I think your second question was about MAESTRO Outcomes and AI path reading. So it's great, you know, that the agency, again, is sort of evolving their perspective on MASH drug development. MAESTRO Outcomes is an event-driven trial, so it doesn't, it's not a histology-driven study. So you know, AI path reading would really wouldn't be relevant there.

那麼，我認為你的第二個問題是關於 MAESTRO Outcomes 和 AI 路徑讀取的。所以，你知道，該機構再次轉變對 MASH 藥物研發的看法，這真是太好了。MAESTRO Outcomes 是一項事件驅動型試驗，因此它不是組織學驅動型研究。所以你知道，人工智慧路徑讀取在那裡真的沒什麼意義。

For MAESTRO-NASH, our F3 study, that is a biopsy-driven trial, but it's a landmark study. So in other words, everybody gets a biopsy at month 54, which is then, you know, compared to baseline. So we would certainly consider using AI path reading as part of our analysis, but it's not the primary assessment we would do. Thanks for the question, Mike.

MAESTRO-NASH 是我們的 F3 研究，這是一項以活檢為主導的試驗，但它是一項里程碑式的研究。換句話說，每個人在第 54 個月都會接受活檢，然後，你知道，將活檢結果與基線進行比較。因此，我們當然會考慮將 AI 路徑讀取作為分析的一部分，但這並不是我們會進行的主要評估。謝謝你的提問，麥克。

Thanks. Next question, please.

謝謝。下一個問題。

Thank you.

謝謝。

Jay Olson, Oppenheimer.

傑伊·奧爾森，奧本海默。

It's always...

總是…

Congrats on the impressive progress, and thanks for taking our question. Just to follow up on the previous question, since you have two all-oral combos, where do you envision the siRNA modality to fit into the future treatment landscape of MASH? And is there any color that you can share with us on the targets of those six siRNA programs, and when should we expect the timing of clinical development? Thank you.

恭喜你們取得如此令人矚目的進展，感謝你們回答我們的問題。針對上一個問題，既然你們有兩種全口服組合療法，你們認為siRNA療法在未來MASH的治療模式中將扮演什麼角色？您能否透露一下這六個 siRNA 計畫的目標是什麼？我們什麼時候可以期待臨床開發？謝謝。

Thanks, Jay. Look, first of all, on the siRNA targets, for competitive reasons, we're not going to disclose the targets at this point, but stay tuned as we move along. We'll certainly be sharing that with you. Look, where does it fit? So first of all, you know, we thought any of the targets that we're looking at, we believe there's a rationale for MASH and potentially making a better product. As I said, it starts with mechanism and the rationale to make a better drug. I'm going to let Dave kind of walk through our whole siRNA strategy, but you know, we really think it's a nice combo when you think about it.

謝謝你，傑伊。首先，關於siRNA靶點，出於競爭原因，我們目前不會透露靶點，但請繼續關注我們的後續進展。我們一定會與您分享的。你看，它應該放在哪裡？首先，我們認為我們正在關注的任何目標，我們都相信 MASH 有其合理性，並且有可能製造出更好的產品。正如我所說，一切都始於機制和研發更好藥物的原理。我打算讓戴夫來詳細介紹我們的整個siRNA策略，但你知道，仔細想想，我們真的認為這是一個不錯的組合。

A every 3- to 6-month injection and a daily pill. Pretty easy. You know, if you get a better effect from that, that is not a -- that's a pretty strong value proposition. What makes it an even stronger value proposition is it's all within the same company. So this isn't going to be a -- it's not a battle for somebody having to optimize a single product. It is us being able to look holistically across the disease and say, what's the right solution for that patient or segment of patients? And we can provide that in an efficient manner. And so it'll always be about what's the right therapy rather than having to sell a therapy.

每 3 至 6 個月注射一次，每天服用一片藥片。很簡單。你知道，如果那樣能帶來更好的效果，那可就不是──那可是一個非常強大的價值主張。更令人驚訝的是，這一切都屬於同一家公司。所以這不會是一場——這不是一場需要優化單一產品的戰鬥。也就是說，我們能夠從整體上看待這種疾病，並說，對於該患者或該部分患者來說，什麼是正確的解決方案？而且我們可以有效率地提供這種服務。因此，關鍵始終在於找到合適的療法，而不是推銷某種療法。

So Dave, maybe I'll pass it over to you.

所以戴夫，也許我會把它交給你。

Yeah, I mean, I think, just to add on, I mean, from a scientific standpoint, you know, as, as Bill mentioned, siRNA technology has really, you know, had a breakthrough over the last 10 years or so, and we can develop now, highly targeted, well-tolerated therapies that last 3to 6 months, as Bill said, or even up to 12 months. You know, the latest technology can even get you that much farther. So we're -- you know, we're very fortunate to be working with Ribo Life Science, you know, a leader in siRNA technology, to be developing these drugs.

是的，我的意思是，補充一點，從科學的角度來看，正如比爾提到的，siRNA 技術在過去 10 年左右的時間裡確實取得了突破性進展，我們現在可以開發出高度靶向、耐受性良好的療法，其療效可以持續 3 到 6 個月，正如比爾所說，甚至長達 12 個月。你知道嗎，最新的科技甚至可以讓你走得更遠。所以，我們非常幸運能與 siRNA 技術領域的領導者 Ribo Life Science 合作開發這些藥物。

And you know, I think the key is that that sort of combination regimen, that sort of approach will make sense for either all patients or some patients. Again, we look for drugs that either have preclinical, clinical, or genetic validation, and all of these targets kind of fit within those categories. And so we think that, you know, with Rezdiffra, that solid foundation to add on these long-acting therapies, this could be a real advantage for patients with MASH.

你知道，我認為關鍵在於，這種聯合治療方案，這種方法，對所有患者或部分患者來說都是有意義的。我們再次尋找那些經過臨床前、臨床或基因驗證的藥物，而所有這些標靶都符合這些類別。因此我們認為，有了像 Rezdiffra 這樣堅實的基礎，再加上這些長效療法，對於 MASH 患者來說可能是一個真正的優勢。

Good. Thanks, Dave. Thanks, Jay, for the question. Next question, please, [Michelle].

好的。謝謝你，戴夫。謝謝傑伊的提問。下一個問題。[米歇爾]

John Wolleben, Citizens.

約翰‧沃勒本，公民。

Thanks for taking the question, and congrats. You guys have talked about this growth of the market. This is the first time you guys have put some numbers to it, and it doesn't seem like any of these dynamics you're attributing it to are going to go away anytime soon. So wondering, how should we think about, you know, five years from here, the F2, F3 target population growing? And then also, should we expect, you know, further growth of the F4 population as well, with patients still advancing? Just trying to get a bigger picture about the road ahead. Thanks.

感謝您回答這個問題，恭喜您。你們之前也討論過市場成長的問題。這是你們第一次用數字來分析這個問題，而且你們認為造成這種情況的這些因素似乎都不會很快消失。所以我想知道，我們該如何看待五年後F2、F3目標族群的成長？此外，隨著患者病情不斷加重，我們是否應該預期 F4 期患者族群會進一步成長？只是想對未來的發展方向有更全面的了解。謝謝。

John, thanks for the question. Yeah, I mean, look, what we said is that we'd expect double-digit growth for the foreseeable future. That's certainly for the 5-year period, so you know, pretty robust growth. I think now, again, you've got a therapy that works. People are talking about the disease and, you know, as I said, we're benefiting from having a competitor that's out there talking a lot about it. And as we know, they need, you know, really lots of patients in order to make MASH a meaningful indication for them. So we think that it's for years of growth.

約翰，謝謝你的提問。是的，我的意思是，你看，我們說過，我們預計在可預見的未來，我們將保持兩位數的成長。這當然是指過去五年期間的情況，所以你知道，成長相當強勁。我認為現在，你又找到了一種有效的治療方法。人們都在談論這種疾病，你知道，正如我所說，我們正受益於我們的競爭對手一直在大肆談論這種疾病。我們都知道，他們需要大量的患者才能使 MASH 成為他們有意義的適應症。所以我們認為這將帶來多年的成長。

And your other question was?

你的另一個問題是？

F4.

F4。

Oh, F4. Look, yes, we would expect to see similar -- not similar growth, but growth there. We're still working through the details of what that F4c population looks like. But I think you can assume that there will be growth. As we get a little bit further into our analysis of the market and we're getting closer to our launch, we'll provide updates as to where that's going. But overall, you know, as MASH grows, F4c will grow as well.

哦，F4。是的，我們預期會看到類似的成長——不是說成長幅度相同，而是成長幅度更大。我們仍在研究F4c族群的具體情況。但我認為可以預見會有成長。隨著我們對市場分析的深入，以及產品發布日期的臨近，我們將提供最新進展資訊。但總的來說，你知道，隨著 MASH 的發展，F4c 也會成長。

Great. Thanks, John. Next question, please, [Michelle].

偉大的。謝謝你，約翰。下一個問題。[米歇爾]

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

Hi, everyone. This is Nicole on the line for Ritu. I'm just wondering about the extent of script growth needed over the fiscal year 2026 to grow revenue off of the increase for the gross to net.

大家好。這裡是妮可，正在幫麗圖報案。我只是想知道，在 2026 財年，劇本需要成長到什麼程度才能透過毛利潤到淨利潤的成長來提高收入。

And just a quick second question, what do you think companion diagnostics would need to be developed to show any genetic predisposition for MASH if you are going to eventually move forward with the siRNAs, if data is positive? Thanks.

還有一個小問題，如果最終要推進 siRNA 療法，並且數據呈陽性，您認為需要開發哪些伴隨診斷方法來顯示 MASH 的任何遺傳傾向？謝謝。

Hey, Nicole, can you just clarify your first question? It was a little...

嗨，妮可，你能把第一個問題解釋清楚嗎？有點…

We missed a word.

我們漏掉了一個字。

Sure. Yeah, absolutely. The extent of script growth or patient adds needed over fiscal year 2026 to see a growth in revenue to offset the increase in gross to net.

當然。是的，絕對的。到 2026 財年，需要實現處方增長或患者增加的幅度，才能實現收入增長，以抵消毛利潤與淨利潤的增加。

Well, okay, so let me -- let me start, but let me be clear. There's -- we're growing. The fundamentals of the business are exceptional. We're steadily adding patients. We are going to see robust growth in 2026 and into the future. So I mean, let me just be crystal clear.

好吧，那讓我——讓我開始吧，但讓我先說明一點。我們正在發展壯大。這家企業的基本面非常出色。我們的病人數量正在穩定增加。我們預計2026年及以後將出現強勁成長。所以，我的意思是，讓我把話說清楚。

When we talk about Q1, Q1 has two Q1 things going on. First of all, the Q1 effect that every single product in the industry experiences, reauthorizations, et cetera. On top of that, though, we have this zero to contracting. So instead of contracting for the two years previously and having a steady increase in gross to net, we held off contracting until the seventh quarter of launch and -- or eighth quarter of launch, I guess. And so you have this zero to contracting effect.

當我們談到第一季時，第一季有兩個面向正在發生。首先，產業內所有產品都會經歷第一季效應，例如重新授權等等。除此之外，我們還有零到零的合約。因此，我們沒有像前兩年那樣簽訂合約並穩步提高毛利潤與淨利潤之比，而是等到產品上市後的第七個季度（或第八個季度）才簽訂合約。因此，就會出現從零到收縮的這種效應。

So we are still, despite that, in the range of the comps that we look at, which is kind of really remarkable. It says how strong the underlying business is. So expect to see growth. Our, you know -- look, we're not going to do the model is the number of patient adds, et cetera, but robust growth now and in the future.

儘管如此，我們仍然處於我們所關注的同類產品的範圍內，這真是非常了不起。它反映了企業基本面的強勁程度。所以預計會看到成長。你知道，我們——你看，我們不會以新增患者數量等為模型，而是以現在和未來的強勁增長為模型。

Mardi, do you have any other comment on that?

瑪蒂，你對此還有其他評論嗎？

Yeah, exactly. We talked about it, Nicole, for 2026. From a consensus standpoint, we feel really good where the street is right now for 2026, which reflects robust growth from where we ended in 2025. So we feel like we're in good shape. We already talked about the Q1 effect and growth net, but steadily adding patients. And I'll just reiterate what Bill said, last week was our best NBRX week ever. So the underlying business is in really good shape, and we anticipate that growth through 2026 and beyond, quite frankly.

對，沒錯。妮可，我們討論過2026年的事。從共識的角度來看，我們對 2026 年的市場前景感到非常樂觀，這反映出 2026 年的市場前景比 2025 年末的市場前景更加強勁。所以我們覺得狀態不錯。我們已經討論過第一季效應和淨增長，但穩步增加患者數量。我只想重申一下比爾所說的話，上周是我們NBRX有史以來業績最好的一周。因此，公司的基本業務狀況非常好，坦白說，我們預計這種成長勢頭將持續到 2026 年及以後。

And yeah, that's right. Go ahead, Dave.

沒錯，就是這樣。請繼續，戴夫。

Yeah, so companion diagnostic, real interesting question. I mean, you know, it's early to sort of comment on that because, you know, to consider a companion diagnostic, you've got to be looking for a particular, for example, genetic or biomarker-type target, to tie your therapy to. So as Bill mentioned, Rezdiffra, of course, doesn't need that because it works very well across all patient subpopulations. We'll see, you know, as the combination products move forward, you know, if there is a need to develop a companion diagnostic, but as of right now, we don't foresee that with these programs.

是的，伴隨診斷，真是一個有趣的問題。我的意思是，你知道，現在評論這個問題還為時過早，因為你知道，要考慮伴隨診斷，你必須尋找一個特定的，例如基因或生物標誌物類型的靶點，以便將你的療法與之聯繫起來。正如比爾提到的那樣，Rezdiffra 當然不需要那樣做，因為它在所有患者亞群中都效果很好。你知道，隨著組合產品的推進，我們會看看是否需要開發伴隨診斷，但就目前而言，我們預期這些項目不需要。

Great.

偉大的。

Just really quickly to follow up, are genetic screenings common in the clinic already?

最後再補充一下，基因篩檢在診所裡已經很普遍了嗎？

They're becoming -- I think, generally speaking, I can't speak in MASH in particular, necessarily, but across general clinical care, genetic screening is becoming more common, yes. But, you know, I think producing a genetic or another biomarker companion diagnostic, you know, takes an additional lift for sure.

總的來說，我認為——我不能具體談論 MASH（美國陸軍醫療隊）的情況，但在一般的臨床護理中，基因篩檢變得越來越普遍。但是，你知道，我認為開發基因或其他生物標記伴隨診斷，肯定需要額外的努力。

Yeah, and just remember, we're let's just put a fine point on this. We are seven quarters into the launch of an entirely new category. There are decades of growth and evolution in front of us. The decisions that we're making today with the pipeline aren't 2026 decisions. They're not even 2027 decisions. These are helping to form treatment, which will include diagnosis, any kind of tests that obviously will be done to segment patients, et cetera, that will evolve in time. So we are very much on the forming side of this.

是的，記住，我們只是想把這一點強調清楚。我們推出一個全新品類已經七個季度了。擺在我們面前的是幾十年的發展和演變。我們今天就輸油管計畫所做的決定，並非著眼於 2026 年的決定。這些甚至不是2027年的決定。這些有助於制定治療方案，其中包括診斷、對患者進行分類的各種測試等等，這些方案會隨著時間的推移而不斷發展。所以，我們目前正處於形成階段。

And remember, we're less than 12% penetrated into the 315. It's less than 8% into the 460 that we talked about. This is at the beginning of a very significant specialty market. We are the company at the front end of it that can drive it, not only for the coming years, but for, we believe, decades in advance.

記住，我們在 315 地區的滲透率還不到 12%。這還不到我們之前討論的 460 的 8%。這標誌著一個非常重要的專業市場的開端。我們是處於產業前沿、能夠引領這一趨勢的公司，我們相信，這種引領作用不僅體現在未來幾年，而且能夠持續數十年。

Great. Thanks. Next question, please, [Michelle].

偉大的。謝謝。下一個問題。[米歇爾]

William Wood, B. Riley Securities.

威廉·伍德，B. Riley 證券公司。

Thank you so much for taking our questions, and congrats on a very nice quarter. Just sort of sticking with what you were just talking about, Bill, in terms of the market increase from 315 to 460,000, I'm just curious if you or, you know, if you see that correlated with the increase of patient prescriber interest and potentially how we should think about that as reading through, just sort of new patient adds. Is this more of a longer term, just more runway in terms of patients, or is this actually feeding increased new patient additions? And then I have a follow-up.

非常感謝您回答我們的問題，恭喜您本季業績斐然。比爾，我還是繼續你剛才說的，關於市場從 315 增長到 460,000，我很好奇你是否認為這與患者處方醫生的興趣增加有關，以及我們應該如何看待這一點，比如通過閱讀新患者數據。這更多的是一種長期規劃，只是為了給患者群體留出更多空間，還是實際上為了增加新患者數量？然後我還有一個後續問題。

Yeah, thanks. Look, so I think one of the real important pieces of this, of the update is if you look and see where that real growth is taking place is in the target specialists that we are calling on. And I think that's really important.

嗯，謝謝。所以我認為這次更新中真正重要的一點是，如果你仔細觀察，你會發現真正的成長發生在我們所聯繫的目標專家身上。我認為這非常重要。

What it's saying is that our efforts really are working, and that patients that are diagnosed are making their way to the specialists that treat MASH. And you know, we've been clear from the beginning, we think this is a specialist disease. That's why we're focused on hepatology, gastroenterology, and now some endocrinology as well. That's where the patients are. Those are the experts that should be treating it, and that's where we're seeing the biggest growth taking place, which is indicative of our wiring of the system being extremely successful.

這說明我們的努力確實奏效了，確診的患者正在前往治療 MASH 的專家那裡就診。你知道，我們從一開始就明確表示，我們認為這是一種專科疾病。這就是為什麼我們專注於肝病學、胃腸病學，現在也包括一些內分泌學領域的原因。病人都在那裡。這些專家才是應該治療這種疾病的人，而且我們看到最大的成長也發生在他們身上，這表明我們系統的建構非常成功。

So I think what you're going to see is, remember, we're still at a very low penetration rate in the already diagnosed. And so we still have a lot of patients to get through just in that initial 315. And then as more and more come in and this becomes standard of care, that's when you see just treatment rates get higher as well as diagnosis rates gets higher. So you know, that just gives you a little bit of flavor around it.

所以我認為你會看到的是，記住，我們在已確診人群中的滲透率仍然非常低。所以，光是最初的 315 名患者，我們就還有很多患者需要診治。然後隨著越來越多的人接受治療，這種治療方法逐漸成為標準，這時你會看到治療率和診斷率都隨之提高。所以你知道，這會給它增添一些風味。

And you said you had a quick follow-up, maybe, if it's just real quick, because we've got to move on.

你說你可能需要快速跟進一下，如果真的只是很快的話，因為我們得繼續前進了。

Yeah, thanks. In reference to your GLP-1 and your DGAT, it looks like GLP-1 might be initiation starting for your Phase 1. It looks like it might be pushed back slightly from first quarter to second quarter. In terms of both those programs, just curious what remaining gating activities still need to be completed.

嗯，謝謝。關於您的 GLP-1 和 DGAT，看來 GLP-1 可能即將開始您的第一階段治療。看起來比賽可能會從第一季稍微推遲到第二季。就這兩個項目而言，我只是好奇還有哪些關鍵環節需要完成。

Yeah, so I think we got it initially to first half, and then we've refined it to second quarter. So there's been no delay. No change, no delay. Okay, thanks.

是的，所以我覺得我們最初在上半部做到了，然後我們又在下半部進行了改進。所以沒有延誤。沒有變化，沒有延誤。好的，謝謝。

Okay. Thanks. [Michelle], we have time for one more question, please.

好的。謝謝。 [米歇爾]，我們還有時間再問一個問題，好嗎？

Kripa Devarakonda, Truist.

Kripa Devarakonda，Truist。

This is Alex calling for Kripa. Thanks for taking our question. Congrats for the progress. Now that we are seeing more and more patients on Rezdiffra for longer time periods, we want to know, have you seen any challenges in the reimbursement process to keep patients on drug for the extended time periods? We can imagine that for many patients with Rezdiffra, that their fibrosis scores could improve, and they might technically be outside of the label requirement. That's that. Thanks.

這是亞歷克斯在呼叫克里帕。感謝您回答我們的問題。恭喜取得進展。現在我們看到越來越多的患者長期服用 Rezdiffra，我們想知道，在延長患者用藥時間方面，您在報銷過程中是否遇到任何挑戰？我們可以想像，對於許多使用 Rezdiffra 的患者來說，他們的纖維化評分可能會有所改善，從技術上講，他們可能已經不符合標籤要求。就這樣。謝謝。

Okay. Thank you very much for the question. So you know, first of all, the reauthorizations we said are very routine. Oftentimes it's physician attestation or showing some kind of stabilization or improvement in one of the NITs that has been used initially. I think, you know, look, we're -- again, we're really early into the treatment of the disease. I think what is very compelling for the community is, I'll go back to the AASLD data, which showed that discontinuation of Rezdiffra led to a return of disease in both F2 and F3 and also F4c patients.

好的。非常感謝您的提問。首先，我們說過，重新授權是非常例行的。通常情況下，需要醫生證明，或證明最初使用的某種 NIT 療法取得了某種程度的穩定或改善。我認為，你知道，你看，我們——再說一遍，我們目前還處於治療這種疾病的早期階段。我認為對社區來說最有說服力的是，我再來看看 AASLD 的數據，數據顯示，停用 Rezdiffra 會導致 F2 和 F3 以及 F4c 患者的疾病復發。

So I think that, you know, more and more, the belief is that this is a chronic disease, and you know, you just can't stop the medicine even if you have a response, because you will have done all that hard work, and then you're just going to have disease come back. So we think that's how it's going to evolve in the future. Again, though, you know, look, it's early, but our belief is that this is a chronic therapy. That's the way the community tends to be using it. So we feel really, you know, quite confident that'll be the case.

所以我覺得，越來越多的人認為這是一種慢性疾病，即使治療有效也不能停止用藥，因為你之前付出的所有努力都白費了，疾病還會復發。所以我們認為它未來會朝著這個方向發展。不過，你知道，現在還為時過早，但我們認為這是一種長期療法。這是社區普遍的使用方式。所以我們真的很有信心，情況會是這樣。

Great. All right.

偉大的。好的。

Maybe we'll end it there. Maybe -- look, just -- maybe I'll finish off just with a remark of just kind of what's the state of the union, if you will. Rezdiffra is performing exceptionally well. This is truly a best launch I've ever been associated with, and I can tell you that is from a -- that's a factual perspective. Nothing's done as well as this. And it's poised for substantial long-term growth in a rapidly growing market. It's because of those two things that we can build a pipeline now to establish long-term leadership.

或許我們就此結束吧。也許——你看，就——也許我最後會簡單談談當前的局勢。Rezdiffra表現非常出色。這真是我參與過的最棒的一次產品發表會，我可以告訴你，這是從事實的角度來說的。沒有比這做得更好的了。而且，它已做好準備，在快速成長的市場中實現長期的大幅成長。正是因為這兩點，我們現在才能建立人才儲備，從而確立長期的領導地位。

Most companies have a pipeline looking for a great product. We have a great product that is performing exceptionally, is poised to perform exceptionally for the future. Now we have a chance to build long-term leadership. It doesn't happen often. This is an opportunity. We are not going to waste the opportunity.

大多數公司都有人才儲備庫，尋找優質產品。我們擁有一款性能卓越的優秀產品，未來也必將持續保持卓越的性能。現在我們有機會建立長期的領導地位。這種情況並不常發生。這是一個機會。我們絕不會浪費這個機會。

With that, we'll close the call. Thanks.

通話到此結束。謝謝。

Perfect. Thanks, Bill. 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 about two hours. Thank you for joining us.

完美的。謝謝你，比爾。感謝各位今天抽空並對此表示關注。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。感謝您的參與。

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。