Madrigal Pharmaceuticals Inc (MDGL) 2024 Q4 法說會逐字稿

Good day, and thank you for standing by. Welcome to Madrigal Pharmaceuticals Fourth Quarter 2024 Earnings Conference Call. (Operator Instructions) As a reminder, today's conference call is being recorded.

您好，感謝您的支持。歡迎參加 Madrigal Pharmaceuticals 2024 年第四季財報電話會議。（操作員指示）提醒一下，今天的電話會議正在錄音。

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

我想介紹首席投資者關係官蒂娜·文圖拉女士。請繼續。

Thank you, Marvin. Good morning, everyone, and thank you for joining us to discuss Madrigal fourth quarter and full year 2024 earnings. We're also sharing this morning new two-year data from the active treatment open label compensated MASH cirrhosis or F4C arm of the Phase 3, MAESTRO-NASH trial. We issued a press release this morning and have a slide deck that accompanies this webcast, which we'll post on the investor relations section of our website right after the call.

謝謝你，馬文。大家早安，感謝您加入我們討論 Madrigal 2024 年第四季和全年收益。今天上午，我們還將分享第 3 階段 MAESTRO-NASH 試驗的積極治療開放標籤補償 MASH 肝硬化或 F4C 組的兩年新數據。我們今天早上發布了一份新聞稿，並附上了與本次網路廣播配套的幻燈片，我們將在電話會議結束後立即發佈在我們網站的投資者關係部分。

On the call with me today is Bill Sibold, Chief Executive Officer; and Mardi Dier, Chief Financial Officer. They'll provide prepared remarks, and then we'll take your questions. Dr. Michael Charlton, our Head of Clinical Development, will join us for the Q&A portion of the call. Dr. Charlton has more than 30 years of experience in MASH as a leading hepatologist, head of the Mayo Clinic Hepatology Group, and a treating physician.

今天與我一起通話的是執行長比爾·西博爾德 (Bill Sibold)；以及財務長 Mardi Dier。他們會提供準備好的發言，然後我們會回答您的問題。我們的臨床開發主管 Michael Charlton 博士將參加本次電話會議的問答部分。查爾頓博士在 MASH 擁有 30 多年的經驗，擔任首席肝病學家、梅奧診所肝病學組負責人和治療醫師。

We plan to keep today's call to about 45 minutes. 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.

我們計劃將今天的通話時間控制在 45 分鐘左右。請注意，今天我們將在投影片 2 上做出某些前瞻性陳述。請您參閱我們向美國證券交易委員會提交的文件，其中討論了可能導致實際結果與前瞻性陳述不同的風險。

And with that, I will now turn the call over to Bill, on slide 3.

現在，我將把電話轉給幻燈片 3 上的比爾 (Bill)。

Well, thanks, Tina. Good morning and thanks for joining. Today I'll provide an update on the significant momentum we're building with the US launch of Rezdiffra. We ended 2024 strong and we're pleased with how we've started the year in 2025.

好吧，謝謝，蒂娜。早安，感謝您的加入。今天，我將向您介紹我們在美國推出 Rezdiffra 所取得的重大進展。我們以強勁的勢頭結束了 2024 年，我們對 2025 年的開局感到滿意。

I'll also share an update on new two-year data from an open label study for F4C patients as Tina mentioned. The results are very promising and support Rezdiffra's potential to benefit this high-risk patient population if approved. But before we look ahead, I want to take a moment to reflect on 2024, a year of remarkable transformation and achievement for the company.

正如蒂娜所提到的，我還將分享針對 F4C 患者的開放標籤研究的兩年新數據的最新進展。研究結果非常令人鼓舞，如果獲得批准，Rezdiffra 將有可能造福這個高風險患者群體。但在展望未來之前，我想花點時間回顧 2024 年，這是公司實現顯著轉型和成就的一年。

I've been in the industry a long time and I've launched a lot of successful medicines. I'll be the first to attest to the tremendous amount of work required for any successful launch, let alone a first in disease therapy. And the launch of Rezdiffra's is no exception. We worked to meet or exceed our high expectations last year and started to lay the foundation for Rezdiffra to potentially become a blockbuster therapy.

我在這個行業已經工作很長時間了，並且推出了許多成功的藥物。我首先可以證明，任何一項成功的研發都需要大量的工作，更不用說在疾病治療領域的首創成果了。Rezdiffra 的推出也不例外。去年，我們努力滿足或超越了我們的高期望，並開始為 Rezdiffra 成為轟動一時的療法奠定基礎。

I'm incredibly proud of our team's accomplishments highlighted on slide 4. These are the things that we said that we would do, and we did them. We built a world class team to drive the launch of Rezdiffra and support Madrigal's long-term aspirations. Our groundbreaking Rezdiffra, Phase 3 trial data were published in the New England Journal of Medicine.

我對我們團隊在幻燈片 4 中所取得的成就感到無比自豪。這些都是我們說過要做的事，我們也確實做到了。我們建立了一支世界一流的團隊來推動 Rezdiffra 的推出並支持 Madrigal 的長期願望。我們開創性的 Rezdiffra 第 3 階段試驗數據發表在《新英格蘭醫學雜誌》。

On March 14th, we achieved the milestone for the MASH field, the landmark approval of Rezdiffra, the first ever treatment approved for this disease. This achievement was further validated by top 2 tier liver societies in Europe and the US, both updating their guidelines to include Rezdiffra as first line therapy for mesh. And we made significant progress expanding Rezdiffra's reach both geographically and clinically, submitting Rezdiffra for approval in Europe and completing enrollment in our Maestro Nash outcomes trial.

3 月 14 日，我們在 MASH 領域取得了里程碑式的進展，即 Rezdiffra 獲得批准，這是第一個獲準治療該疾病的藥物。這項成果得到了歐洲和美國頂級二級肝病協會的進一步認可，兩國均更新了其指南，將 Rezdiffra 列為網狀物的一線治療方法。我們在擴大 Rezdiffra 的地理和臨床覆蓋範圍方面取得了重大進展，提交了 Rezdiffra 在歐洲的審批，並完成了 Maestro Nash 結果試驗的招募。

Importantly, these accomplishments are translating into thousands of patients now benefiting from Rezdiffra and building a strong foundation for Madrigal's future as the leader in MASH. Let's move to the US Rezdiffra launch update on slide 5. As we detailed in our earnings release this morning and first previewed at JPMorgan in January, we generated $103 million in net sales in the fourth quarter of 2024, reflecting 66% quarter-over-quarter growth.

重要的是，這些成就意味著成千上萬的患者現在受益於 Rezdiffra，並為 Madrigal 未來成為 MASH 領導者奠定了堅實的基礎。讓我們轉到幻燈片 5 上的美國 Rezdiffra 發布更新。正如我們今天早上的收益報告中詳細說明並於 1 月份在摩根大通首次預覽的那樣，我們在 2024 年第四季度實現了 1.03 億美元的淨銷售額，環比增長 66%。

This was another strong demand quarter with inventory well within our expected two-to-four-week range. For the full year 2024, we generated $180.1 million in net sales, a remarkable achievement considering we launched in April, and these figures represent just three quarters of performance. Our launch trajectory continues to track in line with some of the most successful specialty medicine launches in the past decade.

這又是一個需求強勁的季度，庫存遠在我們預期的兩到四周。2024 年全年，我們的淨銷售額為 1.801 億美元，考慮到我們是在 4 月推出的，這是一項了不起的成就，而這些數字僅代表了四分之三的業績。我們的發布軌跡繼續與過去十年中一些最成功的專科藥物發布保持一致。

This confirms the urgent need Rezdiffra is addressing in the MASH community, its excellent product profile, and the exceptional execution of our team. These strong financial results are driven by the key performance indicators critical to any successful drug launch. Patients on therapy, prescribers, and access. In the third quarter of 2024 on our payer metric, we reached a key milestone one quarter ahead of schedule, achieving greater than 80% commercial coverage for Rezdiffra.

這證實了 Rezdiffra 在 MASH 社群中解決的迫切需求、其出色的產品特性以及我們團隊的出色執行力。這些強勁的財務表現是由對任何成功藥物上市至關重要的關鍵績效指標所推動的。接受治療的患者、處方者和獲取治療的途徑。2024 年第三季度，根據我們的付款人指標，我們提前一個季度達到了一個關鍵里程碑，實現了 Rezdiffra 超過 80% 的商業覆蓋率。

Since then, we've continued to make great progress on the other two launch metrics. First on patients, as noted on slide 6, we ended the fourth quarter with more than 11,800 patients on Rezdiffra. An incredible accomplishment in just nine months. Crossing the 10,000-patient threshold is a significant milestone, and we continue to steadily add patients at a rate that's consistent with other top tier specialty medicine launches.

自那時起，我們在其他兩個發布指標上繼續取得了巨大進展。首先是患者，如幻燈片 6 所示，在截止第四季度，我們使用 Rezdiffra 的患者超過 11,800 名。僅用九個月就取得了令人難以置信的成就。突破 10,000 名患者的門檻是一個重要的里程碑，我們將繼續以與其他頂級專科藥物上市一致的速度穩步增加患者。

Importantly, this figure represents patients actively on therapy, meaning it accounts for any discontinuations, making it the most rigorous and meaningful metric to track sustained treatment adoption. Yet we're still in the early days. We have penetrated only a fraction of the market with Rezdiffra, less than 4% of the 315,000 diagnosed patients with F2, F3 MASH.

重要的是，這個數字代表了積極接受治療的患者，這意味著它考慮了任何停藥的情況，使其成為追蹤持續治療採用的最嚴格和最有意義的指標。但我們仍處於早期階段。我們的 Rezdiffra 僅佔了一小部分市場，佔 315,000 名確診為 F2、F3 MASH 的患者的比例不到 4%。

We remain focused on the 315,000 diagnosed patients, which represents a highly attractive specialty market. Looking ahead, the stated efforts of the next entrant are focused on expanding the market to many multiples of 315,000. We believe that the strength of Rezdiffra's profile positions it for leadership in either scenario, creating multiple paths to success for Rezdiffra in the years ahead.

我們仍然關注 315,000 名確診患者，這代表著一個極具吸引力的專業市場。展望未來，下一位進入者的努力重點是將市場擴大到 315,000 的數倍。我們相信，Rezdiffra 的實力使其在任何一種情況下都佔據領導地位，為 Rezdiffra 在未來幾年取得成功創造了多條道路。

Our ability to steadily add Rezdiffra patients’ quarter-over-quarter is directly tied to increased penetration of our prescriber base. From day one, we've talked about wiring the system, how we have been laying the foundation to support the patient volume we expect in the years ahead. And we're seeing real progress as we've engaged providers, driven change in clinical practice, and helped build the infrastructure necessary for sustained prescription growth.

我們能夠逐季穩定增加 Rezdiffra 患者數量，這與我們的處方藥基礎滲透率的提高直接相關。從第一天起，我們就討論了系統的佈線，以及如何奠定基礎來支持未來幾年預期的患者數量。隨著我們與供應商合作、推動臨床實踐的變革並幫助建立處方藥持續增長所需的基礎設施，我們看到了真正的進展。

On slide 7, the bar graph on the left illustrates this progress. As a reminder, our field team is focused on a total of 14,000 target prescribers, primarily hepatologists and gastroenterologists, with a concentrated effort on the top 6,000 prescribers. In the fourth quarter, approximately 60% of our top 6,000 targets prescribed Rezdiffra, up from 40% in the third quarter.

在第 7 張投影片上，左側的長條圖顯示了這項進展。提醒一下，我們的現場團隊總共專注於 14,000 名目標開藥者，主要是肝病學家和胃腸病學家，並將精力集中在排名前 6,000 名的開藥者身上。第四季度，我們前 6,000 名患者中約有 60% 處方了 Rezdiffra，高於第三季度的 40%。

We are steadily adding new prescribers, and we are seeing increased depth of prescribing from current writers. Both metrics are tracking exceptionally well with other successful blockbuster launches. As expected, our top target prescribers have driven more than 75% of our prescriptions. Just as we've successfully driven adoption among our top target prescribers. We plan to continue shaping clinical practice and expanding access across our full prescriber base as we build Rezdiffra towards its peak sales potential.

我們正在穩步增加新的處方人員，我們看到現有處方人員的處方深度也在增加。隨著其他成功大片的推出，這兩項指標都表現異常出色。正如預期的那樣，我們的主要目標開藥者已經提供了超過 75％ 的處方。正如我們成功推動了我們的主要目標處方者採用該技術一樣。我們計劃在將 Rezdiffra 推向其高峰銷售潛力的同時，繼續塑造臨床實踐並擴大整個處方人群的使用管道。

We're already making meaningful progress. By year end, approximately 40% of the 14,000 had prescribed Rezdiffra, reflecting a strong and growing foundation of support. Rezdiffra's broad-based uptake is being driven by its attractive profile. It's a liver-directed therapy that halts or improved liver stiffness, a proxy for liver fibrosis in 91% of patients out to three years.

我們已經取得了有意義的進展。截至年底，14,000 人中約有 40％ 已服用 Rezdiffra，反映出支持基礎強勁且不斷增長。Rezdiffra 的廣泛採用是由於其富有吸引力的外形。這是一種針對肝臟的治療方法，可以阻止或改善肝臟硬度，三年內 91% 的患者會出現肝纖維化的症狀。

It's also a once daily, well tolerated pill with simple dosing and with the chronic and serious liver disease like MASH, this favorable profile supports long-term adherence, with early data continuing to indicate persistency rates comparable to other well tolerated oral therapies. We're also hearing overwhelmingly positive feedback on Rezdiffra from both physicians and patients.

這也是一種每日服用一次、耐受性良好的藥丸，服用劑量簡單，對於像 MASH 這樣的慢性嚴重肝病，這種良好的特性支持長期堅持，早期數據繼續表明其持久率與其他耐受性良好的口服療法相當。我們也聽到醫生和患者對 Rezdiffra 的大量正面回饋。

They continue to highlight the benefits of the medicine, including improvements in liver function tests and lipid levels, reduced fatigue, increased physical activity, and improvement in fibrosis. And these real-world outcomes really matter. We recently heard from one Rezdiffra differ patient diagnosed with F2 MASH. She said quote Living with MASH felt like having a time bomb in my body, Rezdiffra gave me hope and my life back, end quote.

他們繼續強調該藥物的好處，包括改善肝功能測試和脂質水平、減少疲勞、增加身體活動、改善纖維化。這些現實世界的結果確實很重要。我們最近聽說一位 Rezdiffra 患者被診斷出患有 F2 MASH。她說：“與 MASH 共存就像是我體內有一顆定時炸彈，而 Rezdiffra 給了我希望，讓我重新擁有了生命。”

Our goal is to be the leader in MASH and help patients for many years to come. As noted on slide 9, our long-term strategy builds on the success of Rezdiffra's US launch. First, we are expanding geographically and remain on track for a mid-year regulatory decision for Rezdiffra in Europe. Assuming a positive outcome, we plan to take a targeted country-by-country approach to commercialization, beginning with Germany in the second half of the year.

我們的目標是成為 MASH 的領導者並在未來許多年裡為患者提供幫助。如投影片 9 所示，我們的長期策略建立在 Rezdiffra 在美國成功上市的基礎上。首先，我們正在進行地域擴張，並將繼續按照計劃在年中為 Rezdiffra 在歐洲做出監管決定。假設取得正面成果，我們計劃採取有針對性的逐國商業化方式，並從今年下半年的德國開始。

Beyond Europe, we are also assessing opportunities to bring Rezdiffra to patients in additional attractive geographies. Second, we're advancing res differ for patients with compensated MASH cirrhosis. Approval in F4C would represent a major step forward for the MASH field and for patients, significantly expanding the treatment landscape and effectively doubling Rezdiffra's market opportunity. I'll spend some more time on the data we shared this morning in a moment.

除了歐洲以外，我們也正在評估將 Rezdiffra 帶給其他有吸引力的地區患者的機會。其次，我們正在為患有代償性 MASH 肝硬化的患者提供不同的治療。F4C 的批准將代表 MASH 領域和患者向前邁出的重要一步，顯著擴大治療領域並有效加倍 Rezdiffra 的市場機會。稍後我將花更多時間討論我們今天上午分享的數據。

And third, we are committed to building a strong pipeline beyond Rezdiffra. We're in the enviable position of providing a highly meaningful medicine to the MASH community today, and we are now focused on building the right pipeline behind it. We are evaluating assets at different stages of development across multiple mechanisms of action, all with the goal of strengthening and extending our leadership position to MASH.

第三，我們致力於在 Rezdiffra 之外建立強大的管道。我們今天能夠為 MASH 社區提供極具意義的藥物，這是一種令人羨慕的地位，我們現在正致力於在背後建立正確的管道。我們正在評估多種作用機制中處於不同開發階段的資產，目的都是為了加強和擴大我們在 MASH 的領導地位。

Moving to slide 10, and the unmet need in compensated [MASH] cirrhosis, it's a chronic progressive liver disease characterized by significant liver damage, loss of liver function, liver cancer, and death. A substantial portion of compensated MASH cirrhosis patients also suffer from portal hypertension, which often leads to life threatening complications such as hepatic encephalopathy, ascites, and varial bleeding.

轉到第 10 張投影片，代償性 [MASH] 肝硬化的未滿足需求，這是一種慢性進行性肝病，其特徵是嚴重的肝損傷、肝功能喪失、肝癌和死亡。相當一部分代償性 MASH 肝硬化患者也患有門靜脈高壓，這常常導致危及生命的併發症，如肝性腦病變、腹水和靜脈曲張出血。

While patients with F2, F3 fibrosis face a 10 to 17 times higher risk of liver-related mortality, F4 patients are at a staggering 42 times increased risk. In this very sick F4 patient population, preventing progression to adverse clinical outcomes is the central treatment goal. This is reflected in FDA guidance which recommends that clinical trials and compensated MASH cirrhosis use outcomes as an endpoint as opposed to biopsy-based surrogate endpoints.

F2,F3 纖維化患者面臨的肝臟相關死亡風險高出 10 至 17 倍，而 F4 患者的風險則高出驚人的 42 倍。對於病情極為嚴重的 F4 患者群體，防止進展為不良臨床結果是治療的核心目標。這反映在 FDA 指南中，該指南建議臨床試驗和代償性 MASH 肝硬化使用結果作為終點，而不是基於活檢的替代終點。

This guidance, along with data from our open label F4C cohort, informed the design of our ongoing MAESTRO-NASH outcomes trial. We believe that Rezdiffra's liver-directed mechanism of action should deliver a benefit not only in F2, F3 MASH patients, but in F4 MASH patients as well.

該指南以及我們開放標籤 F4C 隊列的數據為我們正在進行的 MAESTRO-NASH 結果試驗的設計提供了資訊。我們相信，Rezdiffra 的肝臟導向機制不僅對 F2、F3 MASH 患者有益，對 F4 MASH 患者也有益。

Therefore, as shown on slide 11, we included a separate open label active treatment arm of patients with compensated MASH cirrhosis in our Maestro napped one trial to begin evaluating Rezdiffra's safety and efficacy in F4C. As a reminder, Maestro napped I was a double-blind randomized placebo-controlled Phase 3 safety trial to support regulatory approval.

因此，如幻燈片 11 所示，我們在 Maestro 合作的試驗中納入了針對代償性 MASH 肝硬化患者的單獨開放標籤活性治療組，以開始評估 Rezdiffra 在 F4C 中的安全性和有效性。提醒一下，Maestro napped I 是一項雙盲隨機安慰劑對照的 3 期安全試驗，以支持監管部門的批准。

We previously presented positive one year data from the F4C cohort of this trial and are highlighting new two-year VCTE data in 101 patients on slide 12. VCTE or vibration-controlled transient elastography, is a widely used non-invasive test conducted with a fiber scan that measures liver stiffness as a proxy for fibrosis. It's also a strong predictor of clinical outcomes.

我們先前展示了該試驗的 F4C 隊列的一年積極數據，並在幻燈片 12 上重點介紹了 101 名患者的兩年 VCTE 新數據。VCTE 或振動控制瞬態彈性成像是一種廣泛使用的非侵入性測試，透過纖維掃描進行測量，以測量肝臟硬度作為纖維化的指標。它也是臨床結果的有力預測指標。

The two-year results show that patients achieved a mean 6.7 KPA or kilopascal reduction in liver stiffness at two years, which represents the largest mean KPA reduction reported in an F4C, MASH patient population to date. While this was a single arm open label trial, this reduction was highly statistically significant versus baseline. Physicians use the [Babino] rule of 5 KPA to stratify risk of liver-related events in patients with MAS. So a 6.7% reduction suggests that many patients are moving into a lower risk category.

兩年的結果顯示，患者的肝臟硬度在兩年內平均降低了 6.7 KPA 或千帕，這是迄今為止 F4C、MASH 患者群體中報告的最大平均 KPA 降低量。雖然這是一項單組開放標籤試驗，但與基線相比，這種減少具有高度統計意義。醫生使用 [Babino] 5 KPA 規則對 MAS 患者的肝臟相關事件風險進行分層。因此，6.7% 的減少表明許多患者正在進入較低的風險類別。

51% of patients achieved a 25% or greater decrease in liver stiffness as measured by VCTE. This level of reduction in liver stiffness has been associated with reduced progression to end-stage liver disease, moving patients further away from the risks of cirrhosis and its complications. And Rezdiffra's safety profile was consistent with other Rezdiffra clinical trials with a low rate of discontinuation due to adverse events. We look forward to sharing more details from this two-year cohort at a future medical meeting.

51% 的患者的肝臟硬度透過 VCTE 測量降低 25% 或更多。肝臟硬度的降低與減緩末期肝病的進展有關，使患者遠離肝硬化及其併發症的風險。Rezdiffra 的安全性與其他 Rezdiffra 臨床試驗一致，因不良事件而停藥的比例較低。我們期待在未來的醫學會議上分享有關這項為期兩年的研究的更多細節。

These data add to the growing body of evidence supporting Rezdiffra's potential benefit in this high-risk patient population and support continued confidence in our fully enrolled cirrhosis outcomes trial. As noted on slide 13, MAESTRO NASH Outcomes is a large Phase 3 double blind placebo-controlled trial evaluating progression to liver decompensation events in 845 patients with compensated MASH cirrhosis. We expect to announce data from this trial in 2027.

這些數據進一步證明 Rezdiffra 對這一高風險患者群體具有潛在益處，並增強了我們對全面納入的肝硬化結果試驗的持續信心。如投影片 13 所示，MAESTRO NASH Outcomes 是一項大型 3 期雙盲安慰劑對照試驗，評估 845 名患有代償性 MASH 肝硬化的患者的肝失代償事件的進展。我們預計將在 2027 年公佈此次試驗的數據。

So looking ahead to the opportunity in F4C and assuming today's results translate to MAESTRO NASH outcomes and Rezdiffra obtains regulatory approval, we believe Rezdiffra is and will be the leading therapy in F2 to F4C period. Before I hand it over to Mardi, let me briefly summarize our progress on slide 14.

因此，展望 F4C 中的機會並假設今天的結果轉化為 MAESTRO NASH 結果且 Rezdiffra 獲得監管部門的批准，我們相信 Rezdiffra 是並將成為 F2 至 F4C 時期的領先治療方法。在將其交給 Mardi 之前，讓我先在第 14 張投影片上簡要總結一下我們的進展。

2024 was a transformational year for Madrigal. We secured FDA approval for Rezdiffra and are executing on a highly successful launch. We see significant runway for growth, with less than 4% of the US target market penetrated and an attractive real-world profile. Rezdiffra is well positioned for continued strong momentum in 2025 and beyond.

2024 年對 Madrigal 來說是轉型之年。我們已獲得 FDA 對 Rezdiffra 的批准，並且正在執行一項非常成功的上市計劃。我們看到了巨大的成長空間，滲透率不到4%的美國目標市場和具有吸引力的真實世界概況。Rezdiffra 預計將在 2025 年及以後繼續保持強勁發展勢頭。

We are preparing for global expansion. We see a significant opportunity in F4C and believe we will be first to market, and we continue to build for the future as we actively explore opportunities to expand our pipelines.

我們正在為全球擴張做準備。我們在 F4C 中看到了巨大的機遇，並相信我們將率先進入市場，而且我們將在積極探索擴大通路機會的同時，繼續為未來而建立。

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

說完這些，我會把話題交給馬迪。

Thank you, Bill. Earlier today we issued a press release detailing our full financial results. I will highlight a few key takeaways for the fourth quarter and full year as noted on slide 15. Fourth quarter net sales totaled $103.3 million bringing full year 2024 net sales to $180.1 million an impressive achievement considering this reflects only nine months of commercialization.

謝謝你，比爾。今天早些時候，我們發布了一份新聞稿，詳細介紹了我們的全部財務表現。我將重點介紹第 15 頁幻燈片中列出的第四季度和全年的一些關鍵要點。第四季淨銷售額總計 1.033 億美元，使得 2024 年全年淨銷售額達到 1.801 億美元，考慮到這僅反映了 9 個月的商業化，這是一項令人印象深刻的成就。

We delivered another strong demand quarter with inventory well within the expected two-to-four-week range. Our gross to net discount increased in line with what we previously discussed, as we said, we expect some variability in gross to net early in the launch. Looking ahead to 2025 as expected, we anticipate an increase in the gross to net discount compared to 2024, as is typical at this stage of the of a specialty medicine launch.

我們又度過了一個需求強勁的季度，庫存量遠在預期的兩到四周。我們的毛利與淨利折扣按照我們之前討論的幅度增加，正如我們所說，我們預計在發布初期毛利與淨利折扣會出現一些變化。展望 2025 年，我們預計毛利率與淨利率相比將增加，這在專科藥物上市的這個階段很常見。

Importantly this is already reflected in our expectations for robust year-over-year net sales growth in 2025. R&D expenses for the fourth quarter and full year of 2024 were $25.6 million and $236.7 million respectively compared to $70.6 million and $272.4 million in the prior year periods. R&D expenses decreased by $35.6 million in 2024 due primarily to a reduction in clinical trial accruals and the change in accounting for inventory costs following FDA approval of Rezdiffra, partially offset by an increase in headcount.

重要的是，這已經反映在我們對 2025 年淨銷售額同比強勁增長的預期中。2024 年第四季和全年研發費用分別為 2,560 萬美元和 2.367 億美元，去年同期分別為 7,060 萬美元和 2.724 億美元。2024 年研發費用減少了 3560 萬美元，主要原因是臨床試驗應計費用減少以及 FDA 批准 Rezdiffra 後庫存成本會計的變化，但員工人數增加部分抵消了這一影響。

Looking ahead, we expect a somewhat higher level of R&D spend in 2025 compared to 2024. SG&A expenses for the fourth quarter and full year of 2024 were $141.2 million and $435.1 million respectively compared to $46.5 million and $108.1 million in the prior year periods. This year over year increase was expected and reflects the rapid scale up of our US commercial operations following Rezdiffra's approval in March 2024.

展望未來，我們預計 2025 年的研發支出水準將比 2024 年略高。2024 年第四季及全年的銷售、一般及行政費用分別為 1.412 億美元及 4.351 億美元，而去年同期分別為 4,650 萬美元及 1.081 億美元。今年的同比增長是意料之中的，反映了我們自 2024 年 3 月 Rezdiffra 獲得批准以來在美國商業業務的快速擴張。

Looking ahead, we expect SG&A expenses to increase in 2025 as we continue to invest in the US launch and our international expansion. Turning to our balance sheet, we ended 2024 with $931.3 million in cash. cash equivalents, restricted cash, and marketable securities. With a strong cash position, we are well resourced to support the ongoing launch of Rezdiffra's in both the US and our planned launch in Europe.

展望未來，隨著我們繼續投資於美國市場和國際擴張，我們預計 2025 年銷售、一般及行政開支將會增加。回顧我們的資產負債表，截至 2024 年底，我們的現金餘額為 9.313 億美元。現金等價物、受限現金及有價證券。憑藉著雄厚的現金實力，我們擁有充足的資源來支持 Rezdiffra 在美國持續推出的產品以及我們計劃在歐洲推出的產品。

I'll now turn the call back over to Tina.

我現在將電話轉回給蒂娜。

Thanks, Marty. 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，馬蒂。讓我們進入通話的問答部分。馬文，請繼續並為問答環節提供說明。

(Operator Instructions) Thomas Smith, Leerink Partners.

(操作員指示)Thomas Smith，Leerink Partners。

Hey guys, good morning. Thanks for taking the questions and congrats on the strong launch and the new cirrhosis data. Just had a question with respect to the ongoing there for launch. Now that we're roughly 2/3 of the way through the quarter. So we're wondering if you could comment on what you've seen in the first two months of the year in terms of new patient ads, any change in the cadence of patients starting on drugs or.

嘿，大家早安。感謝您回答這些問題，並祝賀強勁的發布和新的肝硬化數據。我只是想問一下關於正在進行的發布會的問題。現在我們已經完成了本季的約 2/3。因此，我們想知道您是否可以評論一下今年前兩個月的新患者廣告情況，以及患者開始服藥的節奏是否有任何變化。

Anything notable as patients and prescribers' kind of work through their insurance or co-pay, adjustments. And then historically you've, given some high-level guidance based on the comp group of specialty drug launches, I guess any color that you could provide as we think about Q1 and maybe 2025, broadly. Thanks so much.

任何值得注意的事情，例如患者和處方人員透過保險或共同支付進行的工作、調整。然後從歷史上看，您根據專科藥物發布的同類產品給出了一些高層指導，我想當我們考慮第一季以及大約 2025 年時，您可以提供任何具體資訊。非常感謝。

Tom, thanks for the question. Look, just a couple of points first of all 2024 was really an incredible year when you think about going back 12 months from now, there wasn't a product on the market for MASH, and in a very short period of time we've really done, I think, a remarkable job executing and finishing off the year with a $103 million quarters is really very impressive.

湯姆，謝謝你的提問。首先，我想說幾點。 2024 年確實是令人難以置信的一年，當你回想 12 個月後，市場上還沒有適用於 MASH 的產品，而在很短的時間內，我們確實做得非常出色，我認為，我們完成了一項了不起的工作，並以 1.03 億美元的季度收入結束了這一年，這真的非常令人印象深刻。

By any measure you look at as we look at metrics all across the blockbuster launches that you referred to, we're tracking extremely well on all fronts, there's no weakness here on any of them. We carried, I would say, the momentum of '24 into '25 of steadily adding patients and prescribers. So that's we've seen more of that in the first quarter of '25. We also do have, like everyone else, the Q1 dynamic that is, clearly a phenomenon each year.

無論以何種標準來衡量，當我們查看您所提到的所有大片發布的指標時，我們都會發現我們在各個方面都追蹤得非常好，沒有任何弱點。我想說，我們延續了 2024 年的勢頭，在 2025 年穩步增加患者和開處方人員。因此我們在 2025 年第一季看到了更多這樣的情況。和其他人一樣，我們也確實有 Q1 動態，這顯然是每年都會出現的現象。

And teams have been well prepared, and I think we're managing through that extremely well. As I think about what's happening at the prescriber level, each, there, I would say there isn't a prescriber yet. That has maxed out or even close to maxing out the patients that exist in their practice or that are being referred into their practice. And each practice is learning, we talk about wiring the system that's been a lot of hard work and we've done it on a practice-by-practice basis. And as you can see, we continue to add new prescribed. Fibers and we're now at the 60% penetration into that target group.

各隊都做好了充分的準備，我認為我們能夠非常好地應對這一切。當我思考在處方醫師層面上發生的情況時，我想說，那裡還沒有處方醫師。這已經達到或接近其診所內現有或轉診的患者的最大數量。每次練習都是學習，我們討論如何連結系統，這需要付出很多艱苦的努力，而且我們在一次次的練習中完成了這項工作。如您所見，我們繼續添加新的規定。纖維，我們目前對該目標群體的滲透率已達到 60%。

For each of those as they start prescribing, they're doing their wiring. So what we're continuing to do is just bring on, steadily each day, each week, each month, each quarter prescribers, have them get ready to be able to handle the volume of their patients, how work through the system, et cetera. Now from a Q1 dynamic perspective, as I said, certainly that's something that we're seeing like any anyone else. I think the teams have done a good job getting ready to manage through that. No real other challenges that we've seen with the quarter it's pretty standard.

當他們開始開處方時，他們正在進行接線。因此，我們將繼續做的就是，每天、每週、每月、每季穩定地安排處方人員，讓他們做好準備，以處理大量的患者，如何透過系統工作等等。現在從 Q1 的動態角度來看，正如我所說，這肯定是我們和其他人一樣看到的情況。我認為各隊已經做好了應對這一問題的準備。我們在本季沒有看到其他真正的挑戰，這是相當標準的。

Yes, maybe I'll just add a little bit, Tom, to answer your question about the analogs. So we do track very closely with our group of 10 specialty launches over the last 10 years. It gets a little tricky when you go from a Q4 to Q1. So we're not giving specific guidance in that percentage for Q1 and may not go, we may not get that guidance going forward, but we're really tracking with these analogs thus far.

是的，湯姆，也許我只需要補充一點來回答你關於類似物的問題。因此，我們確實密切追蹤了過去 10 年中我們推出的 10 項專業產品。當你從 Q4 轉到 Q1 時，情況會變得有點棘手。因此，我們不會針對第一季的百分比給出具體的指導，也可能不會，也可能不會獲得未來的指導，但到目前為止，我們確實在追蹤這些類比。

But I will also say if we just look at consensus, as Bill, said we're very pleased with what we're seeing going into 2025. And a little commentary there that we believe consensus for Q1 2025 will narrow and go up a little bit. As a result of what we've been seeing so far.

但我還要說，如果我們只看共識，正如比爾所說，我們對 2025 年的前景感到非常滿意。有一點評論說，我們相信 2025 年第一季的共識將會縮小並略有上升。根據我們目前所見的情況。

Great. Thanks, Tom. Marvin, next question, please.

偉大的。謝謝，湯姆。馬文，請問下一個問題。

Andrea Newkirk, Goldman Sachs

高盛集團安德里亞紐柯克 (Andrea Newkirk)

Good morning. Thanks for taking the question. Maybe I can ask you here on the cirrhosis data that you shared. I was hoping you could speak a little bit more on the clinical meaningfulness of achieving that 6.7 kilopascal reduction. And I know in the context of your three-year data for the F2,F3 NASH patient population, we had talked about how a VCTE measure below 10 kilopascals was correlated with fewer liver related outcomes.

早安.感謝您回答這個問題。也許我可以在這裡詢問您分享的肝硬化數據。我希望您能再多講一下實現 6.7 千帕減幅的臨床意義。我知道，在您針對 F2、F3 NASH 患者群體的三年數據中，我們曾討論過低於 10 千帕的 VCTE 測量值與較少的肝臟相關結果之間的相關性。

Just wondering if that same threshold stands for the F4 cirrhotic patient population. And then finally, just how did today's data change how you're thinking about the NASH outcomes trial, if at all? And does that change how you're thinking about the powering of the study? Thanks so much.

只是想知道相同的閾值是否適用於 F4 肝硬化患者群體。最後，今天的數據如何改變您對 NASH 結果試驗的看法？這會改變您對這項研究動力的看法嗎？非常感謝。

Great, thanks for the question, Andrea. I'll turn it over to Michael in a second, but as we think about how does it change our view on MAESTRO-NASH outcomes, look, we've been confident about that study. This is just another piece of information which gives us, I would say, greater confidence in it, we're doing something here which is really again as we've done it with our F2,F3 program, we're pioneering the way. And we believe that we have designed the right trial for MAESTRO-NASH outcomes.

太好了，謝謝你的提問，安德里亞。我馬上就把它交給邁克爾，但是當我們思考它如何改變我們對 MAESTRO-NASH 結果的看法時，看，我們對這項研究充滿信心。這只是另一個訊息，我想說，它給了我們更大的信心，我們在這裡做的事情實際上就像我們在 F2、F3 計劃中所做的那樣，我們正在開闢道路。我們相信我們已經為 MAESTRO-NASH 結果設計了正確的試驗。

This trial that we announced today actually helped us helped to inform our thinking on MAESTRO-NASH outcomes. And with the really exciting news that we presented today, as I said, it gives us even more confidence, but maybe, Michael, do you want to answer the first couple of questions that Andrea had?

我們今天宣布的這項試驗實際上幫助我們了解了 MAESTRO-NASH 的結果。正如我所說，我們今天宣布的令人興奮的消息給了我們更多的信心，但是，邁克爾，你想回答安德里亞提出的前幾個問題嗎？

Yes, It's a great question. The predictivity of decreases in liver stiffness increases with the higher your baseline level. So our baseline level was 25 kilopascals. The productivity really starts to tick up at around 15 kilopascals. So there are 6.7 kilopascal reduction. Some with the starting point to 25 kilopascals, should be highly predictive of decreased risk of clinical outcomes.

是的，這是一個很好的問題。肝臟硬度下降的預測性會隨著基線水平的升高而增加。所以我們的基準水準是25千帕。生產率在15千帕左右才真正開始上升。因此減少了6.7千帕。以 25 千帕為起點，應該可以高度預測臨床結果風險的降低。

Great. Thanks, Andrea. Next question please, Martin.

偉大的。謝謝，安德里亞。馬丁，請問下一個問題。

Yasmeen Rahimi, Piper Sandler.

亞斯明·拉希米，派珀·桑德勒。

Good morning team. And thank you so much for all the great updates. Is there, I guess, could you comment on as we go into 2025, if you will be in a position to provide guidance? I think that Marty, your commentary was very helpful around that the consensus is going to a little increase, tighten a little bit. So just maybe help us understand.

大家早安。非常感謝您提供的所有精彩更新。我想，當我們進入 2025 年時，您能否評論一下，您是否可以提供指導？我認為馬蒂，你的評論非常有幫助，共識將會略有增加，略有收緊。所以也許可以幫助我們理解。

How you're thinking about moving forward, we understand the dynamics of the first quarter, but beyond that, at what point will you feel comfortable to kind of share with us what the 2025 or 2026 guidance would look like? That would be really helpful, and I'll jump back in the queue.

您對未來有何想法？我們了解第一季的動態，但除此之外，您什麼時候願意與我們分享 2025 年或 2026 年的預期？這真的很有幫助，我會重新回到隊列中。

Great, Mardi. Let me pass that over to you.

太好了，馬迪。讓我把它傳給你。

Thanks, Yash. With respect to guidance, we've been very clear we're not giving guidance right now, we consider it internally, but that's not something we're providing at this time. We're just too early in the launch. I did provide a little commentary on Q1 2025, and I think the same commentary goes for the full year '25.

謝謝，Yash。關於指導，我們已經非常清楚我們現在不會提供指導，我們會內部考慮，但這不是我們目前提供的東西。我們發布的日期還為時過早。我確實對 2025 年第一季做了一些評論，我認為對 2025 年全年也做出同樣的評論。

We like what we're seeing, the momentum going into 2025, we commented on the robust year-over-year growth. So where consensus sits for 2025, we expect that to narrow as well and go up a little bit, based on what we're seeing.

我們喜歡我們所看到的，進入 2025 年的勢頭，我們對強勁的同比增長做出了評論。因此，根據目前的情況，我們預計 2025 年的共識也會縮小，並且會略有上升。

Good, thanks, Yash. Marvin, next question.

很好，謝謝，Yash。馬文，下一個問題。

Eliana Merle, UBS.

瑞銀的 Eliana Merle。

Hey guys, thanks for taking the question. Interesting, F4 data, I guess were those fiber scan benefits seen irrespective of the liver fat content at baseline and any color on sort of which patients were more or less likely to show these VCTE reduction. And then just in terms of the study, I guess can we expect any further long term data cuts from the study like the three-year data just curious, the timing here since I think the study has been going on for a few years already. Thanks.

嘿夥計們，謝謝你們回答這個問題。有趣的是，F4 數據，我猜是那些纖維掃描益處，無論基線時的肝臟脂肪含量如何，也無論哪種顏色，患者都或多或少可能顯示這些 VCTE 減少。然後就研究而言，我想我們是否可以期待從研究中得到任何進一步的長期數據，例如三年的數據，只是好奇，這裡的時間是因為我認為這項研究已經進行了幾年了。謝謝。

Thanks, Eli. Look, so more to come this is just some really top line look at the data at an upcoming medical meeting. We'll go into a little bit more detail on things. I think there's certainly still a lot left that we can learn from this study just with the data that we have at two years. Is there anything else, Michael, to comment on? We're not giving out any more than the top line that we've given today.

謝謝，Eli。你看，接下來還有更多，這只是對即將舉行的醫學會議上的一些真正最重要的數據進行觀察。我們將更詳細地討論此事。我認為，僅憑兩年來的數據，我們仍然可以從這項研究中了解到很多事情。邁克爾，還有其他要評論的嗎？我們不會透露比今天更多的資訊。

No, I think, the essential in productivity for these results, the clinical outcomes, and with the decline of 25% based on that study of 10,000 patients respectively, you get 30% to 40% decreased likelihood of a liver-related clinical event. So that's our main takeaway from these results.

不，我認為，這些結果的生產力關鍵在於臨床結果，根據對 10,000 名患者的研究，下降了 25%，發生肝臟相關臨床事件的可能性降低了 30% 至 40%。這是我們從這些結果中得到的主要結論。

Thanks. Ellie. Marvin, next question, please.

謝謝。艾莉。馬文，請問下一個問題。

Ami Li, Jefferies.

Ami Li，傑富瑞 (Jefferies)。

Hey, this is Amy on for [cost]. Thanks so much for taking your question. Starting off, just wanted to get your thoughts on the, competitor FGF 21 data and MAESTRO-NASH and that how that could read across to your F4 outcome study. Also on Part D redesign. I think our preliminary math is getting to a potential full year net sales impact of around 3% to 5% for Rezdiffra going forward. Just wanted to send check this number with you and will you do any additional discounts ahead of the summer launch? Thanks so much.

嘿，我是艾米[成本]。非常感謝您回答這個問題。首先，我只是想聽聽您對競爭對手 FGF 21 數據和 MAESTRO-NASH 的看法，以及如何將其轉化為您的 F4 結果研究。同樣關於 D 部分的重新設計。我認為，我們的初步計算表明，這對 Rezdiffra 未來全年淨銷售額的潛在影響約為 3% 至 5%。只是想把這個號碼寄給您，在夏季推出之前您會做任何額外的折扣嗎？非常感謝。

Well, Amy, thank you. That's a that's a lot of questions to get through. Let me see if we can talk through. First of all, as we launched the product, from a gross tone perspective, we have been extremely diligent about gross tone. We weren't contracting as we launched the product, and when we launched the product, we don't, you don't think about launch in a quarter or two or four.

好吧，艾米，謝謝你。有很多問題需要解決。讓我看看我們能否討論一下。首先，我們在推出產品的時候，從整體音調的角度來看，我們對整體音調非常認真。我們在推出產品時並沒有簽訂合同，而且我們推出產品時也不會考慮在一兩個季度或四個季度內推出產品。

You think about kind of the years ahead and we thought about gross to net anticipating that there will be additional competition in the marketplace in time, additional indications hopefully for us, et cetera. So we take an extremely disciplined approach here. Now we will react to market dynamics as any company does. You always have a dynamic in Q1, which we've talked about as it relates to working with the payers and so forth.

您想想未來的幾年，我們考慮過總收入與淨收入，預計隨著時間的推移，市場上會有更多的競爭，希望對我們來說有更多的跡象，等等。因此我們在這裡採取極為嚴謹的方法。現在我們將像任何公司一樣對市場動態做出反應。您在第一季總是會有一個動態，我們已經討論過它與付款人的合作等等的關係。

There's a constant dynamic there. So we'll continue to react to the market as these dynamics continue to shift. I think your other question was on Part D. I mean, look, Mardi, I think covered it a little bit in some of the opening remarks, but Marty, do you want to make any comments?

那裡有持續不斷的動態。因此，隨著這些動態的不斷變化，我們將繼續對市場做出反應。我認為您的另一個問題是關於 D 部分的。我的意思是，看，馬迪，我認為在一些開場白中已經涉及了這一點，但是馬蒂，你想發表什麼評論嗎？

Yes. I'll just say specifically about the Part D with how it impacts grows to that. Remember, Medicare patients are about 1/3 of our business. And Part D, we've always said that there will be some impact going into 2025 with the redesign. That's absolutely true, but we also had in 2024 we were paying Medicare rebates really, so the impact is a little more incremental in 2025 versus a significant step up.

是的。我將具體談談 D 部分以及它對此的影響。請記住，醫療保險患者約占我們業務的 1/3。在 D 部分，我們一直說重新設計會對 2025 年產生一些影響。這絕對是事實，但我們在 2024 年也確實支付了醫療保險退款，因此，2025 年的影響會稍微漸進一些，而不是大幅增加。

So I think the good news with our growth to net, particularly in 2025, is everything's going as expected, right? So we had to see a little bit of increase in our co-pay is as expected and included in our expectations for net revenue for the year.

所以我認為，我們的淨增長，特別是在 2025 年，好消息是一切都按預期進行，對嗎？因此，我們必須看到共同支付額略有增加，這是預期之內的事情，並且包含在我們今年淨收入的預期中。

Yeah, I mean our excitement and belief in this product and just also where you think about where we are, we're at the very beginning stages. All of this is taken into account to our enthusiasm. And then, maybe on the first question that you had Ellie, look, we're not going to comment on competitive data. But what we do believe is we're very confident in our data.

是的，我的意思是我們對這個產品感到興奮並有信心，而且想想我們現在所處的位置，我們正處於非常起步的階段。所有這些都體現了我們的熱情。然後，也許對於你問艾莉的第一個問題，我們不會對競爭數據發表評論。但我們確實相信我們對我們的數據非常有信心。

We think that the release of this this morning gives us further confidence, as I said, in MAESTRO-NASH outcomes, the 6.7 kilopascal reduction that really is meaningful. Michael team, everyone's really excited and people that we've spoken to in the community as well. That's a number that really gets people's attention, and we think that translates into a real meaningful effect for patients. And as we said, ours is an outcome study. We have followed FDA guidance and believed that we've designed the right study for approval.

我們認為，今天早上發布的結果讓我們對 MAESTRO-NASH 的結果更有信心，正如我所說，6.7 千帕的減幅確實很有意義。邁克爾團隊，每個人都非常興奮，我們在社區中交談過的人也是如此。這個數字確實引起了人們的注意，我們認為這對患者來說具有真正的意義。正如我們所說，我們的研究是一項結果研究。我們遵循 FDA 的指導，並相信我們設計的研究是正確的，可以獲得批准。

Thanks Amy. Next question, Marvin.

謝謝艾米。下一個問題，馬文。

Liisa Bayko, Evercore ISI.

Liisa Bayko，Evercore ISI。

Hi, thanks for taking the question. Just two quick ones for me. First, the Kilopascal change and the changes you talked about today. Could you put that in context of any change in sort of F4 to F3, changes in fibrosis score. And then also just wanted to touch upon some [glut ide] coming to market in NASH and NASH story and how you think about your positioning there in particular with respecting to the pricing differential and how you might handle that. Thank you.

你好，謝謝你回答這個問題。我只想問兩個問題。第一，千帕的變化，還有你今天講的這些變化。您能否將其置於 F4 到 F3 的變化、纖維化評分變化的背景下？然後，我也想談談一些 [glut ide] 在 NASH 和 NASH 故事中進入市場的情況，以及您如何看待您在那裡的定位，特別是在價格差異方面，以及您如何處理這個問題。謝謝。

Thank you for the questions, Liisa. Maybe I'll start off and then I'll pass it over to Michael, with your first question. But as it relates to some, I think, look, we've been really clear. First of all, we're at the very beginning of this market evolution, right, less than 4% penetration. So we've got many years of growth ahead. You then look at the profile of our product. We've got a great profile, as I look towards the future, I don't see any product with the profile that actually is as good as ours.

謝謝你的提問，Liisa。也許我應該先開始，然後再將您的第一個問題交給邁克爾。但就某些問題而言，我想，我們已經說得非常清楚了。首先，我們正處於市場發展的初期，滲透率不到4％。因此我們未來還有很多年的成長空間。然後您來看看我們產品的概況。我們擁有出色的形象，展望未來，我看不到任何產品能與我們的產品一樣好。

SEMA, assuming they come to the market, we're planning for that. We would assume that it's kind of, maybe as early as late Q3, beginning of Q4. That's a very different profile of product. Remember, the problem we're trying to solve here, you've got patients that are one to two steps away from cirrhosis. And what they can't afford is time. And by that I mean, if you're waiting months to dose titrate and then have a high discontinuation rate, now you have to be on a drug for it to work.

SEMA，假設他們進入市場，我們正在為此做計劃。我們推測這可能最早會在第三季末或第四季初發生。這是一個非常不同的產品特徵。請記住，我們在這裡試圖解決的問題是，患者距離肝硬化只有一到兩步。而他們所浪費的就是時間。我的意思是，如果您要等待數月才能調整劑量，然後停藥率很高，那麼現在您必須服用藥物才能發揮作用。

And the one thing that we do know is that with our liver directed therapy, it's easy to take. It works fast, and the results that we're seeing in the real world are extremely promising. So what we believe is that actually, Assuming SMEA does get approved, it's actually going to drive additional market growth, which is something that ultimately as the leader in the space we're going to benefit from.

我們確實知道的一件事是，透過我們的肝臟導向療法，它很容易實施。它運行速度很快，而且我們在現實世界中看到的結果非常有希望。因此，我們相信，假設 SMEA 確實獲得批准，它實際上將推動額外的市場成長，這最終將使我們作為該領域的領導者從中受益。

But I kind of final point, this is a specialty market that can support multiple products being in it. It then comes down to things like profile, which we have a great profile order of entry. We're first and have built this market. So we feel extremely confident in our ability to grow through any of the potential competitive entrants.

但我最後要說的是，這是一個可以支援多種產品的專業市場。然後它歸結為諸如個人資料之類的東西，我們有一個很好的個人資料進入順序。我們是第一家並已建立這個市場的公司。因此，我們對自己在與任何潛在競爭對手的競爭中取得發展的能力充滿信心。

So maybe, Michael, why don't I turn it over to you for the first part of the question?

那麼，邁克爾，我為什麼不把問題的第一部分交給你呢？

It's a great question. The Literature supports that when compared to baseline, a change in liver stiffness, a reduction in liver stiffness of five kilopascals or 25% in a comparable population, compensated cirrhosis is highly predictive for a reduction in fibrosis of one stage or more. So that's how we would look at these stages. We had about over 50% of our patients achieved that 25% reduction threshold.

這是一個很好的問題。文獻支持，與基線相比，肝硬度的變化，在可比較人群中肝臟硬度降低 5 千帕或 25％，代償性肝硬化可高度預測一級或以上纖維化的減少。這就是我們看待這些階段的方式。我們大約有超過 50% 的患者達到了 25% 的減少閾值。

Thank you, Liisa. Marvin, next question, please.

謝謝你，Liisa。馬文，請問下一個問題。

David Lebowitz, Citi Investment Research.

大衛‧勒博維茨（David Lebowitz），花旗投資研究部。

Thank you very much for taking my question. On the emergence of GLP-1, once they actually get approved and they can officially get reimbursed for MASH, how do you think that impacts usage vis a vis Rezdiffra in terms of combination? Do you think it makes it an easier discussion with payers, or do you think it makes it a harder discussion?

非常感謝您回答我的問題。關於 GLP-1 的出現，一旦它們真正獲得批准並且可以正式獲得 MASH 報銷，您認為這對 Rezdiffra 的組合使用有何影響？您認為這會讓與付款人的討論變得更容易，還是會讓討論變得更加困難？

Oh thanks, David. Looking at the data now and we've reported this before, that about 25% of Rezdiffra patients are already on a GLP-1 and when you look at who's already been exposed, it's about 50%. So they're already there being used for the comorbidities and look as a company. We are supportive of GLP-1 being used in comorbidities that can benefit patients such as obesity.

哦，謝謝，大衛。從目前的數據來看，我們之前也曾報告過，大約 25% 的 Rezdiffra 患者已經在使用 GLP-1，而如果查看已經接觸過該藥物的患者，則該比例約為 50%。因此，它們已經被用來治療合併症，看起來像一家公司。我們支持 GLP-1 用於治療肥胖症等可使患者受益的合併症。

So they're already there, that's the thing, and they've been there for 14 years. Now we know that at the lower doses, they clearly haven't had an impact on NASH because we're still seeing. A high diagnosis rates and so forth. So that they haven't, they can only solve it at the highest doses, and we know that that takes time and that there are challenges with tolerability. So we really, as we think about the GLP-1 coming in it's going to be a market expansion focus that they're going to have.

事實是，他們已經在那裡了，而且他們已經在那裡待了 14 年。現在我們知道，在較低劑量下，它們顯然沒有對 NASH 產生影響，因為我們仍然可以看到。診斷率高等等。因此，他們只能透過最高劑量來解決這個問題，我們知道這需要時間，並且有耐受性的挑戰。因此，當我們考慮 GLP-1 的推出時，我們確實會將其作為市場擴張的重點。

And we believe that given their profile and our profile, those patients are going to ultimately, the majority of them anyways, are going to end up on a Rezdiffra anyways because they're going to still need to treat the problem that they're having, which is now a really severe liver disease, right? This is not a mild disease. We hear from patients all the time their stories of family members that have died as a result and how grateful they are to have an opportunity to avoid that.

我們相信，考慮到他們和我們的情況，這些患者最終，無論如何，大多數患者最終都會使用 Rezdiffra，因為他們仍然需要治療他們所遇到的問題，也就是現在的非常嚴重的肝病，對嗎？這不是一種輕微的疾病。我們常聽到患者講述家人因此去世的故事，以及他們多麼感激有機會避免這樣的事情。

So we just, we are fully planning on GLP-1 being here. We expect that with our profile we continue to be the product of choice in the space and as it relates to, I think you alluded to from a kind of an even payer dynamic perspective. We with our profile and with the benefit that we've shown to preventing downstream costs, we think that we have an attractive profile. We've had extremely productive conversations with payers, and we believe that will remain the case with or without the introduction of GLP-1. Thank you very much.

因此，我們正在全力規劃 GLP-1 的應用。我們期望，憑藉我們的產品形象，我們將繼續成為該領域的首選產品，就此而言，我認為您是從某種均衡付款人動態的角度提到的。憑藉我們的概況以及我們在防止下游成本方面所展現出的優勢，我們認為我們擁有頗具吸引力的概況。我們與付款人進行了非常富有成效的對話，我們相信，無論是否引入 GLP-1，情況仍將如此。非常感謝。

Marvin, next question.

馬文，下一個問題。

Andy Chen, Wolfe Research.

安迪陳（Andy Chen），沃爾夫研究公司（Wolfe Research）。

Hey, thank you for taking the question and congrats on the new data. I'm just curious if you can talk about the Europe launch in the second half. So I believe the European regulators, they may be less receptive to your US pricing. Can you talk about the unique challenges and opportunities there? Have you crafted a strategy to win there in that geography? Just curious if you can share some color there. Thank you.

嘿，感謝您回答這個問題，並祝賀您獲得新數據。我只是好奇您是否可以談談下半年在歐洲的發表會。因此我相信歐洲監管機構可能不太願意接受你們的美國定價。您能談談那裡獨特的挑戰和機會嗎？您是否已製定在該地區取勝的策略？只是好奇你是否可以分享一些顏色。謝謝。

Thanks, Andy. I mean, look, man, remember, as we think about Europe, it's not Europe overall, it's going to be a country-by-country review, and we will be extremely disciplined and we have an objective of within two to three years to be positive contribution in any country that we launch in. Obviously, a key piece of that is going to be the pricing.

謝謝，安迪。我的意思是，夥計，記住，當我們考慮歐洲時，它不是整個歐洲，而是一個逐個國家的審查，我們將非常嚴格，我們的目標是在兩到三年內對我們開展業務的任何國家做出積極貢獻。顯然，其中一個關鍵因素就是定價。

We think from an [EPI] perspective there are patients there, the unmet need is there, and that tends to as a Europe overall kind of approximate US patient numbers. Now it's on the regulators aren't obviously involved in the pricing discussion as you go country-by-country, talk to HTAs, et cetera. One of the things that I have found in previous launches is that if you have an innovative product that provides value, that there is a recognition of that value in Europe.

我們認為，從 [EPI] 的角度來看，那裡有患者，有未滿足的需求，而且歐洲的整體患者數量與美國的患者數量大致相同。現在，監管機構顯然沒有參與到定價討論中，因為你要逐個國家地與 HTA 進行談判，等等。我在以往的發表會上發現，如果你有一個能夠提供價值的創新產品，那麼歐洲就會認可它的價值。

Clearly, we'll be having discussions with each of the countries and be making our argument as to the value of the product. Fortunately, we have really great data, and we think that we will ultimately be able to support favorable pricing within Europe. However, as I said, we will be making decisions on a country-by-country basis, and we will pursue the countries where we believe the value of risk differ is recognized.

顯然，我們將與各國進行討論，並就產品的價值提出論點。幸運的是，我們擁有非常好的數據，我們認為最終我們將能夠支援歐洲境內的優惠定價。然而，正如我所說的，我們將根據每個國家的具體情況做出決定，並且我們將追求那些我們認為風險價值不同的國家。

Thanks, Andy. Marvin, next question, please.

謝謝，安迪。馬文，請問下一個問題。

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

Good morning, guys. Thanks for taking the question. Just following up on that though, can you talk a little more to the health technology assessment, algorithms that you are preparing to face, what parts of the data set that you've generated so far? Derive value that the national plans have either in writing or in meetings indicated they're willing to pay for.

大家早安。感謝您回答這個問題。不過，順便問一下，您能否再多談談您準備面對的健康科技評估、演算法，以及您迄今為止產生了資料集的哪些部分？得出國家計劃以書面或會議形式表明願意支付的價值。

And then just a quick follow up on the safety of the F4 open label data set that you presented today. Just given, even with compensated patients they're more fragile KOL focus has been on things like, hypoglycemia and live events. Can you give us the outlines of safety?

然後，我們來快速跟進您今天展示的 F4 開放標籤資料集的安全性。剛才說過，即使是得到補償的患者，他們的脆弱性也更大，KOL 的關注點一直集中在低血糖和現場事件等方面。您能為我們概括一下安全性嗎？

So first of all, with discussions in Europe with the [HTA], I mean, look, as there's a very formal process that you go through in each of the countries, you prepare your value dossier and you know we're at various stages of that depending on the country. But again, a lot of this, a lot of the evaluation looks at are you offsetting downstream costs, et cetera.

因此首先，關於在歐洲與 [HTA] 進行討論，我的意思是，你看，在每個國家你都要經歷一個非常正式的流程，你要準備你的價值檔案，而且你知道我們處於不同的階段，這取決於不同的國家。但同樣，許多評估都著眼於是否抵銷了下游成本等等。

I mean, I take you back to our ICER analysis which showed Rezdiffra tipper to be a very cost-effective therapy. So again they use slightly different tools in each country, but we will be, a part of that process, and we feel that the merits, the severity of the disease and the merits of the product really do stand on their own and you know we're looking forward to, I think, productive discussions that we'll have with each of those entities.

我的意思是，我回顧一下我們的 ICER 分析，該分析表明 Rezdiffra tipper 是一種非常具有成本效益的治療方法。因此，每個國家使用的工具略有不同，但我們將參與這個過程，我們認為，這種疾病的優點、嚴重程度以及產品的優點確實是獨立的，我們期待與每個實體進行富有成效的討論。

Maybe Michael, do you want to comment briefly on the second question?

也許邁克爾，你想對第二個問題簡單評論一下嗎？

Yes, It's an important question. So the same study, of course, included patients in other arms that had lower degrees of fibrosis, and the [AE], the type and frequency was comparable between patients with F4C and non-cirrhotic disease. It's a good question. Good.

是的，這是一個重要的問題。因此，同一項研究當然也包括了其他組別纖維化程度較低的患者，且 F4C 患者和非肝硬化患者的 [AE]、類型和頻率是相當的。這是個好問題。好的。

Thanks, Ritu. Next question please, Marvin.

謝謝，Ritu。馬文，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。

Hi, good morning and thank you so much for taking my questions. So maybe, Bill, you previously talked about, GI drugs being a little bit slower to adopt, but maybe if you can talk about the latest trends there, what you're seeing in terms of the GI's versus hepatologist, for a different. Thank you.

大家好，早安，非常感謝您回答我的問題。所以也許，比爾，你之前談過，胃腸道藥物的採用速度有點慢，但也許你可以談談那裡的最新趨勢，從胃腸道藥物和肝病學家的角度來看，你看到了什麼不同。謝謝。

Great. Thanks for the question. Look, we're predominantly focused on hepatologists and gastroenterologists. If you just look at the numbers of those specialists, there's less than 1,000 hepatologists. So when we start talking about targeting 14,000 prescribers, the overwhelming majority are gastroenterologists.

偉大的。謝謝你的提問。你看，我們主要關注肝病學家和胃腸病學家。如果只看專家的數量，肝病專家還不到 1,000 名。因此，當我們開始談論針對 14,000 名開處方者時，絕大多數都是胃腸病學家。

So on the backs of the gastroenterologists, we've really seen this really strong performance to date. So when we talked about them coming on a little bit slower, it was a little bit more of the time that it takes to kind of wire their practice, they, it's not a disease that they had been treating. So they had to hire staff in some cases if they wanted access to NITs and wanted to have their own NIT internally.

因此，在胃腸病學家的支持下，我們迄今為止確實看到了這種非常強勁的表現。因此，當我們談到他們的進展有點慢時，他們需要更多的時間來進行他們的實踐，這不是他們一直在治療的疾病。因此，如果他們想要訪問 NIT 並希望在內部擁有自己的 NIT，在某些情況下他們必須僱用員工。

So that it's just those mechanics to create the pathway within their practice, but they, when they come on, and by that I mean the gastroenterologists I've been extremely happy with the way that they have adopted the product and as I said, just based upon the numbers they are really the driving force of the performance that we have seen and will likely see in the future.

因此，這些機制只是在他們的實踐中創造途徑，但是，當他們出現時，我指的是胃腸病學家，我對他們採用該產品的方式感到非常高興，正如我所說的，僅基於數字，他們確實是我們已經看到的並且可能在未來看到的表現的驅動力。

Clearly the hepatologists are, I would say and remain further ahead in most cases just because, the liver is what they are most familiar with they're more familiar with the disease and their practices are probably initially a little better suited, but I'm really happy with what we've seen. We've seen some of the big super groups come on and we've seen them go from, I would call more or less dabbling to full on NASH treatment and, literally treating hundreds and hundreds of patients with many more to come.

顯然，我想說，肝病專家在大多數情況下都處於領先地位，因為肝臟是他們最熟悉的領域，他們更熟悉這種疾病，而且他們的做法最初可能更適合，但我對我們所看到的結果感到非常高興。我們看到一些大型超級集團的出現，看到他們從或多或少涉足 NASH 治療到全面治療，已經治療了數百名患者，並且未來將治療更多的患者。

So we're feeling that the evolution of the prescriber base is in a really great place, and I would say that the breadth of prescription that we're seeing in this launch is a true standout and something which is a great prognosticator for future uptake of the product. You need prescribers. You need patients, and we have both of those.

因此，我們感覺處方基礎的發展非常好，而且我想說，我們在這次發布中看到的處方廣度是真正的突出表現，並且是未來產品應用的一個很好的預測指標。您需要開處方的醫生。你需要耐心，而我們兩者都有。

Good, thanks Prakhar. Marvin, it looks like we've got time for one more question, please.

很好，謝謝 Prakhar。馬文，看來我們還有時間再問一個問題。

Catherine Okoukoni, JMP Securities.

JMP 證券的凱瑟琳·奧庫科尼 (Catherine Okoukoni)。

Hi, this is Catherine on John. I just have a quick question about dose adjustment in the open label to year open label extension. Well, do all patients stay at the 80 milligrams dose and also just as far as patient retention goes, how many patients, how many [sciotics] started the study and how many continued through the two-year time point? Thank you.

你好，我是約翰的凱瑟琳。我只是想問一個簡單的問題，關於從開放標籤到一年開放標籤延長期間的劑量調整。那麼，所有患者是否都維持 80 毫克的劑量？就患者保留而言，有多少患者，有多少 [sciotics] 開始了這項研究，有多少人堅持了兩年的時間？謝謝。

Great. Michael, maybe I'll turn this one over to you for those specifics.

偉大的。邁克爾，也許我應該把這個問題交給你來了解這些細節。

The 122 patients entered the second year of the label extension, and these data are from 101 that had a second BCT.

這 122 名患者進入了標籤延長的第二年，這些數據來自 101 名接受第二次 BCT 的患者。

Thank you. And then stay on.

謝謝。然後繼續留下來。

[technical difficulty]

【技術難度】

Great. Thanks, Catherine. 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. So thanks for joining.

偉大的。謝謝，凱瑟琳。感謝大家今天的時間和關注。我們的通話到此結束。大約兩小時後，我們的網站將提供該網路廣播的重播。感謝您的加入。

Ladies and gentlemen, thank you for your participation in today's conference. You may not disconnect. Have a wonderful day.

女士們、先生們，感謝大家參加今天的會議。您不能斷開連線。祝您有美好的一天。