Mirum Pharmaceuticals Inc (MIRM) 2024 Q2 法說會逐字稿

Thank you for your patience everyone. The Mirum Pharmaceutics report second quarter 2024 financial results and provide business update will begin shortly. (Operator Instructions)

感謝大家的耐心等待。Mirum Pharmaceutics 報告 2024 年第二季財務表現並提供業務更新即將開始。（操作員說明）

Good afternoon, everyone and welcome to the Mirum Pharmaceutics report second quarter 2024 financial results and provide business update. My name is Carla and I will be coordinating your call today. (Operator Instructions) I will now hand you over to Andrew Mckibben, Vice President of Investor Relations and Finance to begin. Andrew, please go ahead.

大家下午好，歡迎閱讀 Mirum Pharmaceutics 報告 2024 年第二季財務業績並提供業務更新。我叫卡拉，今天我將協調您的電話。（操作員指示）我現在將把您交給投資者關係和財務副總裁 Andrew Mckibben 開始。安德魯，請繼續。

Thanks, Carla and good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals second quarter 2024 conference call. I'm joined today by our CEO, Chris Peetz; our President and Chief Operating Officer, Peter Radovich, our Chief Medical Officer, Joanne Quan; and Eric Bjerkholt, our Chief Financial Officer.

謝謝卡拉，大家下午好。歡迎您參加 Mirum Pharmaceuticals 2024 年第二季電話會議。今天我們的執行長 Chris Peetz 也加入了我的行列。我們的總裁兼營運長 Peter Radovich、我們的首席醫療官 Joanne Quan；和我們的財務長 Eric Bjerkholt。

Earlier today, Mirum issued a news release announcing the company's results for the second quarter 2024. Copies of this news release and SEC filings can be found in the investor's section of our website. 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.

今天早些時候，Mirum 發布新聞稿，公佈了該公司 2024 年第二季的業績。本新聞稿和 SEC 文件的副本可以在我們網站的投資者部分找到。在開始之前，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 的計劃以及其已批准藥物和產品候選者的市場機會的陳述。

These statements represent our judgment 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目前為止的判斷，本質上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 表格和隨後向 SEC 提交的文件中的風險因素，以了解更多資訊。

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 to everyone. I'm excited to share with you the outstanding progress we've made this quarter with our commercial medicines and pipeline. It's been a strong quarter across the board with continued growth, important regulatory achievements, and positive maralixibat interim results.

謝謝安德魯，大家下午好。我很高興與您分享我們本季在商業藥品和管道方面取得的突出進展。這是一個全面強勁的季度，持續成長、重要的監管成就以及馬拉利昔巴特的積極中期業績。

On the commercial side, adoption of our medicines continues to grow with total net product sales of $77.8 million across with Livmarli, Chenodal, and Cholbam, representing a 139% increase from the second quarter of last year.

在商業方面，我們的藥物採用率持續成長，Livmarli、Chenodal 和 Cholbam 的產品總淨銷售額達到 7,780 萬美元，比去年第二季成長 139%。

Building on the strength, we've also achieved important regulatory milestones for our commercial medicines. We submitted our NDA for Chenodaland CTX, which, if approved, will allow us to take additional steps to reach this under diagnosed population and provide an opportunity for orphan exclusivity.

憑藉實力，我們的商業藥品也實現了重要的監管里程碑。我們提交了 Chenodaland CTX 的 NDA，如果獲得批准，我們將能夠採取額外的措施來涵蓋這一未確診人群，並提供孤兒專營權的機會。

For Livmarli, I'm very happy to say that we are now approved for Cholestasis pruritus and PFIC in the US and for the treatment of PFIC in Europe. And we recently announced a US label update to reduce that age to 12 months and older. We're looking forward to bringing Livmarli to PFIC patients given the impressive clinical impact that we've seen in this population.

對於 Livmarli，我很高興地說，我們現在在美國獲準用於膽汁淤積性搔癢和 PFIC，在歐洲獲準用於治療 PFIC。我們最近宣布了一項美國標籤更新，將年齡降低至 12 個月及以上。鑑於我們在這一人群中看到的令人印象深刻的臨床影響，我們期待將 Livmarli 帶給 PFIC 患者。

I'm also excited to announce the initiation of another potentially label-enabling study for Livmarli in Cholestasis pruritus. I'll let Joanne speak to some of the details, but, in short, Cholestasis pruritus is not limited to allogeal syndrome, PFIC, PFC, and PBC. We see multiple additional rare disease settings where patients develop Cholestasis and experience significant pruritus.

我還很高興地宣布啟動另一項針對 Livmarli 治療膽汁淤積性搔癢症的潛在標籤研究。我會讓喬安妮講一些細節，但是，簡而言之，膽汁淤積性搔癢症不僅限於同種異體症候群、PFIC、PFC 和 PBC。我們還發現了多種其他罕見疾病，患者出現膽汁淤積並出現明顯的搔癢。

Supported by high interest from physicians and compelling response case studies, we are launching the EXPAND study to bring Livmarli to patient communities that would otherwise be challenging to study individually.

在醫生的高度興趣和令人信服的反應案例研究的支持下，我們正在啟動 EXPAND 研究，將 Livmarli 引入患者社區，否則單獨研究將具有挑戰性。

Collectively, across these settings, we estimate there are at least 500 patients in the US alone that would be eligible for this indication. And, finally, we took an important step towards advancing volixibat towards potentially pivotal data with the positive interim readouts of the VISTAS PSC and VANTAGE PBC studies. Our VISTAs PSC study exceeded the pre-specified efficacy threshold and is continuing enrollment to the full study readout. With no approved therapies and PSC, we are positioned to bring the first medicine to this patient community.

總的來說，在這些環境中，我們估計光在美國就有至少 500 名患者符合該適應症。最後，透過 VISTAS PSC 和 VANTAGE PBC 研究的積極中期讀數，我們在推進伏利昔巴特潛在關鍵數據方面邁出了重要一步。我們的 VISTA PSC 研究超出了預先指定的療效閾值，並且正在繼續納入完整的研究讀數。由於沒有獲得批准的療法和 PSC，我們有能力為這個患者群體帶來第一種藥物。

The interim results of the VANTAGE study and PBC were also very encouraging, with a statistically significant improvement in pruritus and a patient population that spans first and second-line PBC. I'm happy to say that enrollment is progressing well for both programs. It was a packed second quarter for Mirum.

VANTAGE 研究和 PBC 的中期結果也非常令人鼓舞，搔癢症以及涵蓋第一線和第二線 PBC 的患者群體有統計學上的顯著改善。我很高興地說，這兩個計畫的招生進展順利。對米魯姆來說，第二季是忙碌的。

So, to dive into the details, I'll turn the call over to Peter to start with our commercial business. Peter?

因此，為了深入了解細節，我將把電話轉給 Peter，從我們的商業業務開始。彼得？

Thanks, Chris. I'm pleased to report another strong quarter across all three commercial products, and we continue to track well towards our full-year revenue guidance of $310 million to $320 million. Starting with Livmarli, total global net product sales grew to $47.2 million this quarter, which represents a 45% increase compared to the same quarter last year.

謝謝，克里斯。我很高興地報告所有三種商業產品又一個強勁的季度，並且我們繼續良好地朝著 3.1 億至 3.2 億美元的全年收入指導目標前進。從 Livmarli 開始，本季全球產品淨銷售額成長至 4,720 萬美元，與去年同期相比成長了 45%。

In the US, sales were $35.5 million, while international sales were $11.7 million. Growth continues to be driven by new Alagille syndrome patient additions comprised of both prevalent patients and newly diagnosed, a dynamic we expect to persist going forward.

在美國，銷售額為 3,550 萬美元，而國際銷售額為 1,170 萬美元。新的阿拉吉爾症候群患者增加繼續推動成長，其中包括流行患者和新診斷患者，我們預計這種動態將持續下去。

We're also beginning to see prescriptions for PFIC patients, and our recent label expansion to include patients 12 months and older provides incremental opportunity, given that PFIC is generally diagnosed when children are young.

我們也開始看到針對 PFIC 患者的處方，而且我們最近的標籤擴展包括 12 個月及以上的患者，這提供了更多的機會，因為 PFIC 通常在兒童年幼時被診斷出來。

Internationally, Livmarli demand growth was strong, and I'm pleased to say that we achieved a favorable outcome in our price negotiations with Germany. Stemming from this, we saw some price reference impact on international sales in Q2.

國際上，Livmarli 需求成長強勁，我很高興地說我們在與德國的價格談判中取得了有利的結果。由此，我們看到第二季國際銷售受到了一些價格參考的影響。

We expect this to run its course in the next quarter or two. We were also very happy with the European Commission's recent endorsement of Livmarli for PFIC three months and older, which highlights the significant benefit of Livmarli for these patients.

我們預計這種情況將在未來一兩個季度內結束。我們也對歐盟委員會最近認可 Livmarli 用於三個月及以上 PFIC 的治療感到非常高興，這突顯了 Livmarli 對這些患者的顯著益處。

Lastly, we saw nice demand growth from Cholbam and Chenodiol in the second quarter, where we recognized net product sales of $30.5 million. Overall, I'm thrilled with the continued strong commercial performance in the first half of the year, and proud of the Mirum team's continued execution. We are on a solid path to achieve our full year guidance of $310 million to $320 million and continued growth.

最後，我們看到第二季 Cholbam 和 Chenodiol 的需求成長良好，我們確認產品淨銷售額為 3,050 萬美元。總的來說，我對上半年持續強勁的商業表現感到興奮，並對 Mirum 團隊的持續執行力感到自豪。我們正在穩步實現 3.1 億至 3.2 億美元的全年指導目標並持續成長。

And with that, I'll turn it over to Joanne. Joanne?

有了這個，我會把它交給喬安妮。喬安妮？

Thanks, Peter. We had an exceptional quarter, highlighted by the impressive interim analyses for the VISTA study in PSC and the VANTAGE study in PVC. I'll give a quick recap of the results. Starting with the VISTA study in PSC, we set a pre-specified threshold for continuation, based on both efficacy and safety.

謝謝，彼得。我們度過了一個出色的季度，其中最引人注目的是 PSC 的 VISTA 研究和 PVC 的 VANTAGE 研究令人印象深刻的中期分析。我將快速回顧一下結果。從 PSC 的 VISTA 研究開始，我們根據療效和安全性設定了預先指定的繼續閾值。

The blinded interim analysis met this threshold, and our independent data review committee recommended proceeding with the 20 milligram BOD dose, and that the study continue without any changes. The blinded analysis confirms a meaningful treatment effect, and also allows us to include these patients in the total patient number for the final analysis. We're happy with how the study is enrolling, and anticipate completing enrollment in the second half of 2025.

盲法中期分析達到了這一閾值，我們的獨立數據審查委員會建議繼續使用 20 毫克 BOD 劑量，並且研究繼續進行，無需任何更改。盲法分析證實了有意義的治療效果，也使我們能夠將這些患者納入最終分析的患者總數中。我們對這項研究的招募感到滿意，並預計在 2025 年下半年完成招募。

Moving on to the VANTAGE study in PVC, we're thrilled with the interim results. Both doses of Volixibat showed a substantial and statistically significant reduction in itch, and approximately 2.3 point improvement over placebo. Based on this, the VANTAGE study will also continue with the 20 milligram BID dose, consistent with the VISTA study.

接下來進行 PVC 的 VANTAGE 研究，我們對中期結果感到非常興奮。兩種劑量的 Volixibat 均顯示出顯著且具有統計意義的搔癢減輕，比安慰劑改善約 2.3 個百分點。基於此，VANTAGE研究也將持續採用20毫克BID劑量，與VISTA研究一致。

The results support Volixiba's potential as an important advance for patients suffering from Cholestatic pruritus. We also observed reductions in serum bile acids, and improvements across multiple dimensions on the PVC40, most notably fatigue. We look to complete enrollment in 2026 for this larger study.

結果支持 Volixiba 對於患有膽汁淤積性搔癢症的患者俱有重要進展的潛力。我們也觀察到血清膽汁酸的減少，以及 PVC40 多個維度的改善，最顯著的是疲勞。我們希望在 2026 年完成這項更大規模研究的招募。

Overall, these results are significant for PVC patients, suggesting that Volixibat has the potential to set a new standard in addressing the burden of cholestatic. We've already ramped up enrollment efforts, and are targeting up to 100 total sites.

總體而言，這些結果對 PVC 患者意義重大，顯示 Volixibat 有潛力為解決膽汁淤積負擔制定新標準。我們已經加強了註冊力度，目標站點總數達到 100 個。

Shifting gears a bit, I would like to talk about the new Phase 3 EXPAND study. Mirum has received a number of requests for compassionate use with Livmarli in patients with cholestatic pruritus across a variety of ultra-rare indications. We believe these conditions share a common pathogenic mechanism, cholestasis, leading to elevated serum bile acids, which results in persistent pruritus.

換個話題，我想談談新的第三階段 EXPAND 研究。Mirum 已收到許多同情使用 Livmarli 治療膽汁淤積性搔癢症患者的請求，涉及各種極其罕見的適應症。我們認為這些病症有一個共同的致病機制，即膽汁淤積，導致血清膽汁酸升高，進而導致持續性搔癢。

Based on the good responses we've seen in some individuals receiving compassionate use, we are optimistic that Livmarli can play a significant role in the treatment of pruritus for these patients. EXPAND is a randomized, double-blind, placebo-controlled study evaluating Livmarli for treatment of pruritus over 20 weeks.

基於我們在一些接受同情使用的個體中看到的良好反應，我們樂觀地認為 Livmarli 可以在這些患者的瘙癢治療中發揮重要作用。EXPAND 是一項隨機、雙盲、安慰劑對照研究，評估 Livmarli 在 20 週內治療搔癢的效果。

EXPAND study will enroll patients with cholestatic pruritus associated with a range of conditions, such as Biliary Atresia, secondary sclerosing Cholangitis, and other less common conditions. Our target is to enroll approximately 45 patients, and we expect to complete enrollment in 2026. I look forward to providing further updates on VISTAs, VANTAGE, and EXPAND in the coming quarters.

EXPAND 研究將招募與一系列疾病相關的膽汁淤積性搔癢患者，例如膽道閉鎖、繼發性硬化性膽管炎和其他不太常見的疾病。我們的目標是招募約 45 名患者，預計在 2026 年完成招募。我期待在未來幾季提供有關 VISTA、VANTAGE 和 EXPAND 的進一步更新。

I'll now turn over to Eric to discuss our financial results. Eric?

我現在將請埃里克討論我們的財務表現。艾瑞克？

Thanks, Joanne. Earlier today, we issued a press release that included financial results for the second quarter, which I'll briefly summarize. Net product revenue in the second quarter 2024 was $77.8 million compared to net product revenues of $32.5 million in the second quarter last year.

謝謝，喬安妮。今天早些時候，我們發布了一份新聞稿，其中包括第二季的財務業績，我將對其進行簡要總結。2024 年第二季的產品淨收入為 7,780 萬美元，而去年第二季的產品淨收入為 3,250 萬美元。

Total operating expense for the quarter ended June 30, were $102 million, which includes R&D expense of $32.7 million, SG&A expense of $49.2 million, and cost of sales of $20.2 million. The total operating expense for the quarter included approximately $17.7 million of non-cash charges, of which $5.7 million was included in cost of sales.

截至 6 月 30 日的季度總營運費用為 1.02 億美元，其中包括 3,270 萬美元的研發費用、4,920 萬美元的銷售成本和 2,020 萬美元的銷售成本。本季的總營運費用包括約 1,770 萬美元的非現金費用，其中 570 萬美元包含在銷售成本中。

For the quarter ended June 30, 2024, net loss was $24.6 million, or $0.52 per share. Our cash, cash equivalents, and investment was $295.4 million as of June 30, 2024, a reduction of $7.4 million from the end of the prior quarter. Cash used in the second quarter included the payment of a $10 million milestone to Takeda upon FDA approval of the Livmarli PFIC indication.

截至 2024 年 6 月 30 日的季度，淨虧損為 2,460 萬美元，即每股 0.52 美元。截至 2024 年 6 月 30 日，我們的現金、現金等價物和投資為 2.954 億美元，比上一季末減少 740 萬美元。第二季使用的現金包括 FDA 批准 Livmarli PFIC 適應症後向武田支付的 1000 萬美元里程碑付款。

With our robust commercial performance and continued financial discipline, we are in an excellent position to support the development of our pipeline and growth of our commercial business.

憑藉我們強勁的商業業績和持續的財務紀律，我們處於有利地位，可以支持我們的管道開發和商業業務的成長。

Now, I'll turn the call back over to Chris for final comments.

現在，我將把電話轉回克里斯以徵求最終意見。

Thnaks , Eric. It's been a great first half of the year. I'm proud of the Mirum team and our strong execution. We are well positioned to continue to advance our four strategic priorities, to grow our commercial business, expand the indications of our improved medicines, advance maralixibat and adult Cholestatic, and continue to look for opportunities to grow the pipeline.

謝謝，埃里克。今年上半年過得很好。我為 Mirum 團隊和我們強大的執行力感到自豪。我們處於有利地位，可以繼續推進我們的四個策略重點，發展我們的商業業務，擴大我們改良藥物的適應症，推進馬拉利昔巴特和成人膽汁淤積症，並繼續尋找擴大產品線的機會。

With that, operator, please open the call for questions

接線員，請撥打電話詢問問題

(Operator Instructions) Dae Gon Ha, Stifel.

（操作員指示）Dae Gon Ha，Stifel。

Hey, good afternoon, guys. Thanks for taking our questions and congrats on the progress. Two from us, one commercial and one clinical, I guess. Starting with commercial, as we look at the approval label across Alagille and PFIC in the US, it's kind of a palindrome between Livmarli and Biliary.

嘿，下午好，夥計們。感謝您提出我們的問題並祝賀我們的進展。我猜我們有兩份，一份是商業的，一份是臨床的。從商業開始，當我們查看美國 Alagille 和 PFIC 的批准標籤時，它有點像 Livmarli 和 Biliary 之間的回文。

So I was hoping if you can maybe comment a little bit on what you've learned from perhaps Biliary's experience in Alagille that you can implement to broaden Livmarli's reach within the PFIC segment before further label expansion can come down the pike.

因此，我希望您能評論一下您從 Biliary 在 Alagille 的經驗中學到的東西，您可以在進一步擴大品牌擴張之前實施這些經驗，以擴大 Livmarli 在 PFIC 細分市場的影響力。

And then in terms of clinical side, Joanne, enrollment progressing favorably sounds great. Is there any initiative for you to perhaps accelerate enrollment into VISTAs and VANTAGE trials? Thanks so much.

然後就臨床方面而言，喬安妮，入組進展順利聽起來很棒。您是否有任何措施可以加快 VISTA 和 VANTAGE 試驗的註冊速度？非常感謝。

Thanks, Dae Gon, for the question. On the first kind of a comment on the labeling and label expansion we've seen for Livmarli, and can circle back for any follow-up questions, but what I think you're asking is just how the sequencing has gone for Livmarli, and it's played out really well.

謝謝大坤的提問。關於我們在 Livmarli 中看到的關於標籤和標籤擴展的第一種評論，並且可以回過頭來詢問任何後續問題，但我認為您要問的是 Livmarli 的測序情況如何，並且效果非常好。

I think we're in a position of kind of very strong leadership in Europe where we're the only product approved for both indications. In the US, we're now, we see it as very equal footing where we're now approved for both indications. Initial reception has been quite strong, and the data for Livmarli in both indications we think tells a really compelling story for prescribers, and that's what we're seeing play out in the real world. So in terms of that kind of label sequencing, I think it's largely played out and to the favor of Livmarli.

我認為我們在歐洲處於非常強大的領導地位，我們是唯一獲得這兩種適應症批准的產品。在美國，我們現在認為這是非常平等的，我們現在已經批准了這兩種適應症。最初的反應非常強烈，我們認為 Livmarli 在這兩種適應症中的數據為處方者講述了一個非常引人注目的故事，這就是我們在現實世界中看到的情況。因此，就這種標籤測序而言，我認為它在很大程度上已經發揮作用並且對 Livmarli 有利。

And I'll let Joanne maybe comment on the enrollment strategies.

我會讓喬安妮評論一下招生策略。

Yeah, thanks for the question. Like I said, we're happy with how the enrollment is going. As you've noticed, we've been very excited by the interim analysis results on the PBC and the PSC, and we share that with our investigators, and they share the excitement on that and really are seeing the potential impact that this has as a medicine for both patient populations. We were continuing to work with our existing sites and continuing the expansion as we previously talked about, so we're happy with where our enrollment is going.

是的，謝謝你的提問。就像我說的，我們對招生的進展感到滿意。正如您所注意到的，我們對 PBC 和 PSC 的中期分析結果感到非常興奮，我們與我們的調查人員分享了這一結果，他們也對此感到興奮，並且確實看到了這所帶來的潛在影響一種適用於兩種患者群體的藥物。正如我們之前討論的那樣，我們將繼續與現有網站合作並繼續擴展，因此我們對我們的註冊進度感到滿意。

Great. Thank you very much.

偉大的。非常感謝。

Thanks for the question.

謝謝你的提問。

(Operator Instructions) Mani Foroohar, Leerink Partners.

（操作員說明）Mani Foroohar，Leerink Partners。

Hey, guys. Thanks for taking the question. A couple of quick ones. First, when we think about the novel expansion population Cholestatic pruritus, can you give us a sense of how you think about the duration of that study and the time horizon which we might see results, recognizing it's a little bit of a heterogeneous population, and then we have a commercial quick follow-up.

嘿，夥計們。感謝您提出問題。幾個快速的。首先，當我們考慮新的擴張人群膽汁淤積性瘙癢症時，您能否告訴我們您如何看待該研究的持續時間以及我們可能看到結果的時間範圍，認識到它是一個有點異質的人群，並且然後我們進行商業快速跟進。

Sure. Thanks for the questions. Maybe Joanne and I'll let Peter take the follow-up.

當然。感謝您的提問。也許喬安妮和我會讓彼得來跟進。

Sure. So we are just launching the study now, and as we said, we plan to complete enrollment in 2026. It is a bit of a heterogeneous group of patients, but we expect that, some patients will have Bilirubin as a cause, some secondary Sclerosing Cholangitis, and then a variety of other causes. And this is really based on our experience in compassionate use.

當然。所以我們現在才剛啟動這項研究，正如我們所說，我們計劃在 2026 年完成入組。這是一個有點異質性的患者群體，但我們預計，有些患者會因膽紅素引起，有些患者會因繼發性硬化性膽管炎，然後還有各種其他原因。這其實是基於我們在同情使用方面的經驗。

So we're actually pretty confident in terms of our understanding the role of IVAD inhibitors in treatment of Cholestatic pruritus and think that this extends its potential use to a wide variety of patients who for each of these, it would be difficult to study. So we're excited to study them all in this expanded study and get some results and hopefully support some wider use.

因此，我們實際上對IVAD 抑制劑在治療膽汁淤積性搔癢中的作用非常有信心，並認為這將其潛在用途擴展到了各種各樣的患者，而對於這些患者，每一種都很難進行研究。因此，我們很高興能夠在這項擴展研究中研究它們並獲得一些結果，並希望支持更廣泛的使用。

That's helpful. And then when you think about sort of more on the commercial side, obviously, there's a little bit of a -- there's some element of seasonality in this market, and sort of the pendulum swings one way early in the year and tends to swing the other, certainly around 3Q, as we saw a couple years ago. How do we think about the tempo of new patient ads and any sort of operational details we should think about in terms of seasonality across the next few quarters looking forward?

這很有幫助。然後，當你更多地考慮商業方面時，顯然，這個市場存在一些季節性因素，而且鐘擺在年初會向一個方向擺動，並且往往會擺動其他的，肯定是在第三季度左右，正如我們幾年前看到的那樣。我們如何考慮新患者廣告的節奏以及我們應該在未來幾季的季節性方面考慮的任何營運細節？

Yeah, thanks for the question. I mean, one thing to just kind of remind on, reflecting back to Q1, we did see in the US with Livmarli and the bile acid products impact on our Q1 number from the changed healthcare cyber attacks. That's one thing to keep in mind as you think about quarter-to-quarter trends here.

是的，謝謝你的提問。我的意思是，有一點需要提醒一下，回顧第一季度，我們確實看到美國的 Livmarli 和膽汁酸產品因醫療網路攻擊的變化而對我們第一季度的數據產生了影響。當您考慮季度趨勢時，請記住這一點。

And as far as seasonality goes across three products, I can't say that we've identified any real seasonality in these products. I mean, they're kind of ultra-rare-to-rare products with relatively low underlying volume, which can lead to kind of quarter-to-quarter variability, quite frankly. But whether that occurs in one quarter versus another, I can't say that there's a really strong effect there.

就三種產品的季節性而言，我不能說我們在這些產品中發現了任何真正的季節性。我的意思是，它們是一種極其稀有的產品，基礎數量相對較低，坦白說，這可能會導致季度與季度之間的變化。但無論這種情況發生在一個季度還是另一個季度，我都不能說那裡有很強的影響。

Okay. And should we, and on what time horizon should we expect sort of the sort of OUS pricing reference dynamics to play out? That's something we should think about sort of recurring and sort of eroding itself playing out over the course of the next couple quarters. Is that primarily a 2Q, 3Q event? Like how should we think about breaking that into sort of how we model?

好的。我們是否應該期待 OUS 定價參考動態的出現，以及在什麼時間範圍內出現？我們應該考慮這種情況在接下來的幾個季度中會反覆出現並逐漸受到侵蝕。這主要是第二季、第三季的事件嗎？例如我們應該如何考慮將其分解為我們的建模方式？

Yeah, exactly. We saw the effect in Q2. We expect it in Q3. And, you know, our expectation is by the time you're into Q4 that that effect is gone and all of the kind of demand volume growth that we're seeing flows through to the top line.

是的，完全正確。我們在第二季度看到了效果。我們預計在第三季。而且，你知道，我們的預期是，當進入第四季度時，這種影響就會消失，我們看到的所有需求量成長都會流入營收。

Perfect. Thanks, guys. I know you've got a bunch of people in the queue. I'll hop off.

完美的。謝謝，夥計們。我知道有很多人在排隊。我就下車了

Thanks for the questions.

感謝您的提問。

Gavin Clark-Gartner, Evercore ISI.

Gavin Clark-Gartner，Evercore ISI。

Hi, guys. This is Yashan for Gavin. Thanks for taking our question. We just have two. The first one, could you just touch on the level of confidence in that 45 patient sample size for EXPAND and maybe how you powered the study and then one follow-up after that?

嗨，大家好。這是加文的雅山。感謝您提出我們的問題。我們只有兩個。第一個，您能否談談對 EXPAND 的 45 名患者樣本量的信心程度，以及您如何推動這項研究以及之後的後續行動？

Yashan, thanks for the question. I think I'll let Joanne kind of comment a bit. But I think the one thing to kind of say to get some context here is that now, at this point, using [IBAT] in these cholestatic settings, I think we've seen the pattern here that you can drive really dramatic response if you're at the right dose on bile acids and Pruritus.

亞山，謝謝你的提問。我想我會讓喬安妮發表一下評論。但我認為要在這裡獲得一些背景資訊的一件事是，現在，在這些膽汁淤積環境中使用 [IBAT]，我認為我們已經看到了這裡的模式，如果您對於膽汁酸和瘙癢症，劑量正確。

So the thinking behind this study design is based on having actually seen that same profile play out in a number of evidence from the individual case studies that in aggregate basically make this population. So feel good about launching the study. That's why we designed it. That's what helped us to put it together. Maybe Joanne can speak a little bit about sample size.

因此，這項研究設計背後的想法是基於實際看到相同的情況在來自個別案例研究的大量證據中發揮出來，這些證據總體上基本上構成了這一人群。因此，對啟動這項研究感到高興。這就是我們設計它的原因。這就是幫助我們將其組合在一起的原因。也許喬安妮可以談談樣本量。

Yeah, thanks for the question. So, the sample size was based on powering based on our primary endpoint, which is an observer-rated issue. So this is a scale that we understand well based on our previous experience -- prior studies with Livmarli. So we feel pretty confident that this is an appropriate sample size for us to see a solid treatment effect.

是的，謝謝你的提問。因此，樣本大小是基於我們的主要終點的供電，這是一個觀察者評級的問題。因此，根據我們先前的經驗——先前對 Livmarli 的研究，我們可以很好地理解這個量表。因此，我們非常有信心，這是一個合適的樣本量，可以讓我們看到堅實的治療效果。

Awesome. Thank you. And then one follow-up was, was there any data from EMBARK that makes you confident enrolling a patients in this trial?

驚人的。謝謝。然後一個後續問題是，EMBARK 是否有任何數據讓您有信心招募患者參加這項試驗？

I'll pass that back to Joanne.

我會把它傳回給喬安妮。

Yeah. Well, thanks for the question. I think it's important to note that the patient population that we're rolling expand is actually quite different than the ones that were, that we did enroll in EMBARK. With expand, we're really -- taking patients really at any point of their journey. And for biliary atresia, many of these patients will have had a PFIC a number of years ago, but over the course of time, their condition deteriorates and they may develop the same.

是的。嗯，謝謝你的提問。我認為值得注意的是，我們正在滾動擴大的患者群體實際上與我們在 EMBARK 中註冊的患者群體有很大不同。透過 Expand，我們真正能夠在患者旅程的任何時刻為他們提供服務。而對於膽道閉鎖，這些患者中的許多人在幾年前就患有PFIC，但隨著時間的推移，他們的病情惡化，並且可能會發展成同樣的情況。

So this is quite a different population EMBARK where we took really incident patients around the time that they had a PFIC. So this is quite a different patient population. And on top of that, we're including other causes of cholestatic pruritus with chronic disease.

因此，這是一個完全不同的人群，我們在他們患有 PFIC 期間收治了真正發生過事件的患者。所以這是一個完全不同的患者群。最重要的是，我們還包括慢性疾病引起的膽汁淤積性搔癢的其他原因。

Yeah. I'd also add on that in those compassionate use case studies, there have been Biliary Atresia patients in there, quite a bit older than the EMBARK eligible to enrolage where they're enrolled as infants. And you do see that kind of hallmark response to IBAT treatment. So I think we've now figured out how to dose these medicines and what settings to advance them in.

是的。我還要補充一點，在那些富有同情心的用例研究中，那裡有膽道閉鎖患者，他們比嬰兒時期有資格參加的 EMBARK 年齡要大得多。您確實看到了對 IBAT 治療的標誌性反應。所以我認為我們現在已經弄清楚如何服用這些藥物以及在什麼環境下推進它們。

Super helpful. Thank you so much.

超有幫助。太感謝了。

Thanks for the questions.

感謝您的提問。

Jessica Fye, JPMorgan.

潔西卡法耶，摩根大通。

Hey guys, good afternoon. Thanks for taking my questions. I had a few. First, where should we look for presentation of the interim PBC data for Volixibat and what kind of additional details should we expect when you present those results?

嘿夥計們，下午好。感謝您回答我的問題。我有一些。首先，我們應該在哪裡尋找 Volixibat 的中期 PBC 數據的介紹，以及當您提供這些結果時我們應該期待什麼樣的額外細節？

For example, are there subgroups where we should expect to learn more? Could we see its results broken down by severity of diseases defined by ALP levels or additional data on liver biomarkers or more details on the improvements observed in the fatigue dimension of the PBC40?

例如，是否存在我們應該了解更多資訊的子群組？我們能否看到其結果按 ALP 水平定義的疾病嚴重程度或肝臟生物標誌物的附加數據或 PBC40 疲勞維度中觀察到的改善的更多細節進行細分？

And then separately on the business development front, can you provide a bit of color about just what type of assets and which disease areas are most interesting to you? And lastly, can you just comment on your IP estate across Livmarli and Volixibat in terms of what IP you currently have and any pending applications? Thank you.

然後，在業務發展方面，您能否提供一些關於您最感興趣的資產類型和疾病領域的資訊？最後，您能否就您目前擁有的知識產權和任何待處理的申請來評論一下您在 Livmarli 和 Volixibat 上的知識產權資產？謝謝。

Thanks, Jess, for the questions. I can kind of, maybe I'll take a shot at the first and the last and pass it over to Peter and talk about our BD strategy. Your first comment on the further data from the PBC study, we're preparing an abstract. We'll work on getting it submitted for an upcoming Congress. You can't really predict when and where that lands and what's in it.

謝謝傑西的提問。我可以，也許我會嘗試第一個和最後一個，然後將其交給 Peter 並討論我們的 BD 策略。您對 PBC 研究的進一步數據的第一次評論，我們正在準備一份摘要。我們將努力將其提交給即將召開的國會。你無法真正預測它何時何地降落以及裡面有什麼。

So just say that we're looking at a number of the elements that you talked about there to consider for that abstract. And then on intellectual property -- actually I'll direct you to our corporate deck and the backup slides. We have a summary of that that's been recently added and highlight the 2040 family of granted and pending patents that really tie back to the quite unique dosing profile for IBAT in general and Livmarli and Volixibat in particular that's led to all of these great advances we've seen across the programs that we're talking about here.

因此，我們正在研究您提到的一些元素，以考慮該摘要。然後關於智慧財產權——實際上我將引導您查看我們的公司幻燈片和備用幻燈片。我們對最近添加的內容進行了總結，並重點介紹了2040 系列已授予和正在申請的專利，這些專利實際上與IBAT 的相當獨特的劑量特性相關，特別是Livmarli 和Volixibat，這導致了我們所有這些巨大的進步。

And there's more detail in the backup of our public materials there that you can reference. Maybe Peter can talk about BD strategy.

我們的公共材料備份中有更多詳細信息，您可以參考。也許Peter可以談談BD策略。

Yeah, thanks for the question, Jess. We -- we're focused in rare disease. We really like rare pediatric opportunities. Essentially asking ourselves the question, programs where we could add a lot of value under appreciated programs. We have a really strong development, regulatory, commercial group in rare disease.

是的，謝謝你的提問，傑西。我們—我們專注於罕見疾病。我們真的很喜歡難得的兒科機會。本質上是問自己這樣一個問題：我們可以在哪些項目中為我們所讚賞的項目增加很多價值。我們在罕見疾病領域擁有非常強大的開發、監管和商業團隊。

So looking -- looking in that kind of a corridor.And we have a high bar. We're very disciplined. We have a really strong base business with a great runway of catalysts in front of it. So we take -- we take a lot of scrutiny to these opportunities.

看著這樣的走廊。我們非常有紀律。我們擁有非常強大的基礎業務，前面有大量的催化劑。所以我們對這些機會進行了大量的審查。

Thank you.

謝謝。

Michael Ulz, Morgan Stanley.

麥可烏茲，摩根士丹利。

Hi, this is Robert Rafter from Mike. Thanks for taking our questions. Just in PFIC, do you expect to pursue a label expansion to patients below 12 months? And I can just talk about how many patients are typically diagnosed that are below 12 months and what the opportunity there is. Thanks.

大家好，我是麥克的羅伯特·拉夫特。感謝您回答我們的問題。就 PFIC 而言，您是否希望將標籤擴展到 12 個月以下的患者？我可以談談通常有多少 12 個月以下的患者被診斷出來，以及有哪些機會。謝謝。

Thanks for the question. You know, overall, I feel that our, we feel that our label now with this PFIC expansion down to 12 months, it's in a really strong place. We are similar to what we do with eligible. We're evaluating the potential to submit yet another NDA based on the infant data that's now mature. But frankly, haven't come to a decision on that yet. So it's something that we could pursue.

謝謝你的提問。你知道，總的來說，我覺得我們的品牌現在隨著 PFIC 擴張期縮短至 12 個月，它處於一個非常強大的位置。我們與合格的人所做的類似。我們正在評估根據現已成熟的嬰兒數據提交另一份 NDA 的可能性。但坦白說，目前還沒有做出決定。所以這是我們可以追求的事情。

So I feel that we're in a position now where we capture most of the Livmarli targeted patients for both Alagille syndrome and PFIC.

所以我覺得我們現在的處境是，我們捕獲了大多數 Livmarli 目標患者的 Alagille 綜合徵和 PFIC。

Thank You.

謝謝。

Thanks for the question.

謝謝你的提問。

David Lebovitz, Citi.

大衛‧萊博維茨，花旗銀行。

Thank you very much, for taking my question. With respect to the EXPAND trial, given the heterogeneous population, how do you think the FDA would view it from a label expansion perspective?

非常感謝您回答我的問題。關於 EXPAND 試驗，考慮到人群的異質性，您認為 FDA 從標籤擴展的角度會如何看待它？

Thanks for the question, David. Last, Joanne, maybe to talk a little bit about some of the thinking that went into that and discussion with FDA.

謝謝你的提問，大衛。最後，Joanne，也許可以談談一些想法以及與 FDA 的討論。

Yeah. Thanks, David, for the question. Interesting that you asked the question that way, because in fact, the study came about because the FDA actually had suggested it. We were receiving compassionate user requests. And so the FDA at one point said -- why don't you put these into a study? So this, the expanded study has been designed, keeping that input in mind.

是的。謝謝大衛提出這個問題。有趣的是，你這樣問了這個問題，因為事實上，這項研究的發展是因為 FDA 實際上已經提出了建議。我們收到了富有同情心的用戶請求。因此，FDA 有一次說——為什麼不將這些納入研究呢？因此，在設計擴展研究時，牢記了這一意見。

And so, we do think the commonality is really Cholestatic Pruritus, -- cholestasis, elevated serum bile acids, and the effect that it has, that I have on pruritus in that setting. So we're pretty confident in terms of our ability to execute the study, and really in terms of the results that we see once it gets executed.

因此，我們確實認為其共通性確實是膽汁淤積性搔癢——膽汁淤積、血清膽汁酸升高，以及它對這種情況下的搔癢的影響。因此，我們對執行這項研究的能力以及執行後我們看到的結果非常有信心。

Got it. Thanks for taking my question. Thanks for the question.

知道了。感謝您提出我的問題。謝謝你的提問。

Steve Seedhouse, Raymond James.

史蒂夫席德豪斯，雷蒙德詹姆斯。

Yeah, good afternoon. Thanks for the questions. Just on EXPAND how are you going to be measuring pruritus?

是的，下午好。感謝您的提問。就在 EXPAND 上，您將如何測量搔癢程度？

Because it seems like this trial would include pediatric and adult patients, depending on the condition. So I'm just curious how you're going to standardize measuring the endpoint across disease types?

因為這項試驗似乎將包括兒童和成人患者，這取決於病情。所以我只是好奇你們將如何標準化測量不同疾病類型的終點？

Yeah, thanks for the question. We have an observer rated intro, which has been validated, and which we do have experience within prior studies. And that's really designed for pediatric population.

是的，謝謝你的提問。我們有一個觀察者評級的介紹，它已經過驗證，我們在先前的研究中確實有經驗。這確實是為兒科族群設計的。

So it's right for you to recognize that in a pediatric versus adult population, we can have different endpoints. But, we feel pretty confident in terms of the design of the study and the selection of the endpoint, and the fact that we have experience with this endpoint.

因此，您應該認識到，在兒童與成人族群中，我們可以有不同的終點。但是，我們對研究的設計和終點的選擇以及我們在該終點方面擁有經驗這一事實感到非常有信心。

Yeah, and just to kind of, follow up on that, that pediatric data set, that's the primary cohort, 45 patients that -- that's where the kind of primary analysis is. So the adults scores will be part of a supplemental cohort. And think of the analysis plan designed in that way, primary is based on the pediatric score.

是的，只是為了跟進這個兒科數據集，這是主要隊列，45 名患者，這就是主要分析的地方。因此，成人分數將成為補充隊列的一部分。想想這樣設計的分析計劃，主要是基於兒科評分。

okay. And so the adults would be self-reported itch, or would there be a second observer? Yeah, so how does the endpoint look?

好的。那麼成年人會自我報告搔癢，還是會有第二個觀察者？是的，那麼端點看起來怎麼樣呢？

Right. So for the adults, it's a self-reported endpoint. And that's one reason for us having them in a separate cohort. Based on our discussions with clinicians and just our experience with compassionate use, we do believe the majority of the patients will be pediatric. But we do think there will be some adult patients, and so we're studying them in a supplemental from to analyze those two.

正確的。所以對於成年人來說，這是一個自我報告的終點。這就是我們將他們分在一個單獨的隊列中的原因之一。根據我們與臨床醫生的討論以及我們在同情使用方面的經驗，我們確實相信大多數患者將是兒科患者。但我們確實認為會有一些成年患者，因此我們正在補充中對他們進行研究，以分析這兩個患者。

Okay. And then the formulation here, is this just going to be the same liquid formulation that's commercially available?

好的。然後這裡的配方，這是否與市售的液體配方相同？

That's right. Yeah.

這是正確的。是的。

Okay. And then just last question -- and thanks for the multipart question. Are biliary atresia patients that enrolled in EXPAND that were maybe pruritic either on enrollment, and that's for -- excuse me, that enrolled in EMBARK eligible to enroll in EXPAND? Or is anyone who's been treated compassionately eligible to enroll in this study? Or are you excluding anyone with prior exposure to Livmarli?

好的。最後一個問題—感謝您提出的多部分問題。參加 EXPAND 的膽道閉鎖患者在入組時可能會感到搔癢，請問，參加 EMBARK 的膽道閉鎖患者是否有資格參加 EXPAND？或者任何受到同情對待的人都有資格參加這項研究嗎？或者您是否排除了之前接觸過 Livmarli 的任何人？

Well, first, just on the -- to reiterate on the differences in the setting. The EMBARK population was so young, they were too young even really to recognize pruritus for the most part. You don't see that show up until basically what would have been the very -- even after the time period that EMBARK was looking at. So it's a very distinct setting to go after these -- what are they going to be? Think of them as getting towards grade school age children for a lot of instances.

嗯，首先，重申一下環境中的差異。EMBARK 族群非常年輕，他們大多還太年輕，甚至無法真正體認到搔癢症。即使在 EMBARK 所關注的時間段之後，你也不會看到這種情況的出現。所以這是一個非常獨特的環境來追求這些——它們會是什麼？在很多情況下，將他們視為小學年齡的兒童。

So just a follow-up on that, Chris. If there are patients that responded by bile acids or bilirubin or some metric in EMBARK, are they eligible to enroll in EXPAND if they're biliary atresia patient?

所以這只是後續行動，克里斯。如果 EMBARK 中有膽汁酸或膽紅素或某些指標有反應的患者，如果他們是膽道閉鎖患者，他們是否有資格參加 EXPAND？

Yes. The EMBARK study results, recall there that we really -- in that setting, you're not seeing a response signal, right? So those patients either had successful Kasai procedures, you wouldn't expect them to progress again for several years, or they had a transplant already. So it's kind of -- it's we didn't even see it as a really relevant question. We can circle back on -- I don't know the exclusion criteria off the top of my head right now, but it was -- it's just such a different patient population. You wouldn't see those necessarily connect.

是的。EMBARK 研究結果，回想一下，我們真的 - 在那種情況下，你沒有看到回應訊號，對嗎？因此，這些患者要么已經成功進行了 Kasai 手術，你不會指望他們在幾年內再次取得進展，要么他們已經接受了移植手術。所以這有點——我們甚至沒有把它視為一個真正相關的問題。我們可以回過頭來——我現在還不知道排除標準，但它是——這只是一個如此不同的患者群體。你不會發現它們之間有必然的關聯。

Okay. Makes sense. Thanks a lot.

好的。有道理。多謝。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

This is Charlie on for Brian. Just a couple of questions on the bile acid portfolio. Previously, it was sitting around low- to mid-20 per quarter. So just wondering -- you said it's demand growth, but what you're seeing, if you could give a little more detail there? As well as if you're planning for any other opportunities to expand the value you're getting out of Cholbam?

這是查理為布萊恩代言的。關於膽汁酸組合的幾個問題。此前，該數字為每季 20 左右。所以只是想知道 - 你說這是需求成長，但你看到了什麼，是否可以提供更多細節？您是否正在計劃尋找其他機會來擴大您從 Cholbam 獲得的價值？

I'll ask Peter to give some color

我會請彼得給一些顏色

Yes. And I think I'd kind of go back to what the bile acid products that -- if you're looking at Q1 versus Q2, just a reminder that Q1 was artificially low because of the cyberattack that occurred that impacted pharmacy claim processing in the US.

是的。我想我會回到膽汁酸產品的問題上——如果你看第一季度和第二季度，只是提醒一下，第一季度的水平被人為地壓低了，因為發生的網絡攻擊影響了藥房索賠處理。

So that is just one dynamic to keep in mind. We do expect kind of steady demand growth kind of in line with historical averages and what you've seen over time with -- reminding you that there is quarter-to-quarter variability with these products.

因此，這只是需要牢記的動態。我們確實預計需求會穩定成長，與歷史平均水平以及您隨著時間的推移所看到的情況一致——提醒您這些產品存在季度與季度的變化。

And in terms of Cholbam expansion, yes, we think the Cholbam label is in a great spot. It facilitates the use and reimbursement of that product across the various settings where it's been established. So no major plans right now to focus on expansion there.

就 Cholbam 的擴張而言，是的，我們認為 Cholbam 品牌處於一個很好的位置。它促進了該產品在建立該產品的各種環境中的使用和報銷。因此，目前沒有重大計劃專注於在那裡擴張。

Thanks for the question, Charlie.

謝謝你的提問，查理。

Jon Wolleben, Citizens JMP.

Jon Wolleben，公民 JMP。

A couple on PFIC for me. Wondering -- without talking about sales here, any metrics on the PFIC launch in the US. Things are going well. Things that you guys could improve upon throughout the rest of the year? And then with the label expansion recently, can you discuss the added risk of the propylene glycol toxicity? Any observation of that in the clinical trials? Or is this just a risk that FDA wanted to include?

一對夫婦在 PFIC 上為我服務。想知道 - 在不討論銷售的情況下，PFIC 在美國推出的任何指標。事情進展順利。你們在今年剩下的時間可以改進哪些事情？隨著最近標籤的擴展，您能討論一下丙二醇毒性的額外風險嗎？在臨床試驗中有什麼觀察結果嗎？或者這只是 FDA 想要納入的風險？

I'll kind of break that up between Peter and Joanne to talk about the commercial and safety aspects.

我將在彼得和喬安妮之間打破這個話題，討論商業和安全方面的問題。

Certainly, real happy with how we've come out of the gate with PFIC. Have seen -- we had a number of patients transition from our clinical trials, expanded access programs to commercial drug. That proceeded very well. As well as de novo prescriptions for PFIC patients to come in. We've talked about it before that we expect revenue contribution from PFIC in 2024 to be pretty modest given reimbursement.

當然，我們對 PFIC 的推出感到非常滿意。我們已經看到 - 我們有許多患者從我們的臨床試驗過渡，擴大了獲得商業藥物的計劃。進展非常順利。以及為 PFIC 患者提供的從頭處方。我們之前已經討論過，考慮到報銷，我們預計 2024 年 PFIC 的收入貢獻將相當有限。

We expect a fair bit of free drug shipment this year for PFIC. It is contemplated a little bit in our guidance, but really expect 2025 to be where PFIC starts contributing more. So a good start. And then with regards to the propylene glycol and the clinical development program, I'll let Joanne speak to that.

我們預計今年 PFIC 將獲得相當多的免費藥品運輸。我們的指導中對此進行了一些考慮，但實際上預計 PFIC 將在 2025 年開始做出更多貢獻。這是一個好的開始。然後關於丙二醇和臨床開發計劃，我將讓喬安妮談談。

Just to be clear, we have not seen PG toxicity in our clinical studies. And in the context of the PFIC label expansion, we and the FDA looked pretty carefully and kind of considered all of that patient experience data. This concern from the FDA really arose in light of the younger patients being considered for the expansion.

需要澄清的是，我們在臨床研究中尚未發現 PG 毒性。在 PFIC 標籤擴展的背景下，我們和 FDA 非常仔細地審視並考慮了所有患者體驗數據。FDA 的這種擔憂確實是由於考慮擴大年輕患者的範圍而引起的。

And we have seen -- warned about PG toxicity with other labels, for instance. So this is not new to us. We do feel comfortable that the physicians who are prescribing this know their patients, they know what to look for, they're appropriately monitoring. So we think from a practical perspective that this is well handled in terms of the routine patient care.

例如，我們已經看到其他標籤警告 PG 毒性。所以這對我們來說並不新鮮。我們確實感到放心的是，開處方的醫生了解他們的患者，他們知道要尋找什麼，他們正在適當地監測。因此，從實際角度來看，我們認為這在常規患者護理方面處理得很好。

Got it. Thanks.

知道了。謝謝。

Thanks for the question.

謝謝你的提問。

Ed Arce, H.C. Wainwright.

埃德·阿爾塞，H.C.溫賴特。

This is Thomas Yip substituting. I got a couple of questions for Ed. Perhaps first, just wondering for Chenodal how do you characterize the additional commercial opportunity in CTX as an on-label indication, I suppose in terms of quantity and also relative to Chenodal existing sales.

這是托馬斯葉 (Thomas Yip) 替補。我有幾個問題要問艾德。也許首先，只是想知道 Chenodal 您如何將 CTX 中的額外商業機會描述為標籤上的指示，我想是在數量方面以及相對於 Chenodal 現有銷售額的角度。

So thanks, Thomas, for the question. I'll ask Peter to comment on that, give some color on the undiagnosed population for CTX.

謝謝托馬斯提出這個問題。我會請 Peter 對此發表評論，對未確診的 CTX 族群進行一些說明。

As we look at the CTX opportunity, the best estimates from literature, market research, KOLs, probably somewhere between 1,000 and 2,000 prevalent patients with CTX in the United States. But only 10% of those are diagnosed right now. So it's the best estimate of what we see. So probably the biggest opportunity is if we can increase that 10% to something higher.

當我們審視 CTX 機會時，來自文獻、市場研究、KOL 的最佳估計，可能是美國 1,000 至 2,000 名 CTX 流行患者。但目前只有 10% 的人得到診斷。所以這是我們所看到的情況的最佳估計。因此，最大的機會可能是我們能否將 10% 提高到更高的水平。

So we are investing in disease state awareness initiatives, reaching out to physicians who may see these patients as they're presenting with various symptoms on their journey to a diagnosis and trying to both increase the rate of diagnosis as well as speed up the time to get to thediagnosis. And have seen a lot of interest from prescribers, neurologists and other physicians kind of take interest in that.

因此，我們正在投資疾病狀態意識倡議，接觸可能會看到這些患者的醫生，因為他們在診斷過程中出現了各種症狀，並試圖提高診斷率並加快診斷時間。我們看到處方醫生、神經科醫生和其他醫生對此表現出了濃厚的興趣。

And then if chenodiol is approved by FDA and we're able to promote -- certainly, the product has never been promoted before. So I think there'll be an opportunity to get out there and, even for the diagnosis patients in clinic, raise awareness of the benefits of --potential benefits of chenodiol, support reimbursement, things like that.

然後，如果鵝二醇獲得 FDA 批准並且我們能夠推廣——當然，該產品以前從未推廣過。因此，我認為將有機會走出去，甚至對於臨床診斷患者來說，提高人們對鵝烯二醇的潛在好處、支持報銷等好處的認識。

Understood. And maybe one more from us. Just one for volixibat. Regarding VANTAGE and VISTAS, has the FDA or the EMA reviewed the interim data that you have so far? Any feedback from any regulatory agencies?

明白了。也許我們還提供了一份。沃利西巴特只有一顆。關於 VANTAGE 和 VISTAS，FDA 或 EMA 是否審查了你們迄今為止掌握的中期數據？有任何監管機構的回饋嗎？

In the cadence here of regulatory review, we have had a pre-IND discussion designing the studies. And the next opportunity would be after we have final results, is what our plans are. So no kind of interim discussions on plans.

按照監管審查的節奏，我們在 IND 前進行了設計研究的討論。下一個機會是在我們得到最終結果之後，這就是我們的計劃。因此，沒有就計劃進行任何臨時討論。

Thank you so much for taking my questions.

非常感謝您回答我的問題。

Yes, thanks for the question.

是的，謝謝你的提問。

And that was our last question. So I will hand back over to Chris Peetz, the CEO, for any final remarks.

這是我們的最後一個問題。因此，我將把最後的發言權交給執行長 Chris Peetz。

Thank you, operator, and thank you all for joining us today. We appreciate the support for Mirum and our programs. Have a good evening. Bye.

謝謝運營商，也謝謝大家今天加入我們。我們感謝對 Mirum 和我們計畫的支持。祝你晚上愉快。再見。

And this concludes today's call. Thank you for joining. You may now disconnect from the call.

今天的電話會議到此結束。感謝您的加入。您現在可以斷開通話。