Mirum Pharmaceuticals Inc (MIRM) 2025 Q3 法說會逐字稿

Hello, and welcome to the Mirum Pharmaceuticals third quarter 2025 financial results and business update. My name is Harry, and I'll be your operator today. (Operator Instructions)

大家好，歡迎收聽 Mirum Pharmaceuticals 2025 年第三季財務業績和業務更新報告。我叫哈里，今天由我來為您接聽電話。（操作說明）

I would now like to hand the conference over to Andrew McKibben, SVP of Strategic Finance and Investor Relations. Please go ahead.

現在我謹將會議交給策略財務與投資者關係資深副總裁 Andrew McKibben。請繼續。

Thanks, Harry, and good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals third quarter 2025 conference call. I'm joined today by our CEO, Chris Peetz; our President and Chief Operating Officer, Peter Radovich; a Chief Medical Officer, Joanne M. Quan; and Eric Bjerkholt, our Chief Financial Officer.

謝謝你，哈里，大家下午好。歡迎各位參加Mirum Pharmaceuticals 2025年第三季電話會議。今天與我一同出席的有：執行長克里斯·皮茨；總裁兼營運長彼得·拉多維奇；首席醫療官喬安妮·M·關；以及首席財務官埃里克·比耶克霍爾特。

Earlier today, Mirum issued a news release announcing the company's results for the third 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發布新聞稿，公佈了該公司2025年第三季的業績。本新聞稿和提交給美國證券交易委員會的文件副本可在我們網站的投資者關係部分找到。

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.

在會議開始之前，我想提醒各位，在本次電話會議期間，我們將根據管理層目前的預期做出一些前瞻性聲明，包括有關 Mirum 公司已獲批准藥物和候選產品的計劃和市場機會的聲明。

These statements represent our judgment and knowledge of events as of today and inherently involve risks and uncertainties that may cause 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 subsequent SEC filings for more information.

這些陳述代表了我們截至今日對事件的判斷和了解，其中必然包含風險和不確定性，可能導致實際結果與所討論的結果有重大差異。我們沒有義務更新這些聲明。有關更多信息，請參閱我們最新的 10-Q 表格及後續提交給美國證券交易委員會 (SEC) 的文件中的風險因素部分。

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

接下來，我想把電話交給克里斯。克里斯？

Thanks, Andrew, and good afternoon, everyone. 2025 continues to be an outstanding year for Mirum. We've created a leading rare disease company, purpose built to create and deliver life-changing medicines to patients. Our success comes from that foundation. The team deeply connected to patients and families turning their insights into meaningful therapies and measurable performance.

謝謝安德魯，大家下午好。 2025年對Mirum來說依然是輝煌的一年。我們創立了一家領先的罕見疾病公司，其宗旨是為患者研發和提供改變生命的藥物。我們的成功源自於此。團隊與患者及其家屬建立了深厚的聯繫，並將他們的見解轉化為有意義的療法和可衡量的療效。

In the third quarter, we delivered strong commercial results, advanced our clinical pipeline and strengthened our financial foundation. I'm proud of the way our team continues to execute with focus and consistency. First, on commercial performance. We reported third quarter revenue of $133 million, representing a nearly 50% year-over-year increase over the same period last year. This performance reflects the strength and breadth of our commercial portfolio, including continued momentum from the US PFIC launch and expanding demand from our international markets.

第三季度，我們取得了強勁的商業業績，推進了臨床研發管線，並鞏固了財務基礎。我為我們團隊持續專注、穩定地執行任務而感到自豪。首先，從商業表現來看。我們公佈的第三季營收為 1.33 億美元，比去年同期成長近 50%。這一業績反映了我們商業組合的實力和廣度，包括美國 PFIC 上市的持續勢頭以及國際市場不斷增長的需求。

Turning to R&D. We remain on track for three potentially pivotal readouts over the next 18-months. First up is the VISTAS Phase 2b study in PSC. With enrollment complete, we expect to announce top line data in the second quarter of 2026. With the successful interim analysis last year and a consistent body of supporting data with IBAT inhibitors across multiple cholestatic diseases, we're optimistic about volixibat's potential to become the first approved treatment in this setting.

轉向研發。我們仍有望在未來 18 個月內獲得三個可能具有關鍵意義的讀數。首先是 VISTAS 針對 PSC 的 2b 期研究。招生工作完成後，我們預計將於 2026 年第二季公佈主要數據。去年成功的期中分析以及 IBAT 抑制劑在多種膽汁淤積性疾病中持續獲得的支持性數據，讓我們對沃利西巴特有望成為該領域首個獲批療法充滿信心。

We are also progressing well with our VANTAGE study of volixibat in PDC, the EXPAND study of LIVMARLI in ultra rare cholestatic conditions and our newly initiated Phase 2, study of MRM-3379 and Fragile X syndrome. We've also taken meaningful steps to further strengthen our financial performance. This quarter, our cash balance grew significantly, and we recognized positive net income for the first time. This is an important milestone that highlights the operating leverage in our commercial model.

我們在 VANTAGE 研究（針對 pDC 中的 volixibat）、EXPAND 研究（針對超罕見膽汁淤積症中的 LIVMARLI）以及我們新啟動的 MRM-3379 和脆性 X 綜合徵的 2 期研究方面也取得了良好進展。我們也採取了實際有效的措施，進一步提升了財務表現。本季度，我們的現金餘額大幅成長，並且我們首次實現了正淨利潤。這是一個重要的里程碑，凸顯了我們商業模式的營運槓桿作用。

In sum, it has been another solid quarter of execution from Mirum. I want to thank the entire Mirum team for their continued dedication to patients. We built a high-growth cash flow-positive rare disease company with a broad pipeline and global footprint, and we're just getting started.

總而言之，Mirum 又一個季度表現出色。我要感謝Mirum團隊全體成員對病人的持續奉獻。我們打造了一家高成長、現金流為正的罕見疾病公司，擁有廣泛的產品線和全球佈局，而這只是個開始。

And with that, I'll hand the call over to Peter.

接下來，我將把電話交給彼得。

Peter?

彼得？

Thanks, Chris. Q3 was another excellent quarter for Mirum with total net product sales of $133 million. This was driven by continued robust performance of LIVMARLI in both the US and international markets as well as steady contribution from our bile acid portfolio.

謝謝你，克里斯。Mirum 第三季業績依然出色，淨產品銷售額達 1.33 億美元。這主要得益於 LIVMARLI 在美國和國際市場的持續強勁表現，以及我們膽汁酸產品組合的穩定貢獻。

LIVMARLI net product sales totaled $92 million for the quarter. In the US, LIVMARLI demand remains healthy in both ALGS syndrome and PFIC with $64 million in net product sales. ALGS syndrome growth remains durable, and PFIC continues to contribute meaningfully, reflecting the real-world benefit of expanded diagnosis and increased genetic screening.

LIVMARLI 本季淨產品銷售額總計 9,200 萬美元。在美國，LIVMARLI 在 ALGS 症候群和 PFIC 方面的需求依然旺盛，淨產品銷售額達 6,400 萬美元。ALGS 症候群的成長動能依然強勁，PFIC 也繼續發揮重要作用，這反映了擴大診斷和增加基因篩檢在現實世界中的益處。

As we begin reaching into broader segments of the medical community, particularly adult-focused providers, we're finding that genetic testing is still less embedded in practice and often requires more education and dialogue. So we view this as an area where sustained engagement can continue to drive incremental gains.

當我們開始接觸更廣泛的醫療界群體，特別是以成人為中心的醫療服務提供者時，我們發現基因檢測在實踐中的普及程度仍然較低，通常需要更多的教育和對話。因此，我們認為這是一個可以透過持續參與不斷取得進展的領域。

Internationally, LIVMARLI demand continues to grow with $28 million in net product sales this quarter. Demand across our direct and partner markets remains robust, supported by expanding reimbursement and launches in new geographies. Q3 was the first full quarter of commercialization for our partner, Takeda and Japan, with in-market adoption dynamics generally consistent with LIVMARLI's US launch.

在國際市場上，LIVMARLI 的需求持續成長，本季淨產品銷售額達 2,800 萬美元。在報銷範圍擴大和新地區產品上市的支持下，我們直接市場和合作夥伴市場的需求仍然強勁。第三季度是我們的合作夥伴武田製藥和日本實現商業化的第一個完整季度，市場接受度動態與 LIVMARLI 在美國的上市情況基本一致。

Our Bile Acid Medicines, CHOLBAM and CTEXLI generated $41 million in net product sales this quarter, supported by increased CTX patient finding following CTEXLI's FDA approval earlier this year. And I'm happy to say that we now expect to land in the upper end of our prior full year 2025 guidance range with $500 million to $510 million in revenues.

我們的膽汁酸藥物 CHOLBAM 和 CTEXLI 本季淨產品銷售額達 4,100 萬美元，這得益於 CTEXLI 今年稍早獲得 FDA 批准後，CTX 患者數量的增加。我很高興地宣布，我們現在預計 2025 年全年營收將達到先前預測範圍的上限，為 5 億美元至 5.1 億美元。

This reflects the continued strength of our US business in both ALGS syndrome and PFIC, steady contributions from our bile acid portfolio along with the typical quarter-to-quarter variability in international partner and distributor ordering patterns. Looking ahead, we continue to see substantial growth potential across our portfolio with peak revenue potential for LIVMARLI, volixibat and MRM-3379 each exceeded $1 billion.

這反映了我們在美國ALGS綜合症和PFIC業務的持續強勁勢頭，膽汁酸產品組合的穩定貢獻，以及國際合作夥伴和分銷商訂單模式典型的季度間波動。展望未來，我們繼續看到我們產品組合中存在巨大的成長潛力，其中 LIVMARLI、volixibat 和 MRM-3379 的峰值收入潛力均超過 10 億美元。

And then with that, I'll turn it over to Joanne for an update on the pipeline.

接下來，我將把麥克風交給喬安妮，請她報告管道的最新進展。

Joanne?

喬安妮？

Thanks, Peter. I'm pleased to provide an update on the continued progress across our clinical pipeline, where we're seeing continued collaboration and momentum with physicians and patients across all of our ongoing studies.

謝謝你，彼得。我很高興向大家報告我們臨床研發管線的持續進展，我們看到在所有正在進行的研究中，我們與醫生和患者的合作都在不斷推進，並取得了良好的勢頭。

Starting with volixibat, we completed enrollment in the Phase 2b VISTAS study and primary sclerosing cholangitis, or PSC, and expect to announce top line data in the second quarter of 2026. PSC represents a significant area of unmet need with no approved therapies and limited treatment options. We're deeply grateful to the investigators and the PSC patient community for their partnership in advancing this important study.

從volixibat開始，我們完成了2b期VISTAS研究和原發性硬化性膽管炎（PSC）的入組，預計2026年第二季公佈主要數據。PSC代表一個亟待滿足的龐大醫療需求領域，目前尚無核准療法，治療選擇也十分有限。我們衷心感謝研究人員和原發性硬化性膽管炎 (PSC) 患者群體在推進這項重要研究過程中給予的合作。

As a reminder, the outcome of the interim analysis of the VISTAS study last year was what we'd hoped for. The recommendation was to keep the current sample size, which we believe reflects a strong signal for the final analysis. It's worth noting that the study was powered using conservative assumptions, a placebo-adjusted treatment effect of 1.75 points and standard deviation of three.

提醒一下，去年 VISTAS 研究的中期分析結果正是我們所希望的。建議保持目前的樣本量，我們認為這反映了最終分析的強烈訊號。值得注意的是，研究採用了保守的假設，安慰劑調整後的治療效果為 1.75 分，標準差為 3。

A case series is being presented at AASLD of eight PSC patients treated with maralixibat under our compassionate use program, a continuation of a case series presented earlier this year at DDW. All of these patients had meaningful reductions in pruritus and four of the eight had complete resolution. This data supports the role for IBAT inhibition as a treatment for PSC.

在 AASLD 上，我們將展示 8 例 PSC 患者在我們的同情用藥計劃下接受 maralixibat 治療的病例係列，這是今年早些時候在 DDW 上展示的病例係列的延續。所有這些患者的搔癢症狀都得到了顯著減輕，其中 8 名患者中有 4 名患者的搔癢症狀完全緩解。這些數據支持 IBAT 抑製作為 PSC 治療方法的作用。

Turning to PBC. The VANTAGE study continues to progress well, and we expect to complete enrollment next year. Interim data presented last year demonstrated statistically significant improvement in pruritus, meaningful reductions in serum bile acids and encouraging improvements in fatigue. We're excited to advance this study through the informatory stage. Additional analyses from the VANTAGE interim will be presented at AASLD which highlights the decreases in fatigue and improvement in sleep, in helipad patients as well as showing a decrease in IL-31 in treated patients.

轉向PBC。VANTAGE 研究進展順利，我們預計明年完成招募工作。去年公佈的中期數據顯示，搔癢症狀有統計學意義上的顯著改善，血清膽汁酸水平有顯著降低，疲勞症狀也有令人鼓舞的改善。我們很高興這項研究能夠順利進入資訊收集階段。VANTAGE 中期研究的更多分析結果將在 AASLD 會議上公佈，這些分析結果突顯了直升機停機坪患者的疲勞減輕和睡眠改善，以及接受治療的患者 IL-31 水平的降低。

Our EXPAND study evaluating LIVMARLI in additional settings of cholestatic pruritus is also enrolling well. This study is designed to broaden access to patients across multiple rare cholestatic diseases who currently have few or no treatment options. It represents a meaningful label expansion opportunity and we're targeting enrollment completion in 2026.

我們正在進行的 EXPAND 研究，旨在評估 LIVMARLI 在其他膽汁淤積性搔癢症的應用，目前研究的招募工作進展順利。這項研究旨在擴大多種罕見膽汁淤積症患者的治療機會，這些患者目前幾乎沒有或根本沒有治療選擇。這代表著一個意義重大的標籤擴展機會，我們的目標是在 2026 年完成註冊。

Finally, I'm excited to share that we've initiated our Phase 2 study of MRM-3379, our brain-penetrant PDE4D inhibitor for Fragile X syndrome. The preclinical data we recently presented from a mouse FMR1 knockout model of Fragile X, showed that MRM-3379 reversed the disease phenotype across multiple behavioral assessments and increases our confidence in the importance of this pathway in Fragile X. Overall, we're very encouraged by the progress across our development programs and look forward to upcoming milestones in 2026.

最後，我很高興地宣布，我們已經啟動了 MRM-3379 的 2 期研究，MRM-3379 是一種可穿透血腦屏障的 PDE4D 抑制劑，用於治療脆性 X 症候群。我們近期發表的來自脆性X症候群小鼠FMR1基因敲除模型的臨床前數據顯示，MRM-3379在多項行為評估中逆轉了疾病表型，這增強了我們對該通路在脆性X綜合徵中重要性的信心。整體而言，我們對各項研發項目的進展感到非常鼓舞，並期待2026年取得新的里程碑式進展。

With that, I'll turn the call over to Eric to discuss our financial results.

接下來，我將把電話交給艾瑞克，讓他來討論我們的財務表現。

Eric?

艾瑞克？

Thanks, Joanne, and good afternoon, everyone. We delivered another solid quarter of financial performance, highlighted by total net product revenue of $133 million representing a 47% increase over the prior year and reflecting growth across all our commercial medicines. This quarter included approximately $5 million in sales to our partner Takeda in Japan.

謝謝喬安妮，大家下午好。我們又實現了穩健的季度財務業績，其中淨產品總收入達到 1.33 億美元，比上年增長 47%，反映了我們所有商業藥物的增長。本季向我們在日本的合作夥伴武田製藥公司銷售額約為 500 萬美元。

We do not expect additional sales to Takeda in Q4 of this year. Total operating expense for the quarter ended September 30, was $130 million, which includes R&D expense of $43 million, SG&A expense of $62 million and cost of sales of $26 million.

我們預計今年第四季不會向武田公司追加銷售額。截至 9 月 30 日的季度總營運費用為 1.3 億美元，其中包括研發費用 4,300 萬美元、銷售、一般及行政費用 6,200 萬美元及銷售成本 2,600 萬美元。

Expenses for the quarter included non-cash stock-based compensation expense of $18 million an intangible amortization and other non-cash items of $6 million. Intangible amortization and other non-cash items expense are largely reflected in our cost of sales.

本季支出包括 1,800 萬美元的非現金股票選擇權費用、600 萬美元的無形資產攤銷和其他非現金項目。無形資產攤銷和其他非現金項目支出主要反映在我們的銷售成本中。

Our cash operating margins continued to improve, and we delivered GAAP profitability in the third quarter, generating approximately $3 million in net income. While this reflects the strength and scalability of our business model, we view quarterly GAAP profitability as a milestone, not yet a consistent expectation as we continue to invest in growth.

我們的現金營運利潤率持續改善，第三季實現了 GAAP 盈利，淨收入約為 300 萬美元。雖然這反映了我們商業模式的實力和可擴展性，但我們認為季度 GAAP 獲利能力是一個里程碑，而不是一個持續的預期，因為我們將繼續投資於成長。

Cash, cash equivalents and investments were $378 million at September 30, an $85 million increase from the beginning of the year. We continue to be well funded and financially independent, providing us the resources required to expand our patient impact and grow our business.

截至9月30日，現金、現金等價物和投資為3.78億美元，比年初增加了8,500萬美元。我們資金充足，財務獨立，這為我們提供了擴大對患者的影響和發展業務所需的資源。

With that, I'll turn the call back to Chris.

這樣，我就把電話轉回給克里斯了。

Thanks, Eric. Before we open the call for questions, I want to close by reflecting on what's been an incredibly productive quarter. Across every dimension of our business, commercial, clinical and operational, we continue to execute with purpose and discipline, anchored by the same patient-centric approach that's driven our success from the start. That's what's enabled us to become a high-growth cash flow positive leading rare disease company. Thanks again to the Mirum team, to the patients and families who inspire our work every day.

謝謝你，埃里克。在正式開始提問環節之前，我想以回顧這個碩果累累的季度作為結尾。在業務的各個方面，包括商業、臨床和運營，我們都秉持著以患者為中心的理念，以目標為導向，不斷執行，正是這種理念從一開始就推動了我們的成功。正是這一點使我們成為一家高成長、現金流為正的領先罕見疾病公司。再次感謝Mirum團隊，感謝每天激勵我們工作的病人和家屬。

With that, operator, please open the call for questions.

接線員，現在開始接受提問。

(Operator Instructions) Jessica Fye, JPMorgan.

（操作說明）潔西卡費伊，摩根大通。

This is (inaudible) on for Jess. We just have two questions. What are going to be the key drivers of LIVMARLI's performance as we look at '26? And can you talk about why the midpoint of the new guidance range now implies 4Q reps flat sequentially from 3Q?

這是（聽不清楚）給傑西的。我們只有兩個問題。展望 2026 年，LIVMARLI 業績的關鍵驅動因素是什麼？您能否解釋一下，為什麼新的業績指引範圍的中點意味著第四季業績將與第三季持平？

I don't think we saw that dynamic last year. Thanks.

我認為去年我們並沒有看到這種趨勢。謝謝。

Thanks for the question. On key drivers in the 2026, I mean, we see a lot of basically what we have today rolling forward into next year. We expect that we'll probably give guidance early in the year next year on what that year looks like. But we are in early innings of the PFIC launch, both in the US and internationally.

謝謝你的提問。關於 2026 年的關鍵驅動因素，我的意思是，我們看到今天很多事情基本上都會延續到明年。我們預計明年年初可能會公佈明年的發展方向。但無論是在美國還是國際上，PFIC 的啟動都還處於早期階段。

So expect that to continue to build in over time. And I think for the guidance this year for Q4, maybe I ask Peter to speak to what we see from kind of the quarter-to-quarter dynamics.

所以預計這種情況會隨著時間的推移而持續發展。對於今年第四季的業績指引，我認為或許應該請 Peter 談談我們從季度間的動態變化中看到了什麼。

Yeah. Thanks, Chris, and appreciate the question. The main dynamic is tried to highlight in our prepared remarks. We see growth for LIVMARLI US. We see the bile acid portfolio continuing to do what it does. It's really the LIVMARLI international line where we expect variability as we move quarter-to-quarter, as we've talked about before, that business has periodic large orders from distributors.

是的。謝謝克里斯，謝謝你的提問。我們在準備好的發言稿中試圖強調主要動態。我們看到 LIVMARLI 美國業務成長。我們看到膽汁酸產品組合繼續發揮其應有的作用。正如我們之前討論過的，LIVMARLI 國際產品線確實存在季度波動，我們預計其業務會定期收到來自分銷商的大訂單。

And we saw those come in Q3, we also mentioned that we had Takeda revenue in Q3, which we also had Q1 in Q2 that we don't expect in Q4. So there's a fair bit of inventory build there. So that's really the dynamic is in the LIVMARLI international line.

我們看到這些收入在第三季到賬，我們也提到第三季有武田的收入，第二季也有第一季的收入，但我們預計第四季不會有這些收入。所以那裡積壓了不少庫存。這就是 LIVMARLI 國際產品線的真正動態。

Josh Schimmer, Cantor.

喬許希默，坎托爾。

Thanks for taking the questions. Maybe I have two quick ones. First, what trends are you seeing in terms of adoption of the solid tablet formulation of LIVMARLI and what percent of sales are for that versus the liquid? And then for volixibat, what are you thinking in terms of the appropriate price analogs, especially after we've seen a significant increase in rare orphan disease prices perhaps over the last year, particularly for conditions that perhaps are less prevalent than PBC and more aligned with PSC.

謝謝您回答問題。或許我可以快速回答兩個問題。首先，您觀察到 LIVMARLI 固體片劑製劑的採用趨勢如何？其銷售額佔總銷售額的百分比與液體製劑的銷售額佔比為何？那麼對於沃利西巴特（volixibat），您認為合適的定價參考值是什麼？尤其是在過去一年裡，我們看到罕見孤兒藥的價格大幅上漲，特別是對於那些可能不如原發性膽汁性膽管炎（PBC）常見，而更接近原發性硬化性膽管炎（PSC）的疾病而言。

Thank you.

謝謝。

Thanks for the questions, Josh. Yeah. So in terms of the solid tablet just launched in the US in mid-June, so this is really our first full quarter with it. And what we've seen a very encouraging kind of uptake and really switches from the liquids. So if you look at the prescribing information, patients are eligible to switch if they're at least 25 kilos.

謝謝你的提問，喬希。是的。所以就這款於 6 月中旬在美國上市的固態平板電腦而言，這實際上是我們使用它的第一個完整季度。我們看到了一個非常令人鼓舞的趨勢，人們開始真正從液體飲料轉向其他飲料。所以，如果你查看處方訊息，你會發現體重至少達到 25 公斤的患者有資格更換藥物。

I think what I could say is that substantial proportion of those who are eligible based on their weight, are switching. So certainly excited about what that can mean long term in terms of persistence and adherence and an easier single tablet per dose format that will be preferred by these adolescents and adults. So excited about that dynamic.

我認為可以說的是，相當一部分符合體重標準的人正在改變做法。因此，我非常興奮地看到，從長遠來看，這對於提高堅持性和依從性，以及每次服用一片的簡便劑量形式，都將受到青少年和成年人的青睞。我對這種動態感到非常興奮。

And then yes, if you look about pricing. Obviously, I haven't made a final decision there to monitor those dynamics that you're talking about. We've kind of base case thinking you can look at the other -- PPARs and the other products that are kind of approved in PBC at [130 to 150] in, but we're still analyzing. I think it's kind of too early to say what the right pricing strategy is --

是的，如果你考慮價格的話。顯然，我還沒有最終決定是否要專注於你所說的那些動態。我們目前的基本情況是，您可以看看其他產品——PPARs 和其他在 PBC 中獲得批准的產品（劑量在 130 到 150 之間），但我們仍在進行分析。我認為現在談論正確的定價策略還為時過早。--

Gavin Clark-Gartner, Evercore.

Gavin Clark-Gartner，Evercore。

Hey guys, thanks for taking the question. Just had one. What's your expectation for Paragraph four filers. Maybe just helpful to lay out your confidence in your whole IP portfolio, especially around the method [patents] and including (inaudible).

各位，謝謝你們回答這個問題。剛吃了一塊。您對第四段申報者有何期望？或許，闡明您對整個智慧財產權組合的信心會很有幫助，尤其是在方法專利方面。（聽不清楚）

Thanks.

謝謝。

Gavin, thanks for the question. Overall, I mean, the -- we're in the window where we could potentially see that in kind of all routine from this point in the life cycle for LIVMARLI, and really quite confident in our overall IP position. In particular, you mentioned the method patents that are specific to dosing of LIVMARLI in these indications. So we've seen this has been really the key fundamental observation that's made all of Mirum possible and the IP behind it, we see is quite strong and a great position and prepared to defend it. So more to come if and when we do see any filers, but nothing to date.

加文，謝謝你的提問。總的來說，我的意思是——我們正處於一個窗口期，在這個窗口期，我們有可能看到 LIVMARLI 從生命週期的這個階段開始，一切都將變得常規化，而且我們對我們整體的知識產權地位非常有信心。您特別提到了針對這些適應症中 LIVMARLI 給藥的具體方法專利。因此，我們看到，這正是Mirum得以實現的關鍵基本觀察，而背後的智慧財產權也相當強大，我們有能力捍衛它。所以，如果真的有申報者出現，我們會及時發布更多信息，但目前還沒有。

[James Condulis, Stifel].

[James Condulis，Stifel]

Hey, thanks for taking our question. This is Mark on for James. So recently on earnings, I know you seem to suggest it's still an open question around sort of what exactly the best endpoint is for the Fragile X study, I wanted to see if you guys had any perspectives on that and sort of the implications for program that you initiated this year.

嘿，謝謝你回答我們的問題。這是馬克為詹姆斯做的報道。最近關於收益，我知道你們似乎暗示脆性X染色體症候群研究的最佳終點究竟是什麼仍然是一個懸而未決的問題，我想看看你們對此有什麼看法，以及這對你們今年啟動的計畫有何影響。

And then we had a second question on PSC and these patients typically kind of have inflammatory disease sort of like morbidities and we know that IBAT inhibitors by nature, sort of have some of the GI side effects. So curious your thoughts on the safety risks there. And if you can see sort of anything in the blinded data on like GI side effects, and whether those look any materially different than, say, PBC or ALGS.

然後我們又問了一個關於原發性硬化性膽管炎 (PSC) 的問題，這些患者通常患有發炎性疾病，我們知道 IBAT 抑制劑本身就具有一些胃腸道副作用。很好奇您對那裡的安全風險有何看法。如果你能從盲法數據中看出一些關於胃腸道副作用的信息，以及這些信息是否與 PBC 或 ALGS 等疾病有實質性的不同。

Thank you.

謝謝。

Yeah, thanks for the question, Mark. I can't really speculate too much on -- is update on what's going on underneath that. But let me turn it to Joanne to talk a little bit about our endpoint strategy and what we're -- our approach on our programs.

是的，謝謝你的提問，馬克。我無法對此進行過多推測——這是關於背後正在發生的事情的最新進展。但讓我把麥克風交給喬安妮，讓她談談我們的最終目標策略以及我們——我們專案的具體方法。

Yeah. Thanks for the question. We feel that we're in a good spot at this point. The preclinical data in terms of this pathway -- the importance of this pathway in Fragile X is quite strong. We recently presented some preclinical data with our compounds in a mouse model, mouse knockout model, which supports efficacy and us moving forward.

是的。謝謝你的提問。我們覺得目前處境不錯。就該通路而言，臨床前數據表明，該通路在脆性X綜合徵中的重要性非常顯著。我們最近展示了一些在小鼠模型和小鼠基因敲除模型中，我們化合物的臨床前數據，這些數據支持了療效，也支持我們繼續前進。

And then we've also had very good engagement with the community with patients and with physicians, we also had a very successful and engaging PND meeting with the FDA earlier this year and they're entirely aware of the range of endpoints that we're looking at, and we're well aware of the types of validations that are needed for these types of outcomes. So I think we're actually in a pretty good spot. A lot of interest in the community, and we're looking forward to conducting the study and seeing what we see.

此外，我們與社區、患者和醫生也保持良好的互動。今年早些時候，我們還與 FDA 舉行了一次非常成功且富有成效的 PND 會議，他們完全了解我們正在研究的終點範圍，我們也清楚地知道這些結果需要哪些類型的驗證。所以我覺得我們目前處境相當不錯。社區對此非常感興趣，我們期待進行這項研究，看看會發現什麼。

And then on the PSC safety standpoint, actually let to Joanne for that.

至於PSC安全方面，其實應該感謝Joanne。

Yeah. And so with regards to that for the PSC study, we've had a data monitoring committee following with us. And so no issues have been raised, no suggested modifications to the protocol. So we feel pretty comfortable there's no big safety issues here. I feel pretty comfortable with moving forward with the way the protocol was initially designed.

是的。所以，關於PSC研究，我們有一個數據監測委員會與我們一起進行追蹤。因此，沒有提出任何問題，也沒有對協議提出任何修改建議。因此我們感覺這裡應該不存在什麼重大的安全問題。我覺得按照最初設計的方案繼續前進是完全可以接受的。

So it's not -- no issues have emerged there.

所以，目前還沒有出現任何問題。

Profile overall is consistent with what we know about IBAT at this point. Thanks for the questions.

整體而言，該概況與我們目前對IBAT的了解相符。謝謝大家的提問。

Joseph Thome, TD Cowen.

Joseph Thome，TD Cowen。

Hi there, good afternoon. Thank you for taking my questions and congrats on the progress. Maybe on the PSC study now that, that one is fully enrolled, are you able to talk a little bit about the baseline criteria of the patients that were enrolled, especially as it relates to the population that was studied in the interim analysis population.

您好，下午好。感謝您解答我的問題，並祝賀您的進展。鑑於 PSC 研究現在已經全部入組，您能否談談入組患者的基線標準，特別是與中期分析人群相關的標準？

And maybe second, can you also discuss a little bit the importance of hitting on quality of life measures or bile acid in addition to ITCH, and will that -- those secondary endpoints be provided in the top line release in the second quarter?

其次，您能否也談談除了 ITCH 之外，關註生活品質指標或膽汁酸的重要性？這些次要終點是否會在第二季的主要報告中提供？

Thank you.

謝謝。

Thanks, Joseph, for the question. I think overall, we've not plan to present or analyze some of the baseline criteria at this point. What we know from -- and we can take it more generally from the enrollment criteria and what was in the interim, is the patients are selected through ITCH. So we do have quite elevated baseline pruritus scores. And it's -- from what we're seeing, it's quite representative of the PSC population in terms of background disease, background medications, things like that.

謝謝約瑟夫的提問。我認為總體而言，我們目前還沒有計劃展示或分析一些基準標準。我們從入組標準和過渡期間的情況中了解到——而且我們可以更普遍地從入組標準和過渡期間的情況中了解到——患者是透過 ITCH 選擇的。因此，我們的基線搔癢評分確實相當高。從我們所看到的來看，就背景疾病、背景藥物等而言，它相當能代表原發性硬化性膽管炎 (PSC) 患者群體。

So overall, kind of in line with what we expected for the population. And shifting to the question about endpoints, the focus from a regulatory standpoint is 100% on that pruritus endpoint being the outcome that we've discussed with FDA.

所以整體而言，這與我們對人口的預期基本一致。再回到終點的問題，從監管角度來看，重點 100% 是搔癢終點，這是我們與 FDA 討論的結果。

We do expect to -- are excited about and expect to see based on other settings. We expect to see movement on things like fatigue and the bile acids. Bile acids, obviously, being a key mechanistic marker fatigue being a really important measure for patients. But again, those are secondary for a reason. The regulatory path is entirely through that pruritus endpoint.

我們確實期待——我們對此感到興奮，並希望根據其他情況看到。我們預計在疲勞和膽汁酸等方面會看到一些變化。顯然，膽汁酸是衡量疲勞的關鍵機制標誌物，疲勞是衡量患者病情的重要指標。但話說回來，這些都是次要的，是有原因的。監管路徑完全是透過搔癢這一終點來實現的。

Ryan Deschner, Raymond James.

Ryan Deschner，Raymond James。

Thanks and congrats on the quarter. Can you remind us what went into the decision to offer BID dosing for the EXPAND study? And how would you expect the dosing instructions to look on an expanded label in cholestatic pruritus patients? And then I have a follow-up.

謝謝，也恭喜你本季取得佳績。您能否提醒我們一下，當初決定在 EXPAND 研究中採用每日兩次給藥方案的原因是什麼？那麼，對於膽汁淤積性搔癢患者，您認為擴展標籤上的劑量說明會是什麼樣的呢？然後我還有一個後續問題。

Thanks.

謝謝。

Thanks, Ryan, for the question. I mean the simple answer is empirical, right? So this is based on observations we've had in compassionate use settings, at dose levels that have explored across a range in this kind of all in the bracket of these elevated dose levels from the Alagille label up to the PFIC label. And empirically, this is where we've seen really great response stories from compassionate use examples.

謝謝瑞恩的提問。我的意思是，最簡單的答案就是經驗性的，對吧？這是基於我們在同情用藥環境中觀察到的，劑量水平涵蓋了從 Alagille 標籤到 PFIC 標籤的各種升高劑量水平。從經驗來看，我們已經從同情使用案例中看到了非常好的反響。

Yeah. How big of an impact has the government shutdown been so far for things like genetic screening programs and other programs related to Alagille and PFIC.

是的。政府停擺至今對基因篩檢計畫以及與 Alagille 和 PFIC 相關的其他計畫產生了多大的影響？

Thanks.

謝謝。

To date, no impact that we've seen across kind of all of our interactions with customers and really across the business.

到目前為止，在我們與客戶的所有互動以及整個業務中，都沒有看到任何影響。

[Mani Foroohar], Leerink Partners.

[Mani Foroohar]，Leerink Partners。

You have Ryan on for [Mani]. Can you just talk a little bit about the pace of new PFIC adds that you guys saw in the third quarter compared to the second quarter. I know you talked a lot about genetic testing and new patient diagnoses.

你們請了 Ryan 來[馬尼]能否請您談談第三季新增PFIC的速度與第二季有何不同？我知道你談了很多關於基因檢測和新患者診斷的話題。

And then maybe more broadly, as you guys start to see consistent positive cash flow and you have several launches on the horizon. Maybe just talk through your BD strategy about adding more products to the pipeline.

然後，或許更廣泛地說，隨著你們開始看到持續的正現金流，並且你們有幾個產品即將推出。或許可以跟他們討論一下你的業務拓展策略，例如增加產品線中的產品。

Thanks.

謝謝。

Yeah, thanks for the question. I'll turn it over to Peter to jump into those.

謝謝你的提問。我會把任務交給彼得，讓他來做。

Yeah. In terms of the pace of PFIC ads, it continues to be healthy. It continues to come from a broad patient population, everything from infants to adults that we've kind of commented on that is a dynamic where the paradigm is really being changed with adult providers to think about kinetic cholestasis as kind of a clinical entity to be suspicious about.

是的。就 PFIC 廣告投放速度而言，目前仍維持健康水準。病例持續來自廣泛的患者群體，從嬰兒到成人，我們已經評論過，這是一種動態變化，即成人醫療服務提供者正在真正改變觀念，將動力性膽汁淤積視為一種需要警惕的臨床實體。

So that's kind of a educational efforts. And some of the major medical centers are on board with that and they're looking into genetic causes of cholestatic liver diseases in the patients they can't explain with other diseases, but most aren't, right?

所以這算是一種教育活動。一些大型醫療中心也認同這一點，他們正在研究無法用其他疾病解釋的膽汁淤積性肝病患者的遺傳原因，但大多數醫療中心並沒有這樣做，對吧？

So that's just kind of a gradual effort and but it's continuing to bear fruit in Q3

所以這只是一個循序漸進的過程，但它在第三季持續取得成效。

Then on BB, yeah, do you want to --

然後，在BB上，是的，你想…--

Sure. I mean, thing we'd say on BD is since the beginning of the company, that's really been at our cores looking for underappreciated programs. So we continue to do that and expect to always be active doing that, but we're in just a fantastic position where the -- there's no urgency and no need. So we have a very high bar. And as you can see from the programs we've brought in since the start of the company, look for good value creation opportunity.

當然。我的意思是，我們BD一直以來都認為，從公司成立之初，我們的核心理念就是尋找被低估的節目。所以我們會繼續這樣做，並且希望一直積極地這樣做，但我們現在處於一個非常好的位置，因為——既沒有緊迫性，也沒有必要。所以我們的標準非常高。從公司成立以來我們引進的專案可以看出，要尋找創造價值的機會。

So that will continue to be the standard we take going forward. And plenty in the company to grow and build and optimistic about adding more down the road. Thanks for question.

所以，這將繼續成為我們今後採取的標準。公司還有很大的發展空間，對未來增加更多業務持樂觀態度。謝謝你的提問。

Mike Ulz, Morgan Stanley.

麥克烏爾茲，摩根士丹利。

Hi, this is Rohit on for Mike. Just with the recent (inaudible) about PDUFA announced for GSK, how do you see the competitive dynamics playing out in PBC?

大家好，我是 Rohit，替 Mike 報道。鑑於最近（聽不清楚）GSK宣布的PDUFA相關消息，您認為PBC的競爭格局將如何改變？

Thanks. Yeah, thanks for the question. Rohit, thanks for the question. I think two overarching things to think about for the competitive landscape in PBC. One is just kind of a reminder on lines of therapy and where the volixibat program in place. And in the VANTAGE study, there is no baseline outline [phosphatase] criteria.

謝謝。謝謝你的提問。羅希特，謝謝你的提問。我認為在PBC的競爭格局中，有兩件需要考慮的重要事情。其中一份只是對治療方案和沃利西巴特計劃的實施情況的提醒。在 VANTAGE 研究中，沒有基線輪廓 [磷酸酶] 標準。

So our program incorporates both first and second-line PBC settings to those that have stable upline phosphatase on UDCA that likely wouldn't be a treatment candidate for some of the PPARs that are recently launched, but still have ITCH. That's a candidate for volixibat study and we expect ultimately looks at market treatment.

因此，我們的方案涵蓋了 PBC 的一線和二線治療方案，適用於那些使用 UDCA 治療後磷酸酶水平穩定的患者，這些患者可能不適合使用最近推出的一些 PPAR 治療方案，但仍患有 ITCH。這是沃利西巴特研究的候選藥物，我們預計最終會考慮市場治療。

And then with respect to linerixibat as a competitor, we're very excited about the interim data that we saw from the VANTAGE study and what it means for the dose level that was selected the placebo-adjusted difference that we saw on ITCH in that data set is striking, it led to breakthrough designation, it's really everything that we had hoped to see from all that we've learned about dosing of this mechanism in these settings. So quite excited about the competitive profile of volixibat given that highly active dose level.

至於競爭對手利奈昔巴，我們對 VANTAGE 研究的中期數據感到非常興奮，以及它對所選劑量水平的意義。我們在該資料集中看到的 ITCH 安慰劑調整差異非常顯著，這促成了突破性療法認定。這確實符合我們從這些情況下對該機制的給藥方式所了解到的所有情況中希望看到的結果。鑑於volixibat具有如此高的活性劑量水平，我對它的競爭優勢感到非常興奮。

Jon Wolleben, Citizens.

Jon Wolleben，市民。

Hey, thanks for taking the question. Wondering if you guys are anticipating seeing similar disease-modifying effects over time with volixibat as you saw with LIVMARLI in PSC and PBC. And if so, what would be the time frame? And do you think that would be a point of consideration for adoption and use over time?

嘿，謝謝你回答這個問題。想知道你們是否預期隨著時間的推移，volixibat 會像 LIVMARLI 在 PSC 和 PBC 中那樣，產生類似的疾病改善效果。如果屬實，時間大概是多久？你認為這會是影響產品長期採用和使用的考慮因素嗎？

HeyJon, thanks for the question. I mean, the overarching first thought there is the first readouts here, we think are probably too soon to be looking at that and focused on the ITCH endpoint and really see that as the -- that's the launch profile. But I'll turn it to Joanne to talk through some of what we'll be looking at and what we'll be able to see over time from the burden.

HeyJon，謝謝你的提問。我的意思是，首先要考慮的是這裡的第一批讀數，我們認為現在關注這些讀數可能為時過早，並且應該專注於 ITCH 終點，真正將其視為——這就是發布概況。但我會把麥克風交給喬安妮，讓她來談談我們將要關注的一些問題，以及隨著時間的推移，我們能夠從這個負擔中看到什麼。

Yeah. Thanks for the question. As Chris alluded to, the whole discussion, especially with the regulators has been around how do we get something in PSC approved. And clearly, that's with pruritus or with the pruritus point. At this point, in the field of PSC, that's really the only approval end point.

是的。謝謝你的提問。正如克里斯所暗示的那樣，整個討論，特別是與監管機構的討論，都圍繞著我們如何讓 PSC 獲得批准。顯然，這是與搔癢有關，或與搔癢點有關。目前，在PSC領域，這確實是唯一的批准終點。

Obviously, we'll look at other things. Look, longer term, we do expect those types of endpoints may take quite a long time to evolve. We'll continue to follow these patients. And obviously, we'll continue to engage with the agency in terms of appropriate endpoints.

當然，我們也會考慮其他方面。長遠來看，我們預期這類終點的發展可能需要相當長的時間。我們將繼續追蹤這些患者的情況。顯然，我們將繼續與該機構就合適的最終目標進行磋商。

But we do think a concrete path forward is with pruritus and we're pretty confident in terms of the ability of the look to affect that in a positive way for patients.

但我們認為，治療搔癢症是一個切實可行的前進方向，而且我們對這種治療方式能夠對患者產生積極影響的能力相當有信心。

Thanks.

謝謝。

Thank you. And with no further questions on the line at this time. I would like to hand the call back to Chris Peetz for some closing remarks.

謝謝。目前沒有其他問題需要解答。我謹將電話交還給克里斯·皮茨，請他作總結發言。

Great. Thank you again, everyone, for joining us today and for your continued support. We look forward to updating you next quarter. Good afternoon.

偉大的。再次感謝各位今天蒞臨，也感謝你們一直以來的支持。我們期待下季向您報告最新情況。午安.

This will conclude the Mirum Pharmaceuticals third quarter 2025 financial results and business update. Thank you to everyone who is able to join us today. You may now disconnect your lines.

至此，Mirum Pharmaceuticals 2025 年第三季財務業績和業務更新報告就結束了。感謝今天所有到場的朋友。現在您可以斷開線路了。