Mirum Pharmaceuticals Inc (MIRM) 2025 Q1 法說會逐字稿

Hello, and welcome to the Mirum Pharmaceuticals reports first-quarter 2025 financial results. My name is Carla, and I will be coordinating your call today. (Operator Instructions)

您好，歡迎閱讀 Mirum Pharmaceuticals 2025 年第一季財務業績報告。我叫卡拉，今天我將負責協調您的通話。（操作員指示）

I would now to hand you over to Andrew McKibben, Senior Vice President of Strategic Finance and Investor Relations, to begin. Andrew, please go ahead when you're ready.

現在，我把發言權交給策略財務和投資者關係高級副總裁 Andrew McKibben。安德魯，準備好了就請繼續。

Thanks, Carla, and good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals' first-quarter 2025 conference call. I'm joined today by our CEO, Chris Peetz, our President; and Chief Operating Officer, Peter Radovich; and Eric Bjerkholt, our Chief Financial Officer. Joanne Quan, our Chief Medical Officer, cannot be with us today as she's at a medical conference in Europe.

謝謝，卡拉，大家下午好。歡迎您參加 Mirum Pharmaceuticals 2025 年第一季電話會議。今天與我一同出席的還有我們的執行長 Chris Peetz、總裁兼營運長 Peter Radovich 和財務長 Eric Bjerkholt。我們的首席醫療官 Joanne Quan 今天不能和我們在一起，因為她正在歐洲參加一個醫學會議。

Earlier today, Mirum issued a news release announcing the company's results for the first quarter of 2025. Copies of this news release and SEC filings can be found in the Investors section of our website.

今天早些時候，Mirum 發布了一份新聞稿，宣布了該公司 2025 年第一季的業績。本新聞稿和美國證券交易委員會 (SEC) 文件的副本可在我們網站的「投資者」部分找到。

Before we start, I'd like to remind you that, during the course of this conference call, we will be making certain forward-looking statements based on management's current expectations, including statements regarding Mirum's programs and market opportunities for its approved medicines and product candidates. These statements represent our judgment as of today and inherently involve risks and uncertainties that may cause the actual results to differ materially from the results discussed. We are under no duty to update these statements. Please refer to the risk factors in our latest Form 10-Q and the subsequent SEC filings for more information.

在我們開始之前，我想提醒您，在本次電話會議期間，我們將根據管理層當前的預期做出某些前瞻性陳述，包括有關 Mirum 的計劃及其已批准藥品和候選產品的市場機會的陳述。這些聲明代表了我們今天的判斷，並且本身涉及風險和不確定性，可能導致實際結果與討論的結果有重大差異。我們沒有義務更新這些聲明。請參閱我們最新的 10-Q 表和隨後的 SEC 文件中的風險因素以獲取更多資訊。

With that said, I'd like to turn the call over to Chris. Chris?

話雖如此，我想把電話轉給克里斯。克里斯？

Thanks, Andrew, and good afternoon, everyone. I'd like to start off by highlighting the tremendous progress Mirum has made in the first quarter of 2025. We continue to deliver across our key strategic objectives, furthering the growth of our commercial medicines and advancing our high-impact pipeline. We are excited to share the details of another record-breaking quarter for Mirum, with total revenues reaching $111.6 million or 61% growth over the first quarter last year.

謝謝，安德魯，大家下午好。首先，我想強調 Mirum 在 2025 年第一季取得的巨大進步。我們將繼續實現我們的關鍵策略目標，進一步促進我們的商業藥品的成長並推進我們的高影響力產品線。我們很高興與大家分享 Mirum 又一個破紀錄的季度的細節，總收入達到 1.116 億美元，比去年第一季增長 61%。

Further, given how strong the year has started across the commercial business, we are updating our full-year revenue guidance to be $435 million to $450 million. This increase is driven by robust growth from all three of our commercial medicines and highlights the Mirum team's continued strong commercial execution.

此外，鑑於今年商業業務開局強勁，我們將全年營收預期更新為 4.35 億美元至 4.5 億美元。這一成長是由我們所有三種商業藥物的強勁成長推動的，並凸顯了 Mirum 團隊持續強勁的商業執行力。

In addition, I'm happy to report we've received three important regulatory approvals since the start of the year, adding growth drivers to the business. First, CTEXLI was FDA approved for the treatment of CTX in February, and we've begun promotional efforts to reach this underdiagnosed community. Second, LIVMARLI was approved in Japan for PFIC and Alagille syndrome through our partner, Takeda. And most recently, a convenient single tablet form of LIVMARLI was approved by the FDA. These milestones highlight our commitment to reach more patients globally.

此外，我很高興地報告，自今年年初以來我們已獲得三項重要的監管批准，為業務增添了成長動力。首先，CTEXLI 於二月獲得 FDA 批准用於治療 CTX，我們已經開始推廣活動以涵蓋這個未被充分診斷​​的群體。其次，LIVMARLI 透過我們的合作夥伴武田公司在日本獲得批准，用於治療 PFIC 和 Alagille 症候群。最近，一種方便的單片形式的 LIVMARLI 獲得了 FDA 的批准。這些里程碑彰顯了我們致力於幫助全球更多患者的承諾。

Our pipeline continues to make great progress as well, starting with the VISTAS study of volixibat in PSC. We are getting close to completing enrollment and now expect to achieve this in the third quarter of this year with top-line data expected in the second quarter of 2026. As a reminder, both the VISTAS and VANTAGE studies successfully passed the dose selection interim analysis last year and are now in their confirmatory portions of the studies.

我們的研發管線也持續取得巨大進展，首先是針對 PSC 中 volixibat 的 VISTAS 研究。我們即將完成招生工作，預計將在今年第三季完成，並預計在 2026 年第二季獲得頂線數據。提醒一下，VISTAS 和 VANTAGE 研究去年都成功通過了劑量選擇中期分析，目前正處於研究的確認部分。

As an example of what impact IBAT inhibitors can have in PSC, I'd like to highlight a recent presentation earlier this week at DDW of a case series of PSC patients receiving maralixibat through our compassionate use program. Encouragingly, we saw reductions in serum bile acids and all patients had a 2-point or greater reduction in pruritus. PSC remains a condition with no approved therapies, and these results build on our conviction for the potential of volixibat to bring life-changing results to patients in need.

作為 IBAT 抑制劑對 PSC 的影響的一個例子，我想重點介紹本週早些時候在 DDW 上透過我們的同情用藥計劃接受馬拉利昔布治療的一系列 PSC 患者病例。令人鼓舞的是，我們看到血清膽汁酸減少，所有患者的搔癢感減少了 2 個點或更多。PSC 仍然是一種沒有核准療法的疾病，這些結果增強了我們對 volixibat 為有需要的患者帶來改變生活的療效的潛力的信心。

Now looking ahead, this Friday at EASL, we are also excited to present the updated 28-week interim data from the VANTAGE study in PBC, where volixibat has been granted breakthrough designation. In this analysis, we showed the rapid, deep and statistically significant improvement of pruritus on volixibat we shared last June is durable through the full 28-week study.

展望未來，本週五在 EASL 上，我們也很高興展示 PBC 中 VANTAGE 研究的最新 28 週中期數據，volixibat 在該研究中獲得了突破性進展。在本次分析中，我們表明，我們去年 6 月分享的 volixibat 對搔癢症的快速、深入和統計上顯著的改善將持續整個 28 週的研究。

In this updated interim analysis, volixibat showed a 3.8-point reduction from baseline and a 2.5-point placebo-adjusted reduction in pruritus. We're excited to advance this program through the confirmatory portion of the study, and we continue to expect enrollment completion next year. And finally, for the balance of the pipeline, we remain on track to initiate our Phase II study for MRM-3379 in Fragile X syndrome this year as well as complete enrollment of our LIVMARLI EXPAND trial in 2026.

在這次更新的中期分析中，volixibat 顯示搔癢感較基線降低了 3.8 個百分點，經安慰劑調整後降低了 2.5 個百分點。我們很高興能夠透過研究的確認部分推進該計劃，並且我們繼續期待明年完成招生。最後，為了平衡產品線，我們仍將按計劃在今年啟動針對脆性 X 綜合徵的 MRM-3379 的 II 期研究，並在 2026 年完成 LIVMARLI EXPAND 試驗的招募。

2025 is set to be another year of meaningful growth for Mirum as we continue to advance our commercial portfolio and pipeline. With strong execution and financial discipline, we are well positioned to continue our leadership in rare disease.

隨著我們繼續推動商業組合和通路建設，2025 年將成為 Mirum 又一個有意義的成長年。憑藉強大的執行力和財務紀律，我們有能力繼續在罕見疾病領域保持領先地位。

And with that, I'll turn it over to Peter to give a brief update on the commercial business. Peter?

接下來，我將把時間交給彼得，讓他簡單介紹一下商業業務的最新情況。彼得？

Thanks, Chris. I'm pleased with the continued strong growth we are seeing across our three medicines. And our commercial team delivered another great quarter, with total net product sales of $111.6 million. Based on the demand we are seeing across our medicines, we are raising our full-year net product sales guidance to between $435 million and $450 million. For LIVMARLI, total global net product sales grew to $73.2 million in the first quarter, an increase of over 70% compared to our first-quarter 2024.

謝謝，克里斯。我很高興看到我們的三種藥物持續強勁成長。我們的商業團隊交出了另一份出色的成績單，產品淨銷售額總計達 1.116 億美元。根據我們所看到的藥品需求，我們將全年淨產品銷售額預期上調至 4.35 億美元至 4.5 億美元之間。對於 LIVMARLI 而言，第一季全球淨產品總銷售額成長至 7,320 萬美元，與 2024 年第一季相比成長了 70% 以上。

US LIVMARLI sales were $49.5 million, driven by robust new patient demand across indications. For the remainder of the year, we expect to see continued growth in both Alagille syndrome and PFIC. And the approval of the tablet formulation adds to these positive dynamics with a single tablet per dose, providing a distinct convenience advantage. LIVMARLI is now the only IBAT offering flexible formulations across all ages, an important milestone as we look to expand options for our patients.

美國 LIVMARLI 銷售額為 4,950 萬美元，這得益於各適應症新患者的強勁需求。在今年剩餘時間內，我們預計 Alagille 症候群和 PFIC 的發生率將繼續增長。片劑劑型的批准進一步增強了這些積極的動力，因為每劑僅需一片片劑，具有明顯的便利優勢。LIVMARLI 目前是唯一為所有年齡層提供靈活配方的 IBAT，這對於我們尋求為患者擴大選擇範圍而言是一個重要的里程碑。

International LIVMARLI sales were $23.7 million. We saw strong demand growth in our direct European markets driven by both continued penetration in Alagille syndrome in established markets and new launches in midsized countries. I'll note that our international distributor and partner revenue this quarter included about $6 million of inventory, which is a new dynamic that not been seen in prior quarter sales numbers. Overall, the continued underlying demand growth across our international territories is the driving trend for this business and we're excited to see the PFIC indication come online in many international markets this year.

LIVMARLI 的國際銷售額為 2,370 萬美元。我們看到，歐洲直接市場的需求強勁成長，這得益於 Alagille 症候群在成熟市場的持續滲透以及中型國家新產品的推出。我要指出的是，本季我們的國際經銷商和合作夥伴收入包括約 600 萬美元的庫存，這是上一季銷售數字中未曾見過的新動態。總體而言，我們國際地區持續的潛在需求成長是這項業務的驅動趨勢，我們很高興看到 PFIC 指示今年在許多國際市場上線。

In Q1, we also saw strong growth from the bile acid products with $38.4 million of net product sales, representing 47% growth over the same quarter last year. With CTEXLI now approved in CTX, our efforts are focused on engaging health care professionals across several specialties to find patients in this undervalued condition. And I'm pleased to say we're starting to see progress as we have seen an increase in new CTX patients since the FDA approval in February.

第一季度，我們也看到膽汁酸產品強勁成長，淨產品銷售額達 3,840 萬美元，比去年同期成長 47%。隨著 CTEXLI 現已在 CTX 獲得批准，我們的努力重點是讓多個專業的醫療保健專業人員參與進來，尋找這種被低估的疾病患者。我很高興地說，我們開始看到進展，因為自從二月 FDA 批准以來，新的 CTX 患者數量有所增加。

Overall, it's been a tremendous start to the year for the commercial business. With the increased full-year guidance of $435 million to $450 million, we look forward to continuing our strong execution throughout the year.

總體而言，對於商業業務而言，今年是一個好的開始。隨著全年指引金額從 4.35 億美元增加至 4.5 億美元，我們期待全年繼續保持強勁執行力。

And now I'll turn it over to Eric. Eric?

現在我將把時間交給 Eric。艾瑞克？

Thank you, Peter. Our financial position is strong and continues to improve. The first-quarter 2025 net product revenue of $111.6 million compared to net product revenues of $69.2 million in the first quarter of last year. Cash, cash equivalents and investments at March 31 was $298.6 million compared with $292.8 million at the beginning of the year. Total operating expense for the quarter ended March 31 was $126.8 million, which includes R&D expense of $46 million, SG&A expense of $57.7 million and cost of sales of $23 million.

謝謝你，彼得。我們的財務狀況強勁且持續改善。2025 年第一季淨產品收入為 1.116 億美元，而去年第一季淨產品收入為 6,920 萬美元。截至 3 月 31 日的現金、現金等價物及投資為 2.986 億美元，而年初為 2.928 億美元。截至 3 月 31 日的季度總營運費用為 1.268 億美元，其中包括研發費用 4,600 萬美元、銷售、一般及行政費用 5,770 萬美元和銷售成本 2,300 萬美元。

R&D expense for the quarter included $7 million in onetime milestone payments related to the progress of our pipeline. Expense for the quarter also included noncash stock-based compensation expense of $15.8 million and intangible amortization and other noncash items of $6 million. The intangible amortization and noncash items expense are largely reflected in our cost of goods sold.

本季的研發費用包括與我們管道進度相關的 700 萬美元一次性里程碑付款。本季的費用還包括 1,580 萬美元的非現金股票薪酬費用以及 600 萬美元的無形資產攤銷和其他非現金項目。無形資產攤銷和非現金項目費用主要反映在我們的銷售成本中。

We were operating cash flow positive for the quarter, and we expect to be cash flow positive for the full year. The cash contribution margin from our commercial business improved from approximately 47% in the first quarter of last year to approximately 53% for the first quarter of this year. In addition, year-over-year R&D and G&A expense improved as a percent of revenue by over 10 percentage points. We continue to be well funded and financially independent, providing us the resources required to execute on our business plan.

本季我們的經營現金流為正，我們預計全年的現金流也將為正值。我們商業業務的現金貢獻利潤率從去年第一季的約47%提高到今年第一季的約53%。此外，研發和一般及行政費用佔收入的百分比年增了 10 個百分點以上。我們繼續擁有充足的資金和財務獨立，為我們提供執行業務計劃所需的資源。

Now I'll turn the call back over to Chris for a final comment.

現在我將把電話轉回給克里斯，請他發表最後的評論。

Thanks, Eric. As a quick recap, we've had a great start to the year. Our three commercial medicines are growing ahead of initial expectations, and we're raising our full-year guidance. In the last few months, we saw three important regulatory approvals that support the long-term growth potential of our commercial medicines, and our growing pipeline is making excellent progress. The VISTAS study of volixibat in PSC will complete enrollment in the coming months, and we are excited to share a great update for volixibat in PBC this Friday.

謝謝，埃里克。簡單回顧一下，今年我們有一個好的開始。我們的三種商業藥物的增長超出了最初的預期，我們正在提高全年指導。在過去的幾個月裡，我們獲得了三項重要的監管批准，這支持了我們商業藥品的長期成長潛力，我們不斷增長的產品線也取得了良好的進展。VISTAS 對 Volixibat 在 PSC 中的研究將在未來幾個月內完成招募，我們很高興在本週五分享 Volixibat 在 PBC 中的重大更新。

We're looking forward to starting the Phase II study in Fragile X syndrome later this year with MRM-3379 and completing enrollment of LIVMARLI Phase III EXPAND and volixibat VANTAGE studies next year. Overall, we are in an excellent financial position, and I look forward to continued progress in the quarters ahead.

我們期待今年稍後使用 MRM-3379 開始脆性 X 症候群的 II 期研究，並於明年完成 LIVMARLI III 期 EXPAND 和 volixibat VANTAGE 研究的招募。總體而言，我們的財務狀況非常好，我期待未來幾季繼續取得進展。

And with that, operator, please open the call for questions.

接線員，請開始提問環節。

(Operator Instructions) Gavin Clark-Gartner, Evercore.

（操作員指示） Gavin Clark-Gartner，Evercore。

Congrats on the great progress. First, for the additional volixibat PBC data that's in the EASL abstract, it looks like the pruritus benefit deepened a bit at 28 weeks. And also, I think there were no discontinuations due to diarrhea beyond the one you saw at 16 weeks. Maybe you can just speak to that and anything else from the abstract there.

祝賀你取得巨大進步。首先，對於 EASL 摘要中的附加 volixibat PBC 數據，看起來搔癢益處在第 28 週有所加深。而且，我認為除了 16 週時出現的腹瀉之外，沒有出現因腹瀉而停藥的情況。也許您可以就此談談摘要中的其他內容。

Thanks for the question, Gavin. Yes, really excited with how the data matured in the interim analysis. So as you point out, the response overall deepens over time with the separation curves looking really strong. We'll have a few more data points that will be included in the presentation as well. So I encourage you to stay tuned for an update there. And overall, the profile and benefit that patients are getting, I think the discontinuation statistic you point out, I think it's a great testament to what this can mean for patients.

謝謝你的提問，加文。是的，對於中期分析中資料的成熟程度，我真的感到很興奮。正如您所指出的，隨著時間的推移，整體響應會加深，分離曲線看起來非常強勁。我們也會將更多的數據點包含在簡報中。因此我鼓勵您繼續關注那裡的更新。總體而言，患者獲得的概況和益處，我認為您指出的停藥統計數據，很好地證明了這對患者意味著什麼。

Great. And then just on the LIVMARLI tablet formulation. Can you just frame the additional IP that could come around with that? And also commercially, where you see adoption of the tablet formulation?

偉大的。然後就只討論 LIVMARLI 片配方。您能否僅建置隨之而來的附加 IP 呢？從商業角度來看，您認為片劑配方在哪裡被採用？

Yes. So I can touch on the IP and then I'll ask Peter to speak a little bit about kind of what we're looking forward to on adoption. For IP, I mean, the tablet permission here did take some work really because of the properties of maralixibat. So it did result in some novel IP. We have an allowed patent that we expect to grant soon. That covers the formulation that would extend coverage out to 2043.

是的。因此我可以談談 IP，然後我會請 Peter 稍微談談我們對採用的期望。對於 IP，我的意思是，這裡的平板電腦權限確實需要做一些工作，因為 maralixibat 的特性。因此它確實產生了一些新穎的 IP。我們擁有一項已獲批准的專利，預計很快就會獲得批准。這涵蓋了將覆蓋範圍延長至 2043 年的方案。

I'll pass over to Peter for the second part of the question.

我將把問題的第二部分交給彼得。

Yes. Thanks for the question, Gavin. And we think that tablet will be a pretty attractive option for really all the LIVMARLI patients over 25 kilos, or you can think of older children and adolescents up to adults. I think that would be a pretty attractive option for many of them. So look forward to seeing how that unfolds in the back half of this year.

是的。謝謝你的提問，加文。我們認為，對於體重超過 25 公斤的所有 LIVMARLI 患者，或者年齡較大的兒童和青少年直至成年人來說，這款平板電腦都是一個非常有吸引力的選擇。我認為這對他們中的許多人來說是一個非常有吸引力的選擇。因此，我們期待看到今年下半年的情況如何。

Jessica Fye, JPMorgan.

潔西卡費伊（Jessica Fye），摩根大通。

Curious how you think your interim Phase II PBC data compares to the pruritus data for linerixibat? And also curious what you make of the placebo response observed on pruritus in that trial. Then I have a second question.

好奇您認為您的 II 期中期 PBC 數據與 Linerixibat 的搔癢數據相比如何？並且也很好奇您對該試驗中觀察到的對瘙癢的安慰劑反應有何看法。那我還有第二個問題。

Thanks for the question, Jessica. Yes. Again, what we've seen really is just the abstract that was posted on the linerixibat program. So I don't want to speak too much to their data. But what it did does do for, at least in our view, is highlight some of the strengths in the volixibat program where not only in change from baseline but in the placebo-adjusted difference having a really strong outcome there.

謝謝你的提問，潔西卡。是的。再說一次，我們看到的實際上只是在 linerixibat 程式上發布的摘要。所以我不想談論太多他們的數據。但至少在我們看來，它確實突出了 volixibat 計劃的一些優勢，不僅在基線方面有所變化，而且在安慰劑調整後的差異方面也取得了非常好的結果。

But a lot of it, we think, driven by the dose volixibat. I really believe that we're at a maximally efficacious dose and optimizing activity for the program here. So that's what stands out for us is that driving that 3.8% reduction from baseline, which then results in the 2.5 placebo-adjusted difference.

但我們認為，這很大程度上是由劑量 volixibat 引起的。我確實相信我們正處於最大有效劑量並優化此處的計劃活動。因此，對我們來說突出的是推動從基線減少 3.8%，從而導致 2.5 個安慰劑調整差異。

Great. And then can you -- maybe switching to Fragile X. Can you just remind us what needs to happen between now and when you start Phase II study in the back half?

偉大的。然後您可以 - 也許切換到脆性 X。您能否提醒我們，從現在到後半段開始第二階段研究時需要發生什麼事？

Yes. Thanks for the follow-up on the MRM-3379. So we're busy putting together the IND now. In the background, what we've been working on is study planning, having a dialogue with FDA on that. And this is an IND with a new division, so that's really what we've been working on to date.

是的。感謝您對 MRM-3379 的關注。所以我們現在正忙著整理 IND。在幕後，我們一直在進行研究規劃，並就此與 FDA 進行對話。這是一個擁有新部門的 IND，所以這確實是我們迄今為止一直在做的事情。

And as we get close to kind of first patient in, we'll provide a more detailed update on what that study design looks like. No change overall from kind of how we thought about from the high-level summary thoughts, but we'll provide further detail later this year.

當我們接近第一位患者時，我們將提供有關該研究設計的更詳細更新。總體而言，與我們的高層總結想法相比，沒有什麼變化，但我們將在今年稍後提供進一步的細節。

Michael Ulz, Morgan Stanley.

摩根士丹利的邁克爾·烏爾茲。

This is Selena on for Mike. Could you give us an update on the LIVMARLI access versus competitors? And how step-through policies in Alagille and PFIC are improving?

這是 Selena 為 Mike 表演的。您能否向我們介紹 LIVMARLI 與競爭對手的訪問情況？Alagille 和 PFIC 的分步政策進展如何？

Yes. Thanks for the question, Selena. Yes, the access to the LIVMARLI in the US is very strong. I really don't see that being a barrier for us in either indication.

是的。謝謝你的提問，賽琳娜。是的，美國的 LIVMARLI 訪問量非常大。我確實不認為這對我們而言是一個障礙。

Yes, as you know, there are some policies that have the LIVMARLI in a preferential position in Alagille indication from a step-through perspective, which is certainly a beneficial aspect. But I think overall, really see the differentiating factors for LIVMARLI being the strong clinical value proposition and the support that Mirum provides and the access is really not a barrier.

是的，如您所知，從逐步的角度來看，有些政策使 LIVMARLI 在 Alagille 適應症中處於優先地位，這當然是一個有利的方面。但我認為總體而言，LIVMARLI 的真正差異化因素是強大的臨床價值主張和 Mirum 提供的支持，而且訪問實際上並不是障礙。

Mani Foroohar, Leerink Partners.

Mani Foroohar，Leerink Partners。

You have Ryan on for Mani. I was just hoping you can talk about your expectations for the VISTAS study in terms of pruritus reduction. Should we look to VANTAGE as a good benchmark for absolute reduction from baseline? And then just how you guys see that volixibat being positioned within the PSC landscape?

你讓 Ryan 代替 Mani。我只是希望您能談談您對 VISTAS 研究在減少搔癢方面的期望。我們是否應該將 VANTAGE 視為基線絕對減量的良好基準？那麼你們如何看待 volixibat 在 PSC 領域中的地位？

Ryan, thanks for the question there. First, you're giving some background on data expectations, and then I'll ask Peter to speak through the competitive positioning on the commercial side for looking forward. In terms of our expectations, how we think about volixibat's activity level, the VANTAGE interim result really is the most robust data set we have. And really, it's consistent with what we see for IBAT that is really fully dosed in the cholestatic pruritus setting. So optimistic that we can be in that range of activity level for the VISTAS study.

Ryan，謝謝你的提問。首先，您給出了一些有關數據預期的背景信息，然後我會請彼得談談商業方面的競爭定位，以供展望。就我們的預期而言，我們如何看待 volixibat 的活動水平，VANTAGE 中期結果確實是我們擁有的最強大的資料集。事實上，這與我們在膽汁淤積性搔癢症環境中觀察到的 IBAT 完全劑量一致。我們非常樂觀，認為 VISTAS 研究的活動量能夠達到這個範圍。

I'd refer back actually to that DDW abstract that I mentioned in my prepared remarks, where with the higher doses of LIVMARLI in that -- in those compassionate use patients, you're driving pretty substantial pruritus reductions. One thing to note is that scale actually is the Clinician Scratch Scale. So only a 0% to 4% range. So getting a 2-point reduction on that scale is really powerful. So overall, we feel good about how we've dosed and set up the study design for VISTAS to use Vantage as an example of what we could be seeing.

我實際上要回顧一下我在準備好的發言中提到的 DDW 摘要，其中，在那些同情用藥患者中使用較高劑量的 LIVMARLI，可以顯著減少瘙癢症狀。需要注意的一點是，該量表實際上是臨床醫生划痕量表。所以只有 0% 到 4% 的範圍。因此，在這個範圍內減少 2 個百分點確實非常有力。因此總體而言，我們對 VISTAS 的劑量和研究設計感到滿意，以使用 Vantage 作為我們所能看到的結果的範例。

I may turn it over to Peter for the market dynamics.

我可能會把市場動態交給彼得。

Yes. And in terms of the market dynamics, Brian, the work we've done in PSC, probably not surprising to you, obviously, no FDA-approved therapies. I'd characterize it as a very satisfied market. It's just not satisfactory therapy from the perspective of prescribers or patients. So you do have some of the off-label therapies that we see get used in our other indications, pediatric as well as adult. But I'd say the satisfaction with those is quite low. So really excited for PSC patients with pruritus upon a potential approval here for volixibat, I think it just really have a strong, highly preferred position in the market without meaningful competition.

是的。就市場動態而言，布萊恩，我們在 PSC 所做的工作可能不會讓你感到驚訝，顯然，沒有 FDA 批准的療法。我認為這是一個非常滿意的市場。從開藥者或患者的角度來看，這並不是令人滿意的治療方法。因此，我們確實看到一些非說明書療法被用於其他適應症，包括兒科和成人。但我想說，人們對這些的滿意度相當低。因此，對於患有搔癢症的原發性硬化性膽管炎 (PSC) 患者來說，當 volixibat 有可能獲得批准時，我真的感到非常興奮，我認為它在市場上確實擁有強大且高度優先的地位，並且沒有實質性的競爭。

David Lebowitz, Citi.

花旗銀行的 David Lebowitz。

A couple of questions on the numbers regarding the inventory, which you said, I believe, was the first time this quarter. Should people see this as being steady state right now? Or are you still learning about where, ultimately, inventory levels will sit. And on the one timers and whatnot in the operating spend, could you just comment on what we should see in that regard later in the year?

關於庫存數字，我有幾個問題，我相信您說這是本季第一次出現這種情況。人們現在應該將其視為穩定狀態嗎？或者您仍在了解庫存水準最終將處於什麼水準。關於一次性支出和其他營運支出，您能否評論一下我們在今年稍後應該看到什麼？

I'll turn it over to maybe Peter to comment on the inventory and have Eric talk through some of the other line items.

我會把它交給彼得來評論庫存，並讓艾瑞克談談其他一些項目。

Yes. I mean, in terms of the inventory and what we saw in Q1, really, as we've expanded our international partner markets, you can kind of think of -- there's really two kinds of orders that we've seen over the years. And up until now, it's really been orders, the first kind, where there's a patient identified, there's a prescriber, there's a payer and there's an order. Oftentimes, they're ordering three or six or even nine months of product, but there's consumption happening right after that order. That's why our international number has been a little bit lumpy over the years.

是的。我的意思是，就庫存和我們在第一季看到的情況而言，隨著我們擴大國際合作夥伴市場，您可以想到——這些年來我們實際上看到了兩種訂單。到目前為止，這實際上都是命令，即第一種，其中有確定的患者、有開處方的醫生、有付款人，然後有命令。他們通常會訂購三個月、六個月甚至九個月的產品，但訂單完成後就會立即消費。這就是為什麼這些年來我們的國際數字一直有點不穩定。

This is a new one here of what we saw in Q1, which is, as we kind of added partners, we have new partners coming online where they're ordering and they're kind of holding [it's] truly stock or in a warehouse. And it will pull through to demand sales in 2025. But I think it's important to think about as you trended out going quarter over quarter that it was really a Q1 event.

這是我們在第一季看到的新情況，也就是說，隨著我們增加合作夥伴，我們有新的合作夥伴上線訂購，並將其作為真正的庫存或存放在倉庫中。並將在2025年實現銷售需求。但我認為，重要的是要考慮，隨著季度變化趨勢的推進，這實際上是第一季的事件。

Yes. And as for your milestone question, yes, we do have [milestones] to our business, both tied to development and regulatory progress as well as commercial projects. This one happened to be tied to development progress. We don't gave specific guidance on what we can expect for the rest of the year. But as we continue to progress our business, we expect and hope there will be additional milestones showing steady progress (technical difficulty)

是的。至於您提到的里程碑問題，是的，我們的業務確實有里程碑，既與開發和監管進度有關，也與商業項目有關。這恰好與開發進度有關。我們沒有對今年剩餘時間的預期給予具體的指導。但隨著我們業務的不斷進步，我們期望並希望會有更多里程碑顯示穩步進展（技術難度）

Ryan Deschner, Raymond James.

瑞安‧德施納、雷蒙‧詹姆斯。

Curious what your expectations for the impact of the tablet formulation of LIVMARLI on demand and competitive positioning is, as well as what proportion of Alagille patients you think or you'd expect to opt for the tablet at a more steady state? And would you expect this to drive meaningful switch demand.

好奇您對 LIVMARLI 片劑配方對需求和競爭定位的影響有何預期，以及您認為或預計有多少比例的 Alagille 患者會在更穩定的狀態下選擇該片劑？您是否期望這會推動有意義的轉換需求？

Yes. Thanks, Ryan. I mean, I think it will be a really attractive option for Alagille and PFIC patients that are -- the label really is for 25 kilos and over, which most of the time that's going to be when you're between 8 and 10 years old. So I think having a single tablet per dose is quite attractive.

是的。謝謝，瑞安。我的意思是，我認為這對 Alagille 和 PFIC 患者來說是一個非常有吸引力的選擇——標籤上實際上寫的是 25 公斤及以上，大多數情況下，這是在 8 到 10 歲之間。所以我認為每劑一片藥片是相當有吸引力的。

Most of these patients are on background therapies or so in other therapies, so pill burden is an issue. So being able to offer one tablet is, I think, pretty attractive. Probably, the average patient is still under 8 years old. So I think probably, in that case, I think the liquid will be preferred there. But a substantial minority of them, I would think, would probably see the tablet as a pretty attractive option.

大多數患者都接受背景療法或其他療法，因此藥物負擔是一個問題。因此，我認為能夠提供一台平板電腦非常有吸引力。可能，平均患者年齡仍未滿 8 歲。所以我認為，在這種情況下，液體在那裡會更受歡迎。但我認為，其中相當一部分人可能會認為平板電腦是一個非常有吸引力的選擇。

And I think this could drive -- we could see patients that are on the liquid solution now on LIVMARLI switch to tablet. You could imagine clinical scenarios where you have a teenager or a young adult who has kind of been thinking about an IBAT or about LIVMARLI, and now you have a more convenient option. They want to be able to go to school, go travel. So you can imagine a variety of different new patients and switch scenarios.

我認為這可以推動——我們可以看到現在使用 LIVMARLI 液體溶液的患者改用藥片。你可以想像臨床場景，你有一個青少年或年輕人，他一直在考慮 IBAT 或 LIVMARLI，現在你有了一個更方便的選擇。他們希望能夠去上學、去旅行。因此你可以想像各種不同的新病人和轉換場景。

(Operator Instructions) Brian Skorney, Baird.

（操作員指示）Brian Skorney，Baird。

This is Luke on for Brian. Congrats on the quarter. On CTEXLI, could you provide a bit of insight on the rate of patient identification since approval as well as your go-forward expectations?

這是盧克為布萊恩表演的。恭喜本季取得佳績。關於 CTEXLI，您能否提供一些關於自批准以來患者識別率的見解以及您對未來的期望？

Thanks, Philip, for the question. I'll actually ask Peter to maybe talk about a couple of our efforts on that front.

謝謝菲利普提出這個問題。我實際上會請彼得談談我們在這方面所做的一些努力。

Yes, yes. And like we said in our prepared comments, we're excited. We've seen a nice uptick from the historical rate, as you know, chenodiol has been available for a while, and we've seen a nice uptick since February. I think some of it is just coming from promotion and kind of being out there and having an FDA-approved product for the indication matters, I think, to clinicians and patients. So we've seen that.

是的，是的。正如我們在準備好的評論中所說的那樣，我們很興奮。我們看到歷史價格出現了良好的上漲，正如你所知，鵝去氧膽酸已經上市一段時間了，自二月以來，我們看到了良好的上漲。我認為部分原因在於推廣和上市，並且擁有經 FDA 批准的適應症產品對臨床醫生和患者來說很重要。我們已經看到了這一點。

We've also invested in disease awareness because a lot of the challenge here is making the diagnosis. So kind of work towards raising awareness of presenting symptoms in neurology where often this can present as ataxia and motor coordination issues. Ophthalmology is other area where you can see patients presenting bilateral cataracts and trying to raise an index of suspicion there to do genetic testing. And those efforts have kind of borne through GI patients with chronic diarrhea without other explanation. So kind of focused in some of these different areas, and that's been kind of where we made progress so far.

我們也對疾病意識進行了投資，因為這裡的許多挑戰在於診斷。因此，我們致力於提高人們對神經病症狀的認識，這些症狀通常表現為共濟失調和運動協調問題。眼科是另一個可以看到雙側白內障患者並試圖提高懷疑指數以進行基因檢測的領域。這些努力對於患有慢性腹瀉的胃腸道患者來說已經產生了效果，無需其他解釋。因此，我們集中精力於這些不同的領域，這也是我們迄今為止取得進展的地方。

Jon Walden, Citizens.

喬恩·沃爾登，公民。

This is Katherine on for Jon. I just had two quick questions. What about PFIC and the launch in the US as well as ex-US. How is that comparing to expectations? And then also, can you comment on the sustainability of the profitability into 2026?

這是凱瑟琳為喬恩表演的。我只有兩個簡單的問題。PFIC 在美國和美國以外地區的推出情況如何？與預期相比如何？另外，您能否評論一下 2026 年獲利能力的可持續性？

Thanks, Katherine, for the question. I mean, a quick comment on PFIC launch, and I'll pass it over to Eric on the profitability question. I mean, the PFIC launch actually has been going -- I'd describe it as quite a bit better than expectations. But it's still -- that means relatively small numbers because PFIC is a small indication overall compared to Alagille.

謝謝凱瑟琳提出這個問題。我的意思是，對 PFIC 的發布做一個簡短的評論，然後我會把它交給 Eric 來回答盈利能力的問題。我的意思是，PFIC 的發布實際上已經開始了——我認為它比預期的要好得多。但它仍然——這意味著相對較小的數字，因為與 Alagille 相比，PFIC 總體上是一個較小的指標。

But we're excited about what we're seeing and really attribute that to a great team here at Mirum that's out there spreading the word. And then also just really compelling data coming out of the Phase III program, where you see placebo-controlled improvements in growth in bilirubin or some of these things that are really impactful.

但我們對於所看到的一切感到非常興奮，並將此歸功於 Mirum 的優秀團隊，他們一直在努力傳播這一訊息。然後，第三階段計畫中也出現了非常令人信服的數據，你可以看到安慰劑對照的膽紅素成長有所改善，或者說，其中一些確實有影響。

And then maybe Eric can speak to the probability question.

然後埃里克也許可以談談機率問題。

Yes. So to be clear, we were cash flow positive in the first quarter, and we're expecting to be cash positive for the full year. Profitability is a different issue because we have a number of non-cash charges. And so we're not expecting to be profitable anytime soon in sort of the GAAP sense, but cash flow positive is what we're focused on.

是的。因此需要明確的是，我們第一季的現金流為正，我們預計全年的現金流也將為正值。獲利能力是一個不同的問題，因為我們有許多非現金費用。因此，我們並不期望在短期內按照 GAAP 原則實現盈利，但我們關注的是現金流為正。

Thank you very much. So that was our final question. I will hand back over to the CEO, Chris Peetz, for any final remarks.

非常感謝。這是我們的最後一個問題。我將把權力交還給執行長克里斯·皮茨 (Chris Peetz)，讓他做最後的演講。

Great. Well, thank you all for joining us today, and hope you all have a great day. Bye.

偉大的。好吧，感謝大家今天的加入我們，並祝福大家有個愉快的一天。再見。

Thank you, everyone, for joining today's call. Have a great day. You may now disconnect.

感謝大家參加今天的電話會議。祝你有美好的一天。您現在可以斷開連線。