Madrigal Pharmaceuticals Inc (MDGL) 2024 Q1 法說會逐字稿

Good day, and thank you for standing by, and welcome to Madrigal Pharmaceuticals first-quarter 2024 earnings conference call. (Operator Instructions) As a reminder, today's conference is being recorded. I would now like to introduce Ms. Tina Ventura, Chief Investor Relations Officer. Please go ahead.

美好的一天，感謝您的支持，歡迎參加 Madrigal Pharmaceuticals 2024 年第一季財報電話會議。（操作員指示）提醒一下，今天的會議正在錄製中。現在我想介紹一下首席投資者關係長蒂娜·文圖拉女士。請繼續。

Thank you, Lisa. Good morning, everyone, and thank you for joining us to discuss Madrigal's first quarter 2024 earnings call. We issued a press release this morning. There is also a supplementary slide deck that accompanies this webcast that will post immediately following the call on the Investor Relations section of our website.

謝謝你，麗莎。大家早安，感謝您加入我們討論 Madrigal 的 2024 年第一季財報電話會議。我們今天早上發布了一份新聞稿。本網路廣播還附帶一個補充幻燈片，該幻燈片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, who will provide prepared remarks, and then we'll take your questions. We're shooting to keep today's call to about 45 minutes. Please note, we'll be making certain forward-looking statements today, and 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.

今天與我通話的是執行長 Bill Sibold；財務長 Mardi Dier 將提供準備好的發言，然後我們將回答您的問題。我們力爭將今天的電話會議時間控制在 45 分鐘左右。請注意，我們今天將做出某些前瞻性聲明，我們建議您參閱我們向 SEC 提交的文件，以討論可能導致實際結果與前瞻性聲明不同的風險。

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

現在，我將把電話轉給比爾。

Well, Thanks, Tina. Good morning, and thanks to everyone for joining the call today. Before we begin, I wanted to take a moment to acknowledge Dr. Stephen Harrison, who passed away at the end of April, Becky and I attended his celebration of life last week, Steven was the leader in the field and a great partner with Madrigal has our principal investigator for the MAESTRO-NASH trial. He worked closely with Becky and had the same tenacity and determination to bring risks differ through clinical development and ultimately FDA approval as the first medicine approved for NASH.

嗯，謝謝，蒂娜。早安，感謝大家今天加入電話會議。在我們開始之前，我想花點時間向史蒂芬哈里森博士致意，他於四月底去世，貝基和我上週參加了他的生命慶祝活動，史蒂文是該領域的領導者，也是Madrigal的偉大合作夥伴我們有 MAESTRO-NASH 試驗的首席研究員。他與 Becky 密切合作，並具有同樣的堅韌和決心，通過臨床開發並最終獲得 FDA 批准，成為第一個批准用於 NASH 的藥物。

We're grateful for his years of dedication that advance this field and our thoughts go out to his family, friends and colleagues. I know that many of you listening to our call today is Stephen well. I'll now move to our earnings call and an update on the business. We are off to a terrific start in 2024 and have made substantial progress against our goal to establish Madrigal as the clear leader in NASH. We achieved US FDA approval on March 14. This followed the landmark publication of our phase MAESTRO-NASH trial in the New England Journal of Medicine following approval, our field teams were deployed and Madrigal patient support program was up and running.

我們感謝他多年來為推動這一領域的發展所做的奉獻，我們向他的家人、朋友和同事表示慰問。我知道今天收聽我們電話的許多人都是史蒂芬。我現在將開始我們的財報電話會議並介紹業務最新情況。我們在 2024 年有了一個良好的開端，並在實現將 Madrigal 打造成 NASH 領域明確領導者的目標方面取得了實質進展。我們於3月14日獲得美國FDA批准。在此之前，我們的 MAESTRO-NASH 階段試驗在獲得批准後在《新英格蘭醫學雜誌》上發表具有里程碑意義，我們的現場團隊已部署完畢，Madrigal 患者支持計劃也已啟動並運行。

In April, we started shipping product to our specialty pharmacy network, and most importantly, patients started receiving this Rezdiffra. From a supply perspective, we are confident in our ability to fully meet demand as we work to expand our leading position in NASH. We're also focused on maximizing the value and future growth of Rezdiffra. To that end, so far this year, we submitted Rezdiffra for approval in Europe. Our MAA was validated, and we expect a decision in the first half of 2025. We continued to advance the MAESTRNO-NASH outcomes trial and F2/F3 patients, and we have the potential to provide first in disease outcomes data years ahead of others. We continue to enroll our outcomes trial in NASH patients with cirrhosis to expand the eligible patient population, which has the potential to double the Rezdiffra opportunity.

四月份，我們開始將產品運送到我們的專業藥房網絡，最重要的是，患者開始接受這種 Rezdiffra。從供應角度來看，我們對完全滿足需求的能力充滿信心，因為我們正在努力擴大我們在 NASH 領域的領先地位。我們也致力於最大化 Rezdiffra 的價值和未來成長。為此，今年到目前為止，我們已提交 Rezdiffra 供歐洲批准。我們的 MAA 已得到驗證，我們預計將在 2025 年上半年做出決定。我們繼續推進 MAESTRNO-NASH 結果試驗和 F2/F3 患者，我們有潛力領先其他人數年提供第一的疾病結果數據。我們繼續在患有肝硬化的 NASH 患者中進行結果試驗，以擴大符合條件的患者群體，這有可能使 Rezdiffra 的機會增加一倍。

And finally, we raised $690 million in gross proceeds from our public offering. As of March 31, we had $1.1 billion in cash on our balance sheet, enabling us to fully resource the launch. So we've accomplished a great deal through the first quarter of this year and are laser focused on a successful US launch of Rezdiffra.

最後，我們透過公開發行籌集了 6.9 億美元的總收益。截至 3 月 31 日，我們的資產負債表上有 11 億美元現金，使我們能夠為此次發布提供充分的資源。因此，我們在今年第一季取得了巨大的成就，並專注於在美國成功推出 Rezdiffra。

You've heard my enthusiasm since I joined Madrigal about this opportunity, the clear unmet need, the product profile and the strong label. And my reason to believe has only been reinforced with the launch. I've been out in the field since approval, engaging with the community and the feedback has been overwhelmingly positive. My sample sizes and small.

自從我加入 Madrigal 以來，您已經聽到了我對這個機會、明確的未滿足需求、產品簡介和強大標籤的熱情。隨著產品的推出，我的信念更加堅定。自從獲得批准以來，我一直在現場，與社區互動，得到的回饋非常積極。我的樣本數又少。

I've met with more than 100 prescribers at their offices in the field with our reps at our speaker trainings and at conferences. And as I think back on the launches that I've led in my career, I haven't seen this level of anticipated for any new drug launch that I've been part of. I'm more confident today that Rezdiffra will be a significant success for Madrigal and especially for the patients that have been waiting for this therapy. Much of the positive feedback has been about the Rezdiffra product profile.

我在現場辦公室與我們的代表在演講培訓和會議上會見了 100 多名處方醫生。當我回想起我在職業生涯中領導的上市活動時，我還沒有看到我參與過的任何新藥上市達到如此預期的水平。今天，我更有信心 Rezdiffra 將為 Madrigal 帶來巨大成功，尤其是對於一直在等待這種療法的患者。大部分正面回饋都與 Rezdiffra 產品簡介有關。

On slide 4, as we discussed on our approval call, where as Rezdiffra has a the best case label that positions it as a foundational therapy in NASH. We have a great indication statement. Rezdiffra is indicated in NASH patients with moderate to advanced fibrosis, exactly the patients we studied in our trials. There is no biopsy requirement. It's a liver-directed oral once daily pill with simple weight-based dosing. And there are no contraindications, no box warning and no monitoring requirements beyond standard of care.

在幻燈片 4 上，正如我們在批准電話會議上所討論的那樣，Rezdiffra 擁有最佳案例標籤，將其定位為 NASH 的基礎療法。我們有一個很好的指示聲明。Rezdiffra 適用於中度至晚期纖維化的 NASH 患者，這正是我們在試驗中研究的患者。沒有活檢要求。它是一種針對肝臟的口服藥，每日一次，劑量簡單，劑量基於體重。而且沒有禁忌症、沒有方框警告，也沒有超出護理標準的監測要求。

We have the enviable position of being the first to market in NASH, which we believe will give us a strong and sustainable competitive advantage first to market medicines usually achieve and maintain higher market share versus subsequent entrants. We intend to take full advantage of this opportunity, positioning ourselves for long-term leadership as we're first to market with the product profile. That's incredibly strong as you can see on slide 5, it's a liver-directed medicine that has set a high bar for efficacy. The only medicine to achieve statistically significant results on both endpoints in phase 3, NASH resolution and fibrosis improvement.

我們擁有成為NASH 市場第一家的令人羨慕的地位，我們相信這將為我們帶來強大且可持續的競爭優勢，首先上市的藥品通常會比後來的進入者獲得併保持更高的市場份額。我們打算充分利用這個機會，將自己定位為長期領導者，因為我們是第一個將產品簡介推向市場的人。正如您在幻燈片 5 中看到的那樣，這是一種令人難以置信的強大藥物，它是一種針對肝臟的藥物，為療效設定了很高的標準。唯一在第 3 階段的兩個終點（NASH 消退和纖維化改善）上取得統計學顯著結果的藥物。

Importantly, Rezdiffra stops or improves fibrosis in more than 80% of patients after only two weeks or one year of therapy. It's well-tolerated with safety data in more than 2,000 patients. And we've resourced the launch the right way to build toward our aspirations for peak sales. So while Madrigal the company might be launching its first ever medicine, our commercial and medical leaders are veterans. Each has more than 25 years of industry experience and have launched dozens of blockbuster medicines.

重要的是，僅治療兩週或一年後，Rezdiffra 就可以阻止或改善超過 80% 的患者的纖維化。根據超過 2,000 名患者的安全數據，該藥物具有良好的耐受性。我們以正確的方式為此次發布提供了資源，以實現我們對高峰銷售的渴望。因此，雖然 Madrigal 公司可能會推出首款藥物，但我們的商業和醫療領導者都是退伍軍人。每位都擁有超過25年的行業經驗，並推出過數十種重磅藥物。

Our field team averages nearly 20 years of experience with strong hepatologists and gastroenterologists relationships we have the team the talent and the resources to make this launch a success. With this product profile and first-to-market advantage as seen on slide 6, we believe Rezdiffra will be positioned as the foundational therapy for NASH patients with F2, F3 fibrosis. Now as the only FDA-approved medicine for NASH and for many years to come, the unmet need is significant and it's urgent There are 315,000 F2, F3 patients diagnosed today under care of the specialists we are calling on who need a liver-directed, well-tolerated therapy like Rezdiffra that will stop or reverse their disease.

我們的現場團隊平均擁有近 20 年的經驗，與肝病學家和胃腸病學家關係密切，我們的團隊擁有人才和資源，可以使此次發布取得成功。憑藉幻燈片 6 所示的產品概況和率先上市的優勢，我們相信 Rezdiffra 將被定位為 F2、F3 纖維化 NASH 患者的基礎療法。現在，作為FDA 批准的唯一一種治療NASH 的藥物，並且在未來的許多年裡，未滿足的需求是巨大且緊迫的。診斷出來，他們需要肝臟導向、像 Rezdiffra 這樣耐受性良好的療法可以阻止或逆轉他們的疾病。

These patients are on the cusp of cirrhosis are at a 10 to 17 times higher risk of liver related mortality and don't have time to wait our trial and F4 patients with well compensated cirrhosis is underway to expand Rezdiffra indication, so even more severe patients. Let's move to Rezdiffra launch progress on slide 7. As we discussed on our approval call in March, over the first 12 months of launch, we are focused on acquiring the system. With a first in disease medicine, it's about spending the necessary time upfront with physicians and their office staff to create the care pathways for patients. This work builds the strong foundation needed to support the future volume of prescriptions we expect.

這些處於肝硬化邊緣的患者的肝臟相關死亡風險高出 10 至 17 倍，他們沒有時間等待我們的試驗，並且代償性良好的 F4 肝硬化患者正在進行擴大 Rezdiffra 適應症，因此甚至更嚴重的患者。讓我們轉到幻燈片 7 上的 Rezdiffra 發布進度。正如我們在 3 月的批准電話會議上討論的那樣，在發布的前 12 個月裡，我們的重點是獲取該系統。作為疾病醫學領域的首創，它需要預先花費必要的時間與醫生及其辦公室工作人員一起為患者創建護理途徑。這項工作為支持我們預期的未來處方量奠定了堅實的基礎。

We are making great progress Rezdiffra has been added to the compendia and subsequently to many electronic medical records systems so that it can be more efficiently prescribed our field team was trained on the Rezdiffra label post approval, enabling them to start calling on their target positions. Our teams are educating providers on the disease and Rezdiffra, as well as the operational aspects of prescribing and ensuring access for patients. This often takes additional calls upfront to familiarize all key staff at the practice. With these details and address their questions. This process will become more and more established as we progress through the year, particularly as commercial payers continue to make Rezdiffra coverage decisions. And as physician offices become educated on those payer requirements.

我們正在取得巨大進展Rezdiffra 已被添加到藥典中，隨後被添加到許多電子病歷系統中，以便可以更有效地制定處方，我們的現場團隊在批准後接受了Rezdiffra 標籤的培訓，使他們能夠開始調用其目標位置。我們的團隊正在向醫療服務提供者提供疾病和 Rezdiffra 的教育，以及處方和確保患者獲得處方的操作方面的知識。這通常需要預先進行額外的通話，以使診所的所有關鍵員工都熟悉。有了這些細節並解決他們的問題。隨著今年的進展，這項流程將變得越來越成熟，特別是隨著商業付款人繼續做出 Rezdiffra 核保決定。隨著醫生辦公室了解這些付款人的要求。

And we expect full Medicare coverage in place beginning early next year, which is another steps towards having patients flow more efficiently through the offices so to evaluate our early progress, we are measuring a number of leading indicators as seen on slide 8, it's about targeting the right doctors with the right level of frequency to build the breadth and depth of prescribers needed to achieve our aspiration. The metrics so far are very encouraging, especially since we're less than a month out from when product was shipped we are driving breadth and depth. Our sales teams has already reached more than 80% of their top position targets. There is remarkable interest and our reps are getting access to physicians that typically don't see reps, they are engaging with the staff to ensure that many of those wiring the system activities I just discussed are completed to allow an office to more efficiently prescribers Rezdiffra.

我們預計明年初開始實行全面的醫療保險覆蓋，這是讓患者更有效地在辦公室流動的又一步驟，因此為了評估我們的早期進展，我們正在衡量幻燈片8 中所示的一些領先指標，這是關於目標合適的醫生以適當的頻率來建立實現我們願望所需的處方人員的廣度和深度。到目前為止的指標非常令人鼓舞，特別是因為我們距離產品發貨還有不到一個月的時間，我們正在推動廣度和深度。我們的銷售團隊已經達到了 80% 以上的頂級位置目標。人們對此表現出極大的興趣，我們的代表正在接觸通常看不到代表的醫生，他們正在與工作人員進行接觸，以確保我剛才討論的許多連接系統的活動都已完成，從而使辦公室能夠更有效地為處方者提供處方Rezdiffra 。

And as payers increased their coverage of Rezdiffra and physician offices build their understanding of the coverage requirements, the volume and pace of prescriptions will increase. We are targeting the right physicians, 75% of prescriptions to date are coming from our top targets. We are on our efforts from the top down as well as from the bottom up. Wiring the system extends beyond individual practices to the large health systems, the IDNs GI super groups, the really large systems across the country. We have an experienced team that has strong relationships across these key accounts. And they are all interested in establishing care pathways for NASH patients that are at various stages of implementation.

隨著付款人擴大 Rezdiffra 的承保範圍以及醫生辦公室對承保要求的了解，處方的數量和速度將會增加。我們的目標是合適的醫生，迄今為止 75% 的處方來自我們的首要目標。我們的努力是自上而下，也是自下而上。連結系統超越個人實踐，延伸至大型衛生系統、IDN GI 超級團體、全國真正的大型系統。我們擁有一支經驗豐富的團隊，在這些關鍵客戶之間建立了牢固的關係。他們都對為處於不同實施階段的 NASH 患者建立護理途徑感興趣。

This means that a physician through their EMR system has a clear guideline to identify, diagnose and treat their NASH patients with moderate to advanced fibrosis. Importantly, these pathways filter down to the associated individual practices, another proof point that not just at a practice level, but at a system level, the launch is progressing well. We are educating health care providers on Rezdiffra to drive clinical conviction for the medicine. We felt speaker training meetings, national broadcast, symposia at conferences and local programs across the country. There is phenomenal interest to attend these meetings more than 1,200 prescribers attended the National broadcasts of very high turnout compared to industry benchmarks. We are engaging with payers.

這意味著醫生可以透過 EMR 系統獲得明確的指南來識別、診斷和治療患有中度至晚期纖維化的 NASH 患者。重要的是，這些途徑滲透到相關的個人實踐，這是另一個證明，不僅在實踐層面，而且在系統層面，發布進展順利。我們正在對醫療保健提供者進行 Rezdiffra 教育，以推動對該藥物的臨床信念。我們感受到了全國各地的演講者培訓會議、全國廣播、會議研討會和地方節目。人們對參加這些會議表現出極大的興趣，超過 1,200 名處方醫生參加了全國廣播，與行業基準相比，參與人數非常高。我們正在與付款人接觸。

To that end coverage is in place for 30% of commercial lives tracking right in line with our goal to achieve 80% by year end. Our reimbursement team continues to have active dialogue with payers with a focus on the comprehensive Rezdiffra clinical dataset and the use of noninvasive tests or NITs as a means for patient identification and monitoring, we expect many of the larger plans to begin to cover Rezdiffra in the months ahead as they work through the typical P&T committee processes and determine prior authorization criteria. The criteria we're discussing with payers and what we are seeing in early coverage are generally aligned with our label.

為此，我們已涵蓋 30% 的商業生活，這與我們在年底實現 80% 的目標是一致的。我們的報銷團隊繼續與付款人進行積極對話，重點關注全面的 Rezdiffra 臨床數據集以及使用非侵入性測試或 NIT 作為患者識別和監測的手段，我們預計許多較大的計劃將開始涵蓋 Rezdiffra未來幾個月，他們將完成典型的P&T 委員會流程並確定事先授權標準。我們與付款人討論的標準以及我們在早期承保中看到的內容通常與我們的標籤一致。

We also expect medical societies such as the ASLD to publish updated NASH treatment guidelines that will include Rezdiffra and help reinforce for both physicians and payers, how and when to use the medicine. Of course, we know you're interested in patient numbers and we'll share more details on patients on our next quarterly call. What we've seen to date is really encouraging. Patient growth is accelerating, which correlates well with the leading indicators we just described and the progress our team is making as we continue to call on more prescribers, spent time with the staff and activate more accounts.

我們還期望 ASLD 等醫學協會發布更新的 NASH 治療指南，其中將包括 Rezdiffra，並幫助醫生和付款人加強如何以及何時使用該藥物的資訊。當然，我們知道您對患者數量感興趣，我們將在下一次季度電話會議上分享有關患者的更多詳細資訊。迄今為止我們所看到的確實令人鼓舞。患者數量正在加速增長，這與我們剛才描述的領先指標以及我們的團隊正在取得的進展密切相關，因為我們繼續呼籲更多的處方醫生，花時間與工作人員在一起並激活更多的帳戶。

The positive momentum we're seeing is also confirmed by market research as noted on slide 9. 90% of physicians familiar with Rezdiffra believe it offers high clinical utility. More than 80% are enthusiastic about Rezdiffra, final label and cited its efficacy. No biopsy requirement and simple dosing as the top three reasons. And in our most recent wave of research with our top physician targets, 78% of respondents said they have prescribed Rezdiffra within the next one to two months.

我們看到的正面動力也得到了市場研究的證實，如幻燈片 9 所示。超過 80% 的人對 Rezdiffra、最終標籤充滿熱情，並引用了其功效。不需要活檢和簡單的給藥是最主要的三個原因。在我們最近一波針對頂尖醫生目標的研究中，78% 的受訪者表示他們在未來一到兩個月內服用了 Rezdiffra。

Spherix, an independent market research firm reported similar findings with more than 75% of providers expecting to prescribe Rezdiffra within six months of launch. We're engaging diagnose patients in a very targeted way as well. Our direct to patient disease education campaign on slide 10 has been underway for a little over a year now to provide patients with NASH information and resources. Post approval, the team is now focused on activating those patients to ask their doctor about Rezdiffra patients are engaged and 50% of those who registered on the site have downloaded the doctor discussion guide.

獨立市場研究公司 Spherix 報告了類似的調查結果，超過 75% 的供應商預計在推出後六個月內開出 Rezdiffra 處方。我們也以非常有針對性的方式讓患者參與診斷。我們在幻燈片 10 上直接針對患者的疾病教育活動已經開展了一年多一點，旨在為患者提供 NASH 資訊和資源。批准後，該團隊現在的重點是激活這些患者向他們的醫生詢問 Rezdiffra 患者的參與情況，並且在該網站註冊的患者中有 50% 已經下載了醫生討論指南。

In addition to the US launch of Rezdiffra, we are making progress in other areas that will extend our leadership, including maintaining our scientific presence at key medical meetings.

除了在美國推出 Rezdiffra 之外，我們還在其他領域取得了進展，這將擴大我們的領導地位，包括在重要的醫學會議上保持我們的科學地位。

On slide 11, you can see we are building on our strong HEOR foundation with additional publications at the recent AMCP. scientific meeting, we received recognition for our abstract that showed NASH patients were progressing even more rapidly than we thought to advanced liver states like cirrhosis, liver cancer, liver transplant and death. In fact, of those that progressed 80% progressed directly to decompensated cirrhosis instead of cirrhosis as one would expect. The results are particularly impactful because this data is from an Optum database, which includes commercially insured patients that are likely receiving better care and are of higher socioeconomic status compared to NASH patients and other care sites, the annual cost per patient that progressed was twofold higher when compared to those that didn't with the cost gap increasing overtime.

在投影片 11 上，您可以看到我們正在建立強大的 HEOR 基礎，並在最近的 AMCP 上發表了更多出版物。在科學會議上，我們的摘要獲得了認可，該摘要顯示 NASH 患者的進展速度比我們想像的還要快，發展為肝硬化、肝癌、肝移植和死亡等晚期肝臟疾病。事實上，在進展的患者中，80% 直接進展為失代償性肝硬化，而不是像人們預期的那樣發展為肝硬化。結果特別有影響力，因為該數據來自Optum 資料庫，其中包括商業保險患者，與NASH 患者和其他護理機構相比，這些患者可能接受更好的護理，並且社會經濟地位更高，每位患者的年度費用要高出兩倍與那些沒有的企業相比，隨著時間的推移，成本差距越來越大。

The conclusion therapies like Rezdiffra that help stop or improve fibrosis may help alleviate the financial burden of NASH. We will also have a strong presence at the upcoming DDW meeting in DC later this month. And at the EASL Congress in Milan in June where 11 abstracts have been accepted. As I referenced at the start of the call, we look to further differentiate and expand the Rezdiffra label with data from the outcomes portion of our pivotal phase 3, the MAESTRO-NASH trial and our MAESTRO-NASH outcomes trial in well compensated cirrhosis or F4 patients.

Rezdiffra 等有助於阻止或改善纖維化的結論療法可能有助於減輕 NASH 的經濟負擔。我們也將強勢出席本月稍晚在華盛頓特區舉行的 DDW 會議。6 月在米蘭舉行的 EASL 大會上，有 11 份摘要被接受。正如我在電話會議開始時提到的，我們希望利用關鍵 3 期、MAESTRO-NASH 試驗和補償良好的肝硬化或 F4 的 MAESTRO-NASH 結果試驗的結果部分的數據，進一步區分和擴展 Rezdiffra 標籤。 。

As noted on slide 12. These studies will allow us to generate outcomes data at years in advance of any potential competitor outcomes data, expand our indication and further extend our leadership in NASH. MAESTRO-NASH outcomes is an event-driven trial enrolling approximately 700 F4 patients with a composite primary endpoints that assesses conversion to decompensated cirrhosis. There is an even higher urgency to treat F4 patients because of their elevated risk of developing serious and costly liver-related complications.

如投影片 12 所示。這些研究將使我們能夠比任何潛在競爭對手的結果數據提前數年產生結果數據，擴大我們的適應症並進一步擴大我們在 NASH 領域的領導地位。MAESTRO-NASH 結果是一項事件驅動的試驗，招募了大約 700 名 F4 患者，其複合主要終點用於評估向失代償性肝硬化的轉化。治療 F4 患者的緊迫性更高，因為他們發生嚴重且昂貴的肝臟相關併發症的風險較高。

Data from this study is anticipated in the 2026, 2027 time frame and an indication in the F4 patient population could double the opportunity for Rezdiffra in the US. The potential for MAESTRO-NASH outcomes trial is supported by data. We've shown to date in 180 patients with compensated NASH cirrhosis study in the phase 3 MAESTRO-NAFLD-1 and MAESTRO-NAFLD-OLE trials.

這項研究的數據預計在 2026 年和 2027 年的時間範圍內得出，F4 患者群體中的跡象可能會使 Rezdiffra 在美國的機會增加一倍。MAESTRO-NASH 結果試驗的潛力得到了數據的支持。迄今為止，我們已經在 3 期 MAESTRO-NAFLD-1 和 MAESTRO-NAFLD-OLE 試驗中對 180 名代償性 NASH 肝硬化患者進行了研究。

Before passing it over to Mardi to cover the financials. Let me wrap up with a brief summary of the launch. It's really remarkable how much we've accomplished in such a short period of time. We were able to achieve FDA approval in March with a best case label and a first to market medicine. We had product in the channel in April, and our teams are out in the field executing. The feedback we're hearing from our customers is overwhelmingly positive. There is high interest. They have the patients and their prescribing Rezdiffra. I'm really encouraged by the early progress so far and even more confident today in the blockbuster potential of this medicine.

在將其交給 Mardi 負責財務之前。讓我對此次發布做一個簡短的總結。我們在如此短的時間內所取得的成就確實令人驚嘆。我們於 3 月獲得了 FDA 的批准，並獲得了最佳案例標籤和第一個上市的藥物。我們四月在通路中有產品，我們的團隊正在現場執行。我們從客戶那裡聽到的回饋絕大多數是正面的。有很高的興趣。他們有病人和他們開的 Rezdiffra 處方。迄今為止的早期進展讓我感到非常鼓舞，今天我對這種藥物的巨大潛力更加充滿信心。

I'll now turn the call over to Mardi.

我現在將把電話轉給 Mardi。

Thank you, Bill. The press release we issued earlier today contains our full financial results. So I'll provide a few highlights for the first quarter of 2024. As we discussed on the launch call, initial Rezdiffra shipments to our specialty distribution network began in April, so we recorded no Rezdiffra revenue for the first quarter. As Bill discussed, there is good momentum with the launch and given the need to wire the system early on and our expectation for it to take 60 days on average to fill a prescription through the first six months of launch, we expect revenue to be weighted to the back half of the year with modest sales in the second quarter. We are still in the early days of the Rezdiffra launch, and we look forward to sharing more about our progress in the coming quarter.

謝謝你，比爾。我們今天早些時候發布的新聞稿包含我們的完整財務表現。因此，我將提供 2024 年第一季的一些亮點。正如我們在發布會上討論的那樣，最初的 Rezdiffra 發貨到我們的專業分銷網絡於 4 月開始，因此我們第一季沒有記錄 Rezdiffra 收入。正如 Bill 所討論的，該產品的推出勢頭良好，考慮到需要儘早連接系統，並且我們預計在推出的前六個月內平均需要 60 天才能配藥，我們預計收入將被加權到今年下半年，第二季度的銷售量不大。我們仍處於 Rezdiffra 發布的早期階段，我們期待在下個季度分享更多有關我們進展的資訊。

R&D expenses for the first quarter 2024, were $71 million compared to $62 million for the first quarter of 2023. This increase was related to timing of manufacturing headcount, growth activities and articles. There's group and stock compensation. We would anticipate a relatively steady level of R&D expense for the rest of the year. SG&A expenses were $81 million compared to $16 million for the first quarter of 2023 and an increase sequentially from $47 million in the fourth quarter of 2023. This significant increase is as expected due to the scale of our commercial operations in anticipation of the March FDA approval Rezdiffra. We hired the field team in January and February. So the second quarter will be more reflective of a full quarter of spend.

2024 年第一季的研發費用為 7,100 萬美元，而 2023 年第一季的研發費用為 6,200 萬美元。這一增長與製造人員數量、增長活動和文章的時間表有關。有團體補償和股票補償。我們預計今年剩餘時間的研發費用將維持相對穩定的水準。SG&A 費用為 8,100 萬美元，而 2023 年第一季為 1,600 萬美元，比 2023 年第四季的 4,700 萬美元有所增加。這一顯著成長符合預期，因為我們的商業營運規模預計將在 3 月 FDA 批准 Rezdiffra。我們在一月和二月聘請了現場團隊。因此，第二季將更能反映整個季度的支出。

Moving to our balance sheet, we announced an oversubscribed public offering that grossed $690 million for the company and further strengthened our financial position. Our net cash balance as of March 31, 2024, stood at $1.1 billion. Note that the green shift from the offering was executed in early April, and therefore, an additional $86 million in net cash will be recognized in the second quarter. We are fully resourced to support a successful multiyear launch of Rezdiffra.

轉向我們的資產負債表，我們宣布了超額認購的公開發行，為該公司籌集了 6.9 億美元的資金，進一步增強了我們的財務狀況。截至 2024 年 3 月 31 日，我們的淨現金餘額為 11 億美元。請注意，此次發行的綠色轉變是在 4 月初執行的，因此，第二季將確認額外 8,600 萬美元的淨現金。我們擁有充足的資源來支持 Rezdiffra 的多年成功推出。

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

現在我將把電話轉回給蒂娜。

Thanks, Mardi. Let's move into the Q&A portion of the call. We'd ask that you limit your questions to one as our goal is to wrap up the call by 8:45.

謝謝，瑪迪。讓我們進入通話的問答部分。我們要求您將問題限制為一個，因為我們的目標是在 8:45 之前結束通話。

So Lisa, please provide instructions for the Q&A session.

麗莎，請提供問答環節的說明。

(Operator Instructions) Yasmeen Rahimi, Piper Sandler.

（操作說明）Yasmeen Rahimi、Piper Sandler。

Thank you for the updates. And maybe before I go further with my question, want to express my sincere condolences to you and the entire team of Madrigal offer Dr. Stephen Harrison, who will be greatly missed what he has done for this space.

感謝您的更新。也許在我進一步提出問題之前，我想向您和 Madrigal 的整個團隊向 Stephen Harrison 博士表示誠摯的哀悼，他將非常懷念他為這個空間所做的一切。

On my question, I guess, team would be wonderful if you could maybe highlight whether there is heterogeneity in the payers' discussions? Or is it seems that majority of the payers are aligned in terms of their requirements of just simple blood based test. So if you could just talk about how many payers you have spoken with the heterogeneity, et cetera, and I'll move back into the queue.

關於我的問題，我想，如果您能強調付款人的討論是否存在異質性，團隊會很棒？或者似乎大多數付款人都同意簡單的血液檢測的要求。因此，如果您能談談您與多少付款人進行了異質性交談，等等，我將回到隊列中。

Thanks for the question, and thanks for the comments about Stephen. Look at regarding the payer discussions, first of all, I think it's still really early. We're out having conversations. Remember, we've been having conversations for a year with the payers, and I can tell you some of the themes some of the themes are, first of all, from a clinical perspective, there's a tremendous interest in a Rezdiffra in NASH. People are aware of the unmet need there. They're very aware of the payers are the costs that NASH patients have to bound. So great interest in learning about the product, learning about our outcomes, just learning about our approach and the reason I say, the approach what's resonated very well with payers it's the fact that we're focusing on 315,000 patients. We are focused on those that are diagnosed that are in the office of specialists, which is also important for them. So that has been the starting point of all of our conversations and whether it be a regional or a national player, we're out meeting with them.

感謝您的提問，也感謝您對史蒂芬的評論。看看關於付款人的討論，首先，我認為現在還為時過早。我們出去聊天了。請記住，我們已經與付款人進行了一年的對話，我可以告訴您一些主題，其中一些主題是，首先，從臨床角度來看，人們對 Rezdiffra 在 NASH 中表現出極大的興趣。人們意識到那裡的需求未被滿足。他們非常清楚支付者是 NASH 患者必須承擔的費用。人們對了解產品、了解我們的成果、了解我們的方法以及我所說的原因非常感興趣，這種方法與付款人產生了很好的共鳴，事實上我們專注於 315,000 名患者。我們專注於那些在專家辦公室確診的患者，這對他們來說也很重要。因此，這是我們所有對話的起點，無論是地區性的還是國家性的參與者，我們都會與他們會面。

P&T committee meetings have been scheduled. We're getting some reads early on as you saw or heard in the prepared remarks, we're at about 30% of covered lives now commercial covered lives well on the way to our target of 80% by the year end. And I would say that at this point, you know, there's no real surprises we're having in these conversations, especially with the with the bigger, the bigger plans we expect to get this resolved, patients are still getting drug. That's really the great thing. While this is going on patients are moving through. We're getting prescriptions. Prior authorizations are required medical necessity in some cases. So right, where we are right now is where I would expect it to be. I'm happy with 30%. We're well on the way to the 80%, there's always going to be some outliers that I talked about even before we launched, we're seeing a little bit of that, but that's certainly by no means the trend.

P&T 委員會會議已安排。正如您在準備好的發言中看到或聽到的那樣，我們很早就收到了一些信息，我們現在大約有30% 的承保生活是商業承保生活，正在朝著我們年底前80% 的目標邁進。我想說的是，在這一點上，你知道，我們在這些對話中沒有真正的驚喜，特別是我們希望解決這個問題的更大、更大的計劃，患者仍在接受藥物治療。這確實是一件偉大的事。當這種情況發生時，患者正在經歷。我們正在拿處方。在某些情況下，出於醫療需求需要事先授權。所以，我們現在所處的位置就是我所期望的位置。能達到30%我就很滿意了我們正在向 80% 邁進，總是會有一些異常值，我在推出之前就談到過，我們看到了一些這樣的情況，但這絕不是趨勢。

Thanks, Jack.

謝謝，傑克。

Lisa, any question please?

麗莎，有什麼問題嗎？

Eliana Merle, UBS.

埃利安娜梅爾，瑞銀。

You mentioned that 75% of prescriptions have been written by top target. And can you give us any color on what proportion of your top physician targets have written a prescription? And then just in terms of the prescriptions that have been written, could you give us any color on physician feedback on the medical exception process that are most physicians going through medical exceptions at this point when they prescribe Rezdiffra.

您提到 75% 的處方是由頂級目標開出的。您能否告訴我們您的頂尖醫師目標中開過處方的比例是多少？然後，就已開立的處方而言，您能否給我們提供有關醫生對醫療例外流程的回饋意見，大多數醫生在開出 Rezdiffra 處方時都會經歷醫療例外。

Thanks, Eli So on the latter, I would say that and most are going through medical exception at this point, that's completely what we would expect. In fact, if any aren't going through medical exception, that would be more of a surprise because there just isn't the established pathways yet. So just to give you the layout, the prescribers and where we're seeing, where we're focusing and where we're seeing the prescriptions. So the universe of physicians is about 14,000. Our target physicians are about 6,000 of them, and that's where we've said that we've seen -- we've had great success in seeing those physicians, the reps have been out and had interactions sometimes now a couple or three interactions with those high prescribers.

謝謝，Eli So，關於後者，我想說的是，大多數人目前正在經歷醫療例外，這完全是我們所期望的。事實上，如果有人沒有經歷醫療例外，那會更令人驚訝，因為還沒有既定的途徑。因此，我只是向您提供佈局、處方者以及我們在哪裡看到的、我們在關注的地方以及我們在哪裡看到的處方。因此，醫生的宇宙大約有 14,000 人。我們的目標醫生大約有 6,000 名，這就是我們所說的——我們在見到這些醫生方面取得了巨大成功，代表們有時會外出並進行互動，現在與他們進行了兩三次互動那些高處方者。

And this is exactly what you'd expect in any launch is that those target physicians should drive the majority of your prescription. In this case, we're really encouraged by the 75% of the prescriptions coming from that from that group. We haven't said how many have prescribed or anything yet, but these are all some stats as we get further along into the launch. I mean, again, we've only had product out in the market for less than a month. It's still really, really early and difficult to project from such a short period of time, but all leading indicators. And that's why we went with the leading indicators are very supportive of things going out really, really well for us.

這正是您在任何發布中所期望的，即這些目標醫生應該負責您的大部分處方。在這種情況下，我們對 75% 的處方來自該群體感到非常鼓舞。我們還沒有透露有多少人已經開了處方或任何其他信息，但這些都是我們進一步推出時的一些統計數據。我的意思是，我們的產品上市時間不到一個月。在這麼短的時間內做出預測還非常非常早，而且很困難，但都是領先指標。這就是為什麼我們採用的領先指標非常支持我們的事情發展得非常非常好。

Great. Thanks, Eli.

偉大的。謝謝，伊萊。

Lisa, any question please?

麗莎，有什麼問題嗎？

Liisa Bayko, Evercore ISI.

莉莎·貝科，Evercore ISI。

Hi. Thanks for taking the question. I wanted to ask about the VA along the lines about an earlier question about heterogeneity and wanted to understand on their requirement for liver biopsy. And can you talk about and how you interpret that, what you can do to lift that? And also what percentage of the 315,000 patients are part of the VA? Thank you so much.

你好。感謝您提出問題。我想向 VA 詢問之前關於異質性的問題，並想了解他們對肝臟活檢的要求。您能否談談您如何解釋這一點，以及您可以採取哪些措施來解決這個問題？315,000 名患者中 VA 的比例是多少？太感謝了。

Thanks for the question, Lisa. And look, the VA is pretty particular right in that if you're going to launch a product inside of a budget year, it's difficult because they have a fixed budget and that requires congressional approval every year. So any changes to the budgets are actually problematic for them. So look, we are disappointed in the decision. It certainly isn't great for patients. It's certainly counter to any guideline that's been written anywhere that says the use of NITs is adequate, and that's certainly where we believe the field is.

謝謝你的提問，麗莎。看，VA 非常特別，如果你要在預算年度內推出一款產品，那會很困難，因為他們有固定的預算，而且每年都需要國會批准。因此，預算的任何變化實際上對他們來說都是有問題的。所以看，我們對這個決定感到失望。這對病人來說當然不是好事。這肯定與任何地方所寫的任何認為使用 NIT 就足夠的指南背道而馳，而這正是我們所認為的領域所在。

So however, the facts are the fact that that's where we are at this point. Now as we look forward to '25 and that's a new budget year, we're going to be working with as the VA to have that corrected. We think that certainly the guidelines and the medical community and certainly the patient community is on our side to have that happen. But, this is just one of the things as I said, as to the 12 months of your wiring, the system, sometimes you have to rewire portions of it. And in this case, this is one of those examples where just based on a number of those reasons where -- we find that's the decision that they made.

然而，事實就是我們目前所處的情況。現在，當我們期待 25 年，這是一個新的預算年時，我們將與 VA 合作糾正這個問題。我們認為，指導方針、醫學界以及病患界肯定會支持我們實現這一目標。但是，這只是我所說的其中一件事，至於你的佈線、系統的 12 個月，有時你必須重新佈線它的一部分。在這種情況下，這是基於許多原因的例子之一 - 我們發現這就是他們所做的決定。

Sorry, Lisa, just jumping in, in terms of the number of patients that the VA covers a very small. So when we do a public mix and we have that 10%, that's Medicaid and VA patient that is in the single digits, it's not going to have a large impact at this point, particularly in '24.

抱歉，麗莎，就 VA 覆蓋的患者數量而言，我只是插話一下。因此，當我們進行公共混合時，我們有 10% 的醫療補助和 VA 患者，其數量為個位數，目前不會產生太大影響，特別是在 24 年。

Lisa, any question please?

麗莎，有什麼問題嗎？

Jay Olson, Oppenheimer & Co., Inc.

傑·奧爾森，奧本海默公司

Oh, hey, congrats on the launch progress and thanks for taking the question. Can you just talk about some of the work you're doing to prepare for launch in the EU? And also how -- what your strategy is for launching in the EU and how that may impact your operating expenses?

哦，嘿，恭喜發布進度，感謝您提出問題。您能否談談您為在歐盟推出產品所做的準備？還有，您在歐盟推出的策略是什麼？

Thank you.

謝謝。

Okay, Jay, thanks for the question. We're really excited, as we said in the call about the opportunity to expand geographically. And the EU is certainly a very interesting market for us course. We announced in the first quarter, obviously that we had filed. We're now working through the strategy for the EU and what we're looking -- and this the way we're making all decisions in the company we're looking at one, three, five years from now and where do we want to be? Where are we today, the realities of where we are today versus what we think we're going to grow and become.

好的，傑伊，謝謝你的提問。正如我們在電話中所說的關於地域擴張的機會，我們真的很興奮。當然，歐盟對我們來說無疑是一個非常有趣的市場。我們在第一季宣布，顯然我們已經提交了。我們現在正在製定歐盟戰略以及我們正在尋找的目標——這就是我們在公司中做出所有決策的方式，我們正在考慮從現在開始的一年、三年、五年以及我們想要的方向成為？我們今天在哪裡，我們今天所處的現實與我們認為我們將成長和成為的樣子。

We want to be the leading company in NASH period. We think that's achievable. And we think that obviously that's going to come not only Rezdiffra, but we'll develop a pipeline and that's going to be geographic expansion as well. So we're working through those details a little early for us to report out and then we'll come back to you on a later call and be more specific about what we're doing in Europe. But it's an exciting moment for us to be able to expand globally and we look forward to reporting out to you on it.

我們希望成為NASH時代的領先公司。我們認為這是可以實現的。我們認為顯然這不僅會出現 Rezdiffra，而且我們還會開發一條管道，這也將是地理擴張。因此，我們正在儘早處理這些細節，以便我們進行報告，然後我們會在稍後的電話中回覆您，並更具體地介紹我們在歐洲所做的事情。但這對我們來說是一個激動人心的時刻，能夠在全球擴張，我們期待向您報告這一情況。

Yeah. The only comment I would make today because we are early in our decision-making there and mapping out the expenses that the investment that we would make the payback would be that would be within one to two year. That's how we look at our strategic decision-making. So that would be an impact likely if we get approval on '25 and going into '26 -- pay itself back.. And that's just looking at Europe specifically. Clearly, the US launch will cover a lot of the ad spend therapy in the EU.

是的。我今天要發表的唯一評論是因為我們處於早期決策階段，併計劃了我們將在一到兩年內收回投資的費用。這就是我們如何看待我們的策略決策。因此，如果我們在 25 年獲得批准並進入 26 年，這可能會產生影響——回報本身。這只是針對歐洲。顯然，美國的推出將涵蓋歐盟的大部分廣告支出療法。

Great.

偉大的。

Thanks, Jack.

謝謝，傑克。

Lisa, next question please?

麗莎，請問下一個問題嗎？

Ritu Baral, TD Cowen.

裡圖·巴拉爾，TD·考恩。

Good morning. Guys. I want to dig in a little further about the noninvasive algorithm for pre-authorization that may be coming together in your insurance discussions. Per Yasmeen's question, are you finding that things are mostly blood-based. Are you finding that there's a blood-based plus in imaging and in which imaging is being preferred? And then how could that ultimately affect time to fill or how could these be affected by AASLD guidelines?

早安.夥計們。我想進一步深入了解您的保險討論中可能會用到的非侵入性預授權演算法。根據亞斯明的問題，你是否發現事物大多是基於血液的。您是否發現基於血液的成像有優勢並且首選成像？那麼這最終會如何影響填充時間，或者 AASLD 指南會如何影響這些？

Thank you.

謝謝。

Ritu. Thank you very much for the question. Really appreciate it. And look, I know it's still early in the process generally, payers are evaluating a menu of the NIT.'s. There isn't 100% consistency across. And I think you've heard me mention even the community is still working through what's the best it sequence, what's the best combination of NITs. I think that the guidelines have started to help with that. I think pending guidelines will hopefully, again provide additional comments on NITs regarding the availability, and I think you hinted to that. We don't see that as a limitation at the moment.

瑞圖。非常感謝你的提問。真的很感激。看，我知道一般來說還處於早期階段，付款人正在評估 NIT 的菜單。不存在 100% 的一致性。我想您已經聽我提到過，甚至社區仍在研究什麼是最佳的序列、什麼是 NIT 的最佳組合。我認為指南已經開始對此有所幫助。我認為懸而未決的指南有望再次對 NIT 的可用性提供額外的評論，我認為您已經暗示了這一點。目前我們不認為這是一個限制。

Certainly any of the decisions that we've seen and the physicians in the area certainly seem to have access to those types of NITs between blood and imaging. I would say it's typically a combination of blood and imaging. But as we have more final decisions and you have friends will be able to report out to you what that looks like. We're really excited about updated guidelines. We know the communities working on them. I think one of the things we have to remember, the guidelines are pretty set. What you need to do now is put Rezdiffra into those guys.

當然，我們所看到的任何決定以及該地區的醫生似乎都可以訪問血液和成像之間的這些類型的 NIT。我想說這通常是血液和影像的結合。但隨著我們有更多的最終決定，並且你的朋友將能夠向你報告情況。我們對更新的指南感到非常興奮。我們了解致力於這些工作的社區。我認為我們必須記住的一件事是，指導方針已經制定得很好了。你現在需要做的就是將Rezdiffra放入那些傢伙體內。

So we're not expecting wild differences were just say they've been void of a treatment before. Now you'll be able to put Rezdiffra in there but -- so I guess conclusion is still early. We're seeing it be at the gamut, if you will, of NITs and it doesn't appear to be any barrier to access to these in that where the decisions have been made. So physicians can test them. And this will be a continue to evolve field as I think the community kind of really -- now that they have a product thinks about how to use the NITs how to sequencing combined.

因此，我們並不期望出現巨大的差異，只是說他們以前沒有接受過治療。現在你可以將 Rezdiffra 放在那裡，但是 - 所以我想結論還為時過早。如果你願意的話，我們看到它處於 NIT 的全部範圍內，並且在做出決策的地方似乎不存在任何訪問這些內容的障礙。因此醫生可以對它們進行測試。這將是一個持續發展的領域，因為我認為社群實際上已經有了一個產品，考慮如何使用 NIT 以及如何將定序結合。

Great, thank you, Bill. Next question, please.

太好了，謝謝你，比爾。請下一個問題。

Thomas Smith, Leerink Partners.

托馬斯史密斯，Leerink 合夥人。

Hey, guys, good morning. Thanks for taking the questions and congrats on the early launch progress on I wanted to follow up on some of the early payer coverage and specifically on the VA decision. Do you expect this will have any read-through to how any other commercial or government plans are likely to cover risks different, at least with their initial coverage policy decisions.

嘿，夥計們，早安。感謝您提出問題並祝賀早期啟動進展，我想跟進一些早期付款人保險，特別是 VA 的決定。您是否期望這會對任何其他商業或政府計劃可能如何承保不同的風險有任何透徹的了解，至少是他們最初的承保政策決定。

And then on how important therapies to the treatment guidelines. With respect to the payer discussions have you received any feedback from payers suggesting that this could help drive either more favorable coverage or less restrictive prior off coverage? Thanks

然後介紹治療方法對治療指引的重要性。關於付款人討論，您是否收到付款人的任何回饋，表明這可能有助於推動更優惠的承保或更少限制的提前保險？謝謝

Great, Thomas, thanks for the thanks for the question. First of all, I don't think there's a read-through there. We're having independent conversations with each payer. And as I said, with the payers, especially the larger players that we're speaking with there is a true acceptance of the seriousness of the disease and appreciation to the clinical data and an appreciation for how we're approaching the launch. So I think that they're independent decisions. I mean, people -- payers all make their own independent decisions. So we don't see that read through in.

太好了，托馬斯，謝謝你提出這個問題。首先，我不認為那裡有通讀。我們正在與每個付款人進行獨立對話。正如我所說，付款人，尤其是與我們交談的較大參與者，真正接受了這種疾病的嚴重性，讚賞臨床數據，並讚賞我們如何接近推出。所以我認為它們是獨立的決定。我的意思是，人們——付款人都會做出自己獨立的決定。所以我們看不到通讀的內容。

The second question was to the guideline Look, I think the guidelines are important. And as you know, as I said in the previous question, the guidelines that are in place are already being referred to I think it will be helpful for the physician community and the payer community, though to have updated guidelines that do contemplate Rezdiffra and provide a little bit more direction about how you would use it when you would use it, et cetera. So we're -- we know that the various bodies are working on it, and we're hopeful that we'll see at least something draft in the not-too-distant future.

第二個問題是關於指南的問題，我認為指南很重要。如您所知，正如我在上一個問題中所說，已經制定的指南已被提及，我認為這對醫生社區和付款人社區會有所幫助，儘管更新的指南確實考慮了 Rezdiffra 並提供關於如何使用它的更多指導，等等。所以我們知道各個機構正在研究這個問題，我們希望在不久的將來至少能看到一些草案。

Great.

偉大的。

Thanks, Tom. Next question, please, Lisa.

謝謝，湯姆。請下一個問題，麗莎。

Akash Tewari, Jefferies.

阿卡什·特瓦里，杰弗里斯。

Okay, thanks so much of the do you have any early color on the patient enrollment forms? Are they exceeding your internal expectations? And when we think about rewiring of the system Bill, you previously indicated we should not expect to see any significant revenues for Rezdiffral in 2024. Is that still the case?

好的，非常感謝您，您的病患登記表上有早期的顏色嗎？它們超出了您的內部預期嗎？當我們考慮重新佈線系統 Bill 時，您之前表示我們不應期望 Rezdiffral 在 2024 年看到任何重大收入。現在還是這樣嗎？

I just want to make sure we're clear on what expectations are going to be. And then maybe if I could sneak this in if semaglutide shows a fibrosis benefit that's in line with Rezdiffra and its upcoming phase 3 trials. Do you expect GLP-1s to be step headed by payers ahead of your product? And would that affect your internal launch projections for next year?

我只是想確保我們清楚我們的期望是什麼。如果索馬魯肽顯示出與 Rezdiffra 及其即將進行的 3 期試驗一致的纖維化益處，也許我可以偷偷地講一下。您是否期望 GLP-1 能夠領先於您的產品而由付款人領導？這會影響你們明年的內部發布預測嗎？

Thank you.

謝謝。

Okay. Thank you. And thank you for the questions. Let me see if I can get through them all here. Look, we aren't providing anything with patient numbers or initiations or anything at this point, it's just too early. And I think I was pretty clear in the call that I'm really pleased with the way things are progressing with the launch. Our focus right now is really just wiring the system. If we don't build a strong foundation, we will not be able to push through high volumes of patients in the future.

好的。謝謝。感謝您提出的問題。讓我看看我是否能在這裡完成所有這些。聽著，我們目前還沒有提供任何有關患者人數或啟動或任何信息的信息，現在還為時過早。我想我在電話中非常清楚地表明，我對發布的進展方式感到非常滿意。我們現在的重點其實只是系統佈線。如果我們不打下堅實的基礎，未來我們將無法應付大量患者。

Lot of companies make the mistake that they're just trying to chase getting patients on drug without preparing the practice payers and the whole system for being able to handle the flow. And we're focusing on that. However, we are still having patients come through, which is really great. So I'm very pleased where we are. I'm now looking forward to as we get through the next quarters of being able to further wire and also to give you a report out on just how things are going and your next question was about the expectations for revenue. Mardi, do you want to have that take that one.

許多公司都犯了一個錯誤，他們只是試圖讓患者接受藥物治療，而沒有為執業付款人和整個系統做好處理流程的準備。我們正在關注這一點。然而，我們仍然有病人過來，這真的很棒。所以我對我們所處的位置感到非常高興。我現在期待著在接下來的幾個季度中我們能夠進一步進行電匯，並向您提供一份有關事情進展情況的報告，您的下一個問題是關於收入的預期。Mardi，你想要那個嗎？

Yeah. So Alkash, just to be really clear what we said, we said, because of the time to wire the system and the time for prescriptions to be sell the first six months, which we estimate on average, the 60 days but we think that comes down to 30 days after six months, that 2Q sale will be modest and that the sales for the year will really be back-end loaded for Q3 and Q4. We haven't given a number to that. We haven't given guidance on that, but we are -- we have validated and said where The Street is as an average or consensus that we feel confident with that's the message regarding revenues for 2024, and then the step at it.

是的。因此，Alkash，為了真正清楚我們所說的內容，我們說，因為連接系統的時間以及前六個月銷售處方的時間，我們平均估計為 60 天，但我們認為這會到來六個月後減少到30 天，第二季的銷售將是適度的，今年的銷售將真正由第三季和第四季的後端加載。我們還沒有給出具體數字。我們還沒有就此給出指導，但我們已經驗證並表示了《華爾街日報》的平均水平或共識，我們對此充滿信心，這就是有關 2024 年收入的信息，然後是採取的步驟。

I think, look, I guess we'll find out more this year, both if anyone manages to show the same impressive efficacy results that we have by hitting on both primary endpoints. So look, looking ahead to the future regardless of what happens, what they show, I think you have to come back to that. The facts are first of all that there's an incredibly high unmet need there's 315,000 patients. So there's a lot of patients. And up until March 14, there was not an approved therapy. Now what was the therapy that was approved risk different and look at that profile. Efficacy hit on both endpoints, greater than 80% of patients have a stop or reverse fibrosis. So the response is deep and the response is wide.

我想，看，我想今年我們會發現更多，如果有人能夠通過達到兩個主要終點來表現出與我們相同的令人印象深刻的功效結果。所以，展望未來，無論發生什麼，無論他們表現什麼，我認為你都必須回到這一點。首先，事實是，有 315,000 名患者的未滿足需求非常高。所以病人很多。截至 3 月 14 日，還沒有批准的治療方法。現在，被批准的治療方法有什麼不同的風險，看看這個情況。兩個終點的療效均達到，超過 80% 的患者纖維化停止或逆轉。所以反應是深的，反應是廣的。

So we have an effective product that happens to be a once-a-day pill that has been shown to be well-tolerated and safe. So we've got a profile which is really a fantastic profile. I mean, it's every drug makers dream to have a once-a-day pill for a serious disease. And you know, I'll take that profile and we will compete against anyone, especially since we're at the beginning of a market. We're not talking about a zero sum game here where market shares are all locked in place and one person is going to lose share. One person is going to gain it.

因此，我們有一個有效的產品，它恰好是每天一次的藥丸，已被證明具有良好的耐受性和安全性。所以我們得到了一個非常棒的個人資料。我的意思是，每個製藥商都夢想擁有一種每天一次的藥物來治療嚴重的疾病。你知道，我會採用這種形象，我們將與任何人競爭，特別是因為我們正處於市場的起步階段。我們在這裡談論的不是一場零和遊戲，即市場份額全部鎖定，而一個人將失去份額。一個人將會獲得它。

We're hopeful that there's going to be other products in NASH because it helps to grow the market and we think that with our profile, which is still emerging, look, we only hey -- we got approved on 52-week data and we saw this as a 54 month study. We some of our best days are ahead actually in showing what this product can do. So will they force a product for a patient to go through a GLP-1? I don't know, I we'll see what they do, but I think that on our profile alone, there's a very compelling reason for patients to be onRezdiffra. So we're extremely confident under any scenario of what anyone else shows data.

我們希望 NASH 領域能夠有其他產品，因為它有助於擴大市場，我們認為，憑藉我們的概況（仍在不斷湧現），看，我們只是嘿 - 我們獲得了 52 週數據的批准，我們這是一項為期54 個月的研究。我們最好的日子實際上是在展示該產品的功能。那麼他們會強迫患者使用的產品通過 GLP-1 測試嗎？我不知道，我們會看看他們會做什麼，但我認為僅從我們的個人資料來看，就有一個非常令人信服的理由讓患者使用 Rezdiffra。因此，在任何其他人顯示數據的情況下，我們都非常有信心。

Thanks Akash. Lisa, next question, please.

謝謝阿卡什。麗莎，請下一個問題。

Jonathan Wolleben, [Citizens].

喬納森‧沃萊本，[公民]。

Wondering if you could talk about the patient services you're providing and if you're expecting patients to start on paid therapy after those 60 to 30 days or if there's going to be a lot of free drug and the system.

想知道您是否可以談談您所提供的患者服務，以及您是否希望患者在 60 到 30 天後開始接受付費治療，或者是否會有大量免費藥物和系統。

Okay. So John, thanks for the question. You mean the types of services that we're going to offer? Or do you want more specifically how we see that mix of patients?

好的。約翰，謝謝你的提問。您是指我們將提供的服務類型？或者您想更具體地了解我們如何看待這些患者的組合？

I guess the latter is more informative, but if you could speak to the first or the former as well?

我想後者資訊更豐富，但是您是否也可以談談第一個或前者？

Yeah. Look, so we've put together a very comprehensive patient support group. We think that's really important. We think it's important that the first interaction that they have with the product through patient support is important and establishes a long-term relationship, hopefully helps them navigate any challenges. They may have along the way through Madrigal patient support, they get co-pay assistance, et cetera.

是的。看，我們組建了一個非常全面的患者支持小組。我們認為這非常重要。我們認為，重要的是，他們透過患者支持與產品進行的第一次互動很重要，並建立了長期關係，希望能幫助他們應對任何挑戰。他們可能會在整個 Madrigal 過程中獲得患者支持、共同支付援助等等。

If they are underinsured or have no insurance, they can qualify potentially for our patient assistance program to receive free drug, et cetera. So it's important not only on the front end, but also as you look over the long term, establishing that long-term relationship and helping through any adherence challenges somebody may hav.e So that we fundamentally believe that a strong patient support services group is important. And we think that we've got a really a great one that we started.

如果他們保險不足或沒有保險，他們可能有資格參加我們的患者援助計劃以獲得免費藥物等。因此，這不僅在前端很重要，而且從長遠來看也很重要，建立長期關係並幫助解決某人可能遇到的任何依從性挑戰。重要的。我們認為我們已經開始了一項非常偉大的工作。

Regarding free drug and so forth, look, you've heard me say before that as you look through that first year, you've got patients that are some are going to be on free drug will have a big bridging program, et cetera. So it's a little bit choppy if you're thinking of it from a gross to net perspective for that first year. What we've committed to the community is this whole notion of equitable access. We don't we want to be able to provide product to patients who need it. So we've focused on affordability for patients. If you're a commercial patient, you can have a $10 co-pay. The challenge right now is with Medicare. Since we missed the window for '24, we're now talking about what will happen in '25. So those Medicare patients are either going to have a opportunity through their own plan if they've made a midyear decision or some of them are going to have to wait for 2025.

關於免費藥物等，你聽我說過，當你回顧第一年時，你會發現有些患者將接受免費藥物，他們將有一個大的過渡計劃，等等。因此，如果你從第一年的總體和淨值角度來考慮，那就有點不穩定了。我們向社區承諾的是公平訪問的整個概念。我們不希望能夠向需要的患者提供產品。因此，我們將重點放在患者的負擔能力。如果您是商業患者，您可以支付 10 美元的自付費用。現在的挑戰是醫療保險。由於我們錯過了 24 年的窗口期，我們現在正在討論 25 年會發生什麼。因此，如果這些 Medicare 患者在年中做出決定，他們要么將有機會透過自己的計劃獲得機會，要么其中一些將不得不等待 2025 年。

So we're going to trying to help those patients, we'll look to see if there's alternatives for them, such as charitable foundations, et cetera. And in the end, if they can't get it through other means and they have a high unmet need. We'll provide a free product. So we will have free patients, but that's not where we are today. We have patients that are coming through the system and they're paid prescriptions. So we feel like we're in a really good place, but we're always going to have this balance of some patients for their structural reasons won't be able to get drug through. That means we're going to help those patients. But we're going to trying to keep things in very much in sync between the various types of patients, whether you're insured uninsured, commercial, Medicare. So that is a little bit of more flavor around it rather than a real specific, a number that I'm giving you but I expect all those components, especially you'll see in this first12-month period.

因此，我們將盡力幫助這些患者，看看是否有其他選擇，例如慈善基金會等。最後，如果他們無法透過其他方式獲得它，並且他們有很高的未滿足需求。我們將提供免費產品。所以我們將有免費的病人，但那不是我們今天的情況。我們的患者透過該系統獲得處方藥。所以我們覺得我們處於一個非常好的位置，但我們總是會保持一些患者的平衡，因為他們的結構性原因將無法獲得藥物。這意味著我們將幫助這些患者。但我們將努力讓各種類型的患者之間的情況保持非常同步，無論您是否有保險、未投保、商業、醫療保險。因此，這是圍繞它的更多風味，而不是真正的具體數字，我給你的數字，但我期望所有這些組成部分，特別是你會在前 12 個月內看到。

Thanks. John, Lisa, looks like we have time for one more question. Please

謝謝。約翰、麗莎，看來我們還有時間再問一個問題。請

Andrea Tan, Goldman Sachs.

安德里亞·譚，高盛。

Thanks for squeezing us in. Maybe one question here on the prescriptions that have come through. Just wondering if you're able to speak about the dynamics that you're seeing today, is that generally one prescription per specialist or maybe multiple prescriptions per specialist? Thanks so much.

謝謝你把我們擠進去。也許有一個關於已經通過的處方的問題。只是想知道您是否能夠談談您今天所看到的動態，通常是每個專家開一個處方還是每個專家開多個處方？非常感謝。

Thanks, Andrea. It varies, right. I mean everyone starts with one, so to speak or actually somewhat started with more than that. But one of the things we expect to see is in this top 6,000 or this target 6,000 is it's going to go beyond one and they're going to go pretty deep actually because we know they have the patients and we know that there's a lot of favorable belief about Rezdiffra. So over time, we're going to see again this notion of breadth and depth, and it's going to be concentrated in that top 6,000. So still pretty early.

謝謝，安德里亞。它有所不同，對吧。我的意思是每個人都從一個開始，可以這麼說，或者實際上某種程度上從更多開始。但我們期望看到的一件事是，在前 6,000 名或目標 6,000 名患者中，它將超越 1，而且實際上他們會深入研究，因為我們知道他們有患者，而且我們知道有很多患者。 Rezdiffra 的好感度。因此，隨著時間的推移，我們將再次看到這種廣度和深度的概念，並且它將集中在前 6,000 名中。所以還很早。

I mean, look, with just what we what we found is that the physicians until drugs available weren't giving a lot of thought to how they are going to process all their patients right now that drugs available, they're making it part of their pathway in their practice. And that takes a little bit of time to think how they're going to do it, right? But we're really encouraged that patients are being prescribed, patients are getting on drug. So we're fulfilling our promise. We're trying to change lives here, and it's really exciting. And maybe I'll just end on that and say, this is a really great and exciting opportunity as you heard me say I'm more excited about the opportunity now than I was six months ago or three months ago.

我的意思是，看，我們發現，在藥物可用之前，醫生並沒有充分考慮他們將如何處理所有患者，現在藥物可用，他們正在將其作為治療的一部分。這需要一點時間來思考他們將如何做到這一點，對吧？但我們真的很高興看到患者正在接受處方，患者正在接受藥物治療。所以我們正在履行我們的承諾。我們正在努力改變這裡的生活，這真的很令人興奮。也許我會在最後說，這是一個非常偉大和令人興奮的機會，正如你聽到我說的那樣，我現在對這個機會比六個月前或三個月前更興奮。

And it's just I can't tell you how much fun it is to be out there with a product that's so meaningful in a disease that has had absolutely nothing. And we get to set the bar for all others that come. It's rare that you get an opportunity to be the first one to establish. How do you engage with companies? What's the expectation you set for patient services and everything along the way we have that opportunity as the leader and our intent is to go out there. And we are leading like leaders first launch, but we have a really experienced team we know what we're doing. We have the resource, we have the product, the opportunity is there. It just takes time to get it right, build the foundation as we wire the system, and we'll put ourselves in a great position to win and be the leader in this.

只是我無法告訴你，推出一款對一種毫無意義的疾病如此有意義的產品是多麼有趣。我們將為所有其他到來的人設定標準。您很難有機會成為第一個建立的人。你如何與公司打交道？您對患者服務以及整個過程中的一切設定的期望是什麼，我們有機會作為領導者，我們的意圖是走出去。我們在首次發佈時就像領導者一樣處於領先地位，但我們擁有一支經驗豐富的團隊，我們知道我們在做什麼。我們有資源，我們有產品，機會就在那裡。只是需要時間來把它做好，在我們連接系統時打下基礎，我們將使自己處於一個有利的位置，贏得勝利並成為這方面的領導者。

Thanks, Andrea. And thanks, Lisa, and thank you all for your time and interest today.

謝謝，安德里亞。謝謝麗莎，也謝謝大家今天的時間和興趣。

That concludes our call. A replay of the webcast will be available on our website in approximately two hours. So thank you so much for joining us.

我們的通話到此結束。網路廣播的重播將在大約兩個小時後在我們的網站上提供。非常感謝您加入我們。

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

女士們、先生們，感謝你們參加今天的會議。你們現在可以斷開連結了。祝你有美好的一天。